Pediatric Blueprints Notes

Pediatric Blueprints Notes Chapter 1 – General Pediatrics Nothing much of note beyond developmental milestones, nutrition guidelines, and specific points for anticipatory guidance -see charts with pertinent info below Chapter 2 – Neonatal Medicine -height, weight, and head circumference are in reference to the patient’s gestational age -weight less than the 10th percentile is considered “small for gestational age” -increased risk of neonatal death compared to the general neonate population -small growth parameters do not necessarily indicate pathology, and many babies are stable on lower curves -weight greater than the 90th percentile is considered “large for gestational age” -common among neonates that are post-term (42nd week or later) -increased risk of birth trauma, polycythemia, and hypoglycemia -intrauterine growth restriction (IUGR) = reduced growth during the fetal period as assessed by imagining -early onset: insult before 28 weeks, but at birth the length and head circumference are appropriate for the neonate’s weight -late onset: insult after 28 weeks (commonly of infectious etiology) that results in relatively normal head circumference with reduced weight and height -initial assessment of newborn: -overall appearance (“well” vs. “toxic”) -general body habitus -distress -color (pink vs. cyanotic) Skin evaluation -common birthmarks: -salmon patch (= nevus simplex, stork bite): non-blanching hemangiotic lesions commonly on the eyelids and posterior neck -become more prominent with bathing but ultimately fade over time -Mongolian spot = flat, dark blue/blat pigmented patches on the lower back -fade over time, but may be mistaken for bruising and abuse -commonly acquired skin lesions in the first month of life: -milia = pearly white or pale yellow epidermal cysts on the nose, chin, and forehead; disappear without treatment within a few weeks -erythemia toxicum = transient papules, vesicles, and pustules that occur on the trunk and spread to the extremities -usually appears 24-72 hours after birth -individual lesions are usually only present for a few hours -resolves without therapy; not clinically significant -infantile seborrhea (= cradle cap) = dry, scaling, crusty lesions on the scalp that usually appear 2-10 weeks after birth -lesions are sharply demarcated from normal skin -treatment is hydration with baby oil, anti-dandruff shampoo, and, in severe cases, hydrocortisone cream/ointment -neonatal acne = pustules and papules that appear 3-4 weeks following birth -due to secondary maternal hormone stimulation -no treatment required; will resolve as hormone levels normalize Cardiac evaluation

-S1 and S2 should be heard clearly, though S2 splitting may not be appreciated due to the quick neonatal HR -murmur may be appreciation during the first few days due to a PDA; typically best appreciated on the left USB -palpate brachial and femoral pulses to ensure that they are equal, not brisk, and not delayed Lung/chest evaluation -rhonchi are common after birth due to amniotic fluid that remains in the lungs -increased RR, grunting, and nasal flaring are signs of respiratory distress and are indications for a work-up -respiratory distress is NOT always due to a primarily respiratory cause; sepsis and congenital heart defects are common disorders that can present with respiratory distress -unexplained hoarseness while crying warrants investigation (possible obstruction, paralysis, infection, etc.) Abdominal evaluation -abdomen commonly appears full due to immature musculature -distension generally indicates a congenital obstruction -the liver and spleen may be palpable -umbilical hernias are very common -become larger with increases in abdominal pressure (e.g., stooling, crying, laughing, etc.) -generally resolve without intervention; persistence past age 3-4 may require surgical repair -inspection of the umbilical cord -ensure that three vessels are present – two-vessel cords are associated with GI and renal abnormalities -the cord stump will eventually fall off in 3-4 weeks; persistence of the cord past 8 weeks is abnormal and may indicate neutrophil dysfunction Genital evaluation -females: -the labia minora and clitoris may appear relatively large -mucus and blood in the introitus is not abnormal -skin tags may be present around the vagina and anus -ambiguous genitalia warrants a work-up (most common cause in females is congenital adrenal hyperplasia) -males: -uncircumcised males typically have a foreskin that is difficult to retract -common abnormalities: -hypospadias: urethral opening present on the inferior side of the penis -chordae: fixed bowing of the penis ventrally due to fibrotic tissue -retractile testes: testes located in the abdomen that can be massaged into the scrotum -cryptorchidism: undescended testes that cannot be palpated in the abdomen or cannot be moved to the scrotum with palpation (repaired surgically if the testis does not descend by 1 year) -inguinal hernia: mass in the groin that increases in size with crying and straining -hydrocele: collection of fluid in the scrotum due to persistence of the processus vaginalis; mass will trans-illuminate and usually resolves by 1 year Head evaluation -asymmetry of the head is a common result of vaginal birth (= “molding”) -caput succedaneum = marked asymmetry of the head due to edema of soft tissues -firm but pits to pressure -associated with vacuum extractions

-cephalohematoma = bleeding into the subperiosteal space; limited by suture lines and does not cross the midline -open anterior and posterior fontanels may be present -a bulging anterior fontanel is usually due to hydrocephalus -the face is also often asymmetric and may be bruised due to delivery -abnormal facial features may be syndromic and warrant precise characterization -newborns are often reluctant to open their eyes due to edema of the lids and environmental brightness -assess for symmetry and the presence of a red reflex -dysconjugate gaze is present during the first 4-6 months -mild asymmetry of the nose is common due to uterine compression -neonates are obligate nose breathers -choanal atresia = blockage of the posterior nasal airway by a membrane or bone -presents with respiratory distress and cyanosis depending upon the severity of obstruction – look for resolution of cyanosis during crying (the only time neonates breath through the mouth) -may be repaired with surgery if obstruction is serve and does not resolve -perioral cyanosis is normal (as is peripheral cyanosis of the hands and feet) -discoloration of the lips or tongue is indicative of central cyanosis and warrants immediate work-up and intervention -inspect for cleft lip, cleft palate, and bifid uvula -some abnormalities may be subtle, impairing speech and feeding later in life -newborn necks are very flexible and relatively short -torticollis = restriction of neck turning due to unilateral fibrosis of the SCM that results in muscle shortening -palpate for masses or cysts Upper extremity evaluation -palpate clavicles to evaluate for clavicular fracture during birth -presence of crepitus does not require XR evaluation unless gross deformities or abnormal arm movements are appreciated -incomplete fractures do not require therapy; complete fractures should be immobilized for proper healing -movement of the arms and hands should be symmetric and free -minor flexion contractures of the elbows, knees, and hips are normal -common abnormalities: -Erb’s palsy (C5-C6 damage) = internally rotated, extended elbow that is held close to the body with the forearm held in a pronation; hand movements are not affected -Klumpke’s paralysis (C7-T1 damage) = weak hand muscles with possible absence of the grasp reflex -both of these usually resolve without intervention within 48 hours -persistent lesions usually see gradual improvements over the next 6-18 months Lower extremity evaluation -creases along the thighs and buttocks should be symmetric; asymmetry warrants investigation for possible hip dysplasia -the feet should be examined for gross abnormalities (e.g., curving of the forefoot, clubbing) Back evaluation -inspect for dimples, hair tufts, and hemangiomas, which may be associated with underlying spinal cord defects -small dimples within 2.5 cm of the anal verge are common and generally benign -if abnormalities are present, imaging with MRI to evaluate for possible spinal cord lesions is appropriate Neurologic evaluation

-neonates should have good tone, be arousable from sleep, and be calmed with sucking or feeding -multiple beats of ankle clonus is not abnormal -the specific newborn reflexes are discussed elsewhere Before the Delivery: Prenatal Conditions Abnormalities in amniotic fluid volume -polyhydramnios = excessive amniotic fluid -most commonly due to impaired fetal swallowing -other common possibilities: multiple fetuses, hydrops fetalis, and gestational diabetes -oligohydramnios = reduced amniotic fluid -most commonly due to renal disease (specifically, bilateral renal agenesis -> Potter syndrome) -usually results in death during the fetal period due to respiratory insufficiency -complications include restriction of fetal movement, inability to expand lungs, and reduced placental blood flow (in severe cases) -common congenital/perinatal infections: Perinatal Infections Infection Transmis Presentati Diagno Treatm Complicat Prevent sion on sis ent ions ion CMV During Usually CMV Supporti Most Antibody gestation; asymptomat detecte ve care; common testing maternal ic; d in gancyclo infectious before or fluids microcephal neonat vir trials cause of during (e.g., milk) y, blueberry al urine currently sensorineu pregnan muffin in ral hearing cy spots, progress loss jaundice, HSM, periventricul ar calcification s, chorioretiniti s HSV Exposure Mucocutane Viral Acyclovir Disseminat Delivery during ous (skin, culture; ed disease by C vaginal eye, mouth) PCR has high section if delivery; lesions, mortality vaginal most encephalitis, (50%); lesions mothers systemic encephaliti are are disease s can result present asymptom in atic permanent neurologic al damage Parvovirus Vertical Hydrops Matern Blood None if n/a fetalis al Ig transfusi fetus levels ons, survives supporti initial ve care infection HIV Vertical Generally PCR HAART Antibody (more asymptomat testing likely with ic; may to

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docume nt infection ; ZDV througho ut pregnan cy and to the infant for 6 weeks decrease s transmis sion to 5 mg/dL -direct hyperbilirubinemia = conjugated bilirubin greater than 2 mg/dL or 15% of total bilirubin level -all other hyperbilirubinemias are indirect -in neonates, unconjugated bilirubin may reach 12 mg/dL in otherwise healthy individuals -physiologic jaundice = elevated indirect bilirubin in the absence of specific pathology or abnormalities in bilirubin metabolism -never presents before 24 hours and generally normalizes over the first 2-3 weeks of life -breast milk jaundice = similar to physiologic jaundice but with higher bilirubin levels for a longer duration of time -etiology is unclear – may be due to unknown factor secreted with maternal milk that increases enterohepatic circulation -current recommendation is to NOT interrupt breast milk feeding even in the face of highly elevated levels -distinguishing between physiologic and non-physiologic jaundice is an important point of the jaundice work-up -findings that suggest a pathologic, non-physiologic jaundice: -jaundice prior to 24 hours of life -jaundice in the setting of traumatic delivery

-need for phototherapy -persistent jaundice (longer than 8 days at term, 14 days pre-term) -jaundice in the setting of an ill-appearing child -family history of hemolytic anemia, liver disease, or a sibling with non-physiologic jaundice -most common cause of non-physiologic jaundice is ABO incompatibility -usually an issue in neonates with A/B blood and a type O mother -results in a hemolytic anemia that lyses RBCs and releases bilirubin -lab findings: positive Coombs and elevated reticulocyte count -other important cause is Rh incompatibility -due to maternal sensitization to Rh (usually via birth of an Rh positive child in a Rh negative mother) and subsequent pregnancy with another Rh positive fetus -same general process as ABO incompatibility, but the hemolysis is generally more severe -treat with prophylactic antibodies to anti-Rh (Rhogam) perinatally -important causes of conjugated hyperbilirubinemia: biliary atresia, hepatitis, infection, and metabolic disease -the production of direct bilirubin suggests that hepatic function itself is likely not impaired; instead, the defect is likely due to processing and/or excretion of direct bilirubin following conjugation -conjugated hyperbilirubinemia is never physiologic -other causes to consider for indirect hyperbilirubinemia: -intrinsic RBC/Hb defects: hereditary spherocytosis, thalassemias, etc. -bacterial sepsis -drug reaction -treatment is centered on preventing kernicterus (= deposition of bilirubin in the brain) -due to deposition, widespread cerebral dysfunction occurs, particularly in the basal ganglia, cerebellum, and brainstem -phototherapy (promotes breakdown of bilirubin) is used in some cases -exchange transfusions can be performed in cases with highly elevated levels Congenital Anomalies Cleft lip and palate -while cleft lip generally does not produce functional problems and is largely cosmetic, cleft palate makes infants more prone to choking -cleft lip repair occurs shortly after birth or when steady weight gain is established -cleft palate repair usually occurs at 9-12 months; complications can include speech difficulties and dental abnormalities Tracheoesophageal fistula (TEF) -strongly associated with esophageal atresia (= incomplete anastomosis between the proximal and distal esophagus) -characterized by abnormal communication between the esophagus and trachea -up to 40% of patients with TEF have other congenital abnormalities -presents with excessive oral secretions (2/2 inability to drain to GI tract), inability to feed, and respiratory distress -on fetal US, may find polyhydramnios 2/2 inability to swallow amniotic fluid -treatment is surgical correction -strictures commonly develop at the site of anastomosis; requires regular dilation to maintain patent lumen Duodenal atresia -due to failure of the lumen to recanalize during weeks 8-10 of gestation -results in a partial or complete anatomic obstruction -commonly associated with other congenital abnormalities, including cardiac defects and GI anomalies (e.g., annular pancreas, malrotation, and imperforate anus) -associated with trisomy 21 -presents with bilious emesis shortly after birth

-abdominal XR usually demonstrates distension proximal to the obstructed site, particularly in the proximal small bowel and stomach (= double bubble sign) -gas in the distal bowel suggests partial obstruction -treatment: surgical correction Congenital diaphragmatic hernia -usually due to a defect in the left posterolateral diaphragm which allows herniation of abdominal contents -lethal when in combination with pulmonary hypoplasia or pulmonary hypertension -presents with decreased breath sounds on the left, right-sided heart sounds, and a scaphoid abdomen (= concave rather than convex curvature of the abdomen) -management includes decompression of the GI tract to minimize pulmonary compression and ventilation/oxygenation support as needed -treatment: surgical correction Omphalocele and gastroschisis -omphalocele = herniation of abdominal viscera through the umbilical and supraumbilical portion of the abdominal wall -results in protrusion of abdominal viscera contained within peritoneum -gastroschisis = omphalocele sans peritoneal covering -surgical emergency – closure occurs immediately after birth Biliary atresia -absence of the common bile duct, resulting in a reduced or absent ability to excrete bile -presents with conjugated hyperbilirubinemia -persistent cholestasis produces liver fibrosis, portal hypertension, biliary hepatitis, and ultimately liver failure -initial management is with a temporary shunt from the liver to the intestine to allow for bile drainage -ultimate treatment is liver transplant Before Discharge Home -term, well-appearing infants are typically discharged from the hospital 48 hours after birth -discharge after 24 hours is appropriate if the family is ready for care and no abnormalities in the child are noted -neonates born by C section are typically discharged after 72 hours -typical screening tests include a blood screen which tests for various state-mandated disorders and a hearing test -antibiotic eye drops (erythromycin) to prevent gonorrhea and chlamydia are provided in addition to an injection of vitamin K to prevent coagulopathy 2/2 vitamin K deficiency Health Maintenance Visits -infants should be seen 1 week after hospital discharge -weight loss of 5-7% following discharge is normal; loss up to 10% warrants close follow-up but is not necessarily pathological -any lost weight is usually regained within 2 weeks -neonates should be started on supplemental vitamin D within a few days of birth to prevent rickets -breast milk does not contain adequate vitamin D Chapter 3 – Adolescent Medicine -puberty = process of hormonal and physical changes that results into maturation into an individual physiologically capable of sexual reproduction -adolescence = process of physical and emotional/cognitive changes that occur during the transition from youth to adulthood -three different phases of adolescence: -early: ages 10-13 -middle: ages 14-17 -late: ages 18-21 -important developmental tasks of adolescence: -development of a strong self-identity

-establishing autonomy -embarking on and desiring achievement -developing personal and sexual relationships -cognitive transition from concrete thinking to more abstraction -because of the increased incidence of high-risk behavior and otherwise modifiable risk factors, regular contact with a physician during adolescence is critical -most of the clinical visit with adolescents should be in the absence of the parent(s) -most states have privacy exceptions with respect to sexual activity and substance use/abuse -never withhold emergent treatment in favor of obtaining parental approval -universal exceptions to confidentiality include plans for self-harm and mandated reporting of abuse -basic male development: testicular enlargement -> pubic hair -> penis lengthening -> maximal height velocity -basic female development: thelarche (breast budding) -> pubarche -> maximal height velocity -> menarche -for sexually active teens, regular screening for gonorrhea, chlamydia, HIV, and syphilis are appropriate -regular pap smears are recommended starting at age 21 or at the onset of sexual activity -hearing screen, H&H, and lipid panel at least once during adolescence are recommended -vision checks every 3 years are also recommended Eating Disorders -desire to be accepted by peers leads to a preoccupation with physical appearance during adolescence -two common eating disorders: -anorexia nervosa: inability to maintain at least 85% of healthy height/weight for age -may present with constipation, syncope, upper/lower GI discomfort -secondary amenorrhea may present in girls that have started their period and is a diagnostic criterion -usually present severely underweight (BMI < 17) -vital signs generally demonstrate hypothermia, bradycardia, and orthostatic hypotension -cardiac murmurs consistent with MVP are common in adults with eating disorders -bulimia nervosa: binge eating followed by some kind of compensatory mechanism to rid the body of excess calories; to be diagnosed, must have at least 2 episodes weekly for 2 months -in general, eating disorders are much more prevalent in women than men (9:1) -the diagnosis is clinical – no specific testing is indicated unless there is concern for more serious, organic causes for weightloss -treatment is multidisciplinary: nutrition support, behavioral therapy, psychotherapy, and correction of medical complications are the main objectives -medical intervention is currently being investigated -full recovery can take years Substance Use and Abuse -drug use = intentional ingestion of exogenous compounds that results in physical, psychological, cognitive, or mood changes -drug abuse = functional impairment directly or indirectly due to drug use -see below for chart of commonly used substances and their effects/complications Violence in the Adolescent Population -traumatic injury is the leading cause of death among teens -strongest risk factor for attempted suicide: prior attempt(s) -living in a home with firearms increases the risk of successful suicide 10-fold Chapter 4 – Nutrition

-certain diets predispose to certain nutritional deficits and warrant careful surveillance -vegan diets: vitamin B12 and D deficiencies -vegan and lacto-ovo vegetarians: iron deficiency -trends on a growth chart are key to monitoring appropriate growth and development -general growth trends: double in weight by 4-5 months and triple in weight by 1 year -height doubles by age 3-4 and triples by age 13 Infant Feeding Issues -breastfeeding is almost ALWAYS preferred over formula -newborns feed on demand (usually every 1-2 hrs) and regulate caloric intake effectively -when introducing foods, introduce one at a time to monitor for allergies or other adverse reactions -whole fat cow’s milk should be introduced at 1 year and continued until 2 years; at that point, switching to a lower fat content milk should occur -infants should not bed fed milk without supervision due to risk of developing milk-bottle cavities and tooth decay Breastfeeding -AAP recommends exclusive breastfeeding through 6 months and continuation of breastfeeding with other dietary intake through 12 months -breastfed infants have lower incidence of infections (2/2 passive immunization from IgA in maternal milk), allergy-based disorders, and feeding intolerance -due to poor vitamin D levels in breast milk, vitamin D supplementation should begin within 1 week of life -contraindications to breastfeeding: maternal HIV infection, untreated/active TB, illegal drug use, and maternal use of some drugs (antithyroid agents, Li, INH, and most chemo agents) Infant feeding intolerance -may present in a variety of ways, but most commonly presents with malabsorption, allergy, or colitis -other nonspecific symptoms include vomiting, irritability, and abdominal distension -the most common cause of feeding intolerance is colic (= recurrent irritability that persists for several hours, generally in the PM, with inconsolable crying that begins and ends abruptly) -exclusive breastfeeding if the child is formula-fed as allergies are a common cause of feeding intolerance -if no other organic cause is found, use of formula with hydrolyzed protein to minimize possible milk/soy allergy is recommended Failure to thrive -defined as persistent weight below the 3rd percentile OR falling from an established growth curve -jumps/falls in the growth curve are not uncommon during the first 9-18 months; at this point, growth is more strongly determined by genetic factors rather than nutritional status -breastfed infants especially may fall slightly when switching over to non-breast milk nutrition -associated with developmental delay, especially if growth failure occurs during the first year (i.e., during period of rapid brain development) -in developed countries, most causes are functional rather than organic -organic causes very seldom present with isolated failure to thrive -detailed diet history, including feeding schedule and content, is critical to diagnosis -information about urination and stooling is also important -psychosocial concerns should be investigated (e.g., inability to acquire formula) in addition to travel/exposure history -on exam, be observant of abnormal interactions with the child – strongly suggests psychosocial involvement -evaluation should include a CBC (anemia evaluation) and BMP to ensure adequate electrolyte levels Obesity

-defined as a BMI over the 95th percentile -a BMI within the 85th-95th percentile is considered overweight -adipose proliferation is especially prominent during 2-4 years and puberty, thus issues with obesity should be addressed early to prevent problems in adulthood -long-term complications include metabolic syndrome (= obesity, hypertension, insulin resistance, and dyslipidemia), depression, OSA, gall bladder pathology, LE skeletal abnormalities, and early onset puberty Chapter 5 – Fluid, Electrolyte, and pH Management -maintaining homeostasis with respect to body fluid chemistry is especially limited in children due to undeveloped organs; this is especially true in children born premature Maintenance Fluids -fluid losses are either sensible or insensible -sensible = losses from urine, stool, and other measurable sources -insensible = losses from the skin and lungs (“insensible” = “not sensed”) which cannot be measured -fluid needs are weight-dependent can be estimated using the Holliday-Segar method -maintenance fluids can be estimated as: 100 mL/kg/d for the first 10 kg, 50 mL/kg/d for the next 10 kg, and 20 mL/kg/d for each kg afterward -can also be stated as the 4-2-1 rule: 4 mL/kg/hr for first 10 kg, 2 mL/kg/hr for the next 10 kg, and 1 mL/kg/hr for each kg thereafter -for each 100 mL of fluids, 3 mEq of Na and 2 mEq of K are required -carbohydrate source is also needed to prevent catabolism (1/4 NS in D5 is usually sufficient) -in adults and adolescents, 1/2 NS in D5 is used Dehydration -usually due to secondary causes, i.e., vomiting and diarrhea -when replacing fluids for dehydration, must provide maintenance fluids AND fluids to replace the initial deficit and any ongoing losses -usually presents with weight loss, decreased urine output, and changes in stool frequency/quality -unlike adults, who generally present with hypotension, children usually present with tachycardia; low BPs in a dehydrated infant indicate severe dehydration and warrants immediate intervention -see below for chart of findings and estimate of degree of dehydration -multiple types of dehydration based on sodium levels: -isotonic dehydration: reduced fluid volume with a normal Na level; correct with isotonic fluids -hypotonic dehydration: reduced fluid volume with Na < 130; common in patients with electrolyte loss in stool; correct with free water or dilute fluid replacement -hypertonic dehydration: reduced fluid volume with elevated Na; usually indicates free water loss (e.g., DI) -severe dehydration may result in reduced kidney perfusion with elevations in BUN and Cr -treatment: oral rehydration therapy with a fluid that contains Na, K, and glucose (free water is NOT recommended as it may precipitate hyponatremia) -in severe cases, IV fluids are indicated; children in shock should receive 20 mL/kg boluses until BP normalizes -deficits are usually replaced with the first 24 hours, with half in the first 8 hours and the rest over the next 16 hours -exception: children with hypernatremia; replace over 48-72 hours to prevent excessive fluid shifts and their complications (e.g., cerebral edema) Hyponatremia -can occur in the context of hypovolemia, euvolemia, or hypervolemia -usually presents with GI and cognitive changes: anorexia, nausea, confusion lethargy, and decreased tendon reflexes -seizures and respiratory arrest are complications of severe hyponatremia (Na < 125)

-Na levels must be corrected in the context of glucose: add 1.6 mEq to serum Na for every 100 mg/dL rise in blood glucose above 100 mg/dL -treatment: fluid replacement as above -Na correction should occur at a rate of 1-2 mEq/hr to prevent fluid shifts unless the patient is unstable Hypernatremia -rare in a setting other than dehydration -treated with NS until normal Na level is achieved (correct at a rate of 1-2 mEq/hr) Hyperkalemia -common causes in children: acidosis, severe dehydration, K-sparing diuretic use, excessive parenteral infusion, renal failure -other more serious causes: crush injury with rhabdomyolysis (K released from myocytes), Bblocker/digitalis ingestion, excessive K supplementation, RTA, and corticosteroid deficiency -presents early with paresthesias and weakness; later findings are cardiac in nature, including peaked T waves and widened QRS complexes -treatment: calcium gluconate, which stabilizes the cell membrane, and sodium bicarb or insulin/glucose, which drive K into the cell -hyperventilation also promotes transcellular K shifts due to H/K transporters involved with CO2 buffering Hypokalemia -usually in the setting of alkalosis 2/2 vomiting, DKA, or excessive use of loop diuretics -presents with weakness, tetany, constipation (all due to altered membrane dynamics), polyuria, and polydipsia -ECG may demonstrate QT prolongation and T wave flattening -treatment: K replenishment, either orally (preferred) or IV (infusion can be painful) Calcium and magnesium homeostasis -hypomagnesemia is generally due to dietary deficiency or renal losses -hypocalcemia and/or hypokalemia are generally precipitated by hypomagnesemia (and may present with their associated symptoms) -magnesium is efficiently excreted by the kidneys, so hypermagnesemia is generally not a problem in the absence of extreme intake or maternal Mg therapy (e.g., due to eclampsia) -treatment for hypermagnesemia: IV calcium (acts as a competitive divalent cation) or, in severe cases, dialysis Metabolic acidosis -defined as pH < 7.35 -due to the loss of bicarb or addition of excess H+ -important diagnostic differentiation: gap vs. non-gap (i.e., is [Na+] – ([Cl-] + [bicarb]) greater than 12 or less than 12) -respiratory compensation begins immediately -to determine appropriate compensation: PaCO2 should be 1.5[bicarb] +/- 8 -treatment: correction of underlying disorder -infusion of bicarb should only occur in serious acidosis Metabolic alkalosis -defined as pH > 7.45 -contraction alkalosis occurs in the setting of fluid loss 2/2 elevated H+/Cl-usually due to vomiting or chronic diuretic use -therapy is volume expansion and correction of electrolyte abnormalities, if present Respiratory acidosis and alkalosis -important: CO2 is equivalent to acid for the purposes of considering acidosis/alkalosis -with this in mind, acidosis is due to retention of CO2 2/2 inability to exhale; causes include anything that can produce respiratory insufficiency -alkalosis is due to excessive “blow off” of CO2; causes include hypoxia, restrictive lung disease, medications, and central hyperventilation -in both cases, treatment is directed at correcting the underlying cause, if possible Chapter 6 – Dermatology

Skin Manifestations of Viral Illnesses Hand-foot-disease – due to Coxsackievirus A; common in spring/summer; football-shaped lesions; supportive treatment Giannoti-Crosti syndrome – acrodermatitis (involvement of the extremities primarily) common in 1-6 y/o following URI; spares the trunk Varicella – due to VZV -lesions start on the trunk and spread peripherally -lesions are at different stages and usually present in “crops -treatment is supportive, don’t use aspirin (Reye’s syndrome) -reactivated in adult life as zoster and lies dormant in dorsal root ganglia -contagious from 24 hours before onset of rash until all lesions have crusted over Molluscum contagiosum – flesh-colord, pearly, umbilicated, dome-shaped papules; -most common in axillae, groin, and butt but can appear anywhere -lesions resolve spontaneously but can be treated via excision, cryotherapy, and various creams Verrucae (warts) – caused by HPV and removed via a variety of means Presumed Viral Exanthems Pityriasis roasea – presents initially with a salmon rash on the trunk, neck, upper extremities, or thigh followed by smaller lesions in a “Christmas tree” pattern; can develop scale and be confused with fungal infection; self-limited with supportive treatment Unilateral thoracic exanthem – variable rash that begins on one side of the trunk and spreads peripherally; often confused with contact dermatitis; resolves over 6-8 weeks, sometimes with desquamation or permanent pigment changes Skin Manifestations of Bacterial Infections Bullous impetigo – due to S. aureus; starts as red macules that progress to bullae that can become large; can be mistaken for cigarette burns Nonbullous impetigo – due to GAS or S. aureus; rash starts as papules that progress to vesicles and then pustules -local disease can be treated with antibiotic creams while diffuse disease can be treated with 1st gen cephalosporin Staphylococcal scalded skin syndrome (SSSS) – due to S. aureus -rare after age 5 -bullae form and rupture quickly with skin tenderness, fever, and irritability -most common in the perioral, neck, axillary, and inguinal areas -positive Nikolsky sign (skin rubs off with light pressure) Folliculitis – infection of the hair follicle shaft usually by S. aureus -deeper infections produce boils and carbuncles -effectively treated with antiseptic washes and topical mupirocin -think of Pseudomonas if recent hot tub exposure Superficial Fungal Infections Tinea capitis – presents with patches of scaling and hair loss on the scalp and boggy, pustular lesions (kerions) Tinea corporis – annular plaques on the skin with peripheral scaling (looks like rings -> called ring worm) Tinea pedis – scaling along the foot, especially between the toes Tinea cruris – erythema, swelling, scaling, and maceration of inguinal creases The above can usually be treated with a topical antifungal (e.g., clotrimazole); systemic therapy (griseofulvin) necessary in severe cases and tinea capitis Tinea versicolor – caused by infection with Malassezia furfur; produces tan or hypopigmented ovals on the neck or upper back/chest/arms Diaper rash – usually due to atopic dermatitis, candidiasis, or irritation dermatitis Acne Vulgaris -disease of the pilosebaceous unit of the skin -prevalence of serious disease is 10x more common in boys than girls

-pathogenesis: multifactorial, including androgen stimulation of sebaceous glands, follicular plugging, proliferation ofPropionibacterium in follicles, and inflammation -comedones (whiteheads and blackheads) are non-inflammatory and generally non-scarring -pustules, papules, and nodules are inflammatory and have an increased risk of scarring -risk factors: family history, puberty, PCOS (girls), and (rarely) diseases that produce androgen excess -treatment is dependent upon severity and inflammatory vs. non-inflammatory: -mild: -non-inflammatory: topical retinoid (anti-comedogenic) -inflammatory: benzoyl peroxide (BP) +/- erythromycin + retinoid -moderate: -non-inflammatory: topical retinoid -inflammatory: BP +/- erythromycin + retinoid + short-term oral antibiotic if initial response is poor -severe: -non-inflammatory: topical retinoid -inflammatory: isotreitinoin if poor response to therapy for moderate -in females, OCP can be considered due to anti-androgen effects Psoriasis -presents with a nonpruritic, papulosquamous eruption with papules that coalesce to form dry plaques with silvery scales and sharp borders with a predilection for extensor surfaces (e.g., elbows) -may be instigated by infection with GAS -removal of scales may result in pinpoint bleeding (= Auspitz sign) -lesions often appear at sites of physical, thermal, or mechanical trauma (= Koebner phenomenon) -multiple lesions on the extremities: nails may detach, accumulation of subungal debris may occur, and scaling/fissuring of the palms and soles may occur -treatment: topical steroids along with aggressive hydration of the skin -can add vitamin D, some evidence of benefit -sunlight/UVB light is helpful in severe cases -methotrexate or etanercept can be considered in particularly severe cases Eruptions Secondary to Allergic Reactions Erythema multiforme -presents with symmetric distribution of lesions that progress through a particular series of morphological changes over the course of several days: -erythematous macules -> papules -> plaques -> vesicles -> target lesions -lesions usually develop dusky, necrotic centers -lesions are most commonly located on the dorsal hand and feet, palms and soles, and extensor surfaces of the extremities with occasional spread to the trunk -lesions may produce burning or itching and often present with fever, malaise, and myalgias -recurrent EM is commonly due to HSV-1 -treatment: symptomatic; lesions resolve over 1-3 weeks, usually leaving hyperpigmentation Steven-Johnson syndrome (SJS) -prodrome of 1-14 days that includes fever, malaise, myalgias, arthralgias, arthritis, headache, emesis, and diarrhea -prodrome followed by sudden onset high fevers, erythematous/purpuric macules with dusky centers, and inflammatory bullae of the mucosa -most common precipitants: NSAIDs, penicillins, sulfonamides, and AEDs Toxic epidermal necrolysis -more severe variant of SJS with involvement of more than 30% of the body surface -presentation resembles that of SSSS with widespread erythema, blister formation, and complete detachment of the epidermis -treat like 2nd degree burn: aggressive fluids, reverse barrier isolation -IVIg is controversial but may have some effect

Allergic Drug Reactions -usually present with urticarial or morbilliform (= measles-like) rash 1-2 weeks after new medication -treatment is supportive, offending drug should be discontinued if possible Infantile Hemangiomas -vascular tumors that usually present in the first month of life, grow over the next year, and begin to involute -multiple types: -superficial = bright red and noncompressible -deep = subcutaneous, compressible, and bluish hue with telangiectasias -mixed = characteristics of both -must distinguish from more aggressive tumors (don’t resolve) and vascular malformations (don’t resolve and generally worsen with time) -involution may take years, but most lesions are resolved by 10 y/o -treatment is generally observation and reassurance with some exceptions: -large lesions may cause heart failure due to hemodynamic instability -lesions along the airway may cause compromise -periocular lesions have a risk of causing blindness -> must treat -multiple lesions may be associated with liver and other visceral hemangiomas -propranolol, corticosteroids (local or systemic), and excision are treatment options -vincristine and IFN-alpha can be used in very severe cases Chapter 7 – Cardiology Heart Murmurs -1/3 of children have benign, functional heart murmurs -symptoms of more concerning murmurs include: -heaves, thrills, or otherwise abnormal precordial activity -delayed or decreased pulses -abnormal splitting of S2 -extra heart sounds, including ejection clicks, opening snaps, murmurs, and rubs -presence of S3/S4 -heart disease usually presents with difficulty feeding, tachypnea, irritability, diaphoresis, cyanosis, and/or failure to thrive -critical points of evaluation: echo, EKG, +/- CXR -normal resting HR by age: -0-1 mo: 80-160 -1-3 mo: 80-200 -2-24 mo: 70-120 -2-10 yr: 60-90 -11-18 yr: 40-90 Cyanosis -characterized by bluish hue of mucous membranes, skin, and nail beds due to reduction in arterial O2 saturation (hypoxemia) -differential includes abnormalities of the cardiac, pulmonary, neurologic, and hematologic systems -cardiac: congenital heart disease (TA, TAPVR, transposition, TOF, tricuspid atresia) -pulmonary: ARDS, pneumomia, pulmonary HTN, airway obstruction, compression of the lungs (pneumothorax, chylothorax, hemothorax) -neurologic: CNS dysfunction (reduced respiratory drive, cerebral dysfunction), muscular atrophy, botulism, myasthenia gravis -hematologic: methemoglobinea (e.g., asphyxia), polycythemia -evaluation: -measurement of SpO2 pre-ductally (RUE) and post-ductally (LUE) -lower post-ductal SpO2 = differential cyanosis, due to deoxygenated blood from the pulmonary circuit

-lower pre-ductal SpO2 = reversible cyanosis, occurs only in the presence of transposition (concurrent pulmonary HTN or coarctation can also be present) -higher UE BPs compared to LEs suggests coarctation -hyperoxia test: measures SpO2 via ABG when breathing on RA vs. 100% O2 -improvement in SpO2 with 100% O2 strongly suggests pulmonary etiology -no improvement in SpO2 with 100% O2 suggests cardiac disease -treatment: -PGE1 should be started if congenital heart disease is suspected to maintain PDA for possible ductal-dependent lesions -if condition worsens with PGE1 administration, suggests obstruction of the pulmonary outflow tract (PGE1 administration -> maintain PDA -> return of unoxygenated blood to circulation 2/2 pulmonary outflow obstruction) Ductal-Independent Mixing Lesions -these lesions do not require a PDA for life but do require a concurrent lesion (PFO, ASD, VSD) to allow for adequate mixing of oxygenated/deoxygenated blood Truncus arteriosus -due to a single arterial vessel arising from the base of the heart from which the pulmonary, coronary, and systemic vessels arise in addition to a concurrent VSD -complete mixing of pulmonary and systemic blood occurs in the vessel -associated with DiGeorge syndrome (22q11 deletions) -CHF develops as pulmonary pressures fall (part of normal development), resulting in shunting of blood from the systemic circuit (high pressures) to the pulmonary circuit (which now has lower pressures) -presents with an ejection murmur at the left sternal border, a non-splitting S2, and widened pulse pressures with bounding pulses -time to presentation is variable and is dependent upon the degree to which blood flow is going to the pulmonary vs. systemic circuits, but usually presents by 1 mo -treatment is closure of VSD, separation of the pulmonary vessels from the TA, and connection of the RV to the separated vessels D-transposition of the great arteries -presents within 24 hours of birth, male predominance -aorta arises from the RV while the pulmonary vessels arise from the LV -deoxygenated blood from the RV enters the systemic circulation while oxygenated blood from the LV reenters the pulmonary circuit -patent foramen ovale (PFO) is necessary for survival to ensure adequate mixing of blood -treatment: PGE1 administration to support mixing of blood via the PDA until surgical switching of the vessels can occur (usually within 1 wk) Total anomalous pulmonary venous connection (TAPVC) -lesion that results in disconnection between LA and pulmonary veins -multiple types which vary based on how the blood from the pulmonary veins is returned to the vascular circuit -a PFO or ASD is necessary to allow oxygenated blood returning from the systemic circuit to get to the left heart and out the aorta -timing and severity of presentation is dependent upon the degree of return of pulmonary circulation and whether pulmonary circulation is obstructed -treatment: emergent surgery if obstruction is present, repair is elective if obstruction is not present Ductal-Dependent with Pulmonary Blood Flow Tricuspid atresia -complete atresia of the tricuspid that results in hypoplasia or absence of the RV -most cases associated with a VSD -> LA/LV provide both pulmonary and systemic outflow -most cases also associated with pulmonary stenosis -severity of symptoms is dependent upon severity of pulmonary stenosis -usually presents with progressive cyanosis during first 2 weeks of life, holosystolic murmur if VSD is present, and left axis deviation of ECG

-may also present with shock following ductus closure if systemic outflow tract abnormalities are present -treatment: start PGE1 to maintain ductus, surgical repair Tetralogy of Fallot -most common congenital heart disease -associated with 22q11 deletions -consists of four independent lesions: 1) VSD 2) RVH 3) pulmonary stenosis (2/2 RVH) 4) overriding aorta (partially obstructs the VSD) -usually presents with cyanosis due to right-to-left VSD (2/2 pulmonary stenosis) -PDA provides a compensatory left-to-right shunt -hallmark presentation: “tet spells” that consist of cyanosis, rapid/deep breathing, and agitation -due to transient increases in right-to-left shunts due to RV outflow tract obstruction -compensated by increasing SVR or preload (squat down, vagal maneuvers) which reverses the shunt -classic finding on CXR: “boot-shaped” heart -25% of TOFs are associated with a right-sided aortic arch -treatment: volume expansion and vasoconstrictors for cyanotic spells, eventual surgical repair Ebstein’s Anomaly -displacement of the septal leaflet of the TV into the RV, resulting in a merging of the RA and RV -produces hypoplasia of the RV along with TR; serious cases of TR require a PDA for a compensatory left-to-right shunt -RA is massively dilated due to ineffective pumping leading to supraventricular tachycardias (SVTs) -associated with maternal Li use -CXR demonstrates marked cardiomegaly and reduced vascular markings -initial treatment is PGE1 infusion to maintain PDA (provides pulmonary flow via fully functional LV) -surgery is AVOIDED due to poor results with TV modification Ductal-Dependent Systemic Blood Flow Lesions Hypoplastic left heart syndrome (HLHS) -combination of abnormal findings: 1) hypoplastic LV 2) AV stenosis or atresia 3) MV stenosis or atresia 4) hypoplastic ascending aorta -results in severely reduced systemic output; an ASD allows for flow from LH to RH, and a patent PDA provides for adequate systemic output -presents with severe shock when PDA begins to close -treatment: PGE1 to maintain PDA followed by palliative surgery (no corrective procedures available) Interrupted aortic arch -extreme form of coarctation of the aorta associated with 22q11 deletions that presents with one of three types (in distal -> proximal order): -type A: interruption distal to the subclavian -type B: interruption between the l. subclavian and l. common carotid -type C: interruption between the brachiocephalic and l. common carotid -systemic flow is dependent upon a PDA depending upon the degree of interruption -presents similarly to HLHS above and is treated similarly (PGE infusion to maintain PDA followed by surgical correction)

Acyanotic Disease (left-to-right shunts) ASDs -female predominance (2:1) -three types of defects: -ostium secundum: defect in the middle portion of the atrial septum -ostium primum: defect in the inferior portion of the atrial septum -sinus venosus: defect found at the junction of the RA and SVC/IVC -results in RA/RV enlargement and increased pulmonary blood flow (flow is left-to-right due to decreased pressures of right heart relative to the systemic circuit) -usually asymptomatic, but can present with exercise intolerance -can also present with SVT (2/2 atrial enlargement) or stroke (paradoxical embolus through ASD -> systemic circulation -> brain) -heart sounds: widely split S2 on inspiration (2/2 increased blood flow through ASD -> delays PV closing further) and systolic murmur in pulmonic window and diastolic rumble across lower right sternal border -secundum ASDs will often spontaneously close if small -ostium and sinus venosus defects must be closed surgically VSDs -five types of defects: -muscular: occur in the muscular portion of the septum -inlet: occur in the inlet portion of the septum beneath the TV (endocardial cushion defect) -conoseptal hypoplasia: occur in the outflow tract of the RV below the PV -conoventricular: occurs in the membranous portion of the septum -malalignment: due to incorrect alignment of the infundibular septum; anterior misalignment produces TOF while posterior misalignment produces aortic stenosis with hypoplasia or interruption of the aortic arch -small VSDs are generally left -> right -large VSDs result in equalization of RV and LV pressures, thus flow direction is dependent upon SVR and PVR -most flows are left -> right due to high SVR relative to PVR, but uncompensated defects may result in increased PVR and eventual reversal of flow (right -> left) (= Eisenmenger syndrome) -smaller VSDs produce harsher murmurs (located at the mid-low left sternal border) due to increased turbulence -most small VSDs close spontaneously -large VSDs must be treated surgically to prevent irreversible changes in the RH and pulmonary vasculature Common AV canal defect -associated with Down syndrome -due to defects in the endocardial cushions: results in a primum type ASD and an inlet VSD -two types: -incomplete: no communication between the AV values due to leaflet attachment to the muscular ventricular septum -complete: communication between the AV values due to no leaflet attachment, resulting in a left -> right shunt -may develop Eisdenmenger’s if untreated -murmurs are best heard at the lower LSB; S2 is split and fixed -surgical repair; complete CAVC is repaired quickly while incomplete CAVC is repaired when symptoms develop Patent ductus arteriosus (PDA) -DA connects the l. PA with the aorta, ensuring adequate blood flow during the fetal period -direction of flow is dependent upon SVR and PVR -small PDA with normal flow likely to be asymptomatic -larger PDA with left -> right shunting results in CHF (overload of the RV)

-physical exam findings: continuous murmur that peaks at S2 and bounding pulses (due to increased LVEDV) -cyanosis results if PVR increases 2/2 increased flow through the pulmonary vasculature (results in right -> left shunting) -treatment: indomethacin (lowers PGE levels, promoting closure; risk of renal insufficiency with treatment) -PDAs usually close by the first month but can be treated with embolization or device closure if it remains patent Coarctation of the aorta -male predominance (2:1) -strongly associated with Turner’s syndrome (45XO) in females -obstruction usually of the descending aorta at the side of DA insertion, increasing LV afterload -infants with severe lesions are PDA-dependent and may present with shock if PDA is closed -smaller lesions may be asymptomatic -physical findings: reduced or absent LE pulses with bounding UE pulses and UE hypertension -treatment is surgical repair (use PGE in severe lesions to maintain PDA) Aortic stenosis -due to thickened, rigid, non-compliant aortic valve (AV) -AV is commonly bicuspid rather than tricuspid -produces LVH due to increased LV afterload -presents with a murmur located at the right USB preceded by an ejection click -treatment is surgical repair, but restenosis is common; valve must usually be replaced at some point Pulmonic stenosis -due to stenosis of the PV -produces RVH due to increased RV afterload -in severe lesions, RV afterload may increase to such a degree that RA pressures increase and maintain a PFO, resulting in right -> left shunting -treatment: surgical or catheter repair; PGE in severe cases to maintain PDA prior to repair Acquired Structural Disease Rheumatic heart disease -complication of acute rheumatic fever (occurs in 50-80% of cases; sequela of GAS infection) -MR is the most common lesion, but aortic insufficiency may also occur -patients with severe disease present with frank CHF Kawasaki disease -may present with pericarditis, myocarditis, coronary arteritis, or coronary artery aneurysm (most severe complication) -aneurysm develops in ~25% of cases but regresses in most cases -early administration of IVIg reduces the occurrence of aneurysm as well as high-dose aspirin therapy -low-dose aspirin is continued after treatment (6-8 weeks if aneurysm has resolved, indefinitely if aneurysm remains) Endocarditis -microbial infection of the endocardium, usually in areas with turbulent blood flow (congenitally defective valves, previously damaged valves, replaced valves, etc.) -risk factors: IV drug use, indwelling central catheter, and prior cardiac surgery -no conclusive evidence that dental, GI, or GU procedures are associated with endocarditis -antibiotic ppx is only recommended in the following cases: -prosthetic valves are present -history of endocarditis -unrepaired cyanotic heart disease OR repaired heart disease with placement of prosthetic devices

-ampicillin/amoxicillin are usually appropriate -most commonly due to alpha-hemolytic strep and S. aureus -gram-negative organisms are rare causes (~5%) -usually presents with nonspecific signs/symptoms: fever, chest pain, dyspnea, arthralgia, myalgia, headache, malaise -changing or new cardiac murmurs are key clues -embolic phenomena (e.g., splinter hemorrhages, petechiae, Osler nodes, Janeway lesions) are rare in children -main complication is complete heart block -treatment: 6-8 weeks of IV antibiotics; failure of antibiotics or severe disease are indications for surgical treatment Functional Heart Disease Myocarditis -usually 2/2 viral infection of the myocardium, commonly by adenovirus, parvovirus, coxsackie A/B, echovirus, and HIV -ECG usually demonstrates ST (usually depression) and T wave (usually inversion) changes -physical exam demonstrates tachycardia, hepatomegaly (2/2 CHF in severe cases), and an S3 gallop -management includes viral PCR from blood, throat, and stool for possible source -endomyocardial biopsy is required to confirm the diagnosis -treatment is supportive; IVIg is used but there is no data demonstrating efficacy -prognosis is directly related to extent of myocardial damage Coronary artery disease -frank CAD is rare in childhood, but the process of atherosclerosis begins in children Dilated cardiomyopathy -characterized by ventricular dysfunction and dilation -can be due to multiple etiologies: -viral (thought to be the cause of most cases of idiopathic DCM) -neuromuscular disease (e.g., dystrophin abnormality) -drug toxicity -genetic defects -physical exam findings: S3 gallop and a murmur consistent with MR -can progress to frank CHF and its findings: dependent edema, RV heave, pulses alternans (variability in beat strength) -ECG demonstrated broad QRS and nonspecific ST and T wave changes -treatment consists of optimization of hemodynamic properties: preload reduction (diuretics), afterload reduction (vasodilators), and contractility increase (inotropes) Hypertrophic cardiomyopathy -characterized by thickening of the IV septum -> outflow obstruction -overall thickening of the LV results in diastolic dysfunction due to reduced compliance -abnormal MV motion results in MR -usually presents with dyspnea on exertion, chest pain, and/or syncope; can also present with sudden death (classically a young athlete) -treatment usually consists of calcium channel blockers or beta-blockers (reduce HR and the risk of arrhythmia) Arrhythmias -usually the result of congenital, functional, or acquired structural heart disease -can also be due to electrolyte disturbances, drug toxicity, or an acquired systemic disease Bradyarrhythmias -usually due to depressed automaticity at the SA node (sinus node dysfunction) or conduction block at the AV node or bundle of His (AV block) -see image below for EKG examples -common causes: -sinus bradycardia: decreased depolarization rate from the SA node -dangerous due to increased risk of arrhythmias (e.g., escape rhythms)

-first-degree AV block: characterized by a prolonged PR interval -second-degree AV block: characterized by P waves with no associated QRS complexes on EKG -Mobitz type I: progressively lengthening PR until a QRS is dropped -Mobitz type II: dropped QRS with no lengthening of the PR; can be fixed (e.g., 2 P waves for every 1 QRS) or random; condition is serious as it can progress to complete heart block -third-degree AV block: complete heart block (P waves are not associated with the QRS) -narrow QRS = escape beat from the AV node; wide QRS = escape beat from the bundle of His -treatment: -second and third degree heart block require pacemaker placement due to risk for development of a fatal arrhythmia Tachyarrhythmias -due to enhanced automaticity or a reentrant circuit that promotes quick depolarization -see image below for EKG examples -important classification: narrow vs. wide complex tachycardia -narrow complex suggests supraventricular origin -wide complex suggests subventricular origin (due to poorly conducted impulse -> poorly synchronized contraction -> prolonged QRS) -reentrant circuits are one of two types: -orthodromic: “normal” impulse comes down through the AV node and back up to the atria via an escape circuit (results in narrow complexes due to “normal” depolarization route) -antidromic: “normal” impulse comes down an escape circuit and back up through the AV node (results in wide complexes due to poor ventricular depolarization) -see below for management of acute SVT (narrow QRS) -see below for management of VT/VF -see below for management of pulseless arrest Chapter 8 – Pulmonology Upper Airway Obstructive Disease -upper airway = nostril/mouth to the thoracic inlet Upper airway obstruction in the neonate/young infant -possible causes to consider: -choanal atresia = narrowing of the nasal passages (can be fatal in infants due to dependence upon nose for breathing) -mandibular hypoplasia = failure of the mandible to develop fully; can cause posterior displacement of the tongue, obstructing the airway -vocal cord paralysis -laryngeal webs = congenital lesions that often disappear following intubation -laryngiomalacia = large, floppy arytenoids or a floppy epiglottis that result in obstruction of the pharynx -laryngeal papillomatosis = multiple, recurrent papillomas along the larynx -findings on physical exam: noisy inspiration, increased work of breathing, and retractions (particularly suprasternal) -obstruction is frequently more prominent during feeding -best diagnostic tool is bronchoscopy, which can directly visualize the airway and identify obstructions -in the absence of severe pathology, only follow-up and observation is indicated Upper airway obstruction in the older child -generally due to acquired lesions (vs. congenital lesions) -causes can include hypertrophic adenoids/tonsils, foreign body aspiration, polyps, and allergic rhinitis Obstructive sleep apnea

-found in children that usually have reduced muscular tone in addition to anatomic predisposition to obstruction (e.g., large tonsils, morbid obesity) -symptoms of sleep apnea: frequent position changes during sleep, irregular snoring with gasps, daytime somnolence, poor growth, behavioral problems, enuresis, and poor academic performance -OSA is associated with marked obesity (= Pickwickian syndrome); can produce chronic hypoventilation with CO2 retention (-> pulmonary HTN and CHF) -test of choice is polysomnography (measures muscle activity, air flow, oxygenation, sleep stage, and HR while sleeping) -treatment is surgical optimization (e.g., removing hypertrophied adenoids/tonsils) followed by CPAP use Lower Obstructive Airway Disease Asthma -chronic disorder characterized by reversible airway obstruction, inflammation, and bronchial hyperresponsiveness -diagnosis is based on symptom recurrence and response to bronchodilators -multiple potential triggers: URIs, pet dander, dust mites, weather changes, exercise, cigarette smoke, and seasonal/food allergies are most common (ask about these in the history) -severity is determined based on severity of symptoms prior to initiation of therapy -degree of control is determined by current impairment (i.e., lung function) and risk -control should be evaluated 2-6 weeks following treatment initiation -in general, control is assessed as: -well-controlled: symptoms less than 2 days/week, no interference with normal activity, night time awakenings less than once/month, SABA use less than twice/week, FEV1/FEV greater than 80%, oral steroid use once/year -not well-controlled: symptoms more than 2 days/week, or more than twice/day, mild interference with normal activity, night time awakenings more than once/month, SABA use more than twice/week, FEV1/FEV 60-80%, oral steroid use 2-3 times/year -very poorly controlled: symptoms throughout the day, severe interference with normal activity, night time awakenings at least once/week, SABA use several times daily, FEV1/FEV less than 60%, oral steroid use more than 3 times/year -degree of control is now considered more important than degree of severity -risk factors: family history, atopy, living in poor urban areas, and African American -wheezing that fails to respond to bronchodilator therapy should prompt an alternate diagnosis (response to bronchodilators is part of the diagnostic criteria) -cough-variant asthma = cough-predominant asthma that may or may not present with wheezing; symptoms improve with oral corticosteroid use -physical findings: wheezing, signs of increased work of breathing, and possible mental status changes (2/2 hypoxia) -absent breath sounds are a sign of potentially serious respiratory collapse -diagnosis is based on PFT results and response to therapy (bronchodilators and/or steroids) -PFTs are generally normal outside of an acute exacerbation -diagnosis can also be made by challenge with an asthma-inducing agent (e.g., methacholine) and reversibility with a bronchodilator -a CXR during an acute exacerbation may demonstrate hyperinflation and atelectasis -treatment is based on removal of triggers and maintenance anti-inflammatory drugs (inhaled corticosteroids, beta-2 agonists, and leukotriene antagonists) -long-acting beta-agonists are not appropriate for monotherapy -bronchodilator abuse can result in tolerance to therapy -the general progression of treatment strategies is: 1) SABA as needed 2) low-dose inhaled steroid (beclomethasone, budesonide, fluticasone, mometasone)

3) medium-dose inhaled steroid 4) medium-dose inhaled steroid and (LABA or leukotriene antagonist [monteleukast, zafirleukast]) 5) high-dose inhaled steroid and (LABA or leukotriene antagonist) 6) high-dose inhaled steroid, oral steroids, and (LABA or leukotriene antagonist) -omalizumab (anti-IgE) can be added for patients with severe allergies; antihistamines should also be considered -theophylline can be added in severe, refractory cases but is not preferred due to adverse effects and toxicity requiring drug level monitoring -anti-cholinergic agents (e.g., ipratropium) can be added in severe exacerbations -epinephrine and tertbutaline are provided to patients too fatigued or uncooperative to accept albuterol therapy -acute exacerbations are usually managed by increasing inhaled steroid doses for 710 days and/or starting a 5-day pulse of oral steroids Cystic fibrosis -multisystem disease characterized by defective exocrine gland function -defect is with the cystic fibrosis transmembrane regulator (CFTR), a cAMP-dependent chloride channel -chloride is unable to exit the cell, drawing in water and other electrolytes, dehydrating the secretions and impairing their release and removal -much more common in white individuals -variety of gene mutations, but 70% are due to the delta-F508 mutation -current life expectancy is in the mid 30s; respiratory compromise is the usual cause of death (often 2/2 infection) -because CF is a systemic disease it may present with a variety of symptoms, however common/key findings include: -nasal polyps (should prompt CF work-up) -recurrent sinusitis/opacification of the sinuses on imaging -recurrent pneumonias (2/2 impaired mucociliary clearance), particularly with Pseudomonas (more common in adolescence) -pancreatic insufficiency -failure to thrive -meconium ileus (essentially pathognomonic) -diagnostic testing: -sweat test is the test of choice – measures electrolyte levels, particularly chloride, in sweat (Cl greater than 60 mEq/mL is diagnostic) -genetic testing (particularly prenatally) is also available -treatment is focused on maintaining appropriate airway clearance -chest PT, vigorous exercise, and frequent coughing help clear secretions -bronchodilators open up the airway -antibiotics minimize inflammation and the effects of bacterial toxins -inhaled hypertonic NaCl and deoxyribonuclease can also clear secretions -pancreatic enzyme replacement (can maintain near-normal growth rates; remaining above the 25th percentile carries a better prognosis) -lung transplantation is an option in patients with a life expectancy of 1-2 years – survival is 50% at 5 years Primary ciliary dyskinesia -diseases characterized by abnormalities in cilia structure and function -similar to CF/asthma symptoms – limited to the respiratory tract -treatment is similar to patients with CF, though recurrent Pseudomonas infections are generally not characteristic Other Causes of Airway Obstruction Congenital abnormalities

-tracheal stenosis: due to tracheal cartilage rings that completely encircle the trachea, resulting in stenosis -nearly all patients require surgical intervention -can present with a “washing machine” inspiratory/expiratory sound, failure to thrive, and hypoxemia -tracheal impingement: usually due to abnormal vascular structures (e.g., double aorta, right-sided aorta, enlarged pulmonary arteries) -tracheomalacia: due to widening of the posterior membranous portion of the trachea; this structure is less stable, and the trachea may spontaneously collapse during exhalation (severe disease), cough, or forced exhalation (more mild) -presents with a croup-like cough – commonly misdiagnosed as recurrent croup -bronchodilator treatment usually worsens symptoms as relaxation of the trachea further enlarges the membranous portion – be suspicious if symptoms worsen with bronchodilator therapy -bronchomalacia: aberrant development of the bronchial tree, due to either poor cartilage or poor elastic recoil -usually presents with wheezing on forced exhalation and does not respond to bronchodilators or steroids Restrictive Lung Diseases -class of diseases due to reduced compliance in either the chest wall or the lungs (thus, inflation of the lungs is “restricted”) -much less common in children than obstructive disease -pectus excavatum/carinatum: deformities of the sternum, producing either a depression (excavatum) or elevation (carinatum) -severe malformations can produce restrictive disease; mild malformations generally do not produce symptoms -scoliosis: deformity of the spine that can reduce the volume of the thorax in addition to compressing the airway -neuromuscular disease: impairs the ability of the diaphragm to contract, resulting in inadequate lung expansion -mass lesions: could be due to a variety of lesions, including effusions (pleural or pericardial), chylothorax/hemothorax/pneumothorax, mediastinal/chest wall masses -pulmonary hemosiderosis: abnormal accumulation of hemosiderin in the lungs due to diffuse alveolar bleeding -source of bleeding should be identified -may present with hemoptysis, hematemesis, or microcytic anemia -in general, restrictive disease may present with pulmonary hypertension, digit clubbing, or respiratory insufficiency if chronic Aspiration Syndromes -patients with reduced or absent vocal cord and cough reflexes are at increased risk for aspiration -can present with coughing, wheezing, or frank respiratory distress; be suspicious if especially acute and seems inappropriate given the child’s past medical history -imaging can be useful, but not all objects are radiopaque – notify the radiologist of your suspicion so that particularly careful examination occurs (lol med-legal) -bronchoscopy provides a definitive diagnosis and can be used for removal -small aspirated objects that are not removed may cause recurrent pneumonias, atelectasis, chronic cough, and bronchiectasis Apnea of Infancy -defined as the cessation of breathing for at least 20 seconds OR breathing cessation of any duration in conjunction with color changes, hypotonia, decreased responsiveness, and/or bradycardia -not associated with an increased risk of SIDS -see chart below for common causes of apnea in an infant Chapter 9 – GI

-chronic abdominal pain is defined as persistent abdominal pain severe enough to affect regular activities for at least 3 months -in the absence of evidence of an organic cause, most abdominal pain in the pediatric population is functional Differential Diagnosis -functional abdominal pain is now called “pain-related functional GI disorder” (FGID) -diagnosis must be distinguished from anatomic, infectious, inflammatory, and metabolic causes -may be associated with hyperalgesia (i.e., increased pain transmission and/or decreased pain threshold) -major types of FGID: -functional dyspepsia – e.g., upper abdominal discomfort -IBS – pain associated with changes in bowel habits -abdominal migraine – paroxysmal pain associated with nausea/vomiting -functional abdominal pain syndrome – pain in the absence of the above -functional constipation is also a common cause of abdominal pain -common causes: lactase deficiency, IBD, celiac disease, eosinophilic GI disorder of the small or large bowel -infectious causes are common in acute abdominal pain but usually not in chronic pain -consider PID in adolescent girls -disorders of the gall bladder are rarer in children but should be suspected with RUQ pain that worsens with eating -vasculitidies (e.g., Kawasaki disease, polyarteritis nodosa, and SLE) are a common cause of abdominal pain -psychiatric causes – especially malingering and conversion disorders – are uncommon in children -abdominal pain CAN be a response to stressors, especially when related to school -can also be a symptom of depression -in the absence of organic causes of abdominal pain, look into social factors Clinical Manifestations -inflammatory vs. colicky pain: -inflammatory pain generally results in a more lethargic child -colicky pain generally results in a more agitated child (more strongly associated with obstruction of a hollow visceral structure) -pain that interrupts sleep is more likely to be from an organic cause (vs. functional) -alarm symptoms that warrant immediate intervention/work-up: -involuntary/unexplained weight loss -deceleration of linear growth -GI blood loss -significant, intractable vomiting -chronic, severe diarrhea -persistent RUQ (biliary pathology) or RLQ (appendiceal pathology) pain -unexplained fever -family history of IBD -key question during the exam: does the child need acute surgical intervention? -does the child ambulate and interact with others normally? -“peritoneal signs” = rebound tenderness, guarding, psoas/obturator signs, and rigidity of the abdominal wall; suggestive of acute abdomen/serious disease -rectal examination is generally indicated to check for hard/bloody stools unless viral gastroenteritis is suspected -pelvic exam is appropriate in adolescent females -lack of positive findings is suggestive of functional pathology -alarm signs on exam: -localized RUQ/RLQ tenderness -localized fullness/mass effect

-hepatomegaly -splenomegaly -CVA tenderness -point tenderness over the spine -perianal abnormalities Diagnostic Evaluation -surgical consultation should be pursued if appendicitis, volvulus, intussusception, testicular torsion, or other serious conditions are suspected -blood in the stool, pertinent travel history, or sick contacts warrant stool culture for possible bacterial infection -CT is appropriate if appendicitis is suspected -functional pain generally warrants no further testing unless an organic cause remains on the differential Appendicitis -due to bacterial invasion of the appendix, usually following obstruction (e.g., by fecalith, a parasite, or lymphadenopathy) -reduced incidence in the 10-15 y/o group and very rare in children younger than 5 -generally presents with fever, emesis, anorexia, and diffuse periumbilical pain that migrates to the RLQ -guarding, rebound tenderness, and obturator/psoas signs may be present depending upon the time course -perforation generally occurs ~36 hours following pain onset -atypical presentations are very common; retrocecal appendicitis is particularly atypical (RLQ pain generally does not present until after perforation) -plain film may demonstrate the presence of fecalith, but CT/US are the imaging modalities of choice -treatment consists of surgical intervention; if perforation occurs, broad-spectrum antibiotic coverage is indicated Intussusception -due to “telescoping” of a proximal segment into a distal segment; this action can result in incarceration and necrosis of portions of the bowel -most occurrences are ileocolic (i.e., the ileum invaginates into the ileocecal valve) -the telescoping action is thought to be made possible by hypertrophy of Peyer’s patches (collections of immunological cells) – look for a history of bacterial/viral gastroenteritis -other common lead points: Meckel diverticulum, intestinal polyp, lymphoma, and foreign body -presents with intermittent episodes of severe agitation, colicky pain, and emesis -rectal bleeding occurs in most patients but usually does not look like the classic “currant jelly” of bright red blood and mucus -plain film may demonstrate an air-fluid level consistent with obstruction; US is more useful as a screening tool -contrast/air enema can be both diagnostic and therapeutic -contraindicated if peritoneal signs are present (i.e., concern for perforation) -laparotomy or direct reduction are indicated if enemas fail or are contraindicated Emesis -not strictly associated with GI causes -complications of severe vomiting: dehydration with a hypochloremic, hypokalemic metabolic acidosis -intractable or forceful emesis can result in a Mallory-Weiss tear and esophagitis -history should differentiate between true vomiting (expulsion of gastric contents) and regurgitation (“spitting up;” usually due to reflux) -timing relative to feeding is also informative -shortly after feeding = likely due to reflux -projectile emesis shortly after feeding in 1-3 m/o suggests pyloric stenosis -emesis in association with a headache or seizure suggests an intracranial process

-the triad of fever, diarrhea, and emesis suggests gastroenteritis -the physical exam should initially focus on hydration status and vital signs -hypoactive bowel sounds suggest obstruction or ileus -hyperactive bowel sounds suggest gastroenteritis -treatment is dependent on the cause -for typical gastroenteritis, hydration is the center of therapy; oral rehydration should be encouraged, but IVF are necessary for severely dehydrated patients or those unable to tolerate oral intake Pyloric stenosis -most common during the first 2-4 weeks, but can present at any point within the first 3 months -male predominance (4:1) -some evidence that erythromycin may precipitate pyloric stenosis -generally presents as intractable, nonbilious vomiting -classic finding of an olive-shaped, muscular, non-tender mass is usually present but difficult to palpate -peristalsis may be superficially visible -stenosis can be visualized directly with US or an upper GI series -treatment is initially with an NG tube to decompress the stomach along with correction of hydration and electrolyte abnormalities (if present) -surgical intervention is appropriate following correction of acute abnormalities Malrotation and volvulus -malrotation is due to in utero malpositioning of the bowels – results in posterior fixation of the mesentery -volvulus is the twisting of the bowel due to abnormal attachment to the mesentery; a portion of the bowel may become ischemic due to mechanical vasoconstriction -most common during the newborn period – emergent surgical correction is indicated -usually presents with a history of bilious vomiting, bloody emesis or stool, abdominal distension, and abnormal positioning of the bowels on imaging -labs may indicate a lactic acidosis 2/2 ischemia GER(D) -defined as the passage of gastric contents into the esophagus -GER = actual event of reflux, GERD = complications of chronic reflux -usually presents with the classic picture of a “happy spitter:” recurrent regurgitation occurs, but the child does not seem otherwise unhappy or distressed -projectile vomiting, forceful emesis, and retching suggest alternative diagnoses -diagnosis is generally clinical with no further work-up necessary -endoscopy is indicated if there is concern for frank esophagitis or other anatomic defects -eosinophilic esophagitis presents as classic reflux symptoms but does not respond to typical GER therapy -furrowing of the esophageal mucosa with a white exudate and eosinophilia on biopsy makes the diagnosis -treatment: -symptoms usually improve with prone positioning, but prone positioning is associated with an increased risk of SIDS -evidence supports a 1-2 week trial of hypoallergenic formula -common food triggers include caffeine, spicy foods, and high fat foods and should be avoided -modifiable risk factors include obesity, tobacco smoke exposure, and alcohol -in children, H2-blockers and PPIs have the same improvement in symptoms, so H2blockers are recommended due to fewer symptoms Diarrhea -defined as the increase in volume and frequency of stooling -most common cause is viral gastroenteritis -major split point: acute vs. chronic

-acute suggests a more benign cause (e.g., viral gastro, food intolerance, etc.) while chronic diarrhea necessitates a more thorough work-up to identify or rule-out more concerning causes -appearance of stools is also important: water vs. mucus vs. blood -be concerned if weight loss or failure to thrive occurs -on exam, hydration status should be determined: severe dehydration is an indication for hospitalization, especially if the patient is unable to tolerate oral intake -abdominal masses suggest an obstructive cause (e.g., intussusception) -diagnostic testing: -mucus or blood in the stool are indications for stool culture -a work-up for chronic diarrhea should include checking for immunodeficiency (recurrent GI infections), pancreatic insufficiency, celiac disease, IBD, and other serious conditions depending upon the presenting symptoms -treatment of acute gastroenteritis is centered on maintaining adequate hydration -the child’s normal diet should be continued if the diarrhea is mild and he/she is wellhydrated -multiple studies have demonstrated that regular diets are more effective at relieving symptoms than restricted diets -refeeding should start as early as possible following stabilization of fluid status -antidiarrheals/antiemetics are NOT recommended -antibiotic therapy should only be started if specific evidence of a bacterial infection is found (e.g., positive culture); some infectious respond poorly to antibiotics Constipation -defined as the frequent passage of hard stools -due to stretching of the bowel 2/2 retained stool; infants may present with a functional ileus -90-95% of cases of constipation outside the neonatal period are functional in etiology -complications of constipation include fecal impaction, anal fissures, rectal bleeding, and UTI 2/2 obstruction of the urethra due to pressure by the retained stool -differential diagnosis: -non-organic: functional constipation (i.e., voluntary withholding), dysfunctional toilet training -dietary: inadequate fiber or fluid intake -GI: functional ileus, Hirschprung’s disease, anal stenosis, rectal abscess/fissure, stricture (particularly following an episode of necrotizing enterocolitis) -drugs/toxins: lead, narcotics, anticholinergics -neuromuscular: meningeomyocele, tethered spinal cord, infant botulism, absent or weak abdominal muscles -metabolic: CF, hypokalemia, hypercalcemia -endocrine: hypothyroidism -usually presents with diffuse, constant abdominal pain, possibly with nausea but generally not with vomiting -diagnostic studies are generally not indicated; an XR may reveal the extent of constipation and possibly identify obstructive lesions if present -treatment includes disimpaction if a mass is present along with osmotic agents if the constipation does not resolve -PEG 3350 is the recommended agent due to palatability and few side effects -other therapies include mineral oil, MgOH, lactulose, and sorbitol -a behavioral program and/or retraining is appropriate if the cause is functional Hirschprung’s disease -due to failure of ganglionic cells of the myenteric plexus to migrate to the distal end of the bowel -results in a tonically contracted bowel that causes obstruction -male predominance (3:1) -most cases do not extend proximally past the splenic flexure

-failure to pass meconium within the first 24-48 should start a search for an organic cause of obstruction (including Hirschsprung’s) -other presenting symptoms include bilious emesis, poor feeding, and abdominal distension -cases that affect limited portions of the bowel may not be diagnosed until much later in childhood -XR will demonstrate collection of feces and a focal point of obstruction -contrast enema may demonstrate a point of obstruction, but a normal contrast enema does not rule out obstruction -biopsy is the diagnostic test of choice and demonstrates an absence of ganglion cells, abnormal AChE staining, and hypertrophied nerve trunks -treatment is surgical correction that includes removal of the aganglionic segment and the formation of an anastomosis between the new end of the bowel and the rectum GI bleeding -important distinction: hematochezia (passage of bright red blood) vs. melena (passage of black, tarry stools that usually test positive for occult blood) -hematochezia is generally indicative of an active lower GI bleed (or an upper GI bleed with rapid transit) -melena is generally indicative of an upper GI bleed -blood-streaked stool is generally indicative of a small bleed (e.g., due to an anal fissure or polyp) -diarrhea with bloody stools is generally indicative of an inflammatory process (e.g., IBD or infection) -see below for common causes of GI bleeding by age -initial evaluation should focus on ensuring adequate volume and perfusion -check vital signs (e.g., tachycardia, hypotension), including orthostatics -evaluation should include a CBC with diff, a platelet count, and coagulation studies UNLESS the source of GI bleeding is clearly from the nose -gastric lavage is indicated if the source of bleeding is unclear or if a GI bleed is suspected (return of clear fluid makes an upper GI bleed highly unlikely) -bloody diarrhea following several days of nonbloody diarrhea is highly suspicious of E. coli O157:H7 infection -bloody diarrhea in the neonate raises concern for necrotizing enterocolitis – XR and sepsis work-up are indicated -large volume, painless rectal bleeding raises concern for a Meckel diverticulum -treatment is centered on maintaining adequate hydration and stopping bleeding; see below for diagnostic/treatment algorithm Meckel diverticulum -due to persistence of the omphalomesenteric duct, which is normally obliterated during the fetal period -most common GI abnormality in the newborn -lesion is located within 1 m of the ileocecal valve in the small bowel -acid-secreting gastric tissue is frequently present in symptomatic cases due to ulceration of mucosa 2/2 acidic damage -most commonly presents as painless rectal bleeding -diagnosis is made by a Meckel scan – essentially consists of ingestion of technetium-99 pertechnetate, which binds to gastric mucosa and localizes the lesion -treatment is surgical repair of the diverticulum Inflammatory bowel disease -generic term for Crohn’s disease and ulcerative colitis -ulcerative colitis: leads to diffuse ulceration of the superficial intestinal mucosa with crypt abscesses -involves the rectum in nearly all cases, usually with contiguous proximal spread but skipping of lesions can occur -does NOT affect the small intestine -rare complications include toxic megacolon and perforation

-increases the risk of intestinal cancer -Crohn’s disease: transmural inflammation in a noncontiguous pattern -may involve any portion of the GI tract from the mouth to the anus -most cases involve both the small and large bowel -complications can include fistula formation, bowel perforation, and stricture formation -most patients present in adolescence -presentation of Crohn’s: crampy abdominal pain, recurrent fever, and weight loss -pain tends to be more severe than UC, usually diffuse with worsening in the RLQ -presentation of UC: bloody diarrhea with mucus/pus, abdominal pain, and tenesmus (feeling of inadequate emptying of the rectum) -both diseases can present with non-GI symptoms: polyarticular arthritis, ankylosing spondylitis, primary sclerosing cholangitis, erythema nodosum, aphthous stomatitis, episcleritis, recurrent iritis, and uveitis -Crohn’s patients are at increased risk of developing kidney stones due to defective oxalate absorption -IBD is distinguished from other disorders by the chronicity of symptoms, but acutely bacterial gastroenteritis, appendicitis, radiation enterocolitis, and eosinophilic GI disease should be considered -treatment attempts to control and minimize inflammation -5-ASA compounds are used as NSAIDs -antibiotics are appropriate as anti-inflammatory drugs in Crohn’s -corticosteroids to reduce inflammation -surgery is used in severe cases that are refractory to therapy – 25% of Crohn’s and 50-75% of UC patients eventually undergo surgery -in Crohn’s, surgical intervention is delayed as long as possible due to high risk of recurrence (50%) Transaminitis -measured with AST and ALT – ALT is more specific for liver pathology (“L for liver”) -differentials are based on the general magnitude of elevation: -AST and/or ALT 1000 (generally suggests a more acute process): bile duct obstruction, Budd-Chiari syndrome, acute viral hepatitis, autoimmune hepatitis, ischemic hepatitis, medications/toxins -alcoholic hepatitis presents with elevated transaminases, but AST > ALT (classically in a 2:1 ratio) Acute liver failure -defined as biochemical evidence of liver dysfunction in the absence of known chronic disease -cause is not found in half of cases -treatment is supportive and correction of the underlying disorder (if identified) Wilson disease -autosomal recessive defect in copper metabolism that prevents incorporation of copper into ceruloplasmin in the bile ducts -copper deposits in the liver due to defected excretion, and copper levels eventually rise and deposit in tissues throughout the body -usually manifests as liver disease in children and neuropsychiatric disease in adults -classic triad: liver disease, decreased ceruloplasmin levels, and Kaiser-Flescher rings (rings of deposited copper around the iris) -treatment: copper chelating agents (D-penicillamine, trientine), zinc, and a low copper diet Alagille syndrome -autosomal dominant disorder that presents with multiple findings due to disordered development of the vasculature, bile ducts, and other tubular structures

-diagnosis requires bile duct paucity and 3 of the following: cholestasis, cardiac murmur/heart disease, skeletal anomalies, ocular findings, and facial features -most common cardiac abnormality is stenosis of the pulmonary vasculature -most common ocular findings: hypertelorism (abnormally large distance between eyes) and bilateral posterior embryotoxon Nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) -most common cause of liver disease in children -presents with fat accumulation (macrovesicular) with inflammation (NASH) or without (NAFLD) -NAFLD predisposes to the development of type 2 DM, hypertension, and dyslipidemias -other risk factors for NAFLD: male, Hispanic ethnicity, Asian (particularly Chinese/Filipino individuals) -physical exam findings: acanthosis nigrans -liver panel demonstrates ALT and AST elevation (ALT>AST), elevated GGT and alk phos, low HDL, and elevated fasting triglycerides -liver biopsy is usually needed for definitive diagnosis -no medical therapy yet: management includes lifestyle modification to promote weight loss Chapter 10 – Infectious Disease Fever of unknown origin -defined as a fever (T greater than 38.3/101) lasting more than 14 days with no clear etiology -usually due to a common disorder presenting in an uncommon way -basic differential: -infectious: sinusitis, hepatitis, CMV/EBV infection, cat-scratch disease, Rocky Mountain spotted fever, endocarditis, septic arthritis, osteomyelitis, abdominal abscess, enteric fever, HIV infection -connective tissue disease: systemic juvenile idiopathic arthritis, SLE -malignancy: leukemia, lymphoma, neuroblastoma -other: IBD, Kawasaki disease, thyrotoxicosis, sarcoidosis, factitious fever -initial diagnostic testing: -CBC, BMP, LFTs, and UA -cultures from urine, blood, stool, and possibly CSF -can consider inflammatory markers (e.g., CRP/ESR) -CXR/PPD for TB infection prudent -in most cases, spontaneous recovery occurs without sequelae Bacteremia and sepsis -bacteremia = presence of bacteria in the blood -most episodes of bacteremia are due to S. pneumoniae -sepsis = bacteremia with a clinically appreciable systemic response that includes altered organ perfusion -in younger children, GBS, enteric gram negative rods, and Listeria are the most common causes -in older children, S. pneumoniae and N. meningitidis are most common -basic work-up includes pan cultures (urine, blood, stool, and CSF) to identify source and immediate initiation of empiric treatment pending culture results Acute otitis media -shorter Eustachian tubes and tube dysfunction predispose children to ear infections -viruses are the most common cause, but bacterial superinfection is relatively common -common bacterial sources include S. pneumoniae, non-typeable H. influenza, and Moraxella -many isolates of these species exhibit beta-lactamase activity -frequently presents following URI symptoms (edema and inflammation of the upper respiratory tract can make the Eustachian tube even more occluded, increasing the risk of infection) -tympanic membrane may appear full/bulging and opaque with an altered light reflex -other possible diagnoses:

-otitis media with effusion: visible fluid behind the TM in the absence of other signs of inflammation -myringitis: inflammation of the TM with no impairment in mobility -otitis externa: ear pain without involvement of the TM (due to inflammation/infection of the ear canal) -treatment: high-dose amoxicillin is first-line -antibiotic use in the last month OR no resolution within 48 hours are indications for second-line treatment: amoxicillin/clavulanic acid, 2nd/3rd generation cephalosporin, or IM ceftriaxone -otitis media with effusion commonly follows otitis media – may take up to 3 months to resolve -frequent ear infections may indicate tympanostomy tube placement -mastoiditis: complication of otitis media due to infection of the mastoid Sinusitis -pathogens most often responsible for sinusitis are identical to pathogens in acute otitis media -two common presentations (can be difficult to diagnose as classic findings of headache, facial pain, and sinus tenderness may not be present): 1) persistent respiratory symptoms (10-14+ days) without improvement with clear or purulent nasal discharge or a daytime cough 2) severe symptoms including high fever and purulent nasal discharge for at least 3 days -primarily a clinical diagnosis – XR of the sinuses may be warranted if the diagnosis is uncertain -treatment is similar to otitis media, but course of antibiotics should be longer (14-21 days) -recurrent sinusitis warrants a work-up for possible CF, ciliary dyskinesia, or a primary immune deficiency Herpangina -symptom complex caused by enteroviruses (commonly coxsackie A/B) -clinical course: high fever and sore throat followed by vesicular lesions on the soft palate, tonsils, and pharynx that progress to ulcers -self-limited and typically resolves in 5-7 days without treatment -when lesions on the palms and soles are noted, the disease is called hand-foot-mouth disease Streptococcal pharyngitis -GAS pharyngitis must be treated due to frequency and severity of complications following untreated infection -spread by oral secretions; 10-15% of otherwise well children are carriers -commonly presents with sore throat, fever, headache, malaise, nausea, and sometimes abdominal pain -pharynx demonstrates enlarged, erythematous, exudative tonsils; petechiae may be present on the soft palate -appearance of a fine, bumpy rash (“sandpaper rash”) on the trunk in conjunction with these symptoms is scarlet fever -definitive diagnosis requires culture and/or antigen testing -rapid testing is very specific (95+%) and is the initial screening test -negative test should be followed by a throat culture -treatment is a 10-day course of penicillin (penicillin resistance is rare but has been reported) -alternatives for those with penicillin allergies include erythromycin, azithromycin, and clindamycin -two important post-infection complications: -acute rheumatic fever: inflammatory condition that involves the heart, joints, and CNS

-diagnosis requires fulfillment of Jones criteria (JONES mnemonic: joints [polyarthritis], carditis [draw “O” of JONES as a heart], nodules [subcutaneous], erythema marginatum, and Sydenham’s chorea) -responds favorably to antibiotics -cardiac valve destruction can occur, so an echo should be considered if cardiac symptoms are present -post-strep glomerulonephritis: due to deposition of immune complexes in glomeruli following infection -does not improve with antibiotic treatment (causative agent is immune complexes, not bacteria or their products) -usually presents ~10 days following infection with hematuria, edema, oliguria, and hypertension -labs demonstrate low C3 -most cases in children resolve without permanent sequelae (in contrast to adults) Infectious mononucleosis -due to infection of older children and adolescents with EBV (though toxoplasmosis and CMV infections can present similarly) -transmitted by mucosal contact of infected body fluids -usually presents with a serve, exudative pharyngitis; fever, generalized lymphadenopathy, and profound fatigue are also common -malaise may remain for several weeks following resolution of pharyngitis -treatment with amoxicillin or ampicillin commonly results in a rash on the face and trunk – be suspicious of a history that includes a supposed bacterial pharyngitis treated with antibiotics -treatment is typically supportive as the infection self-resolves -advise no contact sports due to risk of splenic rupture 2/2 splenomegaly for at least several weeks but up to several months Croup -due to virus-induced inflammation of the laryngotracheal tissues (also called acute laryngeotracheobronchitis) -usually due to a paramyxovirus but may also be due to influenza, RSV, or others -incidence peaks in the late fall/winter and may present with complete airway obstruction if severe enough -usually presents with sudden onset hoarse voice, inspiratory stridor and cough -symptoms may progress to frank respiratory distress due airway obstruction -diagnosis is usually clinical; XR of the neck demonstrates the steeple sign, or narrowing of the airway (present in less than 50% of cases; severity of obstruction does not correlate with disease severity) -other diagnoses to consider: epiglottitis (emergency), foreign body aspiration, anaphylaxis -treatment: typically supportive, with most cases not requiring MD visit -cold, humidified air is an anecdotal but as-yet unproven therapy to help with cough/stridor -in the ED, epinephrine and corticosteroids may be administered in severe cases with respiratory distress Bronchiolitis -acute viral lower respiratory tract infection that results in inflammatory obstruction of the lower airways -mucous plugs and cellular debris accumulate due to impaired ciliary clearance, further obstructing the airways -most common cause is RSV, but other causes include parainfluenza, influenza, human metapneumovirus, and adenovirus -maximal incidence during November-April -children with preexisting disease (e.g., lung disease, heart disease, immunodeficiencies) are more susceptible to severe infection

-alarm symptoms include RR > 70, hypoxia, atelectasis on CXR -acute symptoms usually last 5-10 days with gradual improvement over the next 7-14 days -usually presents with fever, tachypnea, rhinorrhea, and cough with progressive respiratory distress -evaluation: rapid testing for viral products to identify a source -CXR generally not necessary unless another diagnosis is being considered -treatment is supportive treatment (usually oxygen and fluids as needed) -beta agonists (e.g., albuterol) are not generally recommended -corticosteroids are also not indicated due to reduced efficacy Pertussis -due to infection with Bordetella pertussis -presents with a persistent cough in adults but in children can precipitate severe respiratory distress -triphasic illness: 1) catarrhal phase: 1-2 weeks of low-grade fever, cough, and coryza 2) paroxysmal phase: 2-6 weeks of intense coughing spasms followed by sudden inhalation (the etiology of the classic “whoop”) 3) convalescent phase: most symptoms remit but the cough may persist for 2-8 weeks -lab testing may demonstrate a lymphocytosis and a positive PCR culture -CXR is usually normal -hospitalization is appropriate in patients with severe disease that impairs oxygenation -treatment: erythromycin (14 days)/azithromycin (5 days) can reduce duration of symptoms if given in the catarrhal phase -antibiotics do not affect the course of the disease after coughing episodes begin -chemoprophylaxis in household contacts is indicated regardless of immunization status Pneumonia -acute inflammatory process of the lungs that can be of infectious or noninfectious etiology -inflammation can occur in the alveoli (lobar pneumonia), walls of the alveoli (interstitial pneumonia), or the bronchi -common etiologies are based on age (see below for chart) -in young children, viruses are the most common cause -Mycoplasma becomes more common after 5 years along with Chlamydophilia -risk factors: chronic lung disease, neurologic impairment (aspiration, poor mucociliary clearance), GER(D), anatomical defects (TEF, cleft palate), hemoglobinopathies, immunodeficiency (congenital or acquired) -presentation is disease-specific to some extent but generally includes fever, irritability, poor feeding, vomiting, abdominal pain, and/or lethargy -important findings on physical exam: -diffuse wheezing, crackles -> suggestive of viral pneumonia -focal crackles, reduced breath sounds, egophony (“e-to-a change”), dullness to percussion -> suggestive of bacterial pneumonia -effusions can form from any species, but large effusions are more typical S. aureus -primary diagnostic test is CXR: can differentiate between lobar vs. atypical pneumonia and reveal the extent of infection -note: aspiration pneumonia most often occurs in the right middle/lower lobes -if an effusion is present on CXR, tapping and analyzing the fluid is appropriate -rapid testing for influenza is also appropriate if influenza is present locally in the community -treatment is dependent upon the specific organism causing infection -in the community setting, high-dose amoxicillin or amoxicillin/clavulanic acid is appropriate for typical bacterial pneumonia -atypical pneumonia: erythromycin, azithromycin, or clindamycin

-neonates should receive a more substantial work-up (i.e., sepsis work-up) and receive treatment based on culture results Meningitis -infection of the leptomeninges (= pia and arachnoid) or CSF -viral infections are typically acute and self-limited -bacterial infectious are life-threatening with significant morbidity and mortality -aseptic meningitis = inflammation due to antigen stimulation by a non-pyogenic bacterium -the most common etiologies vary with age – see chart below -neonates and children younger than 3 are at greatest risk (and also have the highest risk for bacterial vs. viral infection) -risk factors: trauma, mastoiditis, sinusitis, and cranial defects -in the neonate: low birth weight, prolonged membrane rupture, and chorioamnionitis -classically presents with nausea, vomiting, photophobia, irritability, lethargy, headache, and neck stiffness -viral meningitis typically precedes the above with malaise, fever, sore throat, and/or myalgias -viral infection usually resolves within 2-4 days; symptoms may improve with LP -bacterial infection typically presents more severely: altered mental status, focal neurological signs, seizures, and shock -Lyme meningitis takes a slower course (1-2 weeks) and may present with cranial nerve palsies -two important physical exam signs: -Kernig = pain on knee extension after hip flexion -Brudzinski = involuntary leg flexion with passive neck flexion -these are rare in children less than 1 y/o -CSF analysis is the most important test (do not LP if focal signs or increased ICP are present) -bacterial: 1000+ WBCs (PMNs), high protein, low glucose -viral: less than 500 WBCs (lymphs), normal-high protein, normal glucose -Lyme: less than 100 WBCs (lymphs), normal-high protein, normal glucose -bacteria are commonly recovered on CSF cultures, making culture diagnostically useful -uncomplicated viral meningitis does not typically require hospitalization -treatment options for bacterial meningitis: -neonates: ampicillin (GBS + Listeria) + cefotaxime (GNRs) -infants and older children: vanc + ceftriaxone -typical course is 10-14 days Gastroenteritis -can be caused by a variety of different organisms; diarrhea is induced via a variety of mechanisms (direct bacterial damage, toxin production, etc.) -main complication is dehydration due to excessive stooling +/- poor tolerate to oral intake, leading to electrolyte abnormalities -most common bacterial causes are Salmonella, Shigella, E. coli, Yersinia, and Campylobacter -usually present with fever, significant abdominal cramping, and tenesmus -stool may contain mucus with blood streaking -Shigella may produce neurological findings (lethargy, seizures, altered mental status) -Salmonella undergoes hematogenous spread, increasing the risk for osteomyelitis (particularly in sickle cell patients) and meningitis -Shigella dysenterae and E. coli O157:H7 can present with hemolytic uremic syndrome (= HUS = triad of microangiopathic hemolytic anemia, nephropathy, and thrombocytopenia)

-Yersinia commonly presents with erythema nodosum and may present as pseudoappendicitis due to RLQ localization -rotavirus is the most common cause of non-bacterial gastroenteritis -infections most common in colder months -presents with profuse diarrhea, vomiting, and low-grade fever -norovirus presents similarly to rotavirus, but the length of symptoms is usually more limited -in the US, most common parasitic infection is Giardia -presents with frequent, foul-smelling stool (usually without blood and mucus), nausea, vomiting, anorexia, and abdominal pain -symptoms usually resolve in 5-7 days but may persist for one month -basic diagnostic work-up: -electrolytes to check for abnormalities 2/2 dehydration -abdominal XR is generally not helpful – either normal or nonspecific -stool culture may be helpful -check for C. difficile if there is a recent history of antibiotic use -if symptoms persist and no cause has been identified, endoscopy is indicated -treatment: centered primarily on maintaining adequate hydration -antibiotics should be withheld pending culture results unless the child appears toxic -antibiotics prolong Salmonella shedding and increases the likelihood of developing HUS in E. coli O157:H7 infections due toxin release 2/2 bacterial death -Shigella can be treated with TMP-SMX -Campylobacter can be treated with erythromycin or azithromycin -C. difficile can be treated with metronidazole but typically improves when antibiotics are stopped Pinworm infection -infection with Enterobius -incidence is the greatest in pre-school and school-aged children -usually presents with perianal or perivulvar itching -diagnosis is made using the “Scotch tape test:” examination of tape stuck to the area and investigated under the microscope -tape will pick up eggs present on the skin which are visible under the scope -treatment is with mebendazole, pyrantel pamoate, or albendazole -all family members should be treated, particularly siblings -hand washing is the most effective form of prevention Hepatitis -defined as acute inflammation of the liver resulting in various biochemical abnormalities -discussion will center on infectious causes of hepatitis -HAV and HEV are transmitted by the fecal-oral route -HBV, HCV, and HDV (requires concurrent HBV infection) are transmitted by infected body fluids -chronic carrier states can develop with HBV and HCV -incidence of HAV and HBV is low in the neonatal population due to universal vaccination -in children, acute hepatitis usually presents with anorexia, nausea, malaise, vomiting, jaundice, dark urine, abdominal pain, and low-grade fever -HAV and HEV can present with diarrhea -HBV and HCV rarely present acutely -differential: -infectious causes are limited due to systemic involvement of most other etiologies -non-infectious causes include autoimmune hepatitis, metabolic liver disease, biliary tract disorders, and toxin ingestion -all sources present with liver enzyme elevations -differentiating among infectious sources requires serology -HAV: test for anti-HAV IgM (current infection) -HBV: test for anti-HBs (resolved infection), anti-HBc (active/past infection), and antiHBe (past or chronic infection)

-HCV: viral RNA PCR (presence and severity of infection) -prognosis: -HAV: fulminant hepatitis is rare, but 50% that develop it die -HBV: chronic active infection is rare in children; chronic persistent hepatitis can cause symptoms for a year but usually resolves -HCV: half develop chronic hepatitis with an increased risk of cirrhosis -HDV: when acquired with HBV, increased risk for fulminant hepatitis and progression to chronic disease; when on top of an existing HBV infection, acute exacerbation with accelerated course, including an increased risk of cirrhosis -HEV: no known cases of chronic hepatitis Syphilis -STD caused by Treponema -in pediatrics, can be either a congenital or acquired infection -increased risk in neonates born to untreated mothers and adolescents who have unprotected sex or sex with multiple partners -perinatally, half of infants with congenital infection die -infants that survive typically present with hepatosplenomegaly, mucocutaneous lesions, jaundice, lymphadenopathy, and a bloody, mucopurulent nasal discharge -long-term complications of congenital infection include deafness and mental retardation -sexually transmitted infection presents in three phases: -primary: chancre (well-demarcated, firm, painless ulcer) at the inoculation site; lasts 3-6 weeks before resolving -secondary: widespread dermatologic involvement with generalized erythematous macules that progress to papules; systemic findings include fever, malaise, pharyngitis, mucosal ulcerations, and lymphadenopathy; lasts 1-3 months -tertiary: gummas (granulomatous lesions in the skin, bone, heart, and CNS); very rare in the pediatrics population due to long time course (years after initial infection) -diagnostic evaluation: -scrapings of chancre or aspiration of lymph nodes demonstrate organism under dark-field microscopy -screening utilizes the VDRL or RPR – both have a significant number of false positives, so secondary screening is done with antigen-based tests -LP to check for neurosyphilis (pleocytosis with elevated protein); positive VDRL from CSF is diagnostic -treatment is with penicillin G (IM or IV) – effective regardless of stage Genital HSV infection -usually due to HSV-2 infection, though HSV-1 can cause genital lesions -very common in adults, but congenital infection in the neonate can be severe -typical course of lesions: -genital burning/itching which progresses to vesicular or pustular lesions which burst, ulcerate, and heal without scarring -after lesions, virus travels to the dorsal root ganglia and remains dormant -virus may remain latent or cause reinfection, characterized by recurrent vesicular lesions -diagnosis is made based on demonstration of giant cells with inclusion bodies on microscopy or PCR/fluorescence staining -oral antiviral agents shorten symptom duration but do not eradicate the infection Pelvic inflammatory disease -defined as the constellation of signs and symptoms related to the ascending spread of organisms from the lower to the upper genital tract -typically polymicrobial; Chlamydia and N. gonorrhoeae are most commonly isolated -infection with these in a young child is strongly suggestive of sexual abuse -adolescents have an increased risk of disease due to risky behavior patterns and multiple sexual partners

-diagnosis is based on clinical criteria: -must have 1) cervical motion tenderness or 2) uterine/adnexal tenderness -supporting symptoms: -fever (38.3+) -elevated inflammatory markers -WBCs in vaginal discharge -mucopurulent vaginal discharge -lab evidence of cervical infection with N. gonorrhoeae or Chlamydia -severe disease may also present with peritoneal signs -patients with suspected PID should receive a pregnancy test to both rule-out ectopic pregnancy and ensure use of pregnancy-safe antibiotics -treatment is based on the infecting organism -should receive coverage at least for N. gonorrhoeae and Chlamydia (doxycycline, 14 days); metronidazole or clindamycin for anaerobes -complications include increased risk for ectopic pregnancy (due to mucosal damage), dyspareunia, chronic pelvic pain, and adhesions Vulvovaginal infections -three main etiologies: 1) Trichomonas vaginalis – causes trichomoniasis -most cases are asymptomatic -symptoms include a malodorous, gray frothy discharge and vaginal discomfort -cervix and vaginal mucosa may be visibly irritated or inflamed -microscopy of vaginal discharge demonstrates PMNs and organism -treatment is metronidazole BID for 7 days 2) bacterial vaginosis -increases the risk for PID, chorioamnionitis, and premature birth (used to be considered a benign infection) -no clear cause, but increased concentrations of Gardnerella vaginalis, Mycoplasma hominis, and anaerobes are found -decreased concentrations of Lactobacillus are also common -presents with a thin, white, foul-smelling discharge; emits a fishy odor when mixed with KOH -microscopy demonstrates clue cells (epithelial cells with attached bacteria) -treatment is metronidazole BID for 7 days 3) Candida – vaginal candidiasis -all women are colonized, but some factors increase infection rates (antibiotic use, pregnancy, diabetes, immunosuppression, and OCP use) -presents with thick white vaginal discharge with itching and burning -microscopy demonstrates hyphae and yeast cells -treatment is OTC therapies or a single dose of fluconazole Urethritis -inflammation of the urethra due to a variety of causes -most common etiologies are N. gonorrhoeae and Chlamydia -presents with urethral discharge, itching, dysuria, and urinary frequency (however, asymptomatic infections are common) -diagnosis requires purulent urethral discharge or leukocyte esterase or WBCs on UA or gram negative intracellular bacteria on Gram stain -treatment is with 250 mg ceftriaxone and either 1 dose of azithromycin or 7 days of oral doxycycline HIV and AIDS -HIV infects CD4+ lymphocytes and eventually depletes the population, impairing activation of the immune response and severely increasing the risk of opportunistic infections -AIDS requires either a specific diagnosis with an AIDS-defining illness or a CD4+ count below a threshold for the patient’s age

-prevalence is greatest in urban populations, lower socioeconomic classes, and racial minorities -most children acquire the infection congenitally -risk of fetal transfer is 25% of mother is untreated; treatment with an appropriate antiviral regimen (ZDV) perinatally reduces the risk to 2% -presents in children with generally nonspecific signs/symptoms: lymphadenopathy, hepatosplenomegaly, failure to thrive, recurrent or chronic diarrhea, thrush, parotitis, and developmental delay -adolescents commonly acquire a mononucleosis-like syndrome when presenting acutely; test if concerned -treatment is with antivirals: transcriptase inhibitors, nonnucleoside analogue reverse transcriptase inhibitors, and protease inhibitors -highly efficacious – with good treatment, can remain a chronic condition with few complications vs. active disease with severe morbidity/mortality Viral infections of childhood -see chart below for summary of viral infections Rocky Mountain spotted fever (RMSF) -due to infection by Rickettsia rickettii, transmitted by a tick common in the southern Atlantic states -look for a history for recent travel to endemic areas during prime tick season (AprilSeptember) -initial symptoms are fever, chills, headache, malaise, nausea, vomiting, and myalgias -rash starts 2-5 days later and presents with blanching, erythematous macular lesions that form petechiae -rash starts on the wrists and ankles and spreads to the trunk -differential includes ehrlichosis (also tick-borne) and meningiococcemia (lesions are usually more purpuric and petechial in quality) -because patients frequently do not remember being bit by a tick, coverage should include both -treatment is with doxycycline with ceftriaxone or cefotaxime for meningiococcemia coverage Lyme disease -due to infection by Borrelia burgdorferi which is tick-borne and endemic in New England and the Midwest -most cases are in April-October -incidence is greatest among 5-9 year olds -can present in one of three stages: -early localized: erythema migrans rash that appears 3-30 days after bite – creates a bulls eye shape; also includes fever, malaise, headache, arthralgias, and myalgias -early systemic: multiple erythema migrans lesions, cranial nerve palsy, meningitis, and carditis -late: arthritis (usually of the knee) -early disease diagnosis is a clinical one – false positives are common in lab testing -Western blot is specific but requires a long lead-time before being positive -treatment is dependent upon age: -young children: amoxicillin or cefuroxime -children older than 8: doxycycline -patients with severe symptoms: high-dose penicillin G or ceftriaxone via IV Chapter 11 – Hematology Anemia -defined as a Hb concentration too low to deliver enough oxygen to tissues to meet demands (in practice, defined as Hb concentration 2+ standard deviations below the mean) -physiologic anemia of the newborn is typical – occurs at 6-8 weeks in premature infants and 2-3 mo in terms infants -typically the result of one of 3 etiologies:

1) decreased RBC production -nutritional deficiencies (iron) -bone marrow suppression -bone marrow replacement (leukemia, metastases) -bone marrow failure 2) increased RBC destruction (hemolysis) -autoimmune -enzyme deficiencies/abnormalities 3) blood loss/sequestration -acute splenic sequestration -occult bleeds -trauma -evaluation should include assessment of nutritional intake and a family history of anemia -physical exam may demonstrate pallor of the skin, conjunctivae, or mucosa and reduced capillary refill (prolonged cutaneous blanching following application of pressure) -jaundice may be present (suggests hemolysis) -tachycardia and orthostatic hypotension suggest volume loss -diagnostic evaluation includes CBC with diff, reticulocyte count, and MCV -more specific testing includes LDH (hemolysis), bili (hemolysis), Coombs (autoimmune hemolysis), G6PD assay, Hb electrophoresis, and iron markers -inflammatory markers if anemia of chronic inflammation is suspected -treatment is variable depending upon the etiology – see below for specific disorders and their treatments Iron deficiency anemia -most common cause of anemia with a peak incidence at 6-24 mo -nutritional iron deficiency occurs in the context of rapid growth and, consequently, the development of a relative anemia -dietary risk factors: exclusive breastfeeding without iron supplementation, excessive intake of cow’s milk, and absence of iron supplements -adolescent females are at particular risk due to menstrual losses -poor iron absorption is an uncommon but possible cause -mild anemia is usually asymptomatic -severe anemia may present with CHF, tachycardia, S3 gallop, cardiomegaly, and hepatomegaly -response to iron supplementation is the best diagnostic “test” -treatment is iron supplementation -transfusion is indicated only when symptomatic and rapid correction is necessary (e.g., hemodynamic instability) -transfusions should occur in small mini boluses to avoid acute volume overload and subsequent cardiac insufficiency Thalassemia -characterized by defects in the alpha or beta globin chains of Hb -expression of alpha chain is based on 4 copies of the gene; disease presents with deletion of 1 or more copies -expression of beta gene is based on 2 copies of the gene; mutant alleles can result in reduced or absent expression -disease is due to mismatch in alpha/beta chain quantities – excess chains accumulate and precipitate, causing ineffective erythropoiesis and hemolysis -defined by the severity of disease: -major = transfusion-dependent (can be caused by deletion of all 4 alpha genes or mutant allele that results in absent production in both beta genes) -minor = largely asymptomatic with mild anemia (can be caused by deletion of 2 alpha genes or a single mutant beta allele) -intermedia = all other variants -the alpha chain mutations are inherited in clinically relevant ways

-cis deletions = deletion of two alleles on the same chromosome -trans deletions = deletion of two alleles on different chromosomes -cis deletions are more prevalent in Asians while trans deletions are more prevalent in African Americans -number of deleted alpha alleles correlates to disease severity -homozygous = complete gene deletion -results in gamma-globin tetramers (= Hb Bart) -Hb Bart has high affinity for O2, resulting in tissue hypoxia and eventual death in utero (hydrops fetalis) -alpha-thalassemia intermedia = due to deletion of 3 copies of the gene -also called HbH disease -in neonates, Hb Bart predominantes but is replaced by HbH as fetal Hb is cleared -usually follows a course that includes moderate anemia, possible HSM, and intermittent transfusions -alpha-thalassemia minor/trait = deletion of 2 copies of the gene -manifests with mild anemia, hypochromia, and microcytosis -often confused with mild iron deficiency -Hb electrophoresis may demonstrate decreased A2, but diagnosis is usually by exclusion -carrier state = deletion of 1 copy of the gene -usually have normal Hb and RBC counts -documented with quantitative measurement of chains and/or gene analysis -number and types of beta alleles determines disease severity in beta-thalassemia -three different alleles: normal, mutant (results in reduced production), and null (results in no production) -beta-thalassemia major = complete absence of beta globin; usually caused by the null/null genotype -beta-thalassemia intermedia = various combinations of normal, mutated, and null alleles that results in partially functional beta chain synthesis -beta-thalassemia minor = one altered allele (either mutated or null) -newborns present with normal Hb (beta chain is not produced until later in infancy) -major disease presents with severe anemia, organomegaly, and progressive growth failure -untreated cases develop marrow hyperplasia due to attempts to increase RBC production -death occurs within a few years without treatment -minor disease presents with minor anemia, and Hb electrophoresis may demonstrate increased A2 and F fractions -intermediate disease is similar to alpha intermediate disease: anemia, HSM, and intermittent transfusions -treatment is dependent upon disease severity -major disease requires regular transfusions to maintain Hb of 10 -iron overload is a common complication of beta-thalassemia due to increased iron absorption as a consequence of poor RBC production -definitive treatment is stem cell transplant; transplant from an HLA-matched sibling is ideal -intermediate disease requires transfusions when Hb falls -folic acid supplementations is recommended due to increased basal rate of erythropoiesis and risk for folate depletion -minor disease generally does not require treatment Anemia of inflammation -2/2 increased circulating levels of hepcidin, an acute phase reactant which is also involved with iron regulation

-essentially a functional iron deficiency: appropriate iron levels are present but not available for cellular use due to macrophage sequestration -anemia is typically mild and asymptomatic -treatment is directed at the underlying cause – anemia will typically resolve without intervention once the inflammation is resolved Transient erythroblastopenia of childhood -acquired pure RBC aplasia 2/2 temporary suppression of erythropoiesis -exact cause unknown but thought to be due to a variety of viral infections that may otherwise be asymptomatic -usually limited and spares WBCs and platelets -peak incidence at age 2, with most cases between 6 mo-4 years -typically presents with pallor recognized by a visiting friend/relative (pallor is subtle and may not be appreciated by regular caregivers), otherwise asymptomatic -should be distinguished from frank bone marrow failure (Diamond-Blackfan anemia) -treatment is reassurance; if anemia severe, transfusions can be performed Hemolytic anemia -usually presents with normocytic anemia with increased RBC production -anemia is detected by the renal system which stimulates erythropoiesis; reticulocytosis is usually present -further classified as intrinsic (due to defects with the RBC itself) or extrinsic (due to defects with something other than the RBC) -intrinsic defects can be due to defects in the membrane, RBC enzymes, or Hb -extrinsic defects can be classified as immune (due to antibody and/or complement deposition on RBC) or non-immune (any other cause) Hereditary spherocytosis -abnormal RBCs that result in a spherical rather than biconcave cell shape -can be due to defects in a variety of cell components which include spectrin, ankyrin, band 3 protein, and protein 4.2 -RBCs have a reduced lifespan and are typically eliminated in the spleen by macrophages -most cases are inherited in an autosomal dominant way but 25% of cases have different etiologies -severe disease (severe anemia, growth failure, splenomegaly, and chronic transfusions) is rare – disease is typically asymptomatic and an incidental finding -can present with “hyperhemolytic” episodes which manifest as frank anemia, pallor, and jaundice -usually 2/2 underlying illness and resolves with illness resolution -infection with parvovirus specifically can be problematic due to predilection for RBCs -long-term complications include gallstones 2/2 increased bilirubin production -diagnostic evaluation should include CBC with diff, reticulocyte count, Coombs (to rule out autoimmune hemolytic anemia), and, if the diagnosis is in doubt, eosin-5-maleimide binding -intervention is not necessary in mild cases -splenectomy is curative for the hemolysis – should only be performed if patient is symptomatic due to increased risk for infection by encapsulated organisms Sickle cell disease -due to a defect in hemoglobin that results in hemoglobin polymerization in times of increased oxygen tension -sickle cell disease is due to a homozygous defect; various other conditions (HbSC disease, sickle cell trait) exist with heterozygotes -pathology is due to sickling of the RBC due to Hb polymerization which results in hemolysis and occlusion of small vessels leading to ischemia and infarction -newborn screens typically identify hemoglobinopathies – work-up is not necessary but would include CBC and possibly Hb electrophoresis -anemia and reticulocytosis usually develop by 2-6 months

-splenic infarction and hyposplenism may begin by 3 months – start penicillin prophylaxis to prevent infection by encapsulated organisms -acute vaso-occlusive crises are unusual before 6 mo -first occlusive episode usually presents as dactylitis, but dactylitis is unusual past age 3 -patients are at high risk of pneumococcal sepsis due to asplenia -spleen is rarely palpable past age 6 -also have an increased risk of osteomyelitis (half of cases are due to Salmonella, half of cases are due to S. aureus) -splenic sequestration can occur when the spleen is incompletely infarcted; presents as severe anemia, hypovolemia, and marked splenic enlargement 2/2 high blood volume in the spleen -prompt treatment is needed to avoid splenic rupture -transfusion may be necessary if anemia is severe -acute chest syndrome = pneumonia-like disease caused initially caused by infection that is exacerbated by sickle cell disease -initial infection results in localized hypoxemia which promotes RBC sickling -sickled RBCs occlude the vasculature, further worsening hypoxemia and promoting spread of the infecting organism -leading cause of death in adolescents and adults -treated with oxygen (hypoxemia), hydration to maintain euvolemia, and appropriate antibiotics -stroke is a common complication due to vaso-occlusion in the brain -treatment includes three strategies: 1) hydroxyurea – promotes HbF formation, which reduces the number of sickled cells in the circulation 2) transfusion – reduces the sickled RBC population and provides normal RBCs 3) stem cell transplant – corrects defect and results in production of normal RBCs G6PD deficiency -due to an X-linked defect in glucose-6-phosphate dehydrogenase, which results in reduced NADPH production and increased susceptibility to oxidative stress -two different variants: -the A- variant results in a relatively stable enzyme and is more prominent in African Americans -symptoms are rare and hemolysis is relatively mild other than during acute hemolytic episodes -the Mediterranean variant results in a very unstable enzyme leading to low circulating G6PD levels; more common in individuals of Greek/Italian descent -can result in a life-threatening hemolysis due to very short lifespan of RBCs -oxidized Hb precipitates out of the cytosol in the form of Heinz bodies, which can be appreciated on peripheral blood smear (present as basophilic inclusions) -acute episodes of hemolysis occur during episodes of stress (e.g., inflammation, infection) or exposure to exogenous oxidizing materials (e.g., fava beans, TMP-SMX) -diagnosis rests on measuring G6PD levels -during an acute episode levels may be normal as older RBCs with nonfunctional enzyme have likely lysed -if suspicion is high and test is normal, test again at a future date after RBCs have been repleted -treatment is supportive and transfusions during episodes of severe hemolysis if needed Autoimmune hemolytic anemia -can be post-infectious (more common after infection with Mycoplasma and EBV) or due to underlying autoimmune disease (e.g., SLE) or malignancy (e.g., lymphoma) -hemolysis results following binding of antibodies to RBCs -antibodies can be detected in serum using the Coombs/direct antiglobulin test -anemia can be classified as “warm” or “cold”

-“warm” anemia = IgG-mediated -IgG has maximal activity at 37 C -can fix early complement but cannot agglutinate RBCs or activate the entire complement cascade -RBC elimination is usually in the reticuloendothelial system – macrophages are stimulated by antibody Fc -“cold” anemia = IgM-mediated -IgM has maximal activity at 4 C -can complete complement activation and agglutinate RBCs -hemolysis is primarily intravascular -associated with Mycoplasma and EBV infection -presentation is dependent upon severity: may be mildly anemic with few/no symptoms or in heart failure and severely jaundiced and anemic -treatment is supportive with steroids and transfusions as necessary -IgM disease does not typically respond to steroids – keeping the patient warm to minimize antibody activity can help Macrocytic Anemias -key differentiation is presence of megaloblastosis (presence of increased numbers of immature blasts in the bone marrow) -megaloblastosis suggests a DNA synthesis defect which hints at a possible etiology -causes of megaloblastic macrocytic anemia: vitamin B12 deficiency, folate deficiency, druginduced (e.g., methotrexate, TMP), and metabolic -causes of nonmegaloblastic macrocytic anemia: bone marrow injury/failure, drug-induced (e.g., valproate, carbamazepine), chronic liver disease, and hypothyroidism Vitamin B12 deficiency -vitamin B12 is a coenzyme necessary for DNA synthesis and is normally found in meat, fish, cheese, and eggs -rare in western countries unless the mother (if breastfed) or child is vegan; body contains stores for years, thus dietary deficiency must be chronic in order for symptoms to develop -deficiency can be due to: -inadequate intake -> treat with supplements -reduced intrinsic factor 2/2 pernicious anemia -transcobalamin deficiency (involved with hepatic B12 storage) -ileal resection (site of intrinsic factor binding for B12 absorption) -bacterial overgrowth -fish tapeworm (Diphyllobothrium) infection -causes macrocytic anemia and neurological findings (paresthesias, neuropathies, dementia, ataxia, posterior column degeneration) -blood smear will demonstrate large RBCs possibly with nuclei, Howell-Jolly bodies, and basophilic stippling; hypersegmented neutrophils are present -levels of homocysteine and methylmalonic acid will be elevated -treatment is with parenteral B12; anemia will resolve within 1-2 months following supplementation Folate deficiency -folate is necessary for DNA synthesis and is found in liver, green vegetables, cereals (artificially added), and cheese -more common due to smaller stores (~1-4 months) -deficiency can be due to: -inadequate intake (rare) -poor absorption (e.g., IBC, celiac sprue) -relative folate deficiency during increased RBC turnover (hyperthyroidism, pregnancy, chronic hemolysis, malignancy) -drug-induced (phenytoin, phenobarbital) -typically presents with nonspecific signs of pallor, glossitis, poor growth, and anorexia -no neurological findings

-megaloblastic changes are noted on blood smear -treatment is with supplemental folate -ensure that there is not also a B12 deficiency – administering folate while B12 is deficient will worsen symptoms of B12 deficiency Diamond-Blackfan anemia -congenital pure RBC aplasia; multiple mutations in ribosomal proteins have been identified -anemia develops shortly after birth with most cases diagnosed by 1 y/o -presents with macrocytosis and reduced reticulocytes -25% of cases also present with other congenital defects including short stature, web neck, cleft lip, shield chest, and triphalangeal thumb -diagnostic testing: -Hb electrophoresis may demonstrate increased HbF -RBC deaminase can be elevated in blood -patients are at high risk for bone marrow failure and leukemia in later life -treatment is with very low doses of oral corticosteroids -some patients are well-controlled with steroids indefinitely -patients that do not respond to steroids or lose their response may become transfusion-dependent Fanconi anemia -many different specific causes but the general etiology is defective DNA repair mechanisms, resulting in chromosomal breaks and recombination -presents with pancytopenia, usually by age 8 -other presenting symptoms: café au lait spots, microcephaly, small jaw, short stature, horseshoe/solitary kidney, and absent thumbs -definitive test is demonstration of chromosomal breakage following diepoxybutane exposure -multiple treatment strategies: -transfusions as needed to correct anemia -androgen therapy can result in some hematological improvement -bone marrow transplant will correct hematological disorders Severe aplastic anemia -acquired failure of hematopoietic stem cells, resulting in pancytopenia -may be due to chemical exposure (e.g., benzene), drug exposure (e.g., chloramphenicol, sulfonamides), infectious agents (e.g., hepatitis viruses), or ionizing radiation -specific cause is rarely found -presents with symptoms of anemia (fatigue, pallor), thrombocytopenia (easy bruising, bleeding), and neutropenia (fevers, infections) -progression is usually slow and indolent -diagnosis is made using bone marrow aspiration White Blood Cell Disorders -alterations in WBC count are typically transient or due to an underlying condition (e.g., infection) -WBCs are classified as granulocytes (neutrophils, eosinophils, basophils), lymphocytes (B/T/NK cells), or monocytes (macrophages) -“left shift” describes an increase in “band” neutrophils, which are immature – usually indicative of an acute infectious process that promotes neutrophil proliferation -eosinophils typically seen in allergic and atopic conditions and parasitic infections -basophils may also be involved with allergic responses -lymphocytes are responsible for humoral and adaptive immune responses -a detailed history that catalogues frequency and severity of infections is helpful for recognizing disorders -neutropenia is defined as less than 1500/cm3 in children older than 1 and less than 1000/cm3 in children less than 1 -prolonged neutropenia should warrant a search for possible bone marrow dysfunction

-leukocytosis = increase in WBC count, usually due to infection, inflammation or allergies, but also malignancy (e.g., leukemia/lymphoma) -disorders of leukocyte function are rare but may present with lack of pus formation during ingestion, chronic leukocytosis, and delayed separation of the umbilical cord Disorders of Hemostasis -hemostasis is divided into two distinct phases: -primary hemostasis = platelet plugging with accompanying vasoconstriction -secondary hemostasis = formation of a fibrin clot -defects in primary hemostasis typically result in bruising and mucocutaneous bleeding while defects in secondary hemostasis typically result in larger bleeds (hemarthrosis, hematomas) -platelets abnormalities can be qualitative (defect in function) or quantitative (defect in number) Thrombocytopenia -defined as a platelet count less than 150,000 -can be due to decreased production or increased destruction -causes of decreased production: -Fanconi anemia – pancytopenia -Aplastic anemia – pancytopenia -Leukemia – bone marrow destruction -thrombocytopenia-absent radius syndrome – autosomal recessive disease that presents with absence of the radii and development of thrombocytopenia that resolves after 1 year -Wiskott-Aldrich – results in small platelets -bone marrow suppression – results in reduced production; can be due to drugs or infection -causes of increased destruction (more common, usually immune-mediated): -neonatal alloimmune thrombocytopenia – platelet destruction due to maternal antibodies against fetal antigens -heparin-induced thrombocytopenia – results in destruction of platelets due to heparin-induced exposure of antigen, usually to platelet factor 4 -microangiopathic hemolytic anemias – result in both destruction of platelets and removal from the circulation (“used up”) -causes include disseminated intravascular coagulation, hemolytic-uremic syndrome (commonly from E. coli), thrombotic thrombocytopenic purpura (no ability to inactive von Willebrand factor, which results in thrombosis) Immune thrombocytopenia (ITP) -due to autoimmune destruction of platelets in the reticuloendothelial system -typically presents 1-4 weeks following a febrile/viral illness with petechiae and bruising -severe bleeding (e.g., intracranial bleeds) is rare -blood smear will demonstrate immature platelets with a low count and an otherwise normal CBC -clinical diagnosis: acute onset of bleeding with isolated thrombocytopenia and no other possible causes -extensive work-up is not typically necessary -bone marrow aspiration should be performed if there is a concern for a more serious etiology (e.g., leukemia) -treatment is typically supportive – usually resolves within 6 months -some patients have persistent ITP (6 months) or chronic ITP (12 months) – not indicative of permanent disease -in cases with severe bleeding, steroids, IVIg, and anti-D Ig can be used to temporarily increase the platelet count -anti-platelet meds (e.g., aspirin, NSAIDs) should be avoided if possible Disseminated intravascular coagulation (DIC)

-due to a derangement in coagulation regulation – coagulation and fibrinolysis are abnormally activated -results in fibrin deposition in blood vessels, tissue ischemia, release of fibrinolytic factors, and fibrinolysis -labs will demonstrate low platelets, fibrinogen, factors II, V, and VIII, protein C, and plasminogen due to consumption -bleeding is profuse – constant bleeding from IV access sites and catheters may occur -hallmark finding on blood smear is schistocytes (helmet-shaped cells) formed by shearing across fibrin fibers within the vasculature -treatment is supportive – platelets and fresh frozen plasma should be used if bleeding cannot be controlled -heparin can be considered for thrombosis but should be used with caution Hemophilia A/B -due to factor VIII (hemophilia A) or factor IX (hemophilia B) deficiency -both are X-linked and are more common in males -both disorders present in an identical fashion, and findings are dependent upon disease severity -5-49% of normal factor levels: significant trauma required to induce spontaneous bleeding -1-5% of normal factor levels: may have infrequent spontaneous bleeding but typically requires moderate trauma -less than 1% of normal factor levels: frequent, spontaneous bleeding, often appreciable in infancy -lab findings: reduced factor VIII/IX levels with a prolonged PTT and normal PT -multiple treatment approaches: -infusion of deficient factor, usually only during acute bleeding episode -desmopressin promotes factor VIII release from endothelial cells, thus can be administered instead of factor VIII -most common complication is acquired immunosensitivity to infused factors, eliminating the efficacy of treatment -can be managed by administration of a factor that “bypasses” deficiency (e.g., VIIa) von Willebrand disease -due to a deficiency of von Willebrand factor (vWF), which bridges platelets to subendothelial collagen and carries VIII in the blood -vWF can be quantitatively reduced, qualitatively nonfunctional, or absent -presents similarly to thrombocytopenia: easy bruising, epistaxis, gingival bleeding, menorrhagia, mucocutaneous bleeding -severe disease may also present with severe factor VIII deficiency due to decreased half-life 2/2 lack of vWF carriage -mild reductions may be asymptomatic -diagnosis is based on determination of vWF levels and functionality -bleeding time and PTT may be prolonged -treatment is desmopressin during acute bleeding episodes if severe -desmopressin promotes vWF release from endothelial cells -patients with absent vWF can be given a vWF concentrate Vitamin K deficiency -vitamin K is required for synthesis of factors II, VII, IX, and X and proteins C and S in the coagulation cascade -deficiency is usually due to malabsorption (CF, antibiotics) -usually presents as hemorrhagic disease of the newborn following failure to administer vitamin K to neonates -breast milk is a poor source of vitamin K, so deficiency in the absence of supplementation at the hospital is common -symptoms are generalized ecchymoses, GI bleeding, and bleeding from circumcision site or umbilical stump

-both the PTT and PT are prolonged due to involvement of multiple factors -can present similarly to DIC – differentiated by normal platelets, fibrinogen levels, and factor VIII levels (all of which are reduced 2/2 consumption in DIC) Treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) -rare in children generally, but more common in patients with prolonged hospital stays -obesity and OCP use in women also increases risk of thrombosis -classic presentation is acute, unilateral limb swelling with pain and discoloration and distended superficial veins -multiple genetic conditions can predispose to thrombosis: -factor V Leiden – mutated factor V that cannot be degraded as easily, resulting in prolonged coagulation activation -protein C/S and antithrombin deficiencies – impair deactivation of the coagulation cascade, resulting in thrombosis -pulmonary embolism is a complication of thrombosis – due to capture of a thrombus in the pulmonary vasculature -if large enough, can result in V/Q mismatch and circulatory failure -in both cases, treatment is with anticoagulation -acutely, heparin is typically used -chronic treatment/prevention is with warfarin -thrombolytics (e.g., tissue plasminogen activator = tPA) can be used in acute cases to dissolve the thrombus Transfusion of blood products -different types of products that can be transfused: -packed RBCs (PRBCs) = for symptomatic or severe anemia; results in an immediate increase in O2 carrying capacity due to increased Hb; 10-15 mL/kg of PRBCs increases Hb by 2-3 -platelets = to prevent or stop bleeding in patients with thrombocytopenia or platelet dysfunction -fresh frozen plasma = for replacing deficient coagulation factors -cryoprecipitate is a specific product rich in factors VIII and IX, fibrinogen, and vWF -granulocytes = for severe neutropenia and unresponsive, life-threatening sepsis -important reactions associated with transfusion: 1) febrile reactions – stop transfusion, do transfusion work-up, and administer antipyretics 2) allergic reactions – present immediately following initiation of transfusion with pruritis, rash, and urticaria; stop transfusion and administer antihistamines, may need steroids 3) acute hemolytic reaction – usually due to administration of mismatched blood products with sudden onset fever, chills, tachycardia, tachypnea, and vomiting 4) infections (i.e., due to contaminated products) – very rare, but can occur 5) transfusion-associated acute lung injury – presents with non-cardiogenic pulmonary edema, thought to be 2/2 immune cell reaction to products and destruction of the pulmonary vasculature 6) transfusion-associated graft versus host disease – due to grafting of immunocompetent T cells with the infused product which cannot be suppressed by the host immune system; very rare but fatal; prevented with product irradiation prior to infusion, usually used only if immunodeficient individuals are receiving blood products 7) alloimmunization/delayed hemolytic transfusions – most common in individuals that receive multiple transfusions; due to the development of antibodies against transfused products 8) iron overload – occurs in chronically transfused patients due to inability to eliminate excess iron; chelation therapy can be used if end-organ damage is a concern

Chapter 12 – Oncology -most common cancers in young children are leukemias and brain tumors; in adolescents, Hodgkin’s disease and germ cell tumors are most common -in general, childhood cancers have good prognoses and high cure rates Leukemia -most common childhood malignancy – acute lymphocytic leukemia (ALL) is the most common type -due to malignant transformation and clonal expansion of hematopoietic cells -can be either lymphoblastic (of lymphocyte origin) or myeloid (all other origins) -acute leukemias are the most common (97%): they are rapidly fatal but generally curable -chronic leukemias are more indolent but may undergo transformation to an acute leukemia -leukemias are classified by morphology (appearance of blast cells) and immunology (surface antigen expression) -most common subtype is precursor B cell leukemia -AMLs use a different classification scheme which is based on both morphologic and histochemical criteria -incidence of ALL peaks at 2-5 years while the incidence of AML peaks in adolescence -increased risk of leukemia associated with trisomy 21, Fanconi anemia, Bloom syndrome, ataxia-telangiectasia, X-linked agammaglobulinemia, SCID, past chemotherapy, and twins with an affected sibling -presentation is generally nonspecific: -lethargy, malaise, and anorexia are common -bone pain and arthralgias 2/2 bone marrow expansion 2/2 increased activity may occur -progressive marrow failure may cause signs of anemia and thrombocytopenia -WBC count is NOT consistent – equally distributed among low, normal, and elevated counts in confirmed diagnoses -HSM and lymphadenopathy is typically present at diagnosis -evaluation should include rule outs of rheumatological disease, non-malignant bone marrow failure, infection, and drug-induced hematologic abnormalities -diagnosis is based on CBC and bone marrow findings -CBC may demonstrate blast cells -flow cytometry is used to evaluate surface marker expression -metabolic panel prior to initiation of chemotherapy to evaluate for possible complications (e.g., tumor lysis syndrome) is appropriate -bone marrow biopsy is required for definitive diagnosis and staging -treatment is immediate stabilization and chemotherapy (see below for specifics) ALL therapy -high risk of tumor lysis syndrome (= triad of hyperuricemia, hyperphosphatemia, and hyperkalemia 2/2 expulsion of cell contents following death) -hyperkalemia can cause cardiac arrhythmias -hyperphosphatemia can cause precipitation of calcium phosphate and subsequent hypocalcemia -hyperuricemia can cause precipitation of uric acid stones and renal failure -more common in types with massive proliferation and mediastinal masses -hyperleukocytosis (WBC count above 200k) can lead to vascular stasis and thrombotic complications -treat with hydration to dilute blood or with leukophoresis -large mediastinal masses can result in compression of vital structures (e.g., SVC syndrome, airway obstruction) -treatment plan has 4 phases: -induction therapy = maximum killing phase of malignant cells -occurs over 4 weeks with vincristine, steroids, methotrexate, and asparaginase -nearly all patients achieve remission following induction

-consolidation therapy = killing remaining cells and preventing relapse; regimen is systemic therapy with continuation of methotrexate -interim maintenance = less intense therapy with vincristine, 6-mercaptopurine, methotrexate – goal is to induce deeper remission -maintenance therapy = periodic methotrexate, vincristine, and steroids; goal is to continue remission -patients at high-risk of remission receive additional courses of interim maintenance therapy -total length of therapy is usually 2.5/3.5 years (females/males); early relapse carries a worse prognosis AML therapy -hyperleukocytosis is more common than in ALL -complications are also more common – malignant cells in AML are “stickier,” thus lower WBC counts can result in symptoms -therapy is, in general, more intense than with AML but the overall regimen remains the same -induction is with anthracycline and cytosine arabinoside -results in high rates of remission but relapse within 12 months is common -myelosuppression is severe and requires extensive supportive care -treatment following remission is dependent upon severity of disease -low-risk disease is treated with chemotherapy alone -high-risk disease is treated with a bone marrow transplant Non-Hodgkin’s lymphoma -group of diseases characterized by proliferation of immature lymphoid cells that accumulate outside of the bone marrow -classification is based on histopathology -male predominance (3:1) -increased risk in children with immunodeficiency, Bloom syndrome, and ataxiatelangiectasia -presentation varies with type -T cell lymphoma more commonly associated with mediastinal mass -Burkitt’s lymphoma is very aggressive and may present with tumor lysis syndrome prior to chemotherapy -anaplastic large cell is more indolent with chronic fever -treatment is with combination chemotherapy Hodgkin’s lymphoma -unknown etiology, but environmental and genetic components appear to be involved; patients have increased incidence of immune dysregulation -different types based on pathological findings: nodular sclerosing (most common), lymphocyte predominant, mixed cellularity, and lymphocyte-depleted -rare in children younger than 10, peak incidence is 15-30 years -male predominance (3:1) in childhood -presents with cervical lymphadenopathy and sometimes with systemic symptoms (= “B symptoms:” fever, night sweats, and weightloss) -physical exam typically demonstrates enlarged lymph nodes; HSM may be present and is consistent with advanced disease -evaluation includes lymph node biopsy, CXR (possibly with more advanced imaging) to evaluate for masses, and blood markers (CBC, inflammatory markers, LFTs) -disease follows a highly consistent course and predictable routes of spread -staging uses a standardized scheme: -stage I – involvement of single lymph node or extrahepatic site -stage II – involvement of multiple lymph nodes -stage III – involvement of lymph nodes on both sides of the diaphragm with involvement in the spleen or localized involvement of extrahepatic site -stage IV – disseminated involvement of at least one extrahepatic site

-prognosis is generally good depending upon stage and response to treatment -lymphocyte-predominant subtypes have a better prognosis while the lymphocytedepleted subtype has the worst prognosis CNS tumors -broadly classified as supratentorial (above the tentorium) or infratentorial (below the tentorium) -supratentorial tumors include: cerebral astrocytoma (young children, poor prognosis); craniopharyngeoma (young children, good prognosis); optic glioma (infants, good prognosis); and germ cell tumor (any age, good prognosis) -typically present with signs of ICP or seizures -personality changes, changes in school performance, and change in hand preference suggest cortical involvement -endocrine abnormalities may present with hypothalamic or pituitary involvement -infratentorial tumors include: cerebellar astrocytoma (young children, good prognosis); medulloblastoma (toddlers, moderate prognosis); ependyoma (older infants, moderate prognosis); brainstem glioma (young children, very poor prognosis) -typically present with deficits in balance or brainstem function -non-malignant causes of neurological signs should be ruled out: AV malformation, brain abscess, infection, ICH, vasculitis, and pseudotumor cerebri -diagnosis rests on CT/MRI imaging and CSF cytology -treatment usually uses combinations of surgery, radiation, and chemotherapy -surgery is used for tumor resection, reducing ICP, and establishing diagnosis -radiation is used to control residual disease, dissemination, and for cure -chemotherapy is used as an adjuvant and/or replacement for radiation Neuroblastoma -embryonal malignancy of the postganglionic sympathetic nervous system -tumors are usually found in the abdomen, thorax, head, and/or neck -most common cause of solid tumors outside of the CNS -cause and etiology is unknown -presenting symptoms and disease course are highly variable -symptoms are dependent upon location: -abdominal: pain, distension, systemic hypertension (2/2 renal vasculature compression) -thorax: commonly asymptomatic and an incidental finding on CXR -neck: Horner’s syndrome (unilateral ptosis, miosis, anhydrosis) -nonspecific symptoms include weightloss and fever -best prognosis with stages I, II, and IVS; poor prognosis with stages III and IV (see below for staging details) -staging: -stage I – localized tumor that can be completely excised -stage II – localized tumor that cannot be complete excised; positive (IIA) or negative (IIB) lymph node involvement -stage III – tumor extension beyond the midline or localized disease with contralateral lymph node involvement -stage IV – dissemination of tumor to distant lymph nodes or organs -stage IVS – younger than 1 y/o with dissemination to liver, skin, or bone marrow without bone involvement; tumor would otherwise be classified as stage II/III -can regress spontaneously or with minimal chemotherapy -treatment includes multiple approaches: surgery and chemotherapy (vincristine, cyclophosphamide, doxorubicin, and cisplatin) are standard with radiotherapy and/or biologic therapies added as appropriate Wilms tumor -most common renal tumor in children, due to proliferation of embryonic renal cells -typically includes chromosomal involvement of chromosome 11 (either p13 or p15 segments)

-tumors are typically unilateral and diagnosed by age 5 -typically presents after incidental palpation of mass by caregivers -abdominal pain/fever may develop if tumor hemorrhages -hypertension can occur due to increased renin secretion or vascular compression -in males, spermatic cord involvement may present with varicocele -diagnosis is typically by abdominal US, CT or MRI -most common spread patterns are through the renal capsule, into the IVC, and into the lung and liver -lung metastases typically documented with CXR -treatment is surgical removal of the kidney (if unilateral and possible) possibly followed by chemotherapy and/or radiation -radiation therapy is typically reserved for severe cases -very good prognosis – 4-year survival is 90% Ewing sarcoma -undifferentiated sarcoma that arises from the bone -translocation of chromosome 11 to chromosome 22 is common; cells are clonal -most commonly seen in adolescents with a slight male predilection (1.5:1) -extremely rare in African Americans -presents with localized pain and swelling at the tumor site -most common sites include the femur, pelvis, fibula, humerus, and tibia -tumor is typically in the midshaft (vs. ends as in osteosarcoma) in long bones -primary alternatives include bony metastases from a secondary malignancy, osteosarcoma, and osteomyelitis -radiographs typically demonstrate a lytic bone lesion with periosteal elevation; CT/MRI can demonstrate extent of disease -biopsy demonstrates typical t(11;22) -treatment includes local (radiation, surgery) and systemic (chemotherapy) approaches -most patients have metastases at diagnosis so chemotherapy is necessary -chemotherapeutic agents include vincristine, doxorubicin, cyclophosphamide, etoposide, and ifosfamide -prognosis is worse with metastatic disease; 5-year survival is greater than 66% Osteosarcoma -malignancy in bone-producing mesenchymal stem cells -tumor usually develops from the medullary cavity or periosteum, most commonly in the distal femur, proximal tibia, and proximal humerus -incidence peaks in adolescence with a male predominance (2:1) during growth spurts -presents similarly to Ewing’s except for the absence of systemic findings -primary metastatic site is the lungs -depending upon severity/location, may present with gait disturbances and pathologic fractures -evaluation and treatment is nearly identical to Ewing’s -surgical intervention may include amputation -osteosarcoma is more resistant to radiotherapy -prognosis is generally good, with long-term survival greater than 70% Retinoblastoma -most common childhood ocular malignancy -most cases are sporadic but heritable forms do exist -mutation is in the RB1 gene located on chromosome 13 -nearly all cases occur before age 5 with most before age 2 -referral to an ophthalmologist is critical to rule out other possible etiologies -presence of leukocoria during well-child visit should prompt a work-up/referral -MRI of the head to evaluate for the extent of the tumor is usually performed -treatment can be with enucleation (surgical removal of the eye), chemotherapy, local therapy (cryotherapy, laser therapy), and radiation -chemotherapy used to shrink tumors to allow for more effective local therapies

Soft tissue sarcomas -diverse group of tumors that are broadly classified as rhabdomyosarcomas or nonrhabdomyosarcomas -rhabdomyosarcoma = muscle involvement -young children typically develop rhabdo while older children develop non-rhabdo tumors -CT/MRI is used to evaluate extent of disease; bone marrow biopsy is typically necessary -treatment is variable depending upon specific tumor type but typically involves, surgery, chemotherapy, and radiation Chapter 13 – Immunology, Allergy, and Rheumatology -innate immune system = nonspecific reactions to invading foreign antigens/organisms -adaptive immune system = specific pathogen recognition and elimination -signs of immunodeficiency: severe, persistent, or recurrent sinopulmonary infections; infection by an opportunistic pathogen; family history of immunodeficiency; infection at an unusual site (e.g., brain); failure to thrive; diarrhea; lymphopenia; and chronic gingivitis Disorders of T Cell Immunity -T cells modulate most immune responses and are responsible for recruiting macrophages and B cells and killing pathogens directly -life-threatening emergency in the neonate due to increased risk for severe infection -bone marrow transplants are curative but fraught with complications and risk -congenital T cell deficiency: severe combined immunodeficiency (SCID) -group of disorders that all result in T cell dysfunction -most common defect is in the IL-2 receptor (X-linked) -DiGeorge syndrome may present like SCID due to thymic aplasia (and, thus, no T cell maturation), however other defects (e.g., congenital heart disease, hypocalcemia) typically present first -acquired T cell deficiency: HIV infection -patients with T cell deficiencies have increased risk for developing intracellular and fungal infections (infections that are primarily eliminated by T cells) -testing is done to measure WBC count (should demonstrate lymphopenia) and test T cell function (e.g., intradermal injections of stimulating antigens) -initial treatment is with Ig replacement and aggressive treatment of infections until a bone marrow transplant can occur Disorders of Humoral Immunity -due to defects in B cell maturation or infections -results in low circulating levels of antibodies, increasing the risk of developing extracellular infections -usually presents with a history of recurrent infections with encapsulated organisms (e.g., H. influenzae and S. pneumoniae) -URIs are especially common -failure to thrive may develop -multiple causes: -X-linked agammaglobulinemia: essentially absent B cell populations with absence of circulating Ig; due to a defect in the Bruton tyrosine kinase; becomes evident by about 6 months in boys -common variable immunodeficiency (CVID): reduction in circulating Ig levels, particularly IgG and IgA; increased incidence of lymphoma and autoimmune disease -selective IgA deficiency: increases susceptibility to bacterial infections in the respiratory, GI, and urinary tract -diagnostic testing: -measurement of absolute IgA, IgG, and IgM levels -measurement of albumin to evaluate for possible hypoproteinemia due to a secondary cause -absent titers following immunization with tetanus, diphtheria, and H. influenzae is suggestive of B cell dysfunction

-should be distinguished from transient hypogammaglobulinemia of the newborn; most children develop normal circulating Ig levels by age 2-5 Combined Immunodeficiency Syndromes -increased susceptibility to all infections due to global immune dysfunction -Wiskott-Aldrich: X-linked recessive disorder that affects B/T cells and presents with atopic dermatitis and thrombocytopenia -host antibodies do not respond normally to carbohydrate antigens -poor prognosis due to bleeding, infections, and malignancies -bone marrow transplant is recommended early -hyper IgM syndrome: defective interaction between CD40L on T cells and CD40 on B cells, impairing isotype switching; consequently, patients do not develop the ability to produce mature Ig (e.g., IgM) -presents with recurrent sinopulmonary infections or P. jirovecii pneumonia -diagnosis is made by measuring Ig levels -treatment is with bone marrow transplant Disorders of Phagocytic Immunity -phagocytes = cells that ingest and destroy microorganisms; phagocytosis acts as both a protective and clearing mechanism -disorders can be due to reduced cell counts, cell dysfunction, or inability of phagocytes to migrate to target areas -important causes: -neutropenia: can be either congenital or transient (infection, effect of drugs, etc.) -chronic granulomatous disease (CGD): most common congenital disorder; due to inability to generate microbiocidal products 2/2 NADPH oxidase deficiency -leukocyte adhesion deficiency (LAD): phagocytes are unable to migrate into tissues due to a defect on membrane adhesion proteins -serious disease with neutropenia usually doesn’t develop unless the count is severely low (less than 0.5) and chronic (2-3+ months) -presents with gingivitis, skin infections, rectal inflammation, otitis media, pneumonia, and/or sepsis -ability to mount a systemic inflammatory response is impaired, so typical signs of inflammation may not be evident during infection -evaluation requires bone marrow biopsy to rule out malignancy -chronic disease can be treated with rhG-CSF (recombinant human granulocyte colony stimulating factor), which promotes granulocyte production and differentiation -CGD presents with chronic/recurrent pyogenic infections by organisms that produce catalase (S. aureus, Candida, Aspergillus) and most gram-negative enterics -results in abscess and granuloma formation, particularly in the lymph nodes, spleen, liver, lungs, skin, and GI tract -can also present with failure to thrive, chronic diarrhea, and persistent candidiasis -classic test is the nitroblue tetrazolium test -TMP-SMX prophylaxis is indicated to prevent chronic infections -LAD presents similarly to CGD, but WBC count is extremely high (5-10X normal) and no granulomas are present -delayed separation of the umbilical cord is a classic sign of neutrophil dysfunction -diagnosis is by flow cytometry; most common defect is in CD18, so there will be reduced CD18 levels -definitive treatment is bone marrow transplant Allergy -allergic reaction is an immune-mediated response to an environmental antigen -allergic reactions are never considered adaptive, and they can be mild or life-threatening -allergic triad = atopic dermatitis (eczema), allergic rhinitis, and asthma -allergic march = typical progression of the allergic triad: eczema -> allergic rhinitis -> asthma

Atopic dermatitis -chronic, relapsing and remitting skin reaction to allergens -most commonly associated allergens are milk proteins, egg, fish, wheat, soy, dust mites, and animal dander -rash presents as a pruritic, erythematous, weeping papiulovesicular lesion -progresses to scaling, hypertrophy, and lichenification (thickening of the skin) -most commonly affected areas in infants include the extensor surfaces of the arms and legs, the wrists, face, and scalp (diaper area is spared) -flexor services are affected in older children -differential includes contact dermatitis and psoriasis -treatment is avoidance of allergens and aggressive hydration -tight clothing and heat should be avoided due to association with exacerbations -topical corticosteroids can be used lesions -main complication is infection of exposed lesions Allergic rhinitis -also known as hay fever -uncommon before age 4-5; should distinguish between seasonal and year-round allergies -seasonal allergies suggest an outdoor, likely plant-based allergen -year-round allergies suggest an indoor allergen (more likely to be controlled and, thus, minimize symptom development) -due to a type 1 hypersensitivity reaction – IgE mediated -IgE bound to allergen stimulates mast cells, which release mediators that promote vasodilation, mucus production, and edema -main risk factors are other atopic findings and genetic predisposition -early exposure to cigarette smoke may increase risk of developing allergies -early exposure to pet dander may reduce the risk of developing atopic disease -presents with nasal congestion, profuse watery rhinorrhea, and sneezing -post-nasal drip may cause frequent coughing/throat clearing -key physical exam findings: -allergic shiners = dark circles that develop under the eyes 2/2 venous congestion -allergic salute = crease across the middle of the nose 2/2 wiping -severe allergies may cause children to become obligate mouth breathers -differential: -infectious rhinitis – more common in infants and toddlers; usually presents with mucopurulent (vs. watery) discharge -nasal foreign body – discharge is usually thick, unilateral, and foul-smelling -sinusitis – facial pain, headache, and cough -idiopathic nonallergic rhinitis – similar presentation, but thought to be due to an exaggerated vascular response to irritants (not IgE-mediated) -treatment is centered on allergen avoidance and antihistamine therapy -limiting indoor humidity (promotes dispersion of allergens on water particles) and using air conditioning rather than windows in the summer can reduce allergen loads -frequent washing of bedding can reduce dust mites and fungi -H1-histamine blockers and nasal corticosteroids are typical treatment -immunotherapy can be used and is highly effective for rhinitis, allergic asthma, and insect stings; may also reduce subsequent development of atopic disease Urticaria and angioedema -both are the result of type 1 hypersensitivity reactions -urticaria (also called hives) = raised edematous lesions due to increased vascular dilation and permeability -angioedema = edema in the lower dermis and subcutaneous areas without pruritis, erythema, and warmth -history and exam should focus on identifying new exposures to identify possible triggers -may take up to 48 hours for lesions to develop following exposure

-hereditary angioedema is to due a deficiency in C1 esterase (reduced C1 breakdown -> complement activation -> increased/spontaneous vascular permeability) -treatment is centered on avoiding known allergens and treatment with antihistamine -in emergency situations, sub-Q epi and IV diphenhydramine are appropriate Food allergies -IgE response to ingested allergens – important to distinguish between poor tolerance (e.g., caffeine-induced tachycardia) and actual allergic response -over 90% of food allergies are due to peanuts, eggs, milk proteins, soy, wheat, tree nuts, and fish -though skin testing has a low positive predictive value for identifying allergic triggers, it can be used to rule out possible triggers and prevent potentially severe anaphylactic reactions -gold standard for identifying allergies is the double-blind, placebo/food challenge -possible triggers are removed from the diet and then disguised and reintroduced; placebos are used to separate exposures to different triggers -treatment is avoidance of trigger -patients with severe allergies should have immediate access to an epi pen -infants with milk allergies can be fed hypoallergenic formula -cow milk, soy, egg, and wheat allergies frequently resolve – these foods can be reintroduced into the diet later in life to test for persistent allergies -allergies to peanut, nut, and fish allergies are usually persistent Rheumatic Disease -encompasses a variety of conditions that can be characterized as autoimmune and/or autoinflammatory -various defects in tolerance to self-antigens results in activation of the immune system and end-organ damage (autoimmunity) -abnormal stimulation of the innate immune system results in the development of an inflammatory response (autoinflammation) in an otherwise inappropriate setting -the most common pediatric disease include juvenile idiopathic arthritis (JIA), systemic lupus erythematosus (SLE), and juvenile dermatomyositis (JDM) -as a group, rheumatic disorders are difficult to diagnose due to the long course of disease, predominance of nonspecific symptoms, and highly variable presentation -see below for a table of abnormalities associated with specific disorders JIA -most common rheumatic disease in children -defined as chronic arthritis (6+ weeks) in children younger than 16 with no other identifiable cause -exact etiology is unclear, but disease is associated with certain HLA subtypes -underlying problem is synovitis driven largely by TNF-alpha activity -classically presents with morning joint stiffness and stiffness following periods of immobility -pain is typically not severe – severe pain suggests an alternate diagnosis -multiple subtypes of JIA (see table below for more details): -oligoarticular: arthritis of no more than 4 joints; typically presents in girls that are 2-4 y/o; ANA positivity is common -polyarticular: arthritis of 5 or more joints; can be rheumatoid factor positive and present with rheumatoid nodules (resembles adult RA; worse prognosis) -systemic: arthritis preceded by a daily fever of at least 3 days with transient rash, lymphadenopathy, HSM, and serositis after ruling out infection and malignancy; true autoinflammatory disorder; marked elevation of inflammatory markers is typical -psoriatic: presents with psoriasis or independently with at least 2 of the following: dactylitis (pathognomonic), nail pitting, psoriasis in first-degree relative, involvement of large and small joints -enthesitis-related: arthritis or tendon inflammation (= enthesitis) with at least 2 of the following: sacroiliac tenderness or lumbosacral pain, HLA-B27, onset after age

6 in males, acute anterior uveitis, history of HLA-B27-associated disease in firstdegree relative -differential is extensive and includes: -arthritis: post-infectious, reactive -inflammatory conditions: IBD, connective tissue diseases, vasculitis -infection: septic arthritis, viral arthritis, Lyme disease -malignancy -MSK trauma -evaluation is based on clinical and lab findings: -presence of ANA is typical (except in systemic JIA) -acute phase reactant elevation is typical but nonspecific; systemic JIA has large elevations -treatment is with anti-inflammatory drugs as appropriate -single joints can be treated with intraarticular steroids -disease-modifying drugs (e.g., methotrexate) are appropriate if multiple joints are affected -biologic therapies that target IL-1, IL-6, and T cell stimulatory molecules are now available and highly effective -severe arthritis may result in anatomical and growth deformities -use of biological therapies significantly reduces likelihood of permanent defects (though the disease itself may be permanent) SLE -defined as a chronic, multisystem inflammatory disorder -typically presents in adolescent children (mostly girls) but rarely may present before puberty (equal incidence in girls and boys) -exact etiology is complex, but thought to be due to abnormal apoptosis; these defects generate autoantibodies that then produce disease -difficult to diagnose since findings are highly nonspecific and can masquerade as a variety of other diseases -diagnosis is based on the presence of at least 4 of the following: malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, renal dysfunction, neurologic disorder, hematologic disorder, ANA positive, presence of autoantibodies -may present with general systemic signs (fever, malaise, weight loss) -renal involvement is called lupus nephritis; cerebral involvement is called CNS lupus -diagnostic evaluation is difficult: -elevation of ESR (but not CRP) usually occurs -low complement levels indicate active disease -presence of anti-Smith, anti-dsDNA, anti-RNP, anti-Ro, and anti-La are suggestive of SLE -treatment is organ system dependent -general avoidance of sunlight is recommended – can precipitate both rash and systemic flares -hydroxychloroquine is recommended for preventing mucocutaneous and systemic flares -MSK involvement is treated with NSAIDs -renal and CNS disease requires more aggressive treatment -a regular regimen of corticosteroids is usually started -immunosuppressive agents can be used in serious disease Dermatomyositis -multisystem disease that predominantly affects the skin and MSK with less common involvement of the GI tract -disease is humorally mediated and primarily involves the vasculature -some HLA subtypes are associated with increased risk -primary alternate diagnosis is polymyositis – less common in children and is due to CD8mediated (vs. CD4) direct destruction of muscle fibers

-presents as proximal muscle weakness with sparing of distal strength -other findings: -violet rash of the eyelids (= heliotrope rash), hands, elbows, knees, and ankles -Gottron papules – erythematous, scaly lesions on the extensors surfaces of the fingers, elbows, and knees -key lab findings are markedly elevated creatine phosphokinase (CK), an enzyme abundant in muscle tissue -other enzymes are common elevated (LDH, AST, aldolase) -MRI can demonstrate muscle inflammation -treatment is primarily with corticosteroids -methotrexate is also commonly added, and hydroxychloroquine is effective against cutaneous manifestations -IVIg and cyclosporine are second-line agents -early aggressive treatment may prevent future progression of disease Other connective tissue disorders -quite rare in childhood and are difficult to differentiate -systemic sclerosis: fibrous thickening of the skin and internal organs -presents with Raynaud phenomenon and extremity edema -mortality is due to cardiopulmonary and renal involvement -linear scleroderma/morphea: linear (linear scleroderma) or patchy (morphea) lesions -usually presents with erythematous thickening and hardening of the skin -rarely causes internal disease -Sjogren’s syndrome: lymphocytic infiltration of the exocrine glands, usually the lacrimal and salivary glands -usually presents with dry mouth (xerostomia) and dry eyes (xeropthalmia) -associated with anti-Ro and anti-La antibodies Primary systemic vasculitis -most commonly due to either Henoch-Schonlein purpura or Kawasaki disease; other disorders are rare -Henoch-Schonlein purpura: deposition of IgA immune complexes in vessel walls -most common in children 4-6 y/o with a male predominance -increased incidence in the winter months -usually preceded by a URI (commonly GAS) -rash is typically confined to the lower body but may present on the face in younger children -can present with extremely painful arthritis -glomerulonephritis is a common (40%) complication -treatment is generally supportive, and the condition resolves spontaneously usually by 4 weeks -corticosteroids may be used with severe GI or renal involvement -Kawasaki disease: variety of systemic findings meeting particular criteria with no other known cause -most common in children 2-3 y/o with a male predominance -course has three phases: -acute phase: typical diagnostic features (see below) with extreme irritability; labs demonstrate elevated ESR, CRP, AST/ALT, and WBC with sterile pyuria -subacute phase: thrombocytosis with risk of coronary artery aneurysm -convalescent phase: gradual reduction in disease activity -diagnostic criteria include: bilateral conjunctival injection with limbic sparing, rash, fever for at least 5 days, mucous membrane involvement (commonly strawberry tongue, lip cracking), and cervical lymphadenopathy -treatment is with IVIg (2 g/kg) and high-dose aspirin (80-100 mg/kg); low-dose aspirin (3-5 mg/kg) is continued for several months Periodic fever syndromes

-group of hereditary autoinflammatory disorders due to defects in inflammation, apoptosis, and cytokine processing -fevers are abrupt in both onset and termination and present identically with each recurrence -markers of inflammation (WBC, ESR, and CRP) are typically elevated during fever attacks -primary complication is end-organ damage 2/2 amyloidosis -three important syndromes: 1) familial Mediterranean fever: fevers that last 1-3 days and recur every 4-8 weeks; most common in Arabs, Turks, Armenians, and other Mediterranean populations 2) tumor necrosis factor receptor-associated periodic fever syndrome: fevers last 1-3 weeks and recur 2-3 times annually; may also present with abdominal pain, muscle aches with overlying erythema, conjunctivitis, periorbital edema, and arthritis of the large joints 3) periodic fever, apthous stomatitis, pharyngitis, adenitis syndrome: syndrome with specific clinical criteria that include the eponymous findings with no other identified cause Chapter 14 – Endocrinology -endocrine system = system of glands involved with hormone secretion -axis = series of glands that are related to each other in a linear way -the pituitary is frequently the master gland that secretes a variety of hormones which in turn affect secondary gland activity -hormones are involved in a variety of physiological processes and act by binding a target receptor (intracellular or extracellular depending upon hormone chemistry) Diabetes mellitus -metabolic diseases characterized by high blood sugar usually due to insulin deficiency (type 1) or insulin resistance (type 2) -classically presents with hyperglycemia, polydipsia, polyuria, and polyphagia -can also be drug-induced (e.g., steroids) or the result of an additional disease process Type 1 DM -autoimmune destruction of pancreatic beta-cells which results in reduced insulin secretion -peak onset is at age 10-12 y/o -anti-islet cell antibodies are demonstrated in most patients -lack of insulin activity results in a catabolic state with enhanced gluconeogenesis, lipolysis, proteolysis, and stress hormone production -inability to shift glucose into cells results in hyperglycemia; levels above 180 result in an osmotic diuresis due to saturation of glomerular glucose transporters -ketogenesis results from fat breakdown; this eventually produces dehydration, acidosis, and electrolyte abnormalities -typically presents with a history of weightloss, polydipsia, polyuria, and polyphagia in addition to more acute symptoms (nausea, vomiting, altered mental status) -in severe cases, can present with increased ICP due to electrolyte abnormalities -diagnostic testing: -blood glucose levels are diagnostic (random over 200, fasting over 126, or 2-hours post-glucose challenge over 200 -anti-islet cell antibodies may be present -elevated HbA1c may be present if hyperglycemia is chronic -UA may demonstrate ketonuria and glucosuria -treatment is focused on lowering blood glucose and correcting metabolic abnormalities -fluid deficit should be calculated and replenished over 48 hours -glucose should not be corrected quickly due to risk of cerebral edema -newly diagnosed patients should receive extensive education on the importance of maintaining glycemic control and the role of insulin in management -long-term insulin regimen usually follows a basal-bolus model (long-acting insulin for basic control with addition of pre-prandial short acting insulin as needed)

-complications are primarily due to the effects of hyperglycemia on end organs -retinopathy, nephropathy, and neuropathy are common complications that occur 2/2 osmotic cellular damage -accelerates the atherosclerotic process in large vessels Type 2 DM -due to insulin resistance and subsequent beta-cell dysfunction -initially insulin resistance is compensated for with increased insulin resistance -eventually, however, beta-cells do not secrete insulin in response to elevated glucose levels -associated with obesity and family history of type 2 DM -physical exam usually demonstrates obesity -acanthosis nigrans (darkening and thickening of the skin) may be present, particularly on the back of the neck or other flexor areas -treatment is lifestyle modification, oral glycemic agents, and, if necessary, insulin supplementation Hypoglycemia -defined as blood glucose level less than 60 -can be due to several etiologies: hyperinsulinemia, ketotic hypoglycemia, hormone deficiency, glycogen storage diseases, defects in gluconeogenesis, and defects in fatty acid oxidation (in addition to functional transient hypoglycemia) -presents with sympathetic symptoms (tachycardia, tremors, sweating; due to epinephrine release -> mobilizes glycogen stores) and altered mental status (lethargy, irritability, confusion, syncope) -infants and children are less able to tolerate a long fasting period, thus hypoglycemia is more common -infants born to hyperglycemic mothers often present with hypoglycemia 2/2 elevated insulin levels that also circulate through the fetal system -treatment is with IV glucose followed by dextrose-containing fluids Disorders of Water Regulation -vasopressin = ADH = responsible for stimulating water retention in the kidney (stimulates contraction of arterial smooth muscle -> increases GFR; also increases permeability of the collecting duct -> more water resorption -> increased BP -> increased GFR) Diabetes insipidis -characterized by lack of ADH-stimulated response to fluid loss -can be central (no ADH secretion) or peripheral (no response to ADH at the kidney) -in children, DI rarely presents as an isolated idiopathic disorder – look for cranial pathology to identify possible cause of central DI -presents with abrupt-onset polydipsia and polyuria -without adequate fluid replacement, dehydration and hypernatremia occur -urine is copious (5-10 L/day) and dilute -water deprivation test is the key diagnostic test; essentially compares change in urine osmolarity following water deprivation and administration of ADH -negative test = normal response (i.e., urine becomes more concentrated following ADH administration) -positive test = abnormal response (i.e., urine does not concentrate in response to ADH) -treatment is with desmopressin (ADH analogue) Syndrome in inappropriate secretion of ADH (SIADH) -characterized by ADH secretion with normal or increased volume status resulting in dilution of serum electrolytes -multiple etiologies: drug-induced (lisinopril, carbamazepine, TCAs, and anticancer drugs), head trauma/increased ICP, excessive fluid administration -usually presents as normovolemic hyponatremia (symptoms usually occur when Na is below 125) -diagnosis is by exclusion – must rule out other possible causes -most cases spontaneously resolve, thus treatment is supportive during the episode

-oral intake of fluids should be limited to prevent worsening of electrolyte abnormalities -demeclocycline (ADH antagonist) can be used in chronic cases -Na should be corrected at a rate of 0.5 mEq/hr with a max of 12 mEq in the first 24 hours to prevent cerebral edema Short stature -most cases are due to either familial short stature or constitutional delay -causes of disproportionate short stature include rickets and achondroplasia -prenatal etiologies include IUGR, placental dysfunction, intrauterine infections, and chromosomal abnormalities -most common chromosomal abnormalities are trisomy 21 and Turner’s syndrome -postnatal etiologies include malnutrition, chronic systemic diseases, psychosocial neglect, drugs, and endocrine disorders (e.g., hypothyroidism, GH deficiency, glucocorticoid excess, precocious puberty) -precocious puberty initially presents with increased stature for age but ultimately results in an adult with short stature -GH levels can be evaluated by measuring IGF-I levels -hypothyroidism results in short stature due to diminished bone maturation (check TSH and thyroid hormone levels) -elevated glucocorticoid levels cause a variety of symptoms, including moon facies, buffalo hump, central obesity, truncal striae, hypertension, and hyperglycemia -familial short stature is usually obvious by 2 years as individuals track at or below the 5th percentile on growth charts -constitutional delay becomes obvious when puberty starts late; individuals typically reach normal heights by adulthood -recent onset of reduced growth should raise suspicion for cranial pathology (e.g., mass that results in pituitary dysfunction) -diagnostic evaluation -careful measurement of extremities should be done to check for disproportionate abnormalities in stature -exam generally should focus on attempting to identify signs/symptoms of systemic disease that may explain the short stature -assessment of bone age with wrist XR is indicated – advanced bone age suggests precocious puberty, normal bone age suggests familiar short stature, and delayed bone age suggests constitutional delay -labs to rule out metabolic abnormalities should be drawn -MRI of the brain is appropriate if labs demonstrate hormone abnormalities or if head trauma is otherwise a concern -treatment varies based on the etiology -reassurance is appropriate with constitutional delay -in patients with delayed puberty, a 4-6 month course of appropriate sex hormones can be performed (provides a brief growth spurt that may reduce anxiety until true puberty begins) -patients with GH deficiency should be treated with GH; GH therapy is also appropriate in patients with a predicted adult height at or below the 3 rd percentile -hypothyroidism is treated with thyroid hormone replacement Thyroid Dysfunction Congenital hypothyroidism -most common congenital endocrine defect -considered a medical emergency as delayed treatment may have profound permanent effects (specifically on brain development) -classically presents with elevated TSH (2/2 pituitary attempts to increase thyroid hormone levels) and reduced T4 -most common etiologies are due to thyroid aplasia, hypoplasia, or abnormal migration -defects in thyroid hormone production (e.g., peroxidase deficiency) occur but are rare

Hypothyroidism -most common cause of acquired hypothyroidism is Hashimoto’s thyroiditis -female predominance (4:1) and usually in the setting of a family history of autoimmune disease -most common in adolescence – rare in children younger than 5 -other causes include pituitary deficiency and surgical/radioactive thyroid ablation -usually presents with cold intolerance, diminished appetite, lethargy, and constipation -exam may demonstrate slow linear growth, dry/thin hair, dry skin, and delayed reflexes -treatment is thyroid hormone replacement Hyperthyroidism -most commonly due to Graves disease (antibody stimulation of TSH receptors resulting in thyroid hormone secretion) -usually presents with elevated T4 and reduced TSH -symptoms include increased appetite, heat intolerance, emotional lability, restlessness, excessive sweating, loose stools, and poor sleep -changes in behavior and/or school performance are typically present -physical exam may demonstrate a diffusely enlarged thyroid, tremors, tachycardia, and widened pulse pressure -acute-onset tachycardia, hyperthermia, diaphoresis, fever, nausea, and/or vomiting suggest thyroid storm and may warrant hospitalization -treatment is with antithyroid drugs (methimazole) -propylthiouracil is not recommended due to adverse hepatic effects -beta-blockers can be used to control symptoms though they are NOT appropriate treatment for acute thyrotoxicosis -if chronic, surgical or radioactive ablation can be performed Thyroid nodule -a single nodule in children is more likely to be malignant (vs. older patients where nodules are typically benign) -a “cold” (suggestive of reduced metabolic activity) thyroid scan further supports a malignant etiology -nodules are typically removed surgically Painful thyroid gland -typically suggests infection either by a virus or bacterium -subacute thyroiditis may present following a viral illness with hyperthyroidism (due to release of thyroid hormone from damaged cells) followed by hypothyroidism (due to reduced number of thyroid cells) -bacterial infections are treated with antibiotics, otherwise treatment is supportive Adrenal Dysfunction Hypoadrenocorticism -due to reduced cortisol secretion; may be accompanied by reduced secretion of other cortex products (e.g., aldosterone) depending upon the disease process -common causes in neonates: adrenal hypoplasia, ACTH unresponsiveness, adrenal hemorrhage, and infarction (Waterhouse-Friedrickson syndrome) -in older children, usually due to an autoimmune process -may also be due to reduced ACTH production (secondary adrenal insufficiency) -most commonly due to prolonged steroid administration -> shut down of axis -presents with nonspecific symptoms: weakness, nausea, vomiting, weightloss, headache, emotional lability, salt craving -increased pigmentation suggests increased ACTH secretion -can also present with electrolyte abnormalities if aldosterone production/secretion is impaired -acute treatment is steroids and correction of electrolyte abnormalities -chronic disease may require regular corticosteroid/mineralocorticoid supplementation Congenital adrenal hyperplasia

-due to various defects in hormone production; presenting symptoms depend on the particular defect -common etiologies: -most common is 21-OHase deficiency (90% of cases) -necessary for cortisol and aldosterone production -deficiency results in reduced cortisol and aldosterone -intermediate products are shunted to sex hormone production, resulting in increased levels of 17-hydroxyprogesterone and 17-hydroxypregnenolone -next most common is 11-OHase deficiency -similar effects as 21-OHase deficiency as 11-OHase is the next step in those synthesis pathways -female infants present with ambiguous genitalia at birth with normal internal structures -male infants initially present with poor feeding, failure to thrive, lethargy, dehydration, hypotension, hyponatremia, and hyperkalemia -diagnosis requires documentation of elevated 17-hydroxyprogesterone (5000+) -11-OHase usually presents with hypernatremia, hypokalemia, and hypotension due to retention of weak mineralocorticoid activity -treatment is correction of electrolyte/hemodynamic abnormalities (if present) and steroid supplementation -cortisol is used for corticosteroids, fludrocortisone is used for mineralocorticoids -long-term management should including a plan for stress dosing (increased doses in times of physiologic stress, e.g., illness) Hyperadrenocorticism -due to cortisol excess from any cause -endogenous causes include Cushing’s disease (primary ACTH excess, most common cause), adrenal tumors, and ectopic ACTH production (very rare in children) -presents with typical signs of cortisol excess: moon facies, central obesity, abdominal striae, acne, hirsutism, facial flushing, hyperpigmentation, hypertension, fatigue, muscle weakness, and emotional lability -diagnosis depends on elevated urinary cortisol and testing with the dexamethasone suppression test -test evaluates cortisol levels following exogenous administration of steroids (should reduce endogenous production) -MRI of the adrenals is appropriate if tumor is a concern Disorders of Puberty Precocious puberty -defined as sex characteristics developing in girls prior to 7 and in boys prior to 9 -etiology can be gonadotropin-dependent (central) or gonadotropin-independent (peripheral) -in boys, central pathology is more likely -common causes of peripheral etiology include tumor (gliomas, germ cell tumors, hamartomas), hydrocephalus, head injury, and CNS infection -peripheral involvement is extremely rare but causes include McCune-Albright syndrome, familial precocious puberty, Leydig cell tumors, and ectopic hCG production -in girls, premature thelarche (breast development) occurs around 12-24 months and is usually due to exposure to small estrogen bursts (no significant pathology) -evaluation includes measurement of gonadotropins (will be at prepubertal levels if true precocious puberty) and estrogen/testosterone -can also test response to administered GnRH (response suggests central pathology, lack of response suggests peripheral pathology) -treatment for central etiologies is with leuprolide (GnRH antagonist -> suppresses LH/FSH release) -peripheral pathologies are treated by addressing underlying cause Pubertal delay

-defined as sex characteristic development after age 13 OR lack of menarche 3 years after onset of puberty in girls; in boys, defined as lack of sex characteristics by 14 OR lack of genital growth 5 years after onset of puberty -most cases are due to constitutional delay with no evidence of additional pathology -common causes include gonadal failure (e.g., 45XO in girls, 47XXY in boys) and disruption of the HPA axis -evaluation should include checking LH/FSH, estrogen/testosterone, thyroid function, and prolactin levels Disorders of calcium -usually due to derangements in either PTH or vitamin D -ionized calcium is active – be sure to correct if albumin levels are wacky (Ca is bound to albumin; this is included in the total Ca level but is not physiologically active) -PTH acts to increase Ca resorption in bone, renal sparing of Ca, and active vitamin D production Hypocalcemia -common causes of hypocalcemia: -PTH receptor mutation that results in PTH resistance (pseudohypoparathyroidism) -autoimmune or surgical destruction of parathyroids -hypomagnesemia (Mg is required for PTH secretion) -vitamin D deficiency is common, particularly in individuals with dark skin -presents with classic signs of hypocalcemia: -muscle twitches or spasms (particularly in response to tapping on the face or pressure to the proximal arm), agitation, tetany, seizures, prolonged QT on EKG -evaluation includes measurement of vitamin D, PTH, and Ca/PO4 levels -low vitamin D, Ca, and PO4 with elevated PTH suggest vitamin D deficiency -elevated PTH, low Ca, and high PO4 suggest Ca deficiency -low PTH, low Ca, and high PO4 suggest problem with PTH production -treatment is supplementation of deficient electrolyte/compound Hypercalcemia -can be asymptomatic or present with lethargy, inability to concentrate, depression, seizures, osmotic polyuria, and hypertension -EKG may demonstrate QT shortening -Ca-based renal stones may be present on renal US -treatment is with fluids and furosemide (encourages Ca wasting) -can also use bisphosphonates to reduce bone resorption -> lowers Ca -excess due to excess vitamin D can be treated with steroids or ketoconazole Chapter 15 – Neurology Neurodevelopment -the skills of normal development are divided into five categories: gross motor, fine motor, language, social/emotional, and adaptive -the two screens used to evaluate development include the Denver II and the CAT/CLAMS -developmental delay = development of skills significantly behind average attainment at a given age -developmental quotient = score that quantifies developmental achievement -developmental dissociation = difference in the rates of development between different skill areas -language is considered to be the best predictor of future intellectual potential -when evaluating development, chronological and gestational age should be considered -for example, a 9 week old infant born 5 weeks premature should be evaluating like a 4 week old infant for the purposes of determining appropriate developmental milestones -speech delays can present in a variety of ways -language disorders result in the inability to understand or acquire linguistic conventions -speech disorders involve difficulty with actual physical speech

-phonetic disorders involve difficulty with pronouncing sounds -dysfluency is the interruption of the fluency of speech (for example, stuttering) -children with a suspected language delay should be evaluated by audiology immediately -referral to a speech pathologist is also appropriate -early intervention results in the best outcomes -a global developmental delay is a delay in all five skill categories -many of these children are ultimately diagnosed with a genetic disorder -further workup and examination may be indicated Neurodevelopmental disabilities -mental retardation = IQ score less than 70, onset prior to 18 years, and impaired adaptive functioning -the two tests used to assess IQ are the Weschler scale and the Stanford-Bizet test -a score of 50-70 is mild retardation -a score of 35-55 is moderate retardation -a score of 20-40 is severe retardation -a score less than 20 is profound retardation -causes of mental retardation frequently are not found -treatment is generally directed at maximizing quality and functionality of life Autism spectrum disorders -series of diseases characterized by nonprogressive disabilities in social interaction, communication, and behavior -incidence has been increasing over the past 20 years (possibly due to increased awareness/more consistent diagnostic criteria) -most commonly diagnosed between 18 months and 3 years of age, Although symptoms are usually present from birth -ultimate etiology of the disease process is still unknown, but there is no link to vaccines -typically presents as a child with significant language and communication problems -for example, they typically do not engage in social interactions and frequently avoid eye contact, do not reciprocate emotionally, do not understand emotions, and do not engage in play -repetitive behaviors are very common -Asperger syndrome = difficulty forming relationships and the development of intense interest in specific topics -typically do not have problems with producing language, but cannot understand subtle social cues -treatment consists of a variety of forms of therapy -these include behavioral intervention, sensory integration, speech therapy, social modeling, and family support -early intervention results in better outcomes -screening is recommended in all children less than 2 -best indicator of prognosis is the degree to which language skills develop Attention-deficit/hyperactivity disorder (ADHD) -characterized by inattention, hyperactivity, and impulsivity which manifests as maladaptive behaviors -more common in boys and usually diagnosed in elementary school -girls typically present with the sole symptom of inattentiveness and are diagnosed later -in order to be diagnosed, symptoms must be present by age 7 and persist for at least six months and in multiple environments -symptoms commonly do not present in a clinical setting -diagnosis is clinical and largely based on history provided by parents and possibly educators -signs of inattention include: short attention span, ignoring details, difficulty organizing activities,navoidance of activities that require concentration, and difficulty following directions

-signs of hyperactivity include: excessive activity for age, restlessness, inability to remain seated, inability to entertain oneself, and excessive talking -signs of impulsivity include: difficulty waiting and frequent interruption of others -therapy is multidisciplinary and includes multiple forms of therapy and pharmacological approaches -behavior management program should be developed to help with behavior at home and school -assessment should be performed if child is not performing well in school – many cases of poor performance are due to undiagnosed ADHD -psychostimulants work by increasing dopamine and norepinephrine availability -can cause insomnia, hypertension, nausea, and anorexia -non-stimulant medications are available Cerebral palsy -defined as a nonprogressive disorder of movement and posture that results from a lesion in the developing brain before, during, or after birth -can be due to a variety of etiologies -prenatal causes can include intrauterine infection, prematurity, placental hemorrhage, and multiple gestations -postnatal causes include stroke, trauma, kernicterus, and CNS infections -presents with various kinds of motor impairments, which are classified into different types -spastic – increased muscle resistance in response to passage stretch -due to injury to the pyramidal tracts in the brain -most common type of CP -dystonia is due to increased muscle tone generated by movement -characterized by contraction of both extensors and flexors, resulting in nonproductive movements -infants are usually hypotonic initially -delay in the disappearance of primitive reflexes is a possible early indicator of CP -three subtypes based on where impairments are located: 1) diplegia = legs affected more severely than arms 2) quadriplegia = all limbs are severely affected 3) hemiplegia = one side is involved, usually due to a cortical lesion -extrapyramidal – characterized by involuntary choreoathetoid movements (slow, writhing mvements), dystonia, and postural ataxia -usually due to an identifiable brain insult -ataxic – characterized by hypotonia, truncal ataxia, and bobbing of the head and/or trunk -although the disease is considered nonprogressive, body growth makes the disorder appear progressive due to worsening of physical appearance and anatomic abnormalities -treatment is with a multidisciplinary approach dependent upon the patient’s needs -botulinum toxin can be used for severe spasticity -stretching and serial casting can also be used to correct some contractures -orthopedic surgery may ultimately be necessary to fix contractures (trimming of the muscle or shortening of the muscle tendons) -comorbidities are extremely common in CP patients -learning disabilities are very prevalent -epilepsy develops in up to half of patients Neurodegenerative Disorders -due to tissue degeneration; many are inherited, and most are progressive and debilitating -divided into three categories: -gray matter = due to lipid buildup in neuronal cell bodies; usually present with hypotonia, mental retardation, seizures, retinal degeneration, and ataxia

-white matter = due to abnormally produced myelin; usually presents with focal neurological deficits, spasticity, visual disturbances, changes in personality, and cognitive decline -systemic = affect a variety of nervous system pathways; example is Rett syndrome -presents with repetitive hand wringing, seizures, ataxia, mental retardation, and autistic behavior Seizures -defined as an event due to abnormal and excessive electrical brain activity -can present with positive signs (motor, sensory, autonomic changes) and/or negative signs (loss of awareness, loss of motor tone) depending upon the location of the lesion -epilepsy = occurrence of two or more unprovoked seizures -unprovoked seizure = seizure for which no identifiable clinical cause can be found -no apparent cause can be determined for most cases of epilepsy Febrile seizures -brief seizures that occur in association with fever -most common in children aged 6 mo-6 years -not considered when diagnosing epilepsy -simple febrile seizures are generalized, brief, and single -complex febrile seizures are focal, prolonged, and repetitive -most occur within 24 hours of illness onset in children less than three years old and with fevers of 39° or higher -daily AED use is not indicated -important to ensure that there is not another intracranial process or other identifiable cause for seizures; diagnosis is by exclusion and largely based on history -EEG and neuroimaging is not typically performed -prognosis is excellent - most patients do not develop epilepsy -studies have demonstrated no difference in cognitive ability in children with a history of febrile seizures Epilepsy -recurrence rate after a single unprovoked seizure is 30-40% -recurrence increases for each subsequent seizure -AEDs are usually started after the second or third unprovoked seizure -about half of the children that are diagnosed with epilepsy will grow out of their seizures -initial evaluation should clarify whether the event was a true seizure or not -other possibilities include reflux, syncope, and night terrors -EEG can be performed to support the diagnosis of epilepsy -can also classify seizures as focal or generalized -a normal EEG does not necessarily rule out a seizure disorder -MRI can be used if a focal process is suspected -identifies a cause for new-onset seizures in about 20% of cases -seizures are classified as different types depending upon the symptoms that occur during an episode -partial seizures = typically presents with focal signs -motor seizures can produce focal rhythmic twitching, involuntary movements, or arrest of speech -sensory seizures can produce tingling, numbness, unpleasant odors or tastes, vertigo, flashing lights, or auditory symptoms -autonomic seizures can produce an epigastric rising sensation, vomiting, sweating, pupillary changes, or goosebumps due to piloerection -simple = no loss of consciousness -complex = loss of consciousness -generalized seizure = abnormal activity spread throughout both hemispheres of the brain diffusely -consciousness is impaired -bladder or bowel incontinence may occur

-a tonic-clonic seizure occurs when there is sustained muscle contraction followed by rhythmic, symmetric contractions of the face and extremities -may present with an aura or warning signs before onset -typically followed by a postictal phase characterized by impaired consciousness which resolves with time (usually within an hour) -absence seizure = characterized by brief episodes of staring and altered consciousness -most common in children aged 4-9 -start and stop abruptly with no postictal phase -produces a characteristic pattern on EEG that includes 3 Hz spikes of generalized activity -atonic seizures = characterized by an abrupt loss of muscle tone -myoclonic seizures = characterized by quick jerks like those seen in normal patients when falling asleep -differential is largely composed of other conditions that can present with severely altered consciousness -neonates can perform unusual movements and have apneic episodes that may appear to be seizures -toddlers can have pallid or cyanotic breath holding spells precipitated by pain or agitation -syncope is commonly misdiagnosed as seizure -look for a compatible history -syncopal episodes do not usually produce jerking -movement disorders that can appear similar to seizures: -essential tremor – starts in infancy and usually does not interfere with normal function -spasmus nuitans – head nodding/tilting with rapid, small-amplitude nystagmus that presents in infancy -myoclonic jerks – sudden, involuntary muscle movements similar to those seen in the startle response -treatment is with antiepileptic medications -more than half of patients become seizure-free with medication -specific drugs depends on the seizure type: -partial-onset: oxcarbazepine, carbazepine, valproate, topiramate, and phenytoin -generalized: valproate, ethosuximide, and lamotrigine -after two years of no seizures, can considering weaning AEDs -seizures refractory to medical treatment can be treated with surgery, vagal nerve stimulator implantation, and initiation of a ketogenic diet Emergency management of status epilecticus -defined as a prolonged seizure (30+ min) or a period or rapid, recurrent seizure activity with no intermittent return of consciousness -considered a medical emergency due to risk of hypoxia, brain damage, and death -a convulsive seizure that lasts for more than 5 minutes should be treated emergently -rectal diazepam is first-line -fosphenytoin, midazolam, or phenobarbital can be used if the seizure is initially resistant to medications -a head CT is appropriate if there are any postictal focal changes or if increased ICP is suspected Encephalopathy -cerebral dysfunction that results in altered mental status due to metabolic derangements -many different possible causes, but history and physical exam can generally limit the differential -febrile illness strongly suggests an infectious etiology (most common cause in children)

-acute focal findings suggest HSV encephalitis -sepsis can also result in mental status changes -Shigella can produce an isolated encephalitis -increased ICP: trauma, hydrocephalus, brain tumor, AV malformation or other vascular abnormality -electrolyte abnormalities (sodium and calcium) -metabolic disorders -Reye syndrome (mitochondrial disease associated with aspirin use during a concurrent viral infection) -physical exam should focus on the neurological exam and identifying possible underlying causes -urine, blood, and CSF cultures are appropriate in the setting of fever -head CT is appropriate if there is concern for increased ICP -treatment is focused on correcting underlying disorder and maintaining as much brain function as possible -high-dose acyclovir is recommended in HSV encephalitis -antibiotics should be started if bacterial infection is suspected -metabolic derangements should be corrected Headaches -must distinguish between primary headaches (idiopathic, relatively benign) and secondary headaches (due to a secondary cause, pathologic) -different types of headaches present differently: -tension headache – generalized, constant, band-like distribution -associated with stress/fatigue -most respond to analgesic use -frequent headaches are associated with depression -rebound headache – due to overuse of analgesics (3-4 times/week) -migraine headache – thought to be due to generalized cortical depolarization -described as throbbing, typically frontal pain which lasts for hours -may also present with photophobia, nausea, and vomiting -considered “complicated” when focal neurological signs are also present (weakness, paralysis, sensory loss, difficulty speaking) -history should identify frequency, severity, progression, and setting of onset -response to medications and exacerbating factors are also important -ask about psychosocial stressors or major life changes -common triggers: fatigue, sleep deprivation, fasting, caffeine, menstruation, and stress -headaches that awaken a patient from sleep or are present primarily in the mornings suggest increased ICP -pathologic headaches typically worsen with time, and subtle neurological changes (e.g., personality changes) may occur -imaging is not indicated for nonprogressive, recurrent headaches in the absence of neurological signs -image if any of the following are present: severe, debilitating headaches; increasing severity/frequency; concurrent seizures or neurodevelopmental impairment; or neurologic signs -MRI is preferred but CT will identify most large lesions that can cause increased ICP -primary alternative for recurring headaches is pseudotumor cerebri -most common in overweight, adolescent females -thought to be due to impaired CSF absorption, resulting in increased ICP with otherwise normal imaging -LP to drain CSF results in improvement of symptoms but recurrence is common -treatment is dependent upon headache type -tension headaches can be treated with OTC analgesics and rest; counseling may be helpful if stressors are identified

-migraine headaches require more intense intervention -OTC analgesia is helpful as abortive therapy; triptans are used if headaches are unresponsive to OTC drugs -prophylaxis should be considered if headaches occur more than 3-6 times/month and interfere with regular function -nonpharmacologic approaches include acupuncture, cognitive therapy, vitamin/herbal supplements, and regular meals and sleep Ischemic/hemorrhagic stroke -stroke = sudden-onset neurological impairment due to an interruption in cerebral blood flow -rare in children; usually due to an underlying pathological cause: cardiac disease, vascular disease, hematologic disorders (e.g., sickle cell, coagulopathy), infection, and metabolic disease -most common in the cerebral hemispheres and presents with hemiparesis, visual field defects, and aphasia -diffusion-weighted MRI can identify early strokes -treatment is careful observation and correction of underlying abnormalities Weakness -many diseases can present with weakness: -Guillain-Barre: acute-onset, progressive, ascending weakness caused by autoimmune demyelination of peripheral nerves -most cases develop following respiratory or GI viral illness -deep tendon reflexes wane and disappear -may involve respiratory muscles and require ventilation -usually resolves starting 4 weeks following symptom peak; most cases do not have long-term sequelae -tick paralysis: due to tick bites from ticks that elaborate toxins that block ACh release -resembles Guillain-Barre, but ocular abnormalities are more common -recovery occurs after the tick is removed -myasthenia gravis: chronic autoimmune disorder due to antibody blockade of post-synaptic ACh receptors -presents with easy fatigability and weakness that improves with rest -tensilon test is used: diagnosis is likely myasthenia gravis when treatment with an AChE inhibitor results in transient improvement -nerve studies demonstrate progressive reduction in response to stimulation -treatment is with an AChE inhibitor, corticosteroids, and immunosuppressants (if severe) -many patients can be put into remission but will experience acute exacerbations -Duchenne’s muscular dystrophy: X-linked disorder that results in progressive muscle destruction beginning in the proximal muscles -commonly presents with early motor delay -walking and climbing stairs is usually difficult due to early pelvic girdle involvement; Gower’s sign = using arms to stand up from sitting -corticosteroids slow progression but the disease is ultimately fatal due to respiratory failure or cardiomyopathy -spinal muscle atrophy: inherited disorder that results in degeneration of anterior horn neurons and cranial nerve nuclei -different types that present at different times -cognitive abilities are unaffected -morbidity is usually due to respiratory compromise -EMG, muscle biopsy, and gene testing are diagnostic tests -tumor: due to compression of the spinal cord, resulting in weakness and/or paralysis below the lesion -surgical emergency

-treatment and diagnostic clues addressed above Ataxia -inability to coordinate purposeful movement and/or control balance -usually due to impairment of cerebellar, sensory/motor pathway, or inner ear function -most common causes in children are labyrinthitis, acute cerebellar ataxia, and drug ingestion (sedatives) -chronic ataxia is typically due to a genetic syndrome or a cerebellar malformation -possible causes: -labyrinthitis typically presents as acute ataxia with horizontal nystagmus -acute cerebellar ataxia may be subtle or obvious; most common in children ages 27, and typically resolves without consequence -two genetic causes: -ataxia-telangiectasia = due to defect on chromosome 11, presents in early childhood with progressive neurodegeneration -Friedrich’s ataxia = due to defect on chromosome 9 and presents in later childhood with ataxia, weakness, muscle wasting, and eventually skeletal deformities -history should attempt to identify signs of infection or possible toxic ingestion -exam should identify neurological lesions and include the Romberg test and other tests of coordination (e.g., finger-to-nose, heel-to-shin-to-toe) Neurofibromatosis -two different types that typically present differently -type I – presents with café au lait spots (hyperpigmented patches), axillary/inguinal freckling, hamartomas of the iris, bone abnormalities, and optic gliomas -family history is common -increased risk for gliomas throughout the CNS -fibromas can be removed but will almost certainly recur -due to abnormality on chromosome 17 -type II – presents with bilateral acoustic neuromas -associated with other CNS malignancies (meningiomas, schwannomas, and astrocytomas) -due to abnormality on chromosome 22 -both diseases are progressive Tuberous sclerosis -similar to neurofibromatosis in that it is a neurocutaneous disorder -typically presents with ash-leaf spots (hypopigmented macules/patches), shagreen patches (patches of thickened skin), sebaceous adenomas, and ungual fibromas -neuroimaging demonstrates knob-like periventricular swelling (“tubers”) -mental retardation and seizures are common -tumors may also be present in the kidney, heart, and retina -treatment is focused on preventing seizures and removing neoplastic masses as necessary Sturge-Weber syndrome -neurologic deterioration associated with a port wine stain over the V1 nerve distribution -presents with progressive mental retardation, seizures, hemiparesis, and visual impairment (glaucoma is common) -bilateral port wine stains more strongly associated with Sturge-Weber diagnosis Neural tube defects -due to failure of the neural tube to close during weeks 3-4 of gestation -risk factors include maternal malnutrition, drug exposure, maternal hyperthermia, congenital infections, and radiation exposure -folic acid supplementation prior to conception and during the early weeks of pregnancy is highly effective at preventing defects -presents with abnormalities at any point along the CNS -anencephaly = large skull defects with essentially absent cortex; many neonates are stillborn, but brainstem function is sometimes intact

-encephalocele = protrusion of cranial contents through skull defect; typically results in severe mental retardation, seizures, and motor deficits -spina bifida = incomplete fusion of the vertebral arches; variety of types depending upon the specifics of the defect -myelomeningiocele = protrusion of both neural and meningeal tissue -meningiocele = protrusion of meninges with no neural tissue -spina bifida occulta = bony lesion without any herniation of cord contents; usually presents with birthmarks, dimples, or tufts of hair at the site of the defect -spinal cord may be tethered and be damaged as the child grows, thus surgical correction is necessary to prevent neurological injury -treatment is primarily correction of defect (if possible) and management of complications -hydrocephalus is common – may require ventriculoperitoneal (VP) shunt placement, which drains the cranium -UTI is the major cause of death in the first year; ensuring hygiene and clean catheterization can prevent infection -fetal surgery can repair some defects and preserve motor and sensory function Hydrocephalus -due to pathologic enlargement of the ventricles 2/2 increased CSF production or decreased resorption -increased risk of developmental delay, visual impairment, motor disturbances, and death -can be communicating or noncommunicating: -communicating = no obstruction of the ventricular system (i.e., the ventricles communicate with one another) – suggests a defect in the arachnoid vili resulting in impaired resorption (can be due to meningitis, subarachnoid hemorrhage, or leukemia) -noncommunicating = obstruction within the ventricular system, most commonly called by stenosis of the cerebral aqueduct; acquired causes are usually due to malignancy -signs and symptoms depend on the age of onset and severity -in neonates, may present with bulging of the anterior fontanel, poor feeding, lethargy, irritability, leg spasticity, downward eye deviation, and bradycardia -older children typically present with morning headache that improves with positioning or vomiting, irritability, lethargy, diplopia, and papilledema -neuroimaging is recommended to identify source of obstruction -treatment in chronic cases is usually surgical via shunt placement Abnormal head shapes -microcephaly = head circumference less than 2 SDs below the mean -usually due to genetic or congenital insults -usually results in cognitive and motor delay -associated with seizure disorders -macrocephaly = head circumference greater than 2 SDs above the mean -can be familial but is usually due to a congenital or acquired cause -positional plagiocephaly = flattening of the back of the head -very common in infants who sleep on their backs -flattening of the sides may also occur if the child sleeps on their side -no intervention is required; helmets and possibly surgical correction can be considered for cosmetic concerns -craniosynostosis = premature fusion of the cranial sutures -bone growth continues despite fusion, resulting in abnormal skull morphology -most defects are repaired due to cosmetic concerns, but the exact timing of surgical intervention is controversial Chapter 16 – Orthopedics Developmental dislocation of the hip -consists of a variety of disorders that result in dysplastic hips

-can occur in utero, during childbirth, or rarely as an acquired disorder postnatally -risk factors include breech delivery, female neonates, and first-borns -associated with other orthopedic abnormalities (metatarsus adductus and congenital torticollis) -presents with gluteal fold asymmetry and/or abnormal Barlow/Ortoloni maneuvers -Barlow – posterior-superior dislocation of the hip achieved with posterior pressure when the hip is flexed and adducted -Ortolani – relocation of the hip achieved with abduction -in both cases, dislocation/relocation should be felt and may be heard -other important test is the Galeazzi test – assesses limb length asymmetry when knees are flexed while laying supine with the feet on the ground -radiographs are typically not helpful until 4-6 months -abnormal Barlow, Ortolani, or Galeazzi signs are indications for orthopedic referral -most abnormalities stabilize without additional intervention -harnesses and casts can be used in cases that do not resolve -in severe cases, surgical reconstruction may be performed Foot Deformities -as a general rule, most deformities that can be passively “corrected” rarely require additional evaluation or correction -common conditions: -metatarsus adductus: in-toeing of the forefoot with a normal hindfoot -ankle motion is unrestricted (in contrast to club foot) -mild cases can be passively “corrected” -severe cases may not correct with passive flexion -treatment is with bracing/casting in severe cases; surgical intervention is rare -talipes equinovarus: club foot with CAVE features - cavus of the forefoot, adduction of the forefoot, varus of the hindfoot, andequinus (plantarflexion) of the ankle -dorsiflexion of the ankle is physically impossible -deformities progress without treatment -nearly all cases can be corrected with casting and long-term bracing -toe motion should be specifically checked to rule out neurological causes Limp -can be due to a variety of causes -causes are not limited to the musculoskeletal system -pathology may not be in the affected limb; limp could be secondary to pain/discomfort in another area, particularly in younger children -common causes vary by age: -1-3 years: infection, inflammation, and paralysis syndromes -3-10 years: Legg-Calve-Perthes disease, toxic synovitis, and juvenile idiopathic arthritis -common disorders: -Legg-Calve-Perthes: due to avascular necrosis of the femoral head -unknown etiology; bone is slowly resorbed and repaired -more common in males and younger children (4-8 y/o) -pain can commonly be referred to the knee or thigh -internal rotation and abduction are limited -XR may be normal or demonstrate lucency of the femoral head -treatment includes stabilization of the joint, reshaping of the head, and maximizing range of motion -slipped capital femoral epiphysis (SCFE) -due to separation of the proximal femoral growth plate; the femur head slips off the femoral neck and rotates into an inferior/posterior position -occurs more commonly in males

-trauma is not a contributing factor -internal rotation of the hip and external rotation of the limb are limited -XR is key to diagnosis – may demonstrate epiphyseal widening, decreased epiphyseal height, and a Klein line that does not intersect the lateral epiphysis when drawn from the femoral neck -synovitis is likely following recent URI/viral symptoms -severe pain suggests a fracture or an infectious cause -absence of pain suggests weakness/instability -swelling and stiffness suggests rheumatologic disease -evaluation includes both lab testing and imaging -MRI is the preferred modality for poorly characterized limp -lab testing should include inflammatory markers (rheumatologic disease), CBC with diff (infection), cultures, and aspiration if an effusion is present -testing of CK is appropriate if weakness is the primary complaint to rule out muscular dystrophy or other myopathy -EMG and nerve conduction studies are appropriate if a neurological cause is suspected Common Fractures in Children -young bones are more flexible and resistant to complete fractures; “buckle” and “greenstick” fractures are more common -fractures are much more common than sprains in young children due to increased strength of ligaments relative to young bones -stress fractures = fractures due to repeated use; common in athletes, though they may not be radiographically visible initially -pathologic fractures = secondary to another disease process that has weakened the bone, making it more susceptible to fracture -fractures along growth plates are characterized using the Salter-Harris classification scheme: -type 1: complete fracture on the epiphyseal side of the growth plate – good prognosis -type 2: complete fracture on the metaphyseal side of the growth plate – good prognosis -type 3: fracture along and through the growth plate (T shaped) – fair prognosis -type 4: diagonal fracture from the side of the bone through the growth plate and the edge of the epiphysis – high risk of growth disturbance -type 5: crush injury of the growth plate – high risk of growth disturbance -fractures do not typically appear on radiographs until 2-3 weeks later – a clean XR does not rule out disease! -presents with severe point tenderness over the bone, often with local swelling, bruising, and angulation -radiographs of affected areas should be obtained and perfusion/neurological function carefully evaluated -treatment is with casts and splints in the majority of cases -open fractures through the skin require surgical washout and antibiotic treatment -large bone fractures may need orthopedic hardware for stabilization Subluxation of the radial head -also called “nursemaid’s elbow” -usually caused by rapid extension of the elbow which results in radial displacement from the annular ligament -typically presents with the arm held close to the body, elbow slight flexed, and forearm pronated -treated with reduction: extending the elbow, supinating the hand, and then fully flexing the elbow; motion is usually restored in minutes Osteomyelitis -infection of the bone, usually secondary to hematogenous spread

-involvement of the femur or tibia account for most cases -neonates typically have an infected joint as well -infection usually occurs in the metaphysis due to relatively low blood flow and reduced immune system surveillance -most commonly caused by S. aureus; in neonates, GBS and E. coli are most common -patients with sickle cell frequently get Salmonella infections -puncture wounds are associated with Pseudomonas infections -often presents with a normal WBC and positive blood cultures -aspiration of fluid from the bone before starting antibiotics is critical -bone scans detect abnormalities in 24-72 hours; radiographs take 2-3 weeks -MRI is diagnostic -treatment is high-dose antibiotics for 4-6 weeks -common choices are cefazolin, nafcillin, or oxacillin if S. aureus is a concern -add vanc if MRSA is a possibility -ampicillin for neonates -sickle cell patients should receive a third generation cephalosporin -surgery usually not required unless necrosis occurs Septic arthritis -due to purulent infection of the joint space -high risk of permanent debilitation -in infants older than 6, the hip is the most common site of infection; in older children, the knee is the most common site -neonates usually infected with GBS, E. coli, or S. pneumoniae -N. gonorrhoeae should be considered in older children that are sexually active -usually presents with a painful joint in the setting of fever, irritability, and clearly reduced ROM -aspiration of the joint demonstrates WBC count of 25,000+ and the causative organism -treatment is empiric therapy with IV antibiotics -ceftriaxone is usually appropriate in younger children -synthetic penicillins or cephalosporins are preferred in older children -cefotaxime is the preferred choice in young children Osgood-Schlatter disease -characterized by swelling, pain, and tenderness over the tibial tuberosity 2/2 stress of the distal insertion of the patellar tendon onto the tibia -typically occurs between ages 10-15 during a growth spurt -pain worsens with kneeling, running, jumping, or squatting and relieved with rest -radiographs demonstrate soft tissue swelling with irregularities over the tubercle -treatment is usually activity changes and stretching with a good prognosis Idiopathic scoliosis -excessive lateral curvature of the spine in an otherwise healthy child -screening is important due to ability to prevent progression to serious disease -not usually associated with back pain or fatigue (consider other causes if present) -examination requires observing the spine while the child is standing and bending over to assess for asymmetry -treatment depends on severity -less than 25 degrees is usually followed -25-40 degrees may require bracing during growth spurts (bracing doesn’t reduce curvature but does prevent progression) -greater than 50 degrees is usually treated with spinal fusion Achondroplasia -autosomal recessive disorder of calcification and remodeling of bony cartilage -body habitus is virtually diagnostic: very short with large heads, short and stubby digits, and wide, short, curved long bones -heterozygotes are relatively normal -homozygotes have poorer prognosis due to pulmonary and neurological complications

Osteogenesis imperfecta -group of disorders that results in fragile, brittle bones -each disorder is inherited in a different way and presents with variable severity -be suspicious in a child with multiple fractures early in childhood with no clear cause (may initially raise suspicions for child abuse) Chapter 17 – Nephrology and Urology -primary function of the renal system is to maintain fluid homeostasis, but it is also involved with RBC production (erythropoietin secretion), bone growth (vitamin D processing), and blood pressure regulation -infants are susceptible to renal injury due to reduced efficiency Renal dysplasia -due to abnormalities in the formation of the renal parenchyma, typically in both kidneys -degree of dysplasia determines the severity of symptoms -common causes include: -renal agenesis = failure of one or both kidneys to form -bilateral agenesis results in the Potter sequence (clubbed feet, cranial abnormalities, still born or die perinatally) due to inability to produce urine -multicystic dysplastic kidney – most common renal disease of childhood; presents with multiple, noncommunicating, fluid-filled cysts -affected kidney is nonfunctional -unilateral in nearly all cases -visualized with US -most lesions undergo spontaneous involution; nephrectomy is performed only if symptoms develop or there is concern for malignancy -polycystic kidney disease = inherited disease that can be recessive or dominant -the recessive form results in dilated collecting tubules and cysts that result in poorly functioning organs; gross morphology is typically normal -the dominant form does not typically present until adulthood; unlike the recessive form, the cysts are large and appreciably distort the shape of the kidney -renal function progressively declines until hemodialysis is necessary -results in inability to concentrate the urine; consequently, fluid and electrolyte regulation is impaired -diagnosis is usually based on imaging studies; labs may demonstrate electrolyte abnormalities and elevated creatinine Ureteropelvic junction obstruction -most common cause of hydronephrosis in children -can be primary (intrinsic anatomical defect) or secondary (due to scarring or other anatomic malformation 2/2 different process) -results in increased intrapelvic pressure, dilation of the kidney, and urinary stasis -many cases are bilateral -usually identified on prenatal ultrasound, but in newborns may present as a palpable flank mass -renalgram will demonstrate the specific presence and location of the lesion -treatment is surgical correction Vesicoureteral reflux -due to abnormal ureter length that results in urine reflux – can be unilateral or bilateral -usually presents with recurrent UTI (due to urine reflux); can also cause fetal hydronephrosis but is a less common cause than obstruction of the ureteropelvic junction -voiding cysturethrogram (VCUG) will demonstrate abnormalities in the ureter insertion site -more severe abnormalities can cause distortion of the renal pelvis and calyces and large, tortuous ureters -treatment is antibiotic prophylaxis to prevent infection and surgical correction of severe cases -antibiotics of choice include amoxicillin for neonates and TMP-SMX for older children

-low-grade injuries may resolve spontaneously -surgery is indicated if reflux worsens, renal function is impaired, or infections become resistant to antibiotics and/or severe Posterior urethral valves -occurs only in males – due to valve leaflets that obstruct the ureter, resulting in bladder outflow obstruction -one of the most common causes of end-stage renal disease in male children -presents with bladder distension and hydronephrosis on US -distended bladder may also be palpable -urethra may be described as shield-shaped and very dilated -treatment is ablation of the obstructing valve and antibiotic prophylaxis if reflux is present -early surgical intervention is NOT recommended due to high failure rates and ability of the bladder to compensate over time -primary complication is increased risk of chronic kidney disease Hypospadias -due to incomplete development of the distal urethra; the urethral meatus develops on the underside of the penile shaft rather than at the tip of the glans -curvature of the penis may also be appreciated -circumcision is contraindicated – foreskin may be needed during surgical correction -prognosis is excellent – severe cases may require multiple procedures Cryptorchidism -defined as testes that have not fully descended into the scrotum and cannot be manipulated into the scrotum with palpation -testes that remain outside the scrotum may become nonfunctional -increased risk in premature neonates -bilateral cryptorchidism may result in oligospermia and infertility -treatment is surgical repair if the testes have not descended by 1 year -high success rate, but appears to increase the risk of malignancy Testicular torsion -due to twisting of spermatic cord – may result in infarction of the testis -presents with classic acute onset, unilateral scrotal pain that often wakes a child from sleep -nausea and vomiting are also common -right-sided torsion may be confused with appendicitis -epididymitis may also be considered but is more common in adolescence -primarily a clinical diagnosis – since torsion is a surgical emergency, extensive testing should not be performed if suspicion is high -US may differentiate among possible causes of pain -treatment is surgical correction -should occur within 6 hours of pain onset to minimize risk of ischemia and infarction Hydrocele/varicocele -hydrocele = fluid-filled sac in the scrotal sac -hydroceles that communicate with the peritoneal cavity are at risk for incarceration -communicating hydrocele should be corrected with surgery; noncommunicating hydroceles typically involute spontaneously by 12 months -varicocele = dilation of testicular veins and the pampiniform plexus -become detectable during adolescence and are more common on the left (due to anatomical differences in the testicular vein – the left vein joins the renal vein almost perpendicularly, making frank obstruction eaiser) -evident with standing – results in a “bag of worms” appearance in the scrotum -should be repaired due to increased risk for infertility UTI -infections may be limited to the bladder (cystitis) or the kidney (pyelonephritis) -pyelonephritis is especially concerning due to risk of scarring of the renal parenchyma -common pathogens: E. coli (80%), Proteus, and Klebsiella -patients with anatomical defects (see above) or voiding abnormalities are at increased risk

-increased incidence in both genders prior to 1 year; after 1 year, incidence is femalepredominant (10:1) (onset after 1 year in a male should warrant a search for underlying pathology, particularly if infections are recurrent) -UTI is the most common site of infection in febrile infants generally -UA should be obtained in all febrile patients younger than 1-2 years -compared to cystitis, pyelonephritis presents with high fever (vs. low fever), chills, nausea, vomiting, and flank pain -cystitis typically presents with frequency, urgency, and dysuria -diagnostic evaluation usually consists or UA, urine culture, and blood samples -urine culture is the gold standard, but positive nitrites on UA are also suggestive of infection -preferred methods for urine collection: suprapubic tap > sterile catheterization > clean catch -bagged specimens are not useful for diagnosis of UTI due to high incidence of contamination -treatment is antibiotics and work-up to rule out causes that predispose to UTI -all children younger than 2 years should receive US -the presence of hydronephrosis on US should be followed-up with a VCUG -appropriate antibiotic choices include amoxicillin, ampicillin, nitrofurantoin, and TMP-SMX (5-7 days if culture-proven) -pyelonephritis should be treated with a cephalosporin or ampicillin and gentamicin or cephalosporin with a longer course (10-14 days) -isolated cystitis is typically uncomplicated -complications of pyelonephritis include perinephric abscess, renal scarring, and renal failure Nephrotic syndrome -disorder of the glomeruli characterized by proteinuria, reduced albumin, hyperlipidemia, and edema -most cases are idiopathic; common identified causes include infection, systemic disease, drugs, malignancies, and genetic disorders -by far the most common form is minimal change disease in children -most common in children 2-6 -male predominance (2:1) -typically presents with periorbital edema; children otherwise look healthy -progresses to dependent edema, weight gain, and generalized edema -gross hematuria and hypertension are typically absent – suggests an alternate diagnosis -hallmark finding on diagnostic tests is severe proteinuria (1 g/m2/d) -proteinuria is typically selective and consists largely of albumin -hyperlipidemia is usually present (2/2 loss of lipases in the urine) but does not need to be specifically tested for -renal biopsy is indicated in children outside the 2-6 age range or those with unusual findings (e.g., casts in the urine, severe renal insufficiency) -in minimal change disease, the only abnormal findings on biopsy are loss of podocyte foot processes (responsible for selectivity of the glomeruli) -treatment is dependent upon the severity of the disease -uncomplicated, primary nephrotic syndrome can be treated with salt restriction (to prevent fluid overload) and steroids -stronger immunosuppressants (e.g., cyclophosphamide, tacrolimus) may be indicated if steroids are not effective -renal biopsy is indicated if symptoms do not resolve after 8-12 weeks -long-term complications are rare -primary complication is bacterial infection, particularly by encapsulated organisms due to loss of proteins (e.g., complement) in the urine Glomerulonephritis -due to inflammation of the glomeruli 2/2 deposition of antigen-antibody complexes

-multiple types, but commonly present with hematuria, mild proteinuria, oliguria, edema, and hypertension -red cell casts are detected in the urine -proteinuria is much less severe than in nephrotic syndrome -results in impairment of glomerular filtration and subsequent fluid overload -flank pain may also be present due to swelling 2/2 inflammation -evaluation should determine if true nephritis is present and differentiating among the various types: -low C3 suggests post-streptococcal glomerulonephritis -chronically low C3 suggests lupus or membranoproliferative glomerulonephritis -measurement of anti-streptolysin O and anti-DNAse can be used to confirm streptococcal infection -types of glomerulonephritis: -acute post-streptococcal glomerulonephritis – occur after throat or skin infections with GAS -elevated ASO and anti-DNAse with low C3 is common -biopsy is not indicated as the nephritis is usually transient -Henoch-Schonlein purpura – presents after any type of infection -systemic vasculitis characterized by a rash, crampy abdominal pain, and arthritis -C3 levels are typically normal, and IgA levels are elevated in half of patients -nearly all cases recover without long-term impairment; intervention is not necessary unless the case is severe -IgA nephropathy – due to IgA deposition in the renal mesangium -a quarter of cases progress to renal failure -typically presents with asymptomatic gross hematuria a few days after a respiratory or GI infection -severe disease requires treatment with immunosuppression; mild cases are not treated -rapidly progressive glomerulonephritis – form of nephritis that is progressive and results in renal failure and death -crescent formation within glomeruli on biopsy -rare in children – requires strong immunosuppressant therapy due to high morbidity/mortality -Alport syndrome – due to abnormal basement membrane collagen -X-linked inheritance -associated with sensorineural hearing loss -diagnosis requires renal biopsy and demonstrates splitting of the basement membrane -ultimately progresses to complete renal failure with no treatments currently available to alter the disease course -benign familial hematuria – characterized by asymptomatic microscopic or gross hematuria -due to thinning of the basement membrane -normal renal function -treatments, outcomes, and complications are as mentioned Hemolytic-uremic syndrome (HUS) -due to endothelial injury to the renal vasculature, resulting in microthrombi formation and RBC shearing -most cases are caused by infection with E. coli O157:H7 and bacterial production of Shigalike toxin -typically presents several days after an episode of bloody diarrhea -symptoms include pallor, jaundice, petechiae, and oliguria -diagnosis is based on the triad of hemolytic anemia, thrombocytopenia, and azotemia -Hb is usually less than 8 and platelets less than 100k

-LDH levels are usually highly elevated due to hemolysis -stool culture is appropriate to confirm the diagnosis and for reporting purposes -treatment is supportive – no specific therapy exists -RBC/platelet transfusions should occur when symptoms develop -dialysis may be necessary in some patients -long-term damage to the kidneys is possible but does not usually occur Renal tubular acidosis (RTA) -different forms, but all are characterized by hyperchloremic metabolic acidosis 2/2 impaired bicarbonate or proton transport in the kidney -bicarbonate is resorbed in the proximal and distal tubules while protons are secreted at the distal tubule -defects in any of these mechanisms produces RTA -typically presents with failure to thrive (if congenital), polydipsia, polyuria, rickets, and kidney stones -diagnosis requires lab evaluation; typical lab findings are provided below for the various types -type I (distal) – positive anion gap, urine pH > 5.5, and low or normal K -type II (proximal) – normal anion gap, urine pH < 5.5 -usually present as a component of Fanconi anemia -type IV (distal) – positive anion gap, urine pH < 5.5, hyperkalemia -treatment is with an alkalinizing agent to stabilize pH -proximal RTA may be treated with thiazide diuretics to promote proximal tubule resorption of bicarbonate Nephrogenic diabetes insipidis -characterized by inability of the kidneys to concentrate urine in response to ADH secretion -may be congenital (most cases are X-linked) or due to polycystic kidney disease, pyelonephritis, Li toxicity, or sickle cell disease -presents with polyuria with very dilute urine -excessive water intake is usually reported due to increased urine losses -diagnosis is based on observing response to ADH/desmopressin administration following water restriction -no improvement in concentrating ability following water restriction = central or nephrogenic DI -improvement in concentration following ADH/desmopressin = central DI -no improvement in concentration following ADH/desmopressin = nephrogenic DI -acute treatment consists of rehydration and correcting abnormalities -low-sodium diet is critical to minimize free water loss Hypertension -exact pressure measurements are dependent upon height and age, thus hypertension is defined as a blood pressure greater than the 95th percentile for age and height -hypertension can be primary/essential (idiopathic) or secondary (due to a pathologic cause) -most cases used to be due to secondary hypertension, but the obesity epidemic has increased incidence of primary hypertension -younger patients and/or higher BP readings are more likely to be due to secondary hypertension -rarely manifests with acute symptoms though severe hypertension may cause headache, dizziness, and vision changes -proper technique in measuring BP is critical to proper diagnosis -small cuffs falsely elevate BP while large cuffs falsely lower BP -measurement should occur after the patient has been calm and resting for 1-2 minutes -measurement in all extremities should occur at least once to rule out coarctation and assess for asymmetry -evidence of renal disease (proteinuria, elevated creatinine, anemia) should be sought -hypernatremia with hypokalemia suggests hyperaldosteronism

-best treatment is prevention and lifestyle modification -risk factors include high-salt diet, sedentary lifestyle, cigarette use, alcohol/drug use, hypercholesterolemia, and obesity -salt/calorie restriction and increased cardiac activity are first-line -pharmacotherapy can be initiated after 3-6 months if no improvement is seen after lifestyle modification (or due to noncompliance with modification) -ACE inhibitors are preferred first-line agents -severe hypertension should be treated with nifedipine (calcium channel blocker), beta-blockers, and/or nitrates Acute kidney injury (AKI) -characterized by acute impairment in renal function, usually with accompanying azotemia and increased creatinine -causes fall under 1 of 3 categories: -prerenal = due to reduced renal perfusion; normal physiologic response -most common form of AKI -hypovolemia is the typical mechanism -presents with oliguria or anuria -long-term complications are rare -other causes: hypotension, renal vasoconstriction -intrinsic = due to structural or functional abnormality of the kidney -acute tubular necrosis is the most common cause and is usually the result of prolonged prerenal pathology or drug/toxin ingestion -a significant number of patients progress to chronic kidney disease, particularly if damage is diffuse -postrenal = obstruction distal to the collecting ducts, resulting in reduced GFR and hydronephrosis -causes can be both congenital (see previous) and acquired (e.g., renal stone) -evaluation should include clarification of history and lab evaluation -changes in medication are suspicious for intrinsic injury -episodes of dehydration and shock suggest a prerenal injury -obstruction should be evaluated by US; CT may be necessary -treatment depends upon the etiology -prerenal causes usually respond well to volume resuscitation -postrenal causes are usually relieved with relief of the obstruction -intrinsic injuries are corrected by correcting the underlying cause (in the case of medication-induced injury, stop medication immediately) -correction of electrolyte abnormalities to prevent complications is also critical -cardiac: hypertension, edema, arrhythmias -neurologic: somnolence, seizures, comas -prognosis and complications are dependent upon the severity of injury Chronic kidney disease -defined as a chronic reduction in renal function – impairment resulting in 30% of normal activity is required for formal diagnosis -impairment resulting in 10% of normal activity is considered end-stage renal disease -most causes in children are congenital though CKD may also be the result of a secondary process (e.g., severe nephrotic/nephritic syndrome) -unlike AKI, does not typically present with oliguria -common complaints include polyuria, episodic dehydration, salt craving, and systemic symptoms due to toxin accumulation -lab findings are typically similar to those in AKI -anemia is typically more pronounced due to chronicity -goals of treatment are to minimize symptoms and progression -ACE inhibitors/ARBs are used to treat hypertension and minimize proteinuria -hyperkalemia is managed with dietary restriction or the use of potassium-binding resins (e.g., Kayexylate)

-anemia is managed with iron supplementation and erythropoietin -end-stage renal disease requires dialysis or renal transplant -peritoneal dialysis = standard for children; can be performed at home -hemodialysis = low mortality but complications can occur (e.g., bleeding, thrombosis, infection, and large changes in volume status or electrolyte levels) -renal transplant is the ultimate therapy Enuresis -children usually obtain bladder control by 2-3 years -enuresis = involuntary loss of urine in children older than 5 -primary = patient has never maintained a dry period -secondary = history of dry period(s) with recurrence of wetting -primary nocturnal = due to delayed behavioral control or reduced nocturnal ADH levels -evaluation should differentiate from renal or neurological impairment and voluntary withholding leading to incontinence -treatment is largely by behavioral modification -establishing a regular voiding schedule, especially before bed, can prevent wetting -anticholinergic medications can be used if detrusor instability is present -primary nocturnal enuresis can be treated with intranasal desmopressin -most cases resolve without complication Chapter 18 – Genetic Disorders -congenital defects are classified as “major” and “minor” -minor defects are of little physiologic significance (e.g., skin tags, rudimentary polydactyly) – 15% of neonates have at least 1 defect -major defects have an actual adverse impact on the infant (e.g., cleft palate, congenital heart disease, meningiomyocele) -increased number of minor defects is associated with increased risk of a major defect (can increase suspicion for abnormalities that may not be readily appreciated) -genetic disorders can be due to environmental influence or inherited genetic abnormalities -teratogen = environmental agent known to interfere with the embryonic and/or fetal periods -exposure within first 7 days usually either has no effect or kills the embryo -exposure within first 12 weeks affects organ formation -exposure after the first 12 weeks affects growth and CNS development -see below for table of common teratogens -genetic factors are attributed to specific errors in single genes, chromosomes, imprinting effects, or other aspects of the individual’s DNA Single Gene Disorders -can be accurately described using Mendelian principles -autosomal dominant disorders are expressed with a mutation in at least one gene -very rare and usually lethal -often present with variable severity among a population (incomplete penetrance) -important examples: achondroplasia, adult PKD, hereditary angioedema, hereditary spherocytosis, Marfan’s, neurofibromatosis, protein C deficiency, tuberous sclerosis, von Willebrand’s disease -autosomal recessive disorders are expressed only when both genes are mutated -can occur if a biological process can continue in spite of a 50% reduction in protein levels/activity -most inborn errors of metabolism are autosomal recessive -X-linked disorders are usually recessive and have a predilection for male individuals -females are rarely affected (have 2 X chromosomes, both of which must have the mutant allele – very rare) -males commonly affected (only require 1 mutant X due to presence of Y chromosome)

-important examples: Bruton’s, CGD, color blindness, muscular dystrophy, G6PD deficiency, hemophilia A/B, Lesch-Nyhan’s Chromosomal Disorders -usually due to de novo mutations during gametogenesis; most diseases have high morbidity/mortality -important cause of early fetal demise (up to 50% of first trimester miscarriages) -errors can be identified by karyotype (larger errors), FISH analysis (single loci), and microarray analysis (multiple loci) -chromosomal testing can occur during the fetal period via amniocentesis and chorionic villus sampling Trisome 21 (Down’s syndrome) -most common genetic syndrome (1:700 births) -associated with increased maternal age and usually due to chromosomal nondisjunction during maternal meiosis -presence of mosacism suggests a defect later on in mitosis -presents with typical appearance: flat occiput, flat face, up-slanted palpebral fissures, small ears, flat nasal bridge with epicanthal folds, small mouth with protruding tongue -other findings: single palmar crease; short, broad hands; excessive gap between first two toes; congenital cardiac defects; GI pathology (duodenal atresia and Hirschprung’s disease); and leukemia -later in life, early-onset (age 40) Alzheimer’s is common Trisomy 18 (Edwards’ syndrome) -like trisomy 21, associated with maternal age and usually due to chromosomal nondisjunction during meiosis -presents with prominent occiput; narrow forehead diameter; low-set, malformed ears; small jaw; congenital heart disease; rocker-bottom feet; horseshoe kidney; and lack of subcutaneous fat -high mortality – nearly all die by 1 year Trisomy 13 (Patau’s syndrome) -weaker association with increased maternal age -variety of types of errors -presents with microcephaly; cutis aplasia (absence of skin) of the scalp; small eyes; cleft lip/palate; congenital heart disease; omphalocele; polydactyly; renal defects; agenesis of corpus collosum; and cryptorchidism (absence of testis/testes) Sex Chromosome Disorders Turner’s syndrome -high incidence of death in utero -can be caused by a variety of genotypes but is most commonly 45X -other possible genotypes: 45X mosaics, 45X/46XY mosaics, and 47XXX -results in a variety of morphological defects: lymphedema of the hands and feet; shieldshaped chest; widely-spaced, hypoplastic nipples; webbed neck; low hairline; short stature; multiple pigmented nevi; congenital heart disease; gonadal dysgenesis; learning disabilities; and renal dysfunction -ovaries are normal at birth but develop into “streak” ovaries by puberty that are nonfunctional -horseshoe kidney is common (40%) -specific forms of congenital heart disease include coarctation, aortic stenosis, and bicuspid aortic valve -diagnosis is made by karyotyping and/or FISH analysis -treatment addresses hormonal abnormalities: -short stature can be reversed to some degree by GH -estrogen/progesterone can initiate sex characteristic development Klinefelter’s syndrome -due to 47XXY genotype -physical signs are not usually obvious until puberty

-presents in adolescence with a female body habitus, decreased body hair, gynecomastia, and small phallus/testes -most patients are infertile -increased incidence of learning disabilities but cognitive ability is generally not impaired Imprinting Disorders -imprinting = development of different phenotypes from the same genotype due to variable expression of genes based on paternal/maternal origin -uniparental disomy = inheritance of both chromosomes from a single parent; can present as these disorders Prader-Willi syndrome -associated with a deletion on chromosome 15 of paternal origin and duplication of maternal chromosome 15 -syndrome is due to absence of a fully functional chromosome 15 of paternal origin -presents with narrow head diameter; almond-shaped eyes; down-turned mouth; small hands/feet; short stature; hypogonadotropic hypogonadism and incomplete puberty; severe hypotonia; extreme appetite in later childhood leading to obesity; and mild retardation -usually die of complications related to obesity Angelman syndrome -similar defect as Prader-Willi but the maternal (rather than paternal) copy of chromosome 15 is absent -presents with maxillary hypoplasia; large mouth; short statue; severe mental retardation; impaired/absent speech; inappropriate laughter; jerky arm movements; ataxic gait; and tiptoe walking Cytogenetic Disorders Fragile X syndrome -form of mental retardation that affects males and is due to a trinucleotide repeat in the FMR1 gene -name is derived from characteristic fracturing of the X chromosome that is evident on cytogenetic analysis -presents with testicular edema, large jaw and ears, and mental retardation (sometimes the only manifesting symptom) -female carriers may have learning disabilities Chromosome 22q11 deletion syndrome -characterized by a variety of abnormalities of the heart (TOF, aortic arch defects), thymus (T cell deficiency, thymic aplasia, hypoparathyroidism), and nervous system (cognitive disabilities, behavioral/speech disorders) CHARGE syndrome -acronym for typical presenting symptoms: -coloboma (hole) of the retina or iris -heart abnormalities -atresia of the choanae -retarded growth -genital hypoplasia (males) -ear abnormalities (deafness, inner ear anomalies) -due to a point defect in the CHD7 gene VATER syndrome -exact defect not known but suspected to be a chromosomal disorder -acronym for typical findings: -vertebral anomalies -anal anomalies -tracheoesophageal fistula -esophageal atresia -radial/renal abnormalities Fetal alcohol syndrome -due to exposure to significant serum alcohol in utero

-typically presents with short palpebral fissures, a smooth philtrum, a thin upper lip, hypotonia, poor growth, developmental delay, congenital heart disease, and renal abnormalities Metabolic Disorders -due to protein defects in enzymes critical to metabolic processes, resulting in accumulation of toxic metabolites -symptoms present at different ages for different diseases: -early childhood: urea cycle defects, organic academia -errors in fatty acid oxidation and carbohydrate metabolism present after periods of fasting, usually with hypoglycemia and lethargy -lysosomal storage diseases typically present with progressive hepatosplenomegaly and neurologic deterioration Galactosemia -caused by a deficiency in galactose-1-phosphate uridyltransferase (converts galactose into glucose) -deficiency results in galactose accumulation which causes end-organ damage -presents with liver failure, renal dysfunction, emesis, anorexia, and poor growth -cataracts may develop within 2 months if left untreated -increased risk of developing E. coli sepsis -older children develop severe learning disabilities -females often develop premature ovarian failure -diagnosis rests on detection of reduced RBC galactose-phosphate uridyltransferase -treatment is elimination of all sources of galactose and initiation of a lactose-free, soybased diet Glycogen storage diseases -multiple conditions caused by deficiencies in enzymes involved with glycogen storage or breakdown -typically present with growth failure, hepatomegaly (glycogen storage site), and fasting hypoglycemia -most common types are type I (von Gierke’s) and type V (McArdle’s) Amino Acid Metabolism Disorders Phenylketonuria -due to inability to convert phenylalanine to tyrosine -treatment is restriction of phenylalanine in the diet -all states screen for PKU (not treating can lead to severe mental retardation) Homocystinuria -due to a block in conversion of methionine to cysteine and serine -no symptoms in infancy – first presents in childhood with a Marfan-like habitus (long, thin limbs; scoliosis; sternal deformities; osteoporosis), dislocated eye lenses, mental retardation, and systemic thrombosis -treatment is pyridoxine (50% success rate) and dietary restriction Ornithine transcarbamylase deficiency -unusual due to being X-linked -results in a defect in the urea cycle and the inability to process ammonia -presents with lethargy and possibly coma/seizures following feeding with a protein-rich meal -diagnostic testing includes measurement orotic acid -treatment is initiation of a low-protein diet and alternate nitrogen excretion pathways using benzoic acid and phenylacetate Lysosomal storage disorders -in general, enzyme deficiency results in inability to degrade waste products within the lysosome, resulting in build-up -three important disorders: -Hurler syndrome – deficiency of alpha-iduronidase -leads to accumulation of dermatan and heparan sulfates

-presents with coarse facies, corneal clouding, exaggerated kyphosis, hepatosplenomegaly, umbilical hernia, and congenital heart disease -most patients die in early adolescence -Pompe disease – deficiency of acid maltase which results in lysosomal accumulation of glycogen -characterized by profound hypotonia and extreme hypertrophic cardiomyopathy -treatment is enzyme replacement therapy -death by age 1 is typical if untreated -Gaucher disease – deficiency of beta-glucosidase, resulting in inability to degrade glucocerebroside -classically presents with hepatosplenomegaly and pancytopenia -low enzyme level in WBCs is diagnostic -treatment is enzyme replacement therapy Chapter 19 – Ophthalmology -regular vision screening is critical as early defects in vision can result in permanent dysfunction of the visual system -patients with a history of prematurity, in utero infection, CNS disease, or a family history of ocular disease are at increased risk Strabismus -defined as misalignment of the eyes -in children younger than 4-6, the brain may suppress the image from the deviating eye, resulting in amblyopia -eye can be turned in any direction: inward (esotropia), outward (exotropia), upward, and downward -do vision tests while covering each eye; when the eye is uncovered, drift may be observed -treatment is with corrective lenses and occlusion if possible, but surgery is frequently needed Amblyopia -due to reduced visual power in one eye -typically develops between birth and 7 y/o -the more severe the visual problem, the earlier amblyopia develops (typically) -most cases are due to anisometropia (unequal refraction between eyes, resulting in a blurred retinal image) and/or strabismus -treatment is with vision correction and occlusion as needed -early treatment is critical as treatment after 8 y/o is usually unsuccessful Leukocoria -white pupil due to an abnormal red reflex -can be due to a variety of causes – ophthalmic referral is required -most common causes: retinoblastoma (intraocular malignancy – can spread and lead to death if untreated), cataracts (opacification of the lens), and retinopathy of prematurity (vascular disease associated with prematurity) -treatment is based on the cause: -retinoblastoma – enucleation (removal) of the eye may be necessary -cataracts – should be removed by 2-3 m/o to prevent permanent visual disturbances -ROP – typically resolves spontaneously, but laser and cryotherapy are options to reduce the risk of retinal detachment and scarring Nasolacrimal duct obstruction -also called dacryostenosis, usually due to failure of the membranous end of the nasolacrimal duct to open -presents with chronic tearing in the absence of conjunctival injection -mucopurulent discharge and tenderness over the medial aspect of the lower lid suggests infection -obstruction resolves in nearly all cases by 1 y/o without intervention

-dacryocystitis (infection of the lacrimal gland) can be treated with warm compresses, massage, and antibiotics (in some cases) Ophthalmia neonatorum -defined as conjunctivitis within the first month of life -any discharge should be evaluated as tears are typically absent at this age -common causes: chemical conjunctivitis (complication of birth or possibly antibiotic treatment), Chlamydia, and N. gonorrhoeae -typically presents with eyelid edema, conjunctival hyperemia, and ocular discharge -treatment is based on the suspected etiology: -gonococcal, HSV, or Pseudomonas infection should be managed by an ophthalmologist -conjunctivitis due to other causes can be managed with waiting and referral to ophthalmology if symptoms progress -erythromycin prophylaxis is standard during neonatal observation Infectious conjunctivitis -very common in children – can be due to viral or bacterial etiology (adenovirus specifically is a common cause) -should differentiate from corneal abrasion (abrasion is visible with blue-filtered light following drops of fluorescein) -presentation is usually suggestive of etiology: -mild pain with clear discharge, no itching, and diffuse injection is likely viral -mild pain with mucopurulent discharge, no itching, and diffuse injection is likely bacterial -no pain with clear discharge and itching is likely due to allergies -treatment is a trial of antibiotic drops/ointment for 5-7 days -possible agents include polymyxin-bacitracin, TMP-SMX, sodium sulfacetamide, erythromycin, and ofloxacin -if no improvement, culture for specific guidance Hordeolum and chalazion -hordeolum = acute infection of the meibomian glands or sebaceous glands surrounding the eyelid follicle -usually caused by S. aureus -treatment is with warm compresses – no clear benefit with antibiotic eye drops -chalazion = sterile granulomatous reaction within meibomian glands that may progressively enlarge -area is usually firm but non-tender -treatment may require surgical drainage -frequently recurrent – prevent with good eyelid hygiene Periorbital cellulitis -caused by infection of the eyelids and surrounding skin anterior to the orbital septum -most commonly due to S. pneumoniae, Moraxella, and H. influenzae -must differentiate from orbital cellulitis, which usually presents with severe pain with eye movement, proptosis, vision changes, and decreased ocular mobility (due to impingement on ocular muscles) -CT can confirm the diagnosis and can identify abscesses that may require surgical drainage -periorbital cellulitis presents with warm and tender induration of the skin around the eye -treatment is immediate initiation of IV antibiotics depending upon possible source -penicillinase-resistant penicillin or first gen cephalosporin recommended if a break in the skin is identified -cefuroxime is antibiotic of choice -third gen cephalosporin can be used if spread to the meninges is a concern -should complete a 10 day course of oral antibiotics following resolution of symptoms Chapter 20 – Emergency Medicine

-most important concern in an emergent situation is hemodynamic stabilization -common causes of cardiac arrest in children: -respiratory: upper/lower airway obstruction, V/Q mismatch, ARDS, massive PE, respiratory muscle failure, central hypoventilation -cardiac: congenital heart disease, arrhythmia, myocarditis, pericarditis, cardiac tamponade, CHF -CNS: meningitis, encephalitis, acute hydrocephalus, head/spinal cord trauma, seizure, tumor, hypoxic injury -GI: abdominal trauma, bowel perforation, peritonitis, dehydration -metabolic: DKA, adrenal insufficiency, hyperthyroidism, hypoglycemia, hyperkalemia, hypocalcemia, hyponatremia, acute renal failure -systemic: SIDS, drug intoxication, trauma, anaphylaxis, hypothermia, septic shock -primary assessment = evaluation of CABDEs: circulation, airway, breathing, disability, and exposure (see below for specific notes) -goal is to identify life-threatening conditions and evaluate the need for CPR CPR -cardiopulmonary arrest = absence of a pulse in large arteries in an unconscious patient who is apneic -CPR is not necessary if spontaneous breathing is present -check brachial pulse in infants and femoral/carotid pulses in older children -CPR is indicated if the patient has no pulse, is not breathing, and is unresponsive to stimuli -CPR involves alternating chest compressions (simulate heart beats and provide circulatory support) and rescue breaths (provide ventilation to oxygenate blood) -effective chest compressions = 100 bpm to a depth of 4-5 cm -rescue breaths should be administered after tilting the head and opening the airway -compression:ventilation ratio is 30:2 if solo rescue and 15:2 if two rescuers Circulation -assessed by checking pulses, capillary refill, and BP -heart rate is the most sensitive measure of volume status in children -capillary refill is the most sensitive measure of adequate perfusion -BP is a poor indicator of poor circulation as hypotension develops late Airway -primary goals are to relieve obstructions, promote ventilation, and prevent aspiration -provide 100% O2 and assist with ventilation if necessary Breathing -evaluate chest wall movement to see if spontaneous breathing is present -intubation is not indicated if oxygen and ventilation are adequate and respirations are occurring -measurement of blood oxygen and possibly CO2 is appropriate to ensure adequate oxygenation -intubation of infants/young children occurs in the following process: 1) pre-oxygenate with 100% O2 2) atropine 3-5 min prior to intubation in children younger than 1 3) administer sedative/hypnotic/opioid 4) administer paralyzing dose of neuromuscular blocker 5) assess for apnea, jaw relaxation, and loss of muscle tone 6) intubate with direct visualization 7) confirm correct ET tube placement with at least two methods (auscultation, chest rise/fall, end tidal CO2, mist) Disability -rapid neurological screen – pupillary response, level of consciousness, localized findings -ask about specific adaptive behaviors and their medical history if chronic disease is suspected/present Exposure -rapid heat loss due to large surface area-to-volume ratio – keep warm if possible

-if toxin exposure, removed contaminated clothing and decontaminate as soon as possible Vascular access -3 attempts at peripheral IV access in 90 seconds is appropriate; if attempts are unsuccessful, interosseus line is indicated -if acute bleed is present, control of the hemorrhage and resuscitation with blood is critical Secondary assessment -evaluation of SAMPLEs: signs and symptoms, allergies, medications, past medical history, last meal, and events leading up to condition -completion of thorough head-to-toe physical Tertiary assessment -additional studies that evaluate presence/severity of respiratory and circulatory abnormalities -tests include: ABG, lactate, VBG, central venous oxygenation, Hb concentration, pulse oximetry, CXR, EKG, and peak expiratory flow as appropriate Shock -characterized by the inability of the circulatory system to provide adequate oxygen to tissues to match demand -typical compensatory responses include tachycardia and increased systemic vascular resistance -hypotension is a late finding and indicates impending circulatory demise -important cardiovascular properties to consider: -stroke volume = blood volume put out by the heart with one contraction; dependent upon preload (amount of blood entering heart), afterload (pressure against which blood presses when going out of the heart), and cardiac contractility (strength of contraction) -cardiac output = blood volume put out by the heart in 1 minute (stroke volume x HR) -blood pressure = cardiac output x systemic vascular resistance -severity of shock generally falls into one of three categories: -compensated = essential organ perfusion is maintained via compensatory hemostatic mechanisms -decompensated = failure of compensatory mechanisms and development of ischemia, endothelial injury, and secretion of toxic compounds (may present as altered mental status, weak pulses, tachypnea, decreased urine output, altered skin color, metabolic acidosis) -irreversible = shock that has resulted in irreparable organ damage with measurable functional loss -definition of hypotension in infants is dependent upon the child’s age: -0-28 days: SBP < 50 -1-12 months: SBP < 70 -1-10 years: SBP < 70 + (age x 2) -10+ years: SBP < 90 -four different etiologies for shock: 1) hypovolemic – due to decreased intravascular volume -generally presents with weak pulses and prolonged capillary refill 2) cardiogenic – due to inadequate stroke volume due to poor contractility or arrhythmias -if tachyarrhythmia is present, must differentiate between SVT (narrow QRS) and VT/VF (wide QRS) -hemodynamic instability requires immediate cardioversion of arrhythmias regardless of type -stable SVT can be managed with vagal maneuvers and/or adenosine -stable VT can be managed with amiodarone or procainamide and correction of underlying electrolyte abnormalities, if present -VF should be treated with immediate electrical cardioversion

-asystole/pulseless electrical activity requires 2 min of CPR with epinephrine administration, pulse/rhythm check, and an additional 2 min of CPR -reversible causes (“Hs and Ts”) include: hypovolemia, hypoxia, hydrogen ions (acidosis), hypoglycemia, hypo/hyperkalemia, tension pneumothorax, tamponade, toxins thrombosis 3) distributive – due to abnormal distribution of circulatory volume 2/2 vasomotor tone abnormality; results in a relative hypovolemia with fluid -septic, anaphylactic, and neurogenic shock are all examples 4) obstructive – due to impaired cardiac output caused by physical obstruction into or out of the heart -a history of vomiting, diarrhea, polyuria, burns, trauma, surgery, GI bleeding, intestinal obstruction, long periods in the sun, or pancreatitis is likely hypovolemic shock -a history of congenital heart disease, arrhythmias, or chemotherapy is likely cardiogenic shock -a history of fevers, toxic ingestion, anaphylaxis, or head/spinal cord injury is likely distributive shock -management requires careful monitoring of vital signs -treatment is focused on maintaining adequate perfusion and correcting underlying and metabolic abnormalities -hypovolemic shock requires aggressive fluid administration and possibly blood transfusion -cardiogenic shock may require inotropic support or surgical intervention -distributive shock requires epinephrine, IV fluids, steroids, and possibly albuterol Critically Ill Children Common mechanisms and patterns of injury -children in car accidents can still be injured even when restrained -common injuries include chest and abdominal injuries and lower spine fractures as a result of aggressive flexion against the seatbelt -injuries due to being struck by a car vary in children compared to adults -adults typically present with lower extremity injuries while children usually present with head, chest, and abdominal injuries -in bike accidents children often suffer from fractures, lacerations, and internal organ injuries -falls from heights usually results in orthopedic injuries including fractures of the extremities and head and neck injuries The abused child -abuse is the most common cause of injury and children less than one year -be suspicious of inconsistencies in the history, a delay in seeking care, or discrepancies between the provided history and physical findings -injuries suggestive of abuse include intracranial bleeding, retinal hemorrhages, trauma in the genital or perianal area, evidence of multiple fractures, and unusually shaped injuries on the skin -management of injuries depends on the system -children with injuries to the cervical spine should be immobilized with a collar -children with injuries to the chest should receive a CXR -abdominal injury usually requires abdominal CT -be very suspicious with a history of trauma and hypotension -worrisome lab findings include anemia, hematuria, and elevated liver enzymes due to risk of organ injury -suspicion of child abuse in a young child requires a full skeletal survey -CT of the brain is also indicated to check for bleeding -examination of the retinas to check for hemorrhages should also be done -treatment should focus on maintaining hemodynamic stability -children who present with severe hypertension should be treated immediately hypertension does not develop until 40-45% of blood volume has been lost -children with respiratory insufficiency should be intubated -pneumothorax or hemothorax should be treated with tube thoracotomy

-obvious long bone injuries should be splinted and immobilized -children with head injuries should undergo neurological assessment and receive a CT scan of the head Head trauma -more common in males -recovery depends on severity of injury -approximately 35% of patients will develop a seizure disorder -history of vomiting, severe headache, or mental status changes suggests increased intracranial pressure -signs of serious injury include lethargy, decreased level of consciousness, behavioral changes, vomiting, abnormal pupillary exam, and abnormal posturing -Cushing’s triad = bradycardia, hypertension, and irregular respirations -suggests that herniation is imminent -acutely unequal pupils suggests active herniation] -during the exam, the entire head should be inspected for possible injuries -in young infants, check the pressure of the anterior fontanel and the width of the sutures if still open -deep tendon reflexes should be checked and monitored overtime to check for changes -trauma to the side or back of the head is more likely to result in intracranial bleeding -determination of the child’s Glascow coma scale score should be done -scored out of 15, with 15 being a perfect score -lower scores indicate poorer neurological function -a score of 13-15 is indicative of mild injury, 9-12 of moderate injury, and 8 or less severe injury -all patients should receive a cervical spine film and a CT of the head if loss of consciousness occurred -children without loss of consciousness and a normal neurological exam do not need a head CT -treatment depends on the severity of the injury -early consultation with a pediatric neurosurgeon is indicated -intubation is usually necessary in severe injuries -ensuring adequate perfusion and oxygenation is critical to preventing worsening injury -patients with moderate injury should be observed for a period of time before being discharged to ensure there are no late-onset injuries -the development of worsening symptoms after an injury should warrant a more thorough work-up -cerebral edema is the most significant complication -hyperventilation can be used to reduce pressures and an osmotic agent can be used to remove more volume Chapter 21 – Poisoning, Burns, and Injury Prevention Acute poisoning -see chart below for characteristics of common pediatrics poisoning -particularly common in children younger than 6 (accidental) -another peak in incidence occurs with adolescents, usually due to intentional ingestion as a suicide attempt -history should identify substance, time since ingestion, symptoms, and attempts at treatment -initial evaluation should focus on possible need for cardiopulmonary support and assessing neurological status -O2 saturation, EKG, BMP, and ABG/VBG are all appropriate -toxicology screens can be performed but the ingested substance may not be detected -treatment is focused on immediate stabilization and is substance-dependent

-syrup of ipecac (administered to induce vomiting) is not recommended -activated charcoal is appropriate to decontaminate the stomach -whole bowel irrigation is useful for iron poisoning -gastric lavage is also not indicated – can be helpful within the first hour of ingestion but otherwise is of limited efficacy -specific treatments: -acetaminophen -> N-acetylcystine (regenerates glutathione) -anticholinergic agents -> physostigmine (AChE inhibitor) -CO -> oxygen -ethanol -> correction of electrolyte abnormalities -ethylene glycol -> fomepizole or ethanol (blocks metabolism) -hydrocarbons -> supportive respiratory care -ibuprofen -> activated charcoal, respiratory support, seizure control -methanol -> fomepizole or ethanol (blocks metabolism) -iron -> deferoxamine (chelator) -insecticides -> atropine (anticholinergic) +/- activated charcoal -opiates -> naloxone -salicylates -> gastric empting/activated charcoal, correction of electrolyte abnormalities -sympathomimetics -> activated charcoal, sedatives -theophylline -> activated charcoal, whole bowel decontamination Concussion -defined as an abnormal functional process affecting the brain precipitated by head trauma -usually presents with immediate short-term memory impairment that resolves without intervention -may also experience headache, nausea, vomiting, and vision/balance abnormalities -cognitive abnormalities may be present -loss of consciousness is uncommon; presence is usually indicative of severe neurological involvement -structural changes are typically not evident on imaging -usually a sports-related injury – most common in football, soccer, and lacrosse -exam should focus on identifying head lesions -Sports Concussion Assessment Tool 2 is a standardized scoring tool used to assess severity (validation still ongoing) -CT should be obtained if anatomical damage is suspected or to rule out bleeds, etc. -treatment is essentially “watch and wait” -no physical activity until patient returns to his/her physical/cognitive baseline -increased risk of severe neurological impairment if head trauma occurs while still symptomatic Drowning -highest incidents in infants/toddlers, most commonly in bathtubs -submersion for more than 5 minutes in warm water predicts CPR failure and death -history of near drowning should be evaluated with CXR and ABG to assess for hypoxemia -prevention is key – watch infants/toddlers and physically barricade pools and other bodies of water in the home Foreign body aspiration -in most cases, foreign body is immediately expelled by coughing -greatest incidence in children 6-30 m/o -aspiration into the lower airways is more common than tracheal obstruction -unlike adults, no predilection for the right main stem bronchus -increased risk with inadequate supervision and anatomic abnormalities, particularly of the upper airway -may not present until 1 week after the aspiration -usually presents with wheezing and respiratory distress – often misdiagnosed as asthma

-abnormal findings on lung exam are unilateral -a complete obstruction will likely demonstrate atelectasis on CXR -a partial obstruction is less likely – CXR may demonstrate subtle swelling or hyperinflation on expiration with mediastinal shift -treatment is removal of the foreign body -no airway intervention necessary if the child is crying, coughing, or speaking, which indicates at least a partially clear airway -rigid bronchoscopy may be required to remove the object(s) Burns -a not insignificant number (15-25%) of burns are due to abuse -different types depending upon etiology: -contact – due to direct contact with heat source -flame – less common but high mortality 2/2 smoke inhalation -electrical – frequently due to electrical outlet tampering or chewing on an electrical cord -chemical – due to exposure to strong acid or alkali (alkali more concerning as burns are typically deeper) -severity of burns is based on depth of injury: -first-degree = limited to the epidermis; red, dry, and tender without blistering -second-degree = involves the dermis but does not destroy the skin appendages; are painful and may develop blisters and weeping -third-degree = extension into the subcutaneous tissue; not painful due to complete destruction of nerve fibers -initial treatment is covering with warm, wet gauze and very careful cleaning -severe burns should be managed by specialists -grafting may be necessary in some cases Child abuse and neglect -physical abuse = intentional injuries that increase morbidity/mortality -sexual abuse = child involvement in sexual activities designed to give gratification to an adult -neglect = failure to provide child with basic necessities (shelter, food, clothing, schooling, and safe environment) -greatest incidence in children less than 1 y/o -most victims of sexual abuse are girls, and the perpetrator is typically a male family member -risk factors: poverty, children with special needs, and children younger than 3 -parents with a history of being abused, substance abuse, or extreme stress are more likely to engage in abuse -key findings that should raise suspicion for abuse: injury inconsistent with a provided history, an inconsistent history, and/or a delay in obtaining care -physical exam may demonstrate bruises, burns, or lacerations; lesions on the chest, head, neck, and abdomen are highly suspicious -lesions almost pathognomonic for abuse in the absence of another traumatic cause include subdural hemorrhage, diffuse axonal injury, and diffuse retinal hemorrhages -evaluation should include a full skeletal survey with advanced imaging (e.g., CT) as needed -intracranial injuries are nearly all due to abuse (95%) -concern for sexual abuse should be evaluated with rectal, oral, vaginal, and urethral specimens for culture (look for STDs) -treatment is management of findings -healthcare workers are required to report abuse to state agencies Sudden infant death syndrome (SIDS) -defined as unexpected death of an infant less than 1 year of age with an unclear etiology despite a thorough history and post-mortem evaluation -thought to be due to delayed maturation of the brainstem respiratory or cardiovascular control centers

-risk factors include low birth weight, IUGR, prematurity, lower socioeconomic status, soft bedding, obstructive materials in bed -no association with apparent life threatening events (ALTEs)