Overview of Mucocutaneous Symptom Complex

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AN OVERVIEW OF MUCOCUTANEOUS SYMPTOM COMPLEX ANTONIO E. CHAN, M.D. September 5, 2007 DEFINITION A febrile illness in children associated with skin manifestation (exanthem) and mucous membrane involvement (conjunctiva, throat, respiratory or gastrointestinal tract) • An exanthem is a skin eruption occurring as an integral part of an infectious disease. The corresponding changes in the mucous membranes is an enanthem • Accurate diagnosis not always possible on preliminary examination - judgment should be deferred until rash develops CLASSIFICATION • Maculopapular eruption • Vesiculobullous or vesiculopustular • Petechial or purpuric eruption MORPHOLOGIC TYPES OF RASH • Macule is a flat, circumscribed non-palpable discoloration of the skin; less than 1 cm. in diameter. Often evolve into papules •

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Papules are small nodular elevations of the skin less than 1 cm. in diameter. Vesicles: small blisters containing clear fluid Pustules: small elevations of skin containing pus Petechiae: small hemorrhages beneath the epidermis Ecchymoses: larger areas of hemorrhages Crust/scab: concealed exudate on skin Wheal: localized effusion of fluid into the skin causing a raised, white or pinkish white zone with a halo of erythema Erythema: a diffuse or localized redness of the skin Exanthem – skin eruption occurring as an integral part of an infectious disease Enanthem – changes in the mucous membrane

DESCRIPTIVE DERMATOLOGIC TERMS • Discrete (Rubelliform) • Confluent (Morbilliform) • Reticulated (lace-like network) • Multiform (Polymorphous) • Generalized (widespread) GENERAL STATEMENTS • Many different types of viruses, treponemes, chlamydia, rickettsiae, mycoplasma, bacteria, fungi, protozoan and metazoan agents cause illness with associated cutaneous manifestations • Many possible etiologic agents; hence, no unified epidemiology exist. • Maculopapular rashes are non-specific - a review of epidemiologic and physical findings is most helpful in establishing a diagnosis • These are the most common primary lesions seen during acute febrile illness in children • Associated with mild, febrile upper respiratory or gastrointestinal tract illness • Most exanthematous illnesses in children are benign • Enteroviruses are the leading cause of infection-related exanthematous diseases • Their differential diagnoses is critical because the early cutaneous manifestations of potentially fatal bacterial and rickettsial diseases frequently are similar • Many conditions that will ultimately manifest purpuric, vesicular, urticarial or ulcerative cutaneous lesions may first appear as erythematous macules or papules PATHOGENESIS 1. Dissemination of infectious agents by blood (viremia, bacteremia) which results in secondary infection at the cutaneous site a. Direct result of infectious agents in the epidermis, dermis or dermal capillary endothelium b. An immune response between the organism and antibody or cellular factors in the cutaneous location. 2. Dissemination of known specific toxins of infectious agents 3. A combination of these mechanisms

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VIRAL CAUSES OF MACULOPAPULAR ERUPTIONS • Rubeola virus – Typical, Modified, Atypical • Rubella virus - German measles • HHV 6 & 7 – Roseola infantum (Exanthem Subitum) • Parvovirus B19 – Erythema infectiosum •

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Enteroviral infection – Enterovirus 71 – Coxsackievirus – A2, A4, A5, A7, A9, A10, A16, B1B5 – Echovirus – 1-7, 11-14, 16-19, 22, 24, 25, 30, 38 Epstein Barr Virus – Infectious mononucleosis

BACTERIAL CAUSES OF MACULOPAPULAR ERUPTIONS • Streptococcus pyogenes – Scarlet fever • Salmonella typhi – Typhoid fever • •

Staphylococcus aureus – SSSS, TEN N. meningitidis – Meningococcemia

OTHER CAUSES OF MACULOPAPULAR ERUPTIONS • Kawasaki disease • Drug Eruption

Essential Elements of History • Demographic data – Age – Geographic area: Rickettsial infection (not present in Phil) • Exposure – Ill contacts – Travel (in endemic areas like Rickettsial infxn) – Pets, wildlife, insects (esp. ticks) à cat scratch disease, rat bite fever, rickettsia (tick bite) – Medications and drugs (sulfonamides) – Immunizations • Features of the rash – Temporal associations (onset of rash relative to fever) – Progression and evolution – Location and distribution – Pain or pruritus • Associated signs & symptoms – Prodromal signs & symptoms – Pathognomonic sign • History of previous illness (infectious)

RUBEOLA (MEASLES) • Age: Infants and older children • Mode of transmission: droplet spray during the prodromal period (highly contagious) • Incubation period : 10 – 12 days • Prodromal period (3 – 5 days)

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Conjunctivitis with photophobia Brownish discoloration & branny desquamation Koplik’s spots – grayish white dots usually as small as grains of sand, with slight, reddish areola amm

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UST Medicine & Surgery Pedia II

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Distribution of rash: – Starts behind the ears along the hairline, face then spreads downward over the body – More confluent on the upper part, discrete on the lower part

MODIFIED MEASLES • An attenuated form of infection that may occur in individuals who have received immune globulin after exposure to measles • The clinical manifestations are milder than those of typical infection, and the incubation period is prolonged from 14 to 20 days. ATYPICAL MEASLES • Occurs in individuals infected with natural virus and who previously received killed measles vaccines • Sudden onset of high fever accompanied by abdominal pain, cough, vomiting, and pleuritic chest pain • Koplik spots are rarely present, and rash begins distally and progresses in a cephalad direction, with little involvement of the face and upper part of the trunk RUBEOLA • Diagnosis: Clinical • Treatment: – Supportive – Vitamin A (immunomodulator) • 100,000 IU 6 mos – 1 yr • 200,000 IU > 1 yr • Complications – Otitis media – Pneumonia – Encephalitis – Exacerbate latent PTB • Prevention – Active immunization 9 mos, 15 mos & 4 -6 yr – Passive immunization (gammaglobulin) 0.25 mL / kg max. 15 mL

RUBELLA (GERMAN MEASLES) • Age: Children & young adults – Peak incidence 5 – 14 yrs. old • Mode of transmission: – Oral droplets or transplacental • Incubation period: 14 – 21 days

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Prodromal period: shorter & mild Tender retroauricular, post-cervical lymphadenopathy

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Distribution of rashes are similar to measles but they are discrete and not associated with desquamation Forchheimer spots – red spots are often seen on the palate. Diagnosis: Clinical Treatment: Supportive Complication : None – The most important consequence of rubella is in the pregnant woman “Congenital Rubella Syndrome”

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Clinical Findings in Congenital Rubella Syndrome General IUGR,hepatosplenomegaly, chemical evidence of hepatitis CNS Mental retardation, behavioral disorders, hypotonia, seizures, CSF protein Cardiac PDA, peripheral and valvular, pulmonary stenosis, aortic stenosis, VSD Ocular cataracts,“salt & pepper” retinopathy, corneal clouding, glaucoma Orthopedic radiolucencies in long bones Hematologic transient thrombocytopenia w/ purpura Dermatologic “blueberrymuffin” spots,dermatoglyphic Endocrine Diabetes in 2nd or 3rd decade •

Prevention: – Active immunization 15 mos., 4-6 yrs – Passive immunization for exposed pregnant woman – Gammaglobulin .55 mL/kg

ROSEOLA INFANTUM (EXANTHEM SUBITUM) • Age: 6 mos – 2 yr • Etiologic agent: HHV 6 & 7 • Mode of transmission: Adult saliva • No prodromal period – mild upper respiratory signs, irritability and anorexia, sometime seizures – Nagayama spots, ulcers at the uvulopalatoglossal junction commonly observed in Asian children

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Three-day fever followed by rash at defervescence of fever. Distribution of rash: – Rash starts from the trunk and spreads to the neck, face and proximal extremities amm

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UST Medicine & Surgery Pedia II

3C ‘09

ENTEROVIRAL INFECTION • Age: Infants & Young Children • Mode of transmission: Person-to-person thru fecal-oral or respiratory routes • Causative agents – Coxsackieviruses A2, A4, A5, A7, A9, A10, A16, B1B5; – Echoviruses 1-7, 11-14, 16-19, 22, 24, 25, 30, 38; – Enterovirus 71 • Incubation period: 4 – 7 days • Clinical signs & symptoms – Non-specific – Moderate to high grade fever with respiratory, gastrointestinal or CNS signs & symptoms – Rash variable but starts from face and spreads downward but no desquamation • Treatment : Supportive • Prodrome: – Echovirus 16 (Boston exanthem) prodrome resemble exanthem subitum but fever lower – Fever & constitutional symptoms in Echovirus 4, 6 & 9 may precede but usually coincide with rash appearance • Rash: – May be maculopapular, petechial and vesicular eruptions with Coxsackie A9, A16,A10, A5,B3 and B5 • Diagnosis: Clinical • Treatment: Supportive • Prevention: Basic hygiene (handwashing)

INFECTIOUS MONONUCLEOSIS • Age: Any age group – 90% of children contract EBV infection by 6 years of age – 40%-50% of adolescents have previously experienced EBV infection

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ERYTHEMA INFECTIOSUM • Age: School aged children & Adults • Etiologic agent: Parvovirus B19 • Mode of transmission: respiratory route thru large droplets • Incubation period 4 – 28 days • Mild prodromal period – Low-grade fever, headache, mild upper respiratory symptoms – Joint symptoms common in older adolescents & adults. esp women – Primary target is the erythroid cell line - Transient aplastic crisis - 2nd week • Rash in three stages (17-18 days) 1. Red, flushed cheeks with circumoral pallor (“slapped check” appearance) 2. Maculopapular eruption over upper and lower extremities (the rash assumes a lacelike appearance as it fades) 3. An evanescent stage characterized by subsidence of the eruption followed by recurrence precipitated by a variety of skin irritants (over 1 – 3 wks) • Affected children are not ill-appearing • Older children and adult often complain of mild pruritus • Rash resolves spontaneously without desquamation

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Slapped cheek appearance • • •

Diagnosis: Clinical Treatment: Supportive Prevention: None

Reticulated lesions

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Etiologic agent: Epstein Barr virus – Has latent and lytic life cycle Mode of transmission: saliva (close contact (kissing), mothers fondling their children, toddlers sharing toys) Incubation period : 30 – 50 days Clinical manifestation – Primary infection with EBV in childhood is subclinical or accompanied by mild non-specific symptoms (in 80% – The rash appears (3% to 19%) during the first few days of illness, lasts 1 to 6 days can be erythematous, macular, papular or morbilliform, usually located on the trunk and arms, rarely on the palms – 80% of infected patients treated with ampicillin or amoxacillin experienced “ampicillin rash” Diagnosis – Clinical triad (Exudative pharyngitis, cervical lymphadenopathy and splenomegaly – Presence of atypical lymphocytes in the peripheral blood – Serologic test - + Heterophile antibody (appears during 1st or 2nd wk of illness) Exudative pharyngitis Cervical lymphadenopathy Hoagland’s sign: Lid edema Atypical lymphocytes (Downey cell) Confirmatory test – Presence of antibody for specific antigens – IgM antibodies to viral capsid antigen (VCA) are transient whereas IgG antibodies for VCA persist for life – Antibodies against the early antigen (EA) complex appear later in the course of acute infection and disappear after 6 months Confirmatory test – Antibodies against Epstein Barr nuclear antigen (EBNA) complex appear more slowly, they often take from 1 to 6 months to become detectable and levels rise during convalescence. amm

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UST Medicine & Surgery Pedia II

TYPICAL SEROLOGIC FINDINGS RELATED TO THE STAGE OF EBV INFECTION Stage of infection Presence of Antibody Primary VCA IgM or IgG (usually high) ±EA (usually high), no EBNA Convalescent or Past VCA IgG ± EA (low), EBNA Reactivation VCA IgG (high) ± EA (high), EBNA • •

Treatment: – Bed rest & symptomatic management Complications: Rare – Airway obstruction – Subcapsular splenic hemorrhage – Splenic rupture

3C ‘09

TYPHOID FEVER • Age: Any age group • Etiologic agent: Salmonella typhi • Mode of transmission: Food & water contaminated with human feces • Incubation period: 7 – 14 days • The clinical manifestations of enteric fever depend on age • In infants and young children ( children – Trunk predilection – Rash 10 days after fever – Step ladder pattern fever (When peak it stays there for 3 weeks) – Even w/o tx, usually resolve after 3 Culture: weeks Blood – 1st week – Bradycardia ≠ high fever Urine – 2nd week – Intestinal symptoms Stool – 3rd week – Definite: BM culture Measles – Complication: 1. Pneumonia (most common) 2. gastroenteritis – diarrhea precede/accompany/ follow measles (mucosa GIT affected) – Sequelae of measles – Pneumonia – State of ANERGY: temporary state of immunosuppresion – Reactivation RF, latent PTB – Otitis media – Croup laryngotracheobronchitis – Encephalitis (acute, SSPE) – Meningitis – aseptic meningitis

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