Disease Cheat Sheet

Disease

Actinic Keratoses (AK)

Clinical Variants

Hypertrophic AK (thickened), pigmented AK, actinic chelitis (lips)

Nodular (can be pigmented in darker pts) Basal Cell Carcinoma (BCC)

Superficial (more scaly, less thick) Morpheaform (scarring, loss of pigment; MORE AGGRESSIVE)

Basal Cell Nevus Syndrome (BCNS)

N/A

Squamous Cell Carcinoma (SCC)

Worrisome when recurrent, location on forehead / temple/ ear/ lip, large size (>2cm), poor differentiation, invasion (in-transit met to lymphatic channels), perineural invasion

Defining Characteristics

small, raised scaly spots on chronically sun-exposed skin; scattered, thick erythematous patches

Pathogenesis

UV induced mutations in p53 cause unrestrained growth and damage to repair genes prevents tumor rejection

UVB causes direct DNA damage to p53 and overexpression of originate from keratinocytes from epidermis or follicular bcl-2, which prevents apoptosis; carcinoma of follicular epithelium; unlikely to metastasize; most common skin cancer keratinocytes & found above clavicle

TONS of BCCs as child, megaloblastomas, palmar pits, bifid ribs, frontal bossing of scalp

Asymptomatic until fast growing --> painful, grows faster than BCC, ulceration/ verruca-like, common in transplant pts, metastatic potential

Etiologies

Epidemiology

sun exposure immunosuppression genetic conditions

Chronic UVB exposure, immunosuppression, inherited conditions (Gorlin Goltz basal cell nevus syndrome, XP), chronic arsenism, patch mutations, previous BCC

750,000 new cases/yr, growing incidence among younger ages (30-40s)

Risk factors

Lab/Imaging

Treatment

skin type I, age > 70, field disease on upper limbs/ head/ neck

Histology? Surface changes at epidermis

cryosurgery, topicals (5-FU, imiquimod, PDT w/ photosensitizer ALA, chemical peel, reduction of immunosuppressants to safe levels

male, older age, fair complexion, tendency to burn, outdoor occupation

Clinical

surgical excision, Moh's, PDT w/ ALA, radiation tx (for non-operable), topical tx for field dz (5-FU, imiquimod), reduction of immunosuppressants to safe levels

Deficiency in patch (negative regulator of Shh) causes constitutive action of positive regulator (Shh), increasing incidence of BCC

Vismodegib (targets Shh to decrease tumor size; but still residual tumor so perhaps development of resistance)

Shh binds and inhibits patch; without patch, smoothened causes increased transcription of GLI-1,2,3, causing increased cell proliferation Chronic UVB exp Originates from interfollicular keratinocytes following direct DNA chem carcinogens damage to p53 from UVB; SCC make VEGF so highly genetic disorders angiogenic immunosuppression HPV Apoptosis loss possibly due to ROS resistance of SCC chronic inflam (leg ulcers, DLE, Genetic predisposition for loss of p53 (XP, HPV) osteomyelitis)

250,000 new cases/yr; growing incidence among younger ages (30-40s)

Complications

Most common precursor to SCC

Loss of taste (and ultimately anorexia) is a side effect of tx

surgical excision, Moh's, PDT w/ ALA, radiation tx (for non-operable), topical tx for field dz (5-FU, imiquimod, cryosurgery), reduction of immunosuppressants to safe levels

Heart/lung transplant recipients Chronic lymphocytic leukemia XP

genetic mutations (MC1R mutations- red hair & predispose to B-raf mut; familial loss of p16) less common than other skin cancers (BCC>SCC>>MM)

Superficial spreading melanoma (SSMM) Nodular melanoma (NM) Malignant Melanoma (MM) "know your ABCDEs"

Lentigo maligna melanoma (LMM) Acral lentiginous melanoma (ALM) - hands, feet, mouth, genitals Mucosal melanoma (very rare!)

SSMM (common, pagetoid - migration to place not typically found, trunk of men, legs of female; regression = loss of pigment/scarring) - NM (no radial growth- often ulcerated, rapidly growing, can lack pigment; trunk of men, invades through dermal/epidermal jx); - LMM (sun exposed areas; slowest growth rate and longest radial growth stage); usually appears as growing freckle, freckle in unusual place, or freckle that crosses anatomic boundaries - ALM (palms, soles, subungal; Hutchinson's sign, melanonychia striata, abnl nail)

Malignant tumor arising spontaneously from melanocytes in basal epidermis or from dysplastic nevi; dysplastic nevi then undergoes radial growth where it becomes invasive until able to grow vertically; once vertical growth phase reached, the tumor has high metastatic potential

ALM can sometimes occur in conjuction with 4% of cancer cases, but vitiligo (autoimmune more than 75% of skin dz); associated with cancer deaths; 5th & mutations in C-kit 7th most common Associated with oxidative damage from UVA cancers in men & Melanoma in sunwomen; 70,000 new protected areas can Staging depends on Breslow's depth, ulceration, # mitotic cases/yr; primarily result from mutations in figures, lymphatic/ vasculature entry younger adults; b-raf or N-ras increased incidence B-raf mutation --> loss of PTEN --> activation of oncogene Akt - oncogenes due to recreational -> transformation of radial/noninvasive melanoma to habits vertical/invasive MM LACK MUTATIONS IN p53 N-ras mutation --> activation of oncogene Akt

young adults FH of MM or DN UV light rptd childhood sunburns # (>50) & size (>5mm) of nevi CN PMH of MM high SES Skin types 1&2 latitude DNA repair defects immunosuppression

Evaluation includes history, TBSE, LN exam, CXR, routine labs, & MRI brain/CT of chest (for late-stage) HIGH risk for metastasis Histology? Sun exposure signs (loss of elastin fibers, solar Surgical removal/ excisional bx elastosis - abnl elastin in upper dermis) Sentinel LN bx to stage metastasis Excisional (or incisional punch) bx for Breslow's depth to LNs (used for melanomas >1.0mm in depth)

later detection and higher stage associated with higher mortality Pts with p16 mutations have increased risk of pancreatic cancer too!

Braf inhibitors (PLX4032) prolongs survival but not curative

NM in middle-aged men; LMM in older pts w/ chronic UVB exposure & age spots; ALM more common in dark/Asian pts

uniform pigmentation, symmetrical shape, sharply demarcated borders, wide distribution and colors

Benign Nevi

Dysplastic Nevi

Dysplastic nevus syndrome (DN) - multiple benign with characteristics of precursor melanoma: irregular family members w/ melanoma and multiple DN growth, variation in color/size, multiple asymmetric lesions in pt (also have only one copy of p16)

Congenital Nevi

Giant Melanocytic Nevus

Present at birth or within first year of life; important to monitor changes in size/color/symmetry

Xeroderma pigmentosum (XP)

N/A

marked increase in skin malignancies at young age, photosensitivity, impaired DNA damage repair systems

Arise from melanocytes

can be sporadic or familial

b-raf mutations

Relative risk for melanoma depends on size of CN

N-ras mutations

Prophylactic removal during teen years; staged surgical removals if large

At least 10 DNA repair defects

New tx include mimics of photolyases (enzymes in other organisms that repair CPDs)

Defective NER (nucleotide excision repair); accumulation of oxidative and DNA damage Determined by total UVB energy absorbed (ind of duration)

Sunburn

N/A

Inflammation, erythema

Inflammation (cytokines, histamine, prostaglandins, serotonin) cause redness; increased adhesion protein expression --> immune cell recruitment

Failed or incomplete repair of thymine dimers --> mutations in p53 (higher risk for nonmelanoma skin cancers)

Change in existing melanin (immediate pigment darkening caused by redistribution of melanin - IPD, persistent pigment darkening- PPD) Sun tan

N/A New melanin (delayed tanning) formed when keratinocytes release MSH in response to UVR; MSH binds MC1R on melanocytes --> increased melanin production and proliferation

Ichthyosis

Psoriasis

N/A

Inherited disease causing generalized scaling and thickened skin

Excess stratum corneum due to altered epidermal differentiation

Localized scaly plaques, can be raised; less prone to infections (abundant AMPs)

Excess stratum corneum from low epidermal turnover

mutations in filaggrin (which binds to keratin) causes bundling/collapsing of keratin fibers

Histology? Endothelial swelling, decreased langerhans, neutrophil recruitment, apoptotic keratinocytes (bright pink) areas of hyperplasia (thickened stratum corneum, epidermis, dermis)

High rate of MM, SCC, freckles

Major risk factor for nonmelanoma and melanoma skin cancers

Disease Epidermolysis bullosa (EB)

Clinical Variants (General)

Defining Characteristics blisters on hands and feet

Pathogenesis

Less severe bc blistering in higher skin layers EB Simplex

Dominant mutation causes complete disruption of the keratin more superficial (but painful blisters), non-scarring, localized to polymer (even if you have one nl K14) hands/ feet/ extremities, no mucus membrane involvement Recessive mutation causes truncated protein or loss of protein but not as problematic Very serious bc blistering in middle skin layers

Junctional

Generalized blisters at birth, periorificial granulation tissue, nail shedding/dystrophy, denuded areas, enamel defects, growth retardation, anemia, epithelial blistering of mucosal membranes (Resp, GI, GU)

Etiologies

Epidemiology

Risk factors

Lab/Imaging

Treatment

Complications

Inherited disorder w/ defects in cellular attachments, causing epidermis to no longer stick to dermis Superficial blistering within the epidermis caused by disorganization of keratin intermediate filament network Genetic defects w/ keratin (arginine at position G of alpha-helix heptad is mutated)

Histology? Cytolytic fracture / cleavage plane below the nuclei of basal cells --> aggregation of keratin fibers

premature stop codon in laminin 5 genes Blistering in the lamina lucida

Can be lethal in early childhood

sometimes defects w/ collagen 17 or B4/a6 integrins

Subepidermal blistering w/ scarring Dystrophic (Recessive-RDEB or DominantDDEB)

Epidermolysis bullosa acquisita

milia (cysts on newborns) that scar upon healing, Subepidermal blistering absent/dystrophic nails, Mitten deformities (fusion of finger scar tissue (RDEB)); mucosal surfaces involved, malnutrition, growth retardation, anemia Autoimmune-mediated blistering disease caused by antibody deposition against collagen VII

Premature stop codon in collagen VII genes

Severe scarring

Autoantibodies against Collagen VII

Significant scarring

Bullous pemphigoid (BP) Bullous pemphigoid

blistering disease where epidermis is lifting off of basement membrane; usually on lower extremities of older patients Itchy, tense blisters (do not break easily!),

Autoimmune blistering disorder where antibodies are directed at hemidesmosomes (sub-basal) so loss of epidermal attachment to basement membrane

Autoantibodies against BPAG1 and/or BPAG2

Autoantibodies against BPAG2, laminins, integrins

Mucus membrane pemphigoid

red line along gingivial sulcus (white picket fence), no scarring

Autoimmune blistering disorder where antibodies are directed at hemidesmosomes (sub-basal) so loss of epidermal attachment to basement membrane

Ocular cicatricial pemphigoid

severe ocular disease, symblepharon (fibrous bands where eyelid fuses to conjunctiva)

Severe inflammation of the eye causes thick & fibrous scarring that fuses with the eye conjunctiva as symblepharon

Histology? Subepidermal blister (white space btwn epidermis & dermis) (sub-basal split), healthy epidermis, +eosinophils (pink) Dx confirmed w/ immunofluorescent Abs binding to basement membrane Histology? Subepidermal blister (white space btwn epidermis & dermis) (sub-basal split), healthy epidermis, +eosinophils (pink) Dx confirmed w/ immunofluorescent Abs Possible blindness as skin covers cornea if no aggressive treatment

Pemphigus Pemphigus vulgaris

Autoimmune blistering disorder where antibodies (IgG) are Autoantibodies against attacking intra-epidermal (suprabasal) proteins of desmosome, desmoglein 3 and/or resulting in compromised cell-cell adhesion [basal layer splits desmoglein 1 from spinous layer]

Chronic dermatitis

Autoimmune blistering disoder where antibodies (IgG) attack Autoantibodies against intra-epidermal (suprabasal) proteins of the desmosome, resulting in compromised cell-cell adhesion [basal layer splits desmoglein 1 from spinous layer] Mutation in Loss of desmosomal cadherin organization and mediation of desomosomal Fragility syndrome subsequent adhesion cytoplasmic plaque protein (plakophilin) Tyrosinase mutation causes inability of melanocytes to produce Hypopigmentation melanin Hypopigmentation - usually splotchy; symmetrical involvement of Autoimmune destruction of melanocytes produces decreased body parts or absent melanocytes Exuberant scar usually from trauma Excessive collagen in the dermis Inflammation of subcutaneous adipose tissue Yellowing, hyperkeratosis of nails; possible presence of debris Tinea unguium (see Fungal infection of nail under nails Dermatophytosis) Edematous epidermis causes skin to become swollen, raised, Inflammation of skin inflamed --> erythema and itchiness severe inflammation and edema causes edema fluid to leak oozing, crusted vesicles (poison ivy) from skin surface --> oozing & crusting Lichenification

Subacute dermatitis

Lichenification and spongiosis with crusting on surface

Pemphigus foliaceus Ectodermal Dysplasia N/A

Albinism

N/A

Vitiligo

N/A

Keloid Panniculitis

N/A N/A

onychomycosis

N/A

Dermatitis

Inter-epidermal blisters, jagged & flaccid blisters w/ positive Nikolsky sign (easy to deform w/ slight pressure), hyperpigmentation in healing areas, not too much scarring, severe nail disease, oral lesions

General Acute dermatitis (eczema)

Histology? Basal epidermis still attached to BM, and rete ridges still visible but huge white space above represents blister (suprabasal split) Chicken wire appearance w/ direct immunofluorescence

Immunosuppressants, corticosteroids; new therapies (tyrosine kinase inhibitors to increase resistance to pemphigus IgG)

side effects of steroids; high fatality w/o tx

Immunosuppressants, corticosteroids

side effects of steroids

Histology? Melanocytes present (just not making melanin!) Histology? No melanocytes seen African American race

Histology? Dermis has taken over! Histology? KOH prep or PAS stain reveals hyphae Histology? Epidermal spongiosis (intercellular edema; white) Histology? Spongiosis causing fluid-filled vesicles (subcorneal vesicles) Histology? Acanthosis of epidermis (thickening) Histology? Marked acanthosis, elongation of rete ridges, spongiosis

Hypersensitive, twitchy skin - overreaction to various stimuli, causes skin to turn red--> white when scratched; same "twitchiness" also seen in lung/nasal membranes

Atopic Dermatitis (AD)

Abnormal cytoskeleton? Mutation in filaggrin causes abnl barrier fx so increased dryness; mutation also causes chronic, pruritic dermatitis that waxes & wanes; face & extensor bundling/collapsing of keratin fibers extremities of infants; flexural surfaces of older children/adults; lichenification and linear excoriations can be present (chronic); Aberrant inflammatory response? abundance of TH2 cells in xerosis, dermatographism dermal inflammatory infiltrate

Once child outgrows AD, can have asthma/ allergies later; higher prev in developed countries suggest environmental factor

Moisturizers for xerosis, antiinflammatory cortisone creams; if no relief to those, systemic immunosuppressants for severe cases (prednisone, cyclosporin); oral antibiotics for presence of secondary infections; acyclovir for secondary HSV infections (especially if periorbital)

20% of children, 1% of adults "childhood eczema"; 2More common if parent has AD 3x more common now; more developed countries

Hygiene hypothesis? overreaction upon antigen exposure due to "too clean" of environment

Lichen Simplex Chronicus (LSC)

Acne

Tinea versicolor

Xerosis, erythema, red-brown discoloration from hemosiderin OLD theory - SD caused by stasis and hypoxia, but pts actually deposits and degraded extravasated RBCs, dilated superficial have high flow rate and oxygen veins; often involves medial ankle, possible lipodermatosclerosis (hard feeling from underlying fat Abnormal microcirculation - increased permeability of dermal necrosis); hypopigmentation, ulceration capillaries allows leakage of fibrinogen, which polymerizes to fibrin to form fibrin cuff around capillaries --> ultimately inflammation May or may not have underlying primary dermatitis; skin itches Lichenification of skin, very pruritic beginning chronic scatching cycle that causes the skin to lichenify

Contact Dermatitis 1. Irritant 2. Allergic (ACD)

Itching, redness, erythematous papules; possible spongiosis and 1. edema --> crusted vesicles; 2. Allergic - patient becomes sensitized from previous allergen exposure (no rash at first exposure); upon re-exposure to Diaper dermatitis (irritant, also caused by Candida), poison ivy ACD - due to oleoresin in Rhus group of plants); nickel ACD antigen, there is a delayed-hypersensitivity reaction neomycin ACD; formaldehyde ACD

Seborrheic Dermatitis

variation of dandruff, can be on scalp/face

N/A

N/A

hyper- or hypopigmented patches with readily inducible scale; chest & back; warm/moist environment; usually asymptomatic but may be pruritic

Secondary infections of AD skin with S. aureus, MRSA, HSV (tingling, stinging at lesion), molluscum --> pustulosis or folliculitis, weeping/oozing/yellow crust - have less AMPs due to acute/chronic lesions! Food allergies

Probably all of these! Abnormal circulation in skin comprises the skin barrier, causing dryness and inflammation --> itch --> LSC & SD

Stasis Dermatitis (SD)

Complications due to abnl barrier function of skin or abnl immune response?

Often require hospitalization for tx of Can be complicated by LSC venous ulcers

Venous insufficiency

Can complicate other types of dermatitis

Histology? Acanthotic 1. irritant - not allergic, but burned/inflamed by substance (occur in anyone exposed) 2. Allergic - allergy response (poison ivy, does not occur in everybody)

Patch testing

Inflammation of skin related to host response to normal P. ovale flora Starts w/ occlusion of follicle and formation of microcomedone, leading to hyperkeratosis of the opening that blocks eggressive sebum. Cyst forms with sebaceous material, forming comedone. Follicular unit further expands, allowing Propionibacteria acnes growth of Propionibacterium acnes and inflammation that (nl skin flora) leads to follicular wall rupture Inflammation mediated by bacteria intxn w/ TLR2 on monocytes Colonization at birth that peaks in early adult life with increased sebaceous gland activity Malassezia furfur (P. ovale, P.orbiculare; nl Unclear factors trigger overgrowth & conversion of yeast to skin yeast) pathogenic hyphal form

Avoid irritant/allergen; wash immediately after exposure; calomine to soothe/dry out (AVOID sensitizers like topical benadryl/Caladryl); topical corticosteroid Anti- fungals controling Pityrosporum carriage Topical/oral antibiotics (reduce bacterial density and macrophage activation) Retinoic acid (downregulates TLR2 expression on monocytes)

People living in warm/ humid climates have higher bacterial carriage

Do NOT give topical steroids!

Possible scarring

Disease

Clinical Variants

Pityrosporum folliculitis

Defining Characteristics

Follicular centered inflammation on chest or back

Pathogenesis

Inflammation of hair follicle due to fungal colonization/infection

Etiologies

Epidemiology

Hot tub folliculitis

Follicular centered pustules or erythematous papules that are slightly pruritic and/or tender

Diffuse folliculitis

Bacterial infection of hair follicles transmitted from direct contact with infected person or autoinoculation

Exposure to Pseudomonas in water that has not been sufficiently chlorinated

Lab/Imaging

Treatment

Complications

People living in warm/humid climates

Histology? Massive infiltration of neutrophils around hair follicle

Responds to anti-fungal tx

Do NOT give topical steroids!

S. aureus, occlusion of non-dermatologic areas

Chronic S. aureus carrier Irritation Shaving Occlusion

Clinical (pustules/papules w/ hair follicle in middle) Gram stain/Cx

Topical Abs Oral Abs (if extensive, recurrent)

Abscess formation

Bacterial folliculitis Bacterial folliculitis

Risk factors

Hot/humid environment AB use Immunosuppressant Hi sebum prod

Pseudomonas aeruginosa

Clinical

Self-limited Sx usually don't require tx May give Ciprofloxacin if needed

Bullous impetigo (S. aureus) Impetigo Impetiginized eczema (2ndary inf)

Furuncle (smaller) Furuncles/ Carbuncles Carbuncle (larger!)

Small vesicles/pustules, erosions w/ golden honey-colored crust

Superficial bacterial infection of epidermis caused by S. aureus, GAS; highly contagious (direct contact)

Inflammatory, tender nodules or abscesses around follicle (or underlying tissue if carbuncle) that is purulent or necrotic; hot/red, fluctuant (compressible)

Continuum from folliculitis --> furuncle --> carbuncle that is transmitted via autoinoculation/direct contact

S. aureus, GAS

Increased incidence in SE, day care settings

S. aureus

Localized? Topical antibacterial cream (Mupirocin)

Childhood Crowded areas Heat/humidity

Clinical (honey crust) Gram stain/Cx

Chronic S. aureus carrier Folliculitis Obesity Immunodeficiency

Clinical Gram stain/Cx

Widespread? Oral Abs (Dicloxacillin, cephalexin, erythromycin, etc) Drainage (hot compresses or surgical) Oral Abs (dicloxacillin, Cephalexin, Bactrim)

Rare

Abs not effective until necrotic/purulent tissue is DRAINED!! Recurrence Bacteremia (rare)

"Spider bite phenomenon" CA-MRSA

Looks like spider bite, furuncle, abscesses, pyomyositis, cellulitis Bacterial infection caused by methicillin resistant S. aureus

CA-MRSA

asymptomatic --> fatal

Dermatophytosis

Tinea pedis (athlete's foot) T. unguium (onychomycosis) T. cruris (jock itch) T. corporis/faciei (ring worm) T. capitis (cradle cap)

Well demarcated scaly plaque w/ hyperkeratosis, may be pruritic Fungal infection of non-viable, keratinized structures like or erythematous (jock itch), moccasin scale or toe web stratum corneum, hair, nails; transmitted person-person, maceration (tinea pedis), annular w/ central clearing (tinea contact with infected fomites, autoinoculation corporis/faciei), alopetic patch w/ possible neck LN swelling (tinea capitis) Keratinases of fungal hyphae

Verruca vulgaris

Verrucus (bumpy/rough), hyperkeratotic skin colored papules; usually asymptomatic unless 2ndary infection/inflammation

Filamentous fungi (Microsporum, Trichophyton, Epidermophyton)

Often none Humid/occluded skin Common infection even Atopy (eczema) in healthy hosts Immunodeficiency TOPICAL STEROIDS

HPV 2, 4

VERY common 20% of kids have at some time

HPV 1

Common in adults

Verruca (warts)

Condylomata acuminata Filiform warts

Infection of basal layer of skin with HPV (dsDNA virus), resulting in the slow division of cells in the spinous layer; Hyperkeratotic papules/plaques that are less exophytic, black eventually leads to hyperkeratosis and papillomatosis macules of thrombosed capillary loops ("seeds" = lay term) Transmitted from skin to skin contact, autoinoculation, Genital warts; flatter, gray/brown papules contaminated surfaces Thinlike projections common on face

Verruca plana

Pinkish warts common on hands/face

Verruca plantaris

Molluscum Contagiosum N/A

Herpes Simplex Virus (HSV)

Varicella Zoster Virus (VZV)

HSV-1 (classically oral) HSV-2 (classically genital)

Umbilicated (central), small, dome-shaped, pink papules

PAINFUL, TENDER grouped vesicles or erosions on erythematous base; prodrome (tingling); can occur on lips, finger (Whitlow), genitals

Increased prevalence as SSTI, furunculosis; can cause infections in Pts lack typical risk factors pts typically lacking RFs for MRSA (hospital/prison/ sports)

HPV

Children HIV Sexually active young adults

Superficial poxvirus infection of epidermis only transmitted via Molluscum skin to skin (considered STD in young adults) contagiosum virus

HSV infection of keratinized skin/mucus membranes transmitted skin-skin, skin-mucosa (possible STD)

PAINFUL, DERMATOMAL vesicles, crusted papules, erosions often in unilateral fashion

(Shingles)

NOT contagious (represents reactivation state) but patients with varicella zoster can transmit chicken pox to those who have never had it

Varicella zoster virus

Histology? Fungal hyphae caused by dermatophytes in stratum corneum KOH prep Fungal Cx (takes wks) Wood's lamp (hair) Bx for histology w/ PAS stain

Lifetime risk of 10-20%

Topical anti-fungals (Azoles, TOPICAL STEROIDS CAN allylamines: naftifine, terbinafine) MAKE WORSE!!! Oral anti-fungals (azoles, allylamines, griseofulvin) for hair/nail infections

Nail disfigurement (rare) Alopecia

Spontaneously resolution (SLOW) Histology? Hyperkeratosis of epidermis and granular layer, inward bending of rete ridges, papillomatosis (fingerlike projections of epithelia)

Clinical Crush prep Bx (rare) Histology? Henderson-Patterson bodies (eosinophilic inclusion bodies)

None - pretty ubiquitous virus

Clinical Tzanck prep (cannot distinguish HSV from VZV) Direct fluorescent antibody (CAN distinguish HSV from VZV) Viral culture Bx (rare)

advancing age immunosuppression Stress!

Clinical Tzanck prep DFA (distinguish HSV from VZV) Viral Cx Bx (rare)

Latency phase, asymptomatic shedding

Erythromycin & methicillin resisitant

Use Bactrim or clindamycin

Clinical Bx (rare) DNA testing to determine type of HPV present

VZV goes latent after active infection/vaccination in the ganglia until risk factors cause reactivation of varicella zoster virus N/A

Often none HIV Organ transplantation

Culture w/ sensitivity testing

NO beta-lactams, possible adjunct therapy

Various OTC tx modalities that aren't all that effective (Salicylic acid, imiquimod, duct tape)

possible some HPV types are cancer-forming

Paring Cryosurgery Podophyllin (topical chem agent) Spontaneous resolution (can take up to 2y) Imiquimod Canthardin (good for kids) Liquid nitrogen Curettage Self-limited in immuno-competent host Oral antivirals for immunocompromised/ recurrent or severe episodes

Potential risk for wide-spread dissemination Neonatal transmission POST-HERPETIC NEURALGIA

ORAL ANTI-VIRALS ASAP!! (w/I first 48-72h)

dissemination transmission of varicella (chicken pox)

Topical creams (scabicides)

Scabies

N/A

Carbuncles w/ pus present? Think S. aureus Cellulitis Diffuse erythema w/ no pus? Think GAS

Eryisipelas

Diabetic foot ulcers

N/A

PRURITIC, thread like linear burrows produced by the tunneling of the mite; can have erythematous papules; commonly seen on wrists, genitals, waistline, axilla, web spaces

Eruption caused by tunneling of mite in stratum corneum that causes delayed type IV hypersensitivity response and Sarcoptes scabiei var. diffuse pruritic eruption after 4-8 weeks hominis Transmitted via skin-skin contact or contact with fomites

Rapidly spreading areas of edema, redness, heat; possible vesicles/bullae/cutaneous hemorrhage; systemic sx (fever, tachycardia, confusion, hypotension, leukocytosis)

Acute infection arising when organisms enter the deep dermis/subcutaneous layers through skin breaches

Group A Strep Other beta-hemolytic strep S. aureus (CA-MRSA)

Raised, sharply demarcated erythematic lesions, commonly seen on face; acute onset

Acute infection caused by GAS entering the upper dermis

Group A Strep

Infection by S. aureus or B-hemolytic Streptococci Often polymicrobial infection with enterococci, obligate anaerobes, P. aeruginosa, and/or Enterobacteriaceae

Necrotizing fasciitis (NF)

Polymicrobial

Gas gangrene (myonecrosis)

N/A

Deep incisional (fascia/muscle) Organ/space

EMPIRICAL KNOWLEDGE (cx not always positive, low sensitivity of needle aspiration cx)

Initial break in skin from trauma or surgery causes advancing infection to fascial and/or muscle compartments

Less common in children Aerobic + Anaerobic bowel flora

Rapidly progressive, toxemic infection in previously injured muscle (blunt trauma), edema, crepitus (gas bubbles), brown bullae; abrupt pain

Blunt trauma causes non-viable tissue to lose blood supply, creating anaerobic environment for spore-forming, gram positive rod bacteria to infect injured muscle

Can be early onset or take 5-14 days

Adverse infection associated with hospitalized patients who have undergone recent surgery

treatment of fomites and close contacts

Clostridium perfringens C. novyi C. histolyticum Early? Think GAS or Clostridium GI or female GU surgery? Bowel flora Clean procedure? Skin flora (S. aureus, Strep sp)

Historically seen with war injuries but now associated w. blunt trauma

Rare (psychological burden?)

can use oral anti-parasitic if severe (ivermectin) Antibiotics that cover staph and strep (dicloxacillin, some cephalosporins- Cefazolin, Cephalexin; vancomycin- if MRSA; Unasyn --> Augmentin if from bite) NOT Bactrim! Penicillin DOC

clindamycin Unasyn (ampicillin + SulbactamIV) GAS, S. aureus, or anaerobic streptococci

Initially presents with cellulitis, blood-filled bullae, ecchymosis, systemic toxicity, elevated CPK

Superficial incisional (subq space) Surgical Site Infections (SSI)

Mineral oil prep? Mites with oval gray eggs and fecal pellets

Less common than cellulitis

Chronic

RED FLAGS: severe pain out of proportion w/ skin findings, large bullae, skin necrosis/ecchymosis, wooden hard feel of subq tissue, numbness of skin, systemic toxicity, rapid spread w/ AB tx

Previous cutaneous damage (trauma, ulceration, fissured toe webs, inflammatory dermatoses) Obesity Edema (venous insufficiency, lymphatic obstruction)

Histology? Mites (ovals) in stratum corneum

More common in infants/ children/ elderly

Acute

Monomicrobial

Nursing home residents Children Hospitals Close contact areas

NSAIDs Diabetes Venous insufficiency Completely normal hosts Abdominal Surgeries Decubitus ulcers Perianal ulcers Bartholin abscess IVDU h/o severe penetrating trauma or crush injuries

Inherent risk with clean contaminated, contaminated, or dirty-infected operative wounds

Possible CA-MRSA infection associated with worse outcomes

Extensive debridement, surgery Monomicrobial - clindamycin + penicillin G

Usually bacteremic 30-60% mortality

Polymicrobial - Ampicillin, clindamycin, and ciprofloxacin Aggressive surgical debridement XR shows edema and gas in soft tissue PCN + clindamycin

Prophylactic superficial antisepsis Perioperative ABs Incision & Drainage

Spontaneous (hematogenous) gangrene from Clostridium septicum in pts with GI malignancies or neutropenia

Disease Osteoporosis

Clinical Variants N/A

Defining Characteristics BMD T-score < -2.5, increased incidence of fractures

Pathogenesis

Etiologies

skeletal disorder characterized by compromised bone strength (bone density & bone quality- arch, turnover, mineralization, damage accum) predisposing a person to increased risk of fracture

Loss of bone trabeculae (microarchitectural deterioration)

With age, lose trabecular volume, #, thickness, connectivity

Genetic predisposition

Decreased estrogen is related to high bone turnover that results in stressful micro-cracks and loss of bone density

Estrogen deficiency activates immune response

Estrogen deficiency = oxidative stress in bone marrow = increased ROS = activation of T cells = increasd TNF = formation of osteoclasts and bone marrow stromal cells via RANKL

Epidemiology

Risk factors

Lab/Imaging

Age Postmenopause FH of osteoporosis

Treatment Low dose Ca/VitD Estrogen calcitonin raloxifene (estrogen Ag in bone, Antag in breast) Bisphosphonates -Alendronate, Zoledronic acid (Reclast)

Adjustable RF? Excessive alcohol sedentary lifestyle

Complications Long term bisphosphonate use causes increased BMD but increased fractures, increased osteonecrosis of jaw (rare) High dose calcium linked to CV events and vascular calcification

Anti-RANKL Ab - Denosumab

Increased RANKL

Anabolic agentForteo (teriparatide) - transient PTH = bone formation Odanacatib - Cat K inh Sclerostin Ab

Polyostotic Paget's disease Monostotic

Autosomal recessive infantile malignant (ARO)

Genetic predisposition (chrom 18, overlap w/ familial expansile 3 stage of localized, chaotic(mosaic) bone remodeling: misshaped legs/head, gait problems, progression over 1. osteoclastic activity osteolysis, p62 time,warm to touch; moth-eaten deteriorated bone, pitting of 2. mixed osteoclastic-osteoblastic activity, where osteoblasts try mutation- nl degrades pagetic bone; usually involves spine/ skull, most painful in to compensate with deposition of disorganized, RANKL signaling; pelvis/long bones hypervascularized lamellar bone Juvenile Paget's 3. exhaustive (burnout) stage (dense pagetic bone as mutated OPG) hearing loss, platybasia (softening at skull base--> headache hypercellularity of bone diminishes) w/ valsalva), Pagetic steal syndrome (shunt blood to ext Problem with osteclasts carotid, stroke-like sx), osteoporosis circumscripta (bone loss All results in deformity, fracture, metabolic derangement (inc #, size, nuclei, fx, around skull), leontiasis ossea (rare, enlarged facial/jaw bones), sensitivity to vitD); nl DIsorganized communication btwn osteoclasts and osteoblasts osteoblasts high output heart failure (coupled chaotic activity) possible involvement of slow viral inf Dense, brittle bone that fractures, bleeding/infections, hypersplenism, hemolytic anemia Count osteoclasts - RANKL mutation (low OC #) v. TC1RG1/ ClCN7 (nl OC #)

Osteopetrosis Autosomal dominant (Albers-Schonberg) (ARO)

Spine sclerosis with sandwich vertebrae (rugger jersey spine), variable penetrance/ severity Disproportionate (big head, small body), pectus excavatum, lumbar lordosis, nail hypoplasia (missing nails)

Pycnodysostosis

N/A Facial dysmorphism? Missing jaw look, large forehead, underdeveloped nose, asymmetry renal tubular acidosis, cerebral calcifications, hypotonia, weakness, mental subnl Phenotype less severe w/ age

Carbonic Anhydrase II deficiency

Progressive Diaphyseal disease

Camurati-Engelmann

Endosteal hyperostosis Sclerosteosis

Van Buchem

Worth type

Fibrodysplasia ossificans N/A progressive (FOP)

Osteomyelitis

Acute

Chronic

Hematogenous

gradual appearance of symmetric hyperostosis on periosteal and endosteal surfaces of long bones

Mutation in RANKL (rare) or ion pumps (TC1RG1, ClCN7) causes defective bone resorption and apoptosis of osteoclasts Mutation in TC1RG1 causes inability of osteoclast to secrete hydrogen ions into the bone matrix, thereby decreasing bone resorption

bactermic seeding of bone, swelling, long bones (kids), vertebrae (adults), periosteal abscesses in kids Long bones - fever, chills, malaise, soft tissue swelling and pain Vertebrae- neck/back pain, localized tenderness, low/absent fever, neurological deficits (epidural abscess)

Age 200,000 cases in U.S. (~3% prev) 5-20% w/ symptoms M>F

Bone scan? show sclerotic dz

Bone overgrowth due to Infancy loss of osteoclast resorptive fx Late childhood/ adolescence onset

Mutation in CAII renders the cell unable to generate protons from CO2 and H2O, causing loss of osteoclast resorptive function and generalized disease

Bone overgrowth due to loss of osteoclast resorptive fx

mutation in TGF-B1, a latency protein that is a normally a chronic sequesterer and inhibitor of TGF-B in bone

Unregulated TGF-B causes overstimulation Variable age, severity, of osteoblasts and course excessive bone formation

Osteoclast number, anemia labs

hypercalcemia tx if know pt will be immobilized

Bone marrow transplantation

Bacterial infection from localized ulceration/ trauma travel Diabetic osteomyelitis? Painless (due to peripheral neuropathy further to the bone in most DM pts) ulcer extending to bone, mild cellulitis, crepitance [If it probes to the bone, it's osteomyelitis]

hypercalcemia (immobilization)

Cranial nerve compression --> blindness, deafness

Fractures, osteomyelitis, possible nerve compression

XR? Dense orbital ridge, sclerotic skull base, hypoplasia of facial bones, dense vertebrae w/ preservation of TVP

Recurrent fractures in lower limbs

UA - check for RTA Measured in erythrocytes

Glucocorticoids for pain relief

Autosomal recessive inheritance

Deactivating mutation in SOST (Wnt inhibitor)

Dutch ancestry (Afrikaners)

Nl OC Possible inc alk phosphatase Possible optic atrophy, facial nerve palsy, deafness

Deactivating mutation in SOST (Wnt inhibitor)

Autosomal recessive inheritance

Mutation in LRP5, prevents binding of DKK1 (Wnt inhibitor)

Autosomal dominant inheritance

Patients usually die of R heart failure, Pulmonary HTN

Excessive BMP stimulation --> increased osteoblast formation

NO BIOPSY!!!! Require wheelchair by 3rd decade More common in kids

XR? Moth eaten appearance of bone

Ortho surgeries

Kids- S. aureus, GBS (infants), CoAN staph Elderly- S. aureus, Gram-

Nl OC Possible inc alk phosphatase

Assess response after tx with ESR, CRP

MOST common in kids IVDU - novel organisms in unique Adults - elevated ESR/CRP sites XR? Takes a while to show signs, but periosteal elevation, areas of demineralization, loss of sharp bony margins, moth eaten appearance, possible soft tissue swelling CT? sensitive Bone scan? Early dz (lots FPs) MRI? GOLD Standard! detects early changes & abnl soft tissu; adjacent vertebrae involvement

IVDU- S. aureus, P. aeruginosa, Serratia

Surgical debridement, drainage, obliteration of dead space, wound coverage Cure = resolution of signs and sx for >1y Kids - use AB that covers TB can cause Pott's disease in staph/strep (empirical) spine CT guided needle bx (adults) for Cx 4-6 wks AB tx MSSA- nafcillin, oxacillin MRSA- vanco, dapto Strep- PCN G, ceftriaxone, cefazolin Enteric GNs- Cipro, ceftriaxone Serratia, Pseudomonasceftazidime, cefepime, piperacillintazobactam Anaerobes- clinda, metronidazole Surgical debridement if necrotic

Contiguous

Osteosarcoma!! (10% of older pts) - but no inc in non-skeletal malignancy!

Death by 10y.o. if not treated

Sickle cell- S. aureus, Salmonella

increasing pain, skull/mandible/ small bones hand/ long bones/feet, mild fever, minimal drainage

Fractures

XR? Rugger jersey spine

Immunocomp - fungi IV DRUG USERS? Sternoclavicular joint, SI joint, pubic bones

Advanced disease? Use osteoporosis drugs (bisphosphonates, since they too kill osteoclasts)

Spinal cord/nerve root compressions

Autosomal recessive

untreated acute osteomyelitis

In presence of bacteremia, bacteria may get trapped in small end vessels. In kids, bacteria enter venous sinusoids of metaphysis in long bones via leaky capillary fenestrations. In adults, bacteria often seed in vertebral bodies (wellvascularized) or bugs can drain from Batson's venous plexus (from urinary tract)

XR? Pagetic flame lytic lesions, cotton wool skull, sclerotic + resorbed areas, inc Calvarian thickness), picture frame vertebral bodies (thick cortex frames lesion), fissure/chalk stick fractures (straight across)

sx? NSAIDs, COX2 inh, PT, surgery for fx

Pagetic bone is hemorrhagic so activity needs to reduced before surgery

gout (23% of pts w/ gout have paget's)

Mutation/defect in cathepsin K, so osteoclasts can no longer function properly in bone resorption

Disruption of Wnt signaling system causes decreased inhibition of Wnt, resulting in the inhibition of APC/GSK3 complex. Now, B-catenin is active and able to promote transcription of genes involved in osteoblast differentiation, Heavy bones! causing osteosclerosis Progressive asymmetrical enlargement of mandible (w/o Disruption of Wnt signaling system causes decreased dental malocclusion like osteopet), pain w/ point pressure on inhibition of Wnt, resulting in the inhibition of APC/GSK3 longbones complex. Now, B-catenin is active and able to promote transcription of genes involved in osteoblast differentiation, Heavy bones! causing osteosclerosis BMD T-score >0, no fractures, nl bone remodeling, flat forehead, Disruption of Wnt signaling system causes decreased elongated mandible, toras palatinus (bony protrusion of palate), inhibition of Wnt, resulting in the inhibition of APC/GSK3 benign presentation complex. Now, B-catenin is active and able to promote transcription of genes involved in osteoblast differentiation, Heavy bones! causing osteosclerosis Inflammatory swelling of soft tissues that eventually transforms into encasement of bone during first decade of life via Soft tissue swelling that progressively turns to bone esp at sites endochondral ossification of injury (avoid trauma!!); malformed great toe, progressive heterotopic ossification pattern; spares heart/ diaphragm/ Missense mutation of ACVR/ALK2 inactivates binding site for extraocular muscles inhibitor (FKBP12), causing excessive and constitutive BMP stimulation occurs rapidly over days-wks, new bone pain at site of inf, Infection of the bone via hematogenous entry, contiguous swelling spread, or inoculation via trauma

Occurs over weeks/months/yrs; necrotic bone w/ loss of vascular supply, swelling

Histology? Woven mosaic bone adult disease (~60y.o.)

Onset in infancy, early Bone overgrowth due to childhood loss of osteoclast resorptive fx Very rare!

TALL, heavy, Dutch ancestry, syndactyly, pain w/ point pressure on long bones

Elevated bone-specific alkaline phosphatase (overactive osteoblasts, >2x inc)

More common in people from British Isles, Caucasians

Most people are asymptomatic

Possible polymicrobial (see diabetic foot ulcer bacteria) Mixed gram+/-, anaerobes

MOST common in adults

Chronic skin ulcers (arterial sclerotic dz), trauma, diabetes, post-op ortho surgery, chronic edema

Imaging hard to interpret bc surrounding soft tissue inf

Revascularization

Bone scan sometimes reveals contiguous spread from ulcer site

Amputation/ surgical debridement

Bone sample for culture

Abs for 4-8wks (Avoid empiric ab tx)

Disease Septic arthritis

Clinical Variants

Defining Characteristics

Pathogenesis

Etiologies

Epidemiology

Acute bacterial swollen, hot, monoarticular arthritis w/ passive motion; less Generally hematogeous spread of bacteria or possible uncommon - fever/chills iatrogenic spread (joint injections for RA/OA) Chronic septic arthritis

Disseminated gonococcial infection (DGI)

Bactermic form: Dermatitis that coincides w/ pustules/papules that are sometimes hemorrhagic; centrifugic distribution, fever, tenosynovitis, polyarthalgia/arthritis

S. aureus Streptococci GN rods

Other infectious diseases causing arthritis

Mycobacteria (Tb) Lyme disease Fungi Rubella, mumps, parvovirus

Arthritis associated with gonococcal bacteremia

Neisseria gonorrhoeae

F>M declining incidence

Localized form: purulent arthritis (1,2 joints) Acute onset joint pain, effusion, erythema, warmth, fever

Prosthetic joint infection Early (2y)

S. aureus, Streptococci, Gram rods, enterococci, anaerobes, fungi (rare)

Ehlers Danlos Syndrome (EDS) Classical

Rising incidence w/ increased joint replacement surgeries

Risk factors Recent trauma (animal/ human bites) Immunocompromised RA/gout/sickle cell IVDU

Skin & joint hypermobility (Beighton's score >5 for joints), atrophic scarring (not well healed), easy bruising, smooth/velvety skin, hypotonia & decreased motor development

Sonication of removed prosthesis for cx

long term Ab (3-6m) for all Clinical exam for manifestations

1/5000 individuals; classical form is most common

Mutation in collagen type V (COL5A1, COL5A2), disrupting structural integrity of connective tissues

debridement and retention (stable joint w/ early inf)

Beighton score Autosomal dominant baseline echocardiogram for kids 2cm? Osteoblastoma Benign

Treatment

Dominant inheritance pattern

Pain in femur/tibia/vertebrae @ night, relieved by NSAIDs

Chondroma / Endochondroma

Lab/Imaging

Residual bits of cartilage that were displaced during development

XR? Popcorn calcifications Histology? Benign cartilage

Occurs when bits of cartilage from the physis that get incorporated into the bone begin to grow, producing a stalk in the bone

Histology? Cartilage cap, bone marrow inside

None - benign If cartilage cap >1cm, start to worry about development into chondrosarcoma (RARE)

Autosomal dominant disease XR? Benign polypoid projections from cortical bone Increased alkaline phosphatase XR? Lysis, blastic sclerotic bone, or even mixed; ill defined border (R/O osteomyelitis), elevated periosteum (periosteal rxn)

Kids: occurs around knee Adults: axial skeleton M>F

Neoadjuvant therapy (Chemo before surgery)

Histology? Periosteal rxn

Occur in the metaphysis, knee pain/swelling (loss of ROM),weight loss (disseminated), pathologic fx w/ nl activity

80% of metastases are to the lungs

Tumor resection, prosthesis MRI? Soft tissue extension CT? metastases

Trunk/pelvis/long bones; pain, swelling, resistant to radiation/chemo (low blood supply/growth), possible dedifferentiation (abrupt transition from low--> high grade tumor)

Chondrosarcoma

VERY VERY RARE M>F Adolescents/ young adults

XR? Popcorn calcification

Surgery only

Histology? "small round blue cell tumor"

Flat or long bones of young children

Translocation btwn EWS gene and FLI1 gene so ETS DNA binds at ETS DBD spot, causing loss of RNA recognitiion motif from EWS

Duchenne MD

Pseudohypertrophy (large calves), scoliosis, lumbar lordosis, protuberant abdomen, toe walking, Gower's sign, mental deficits

Caused by X-linked recessive mutation of dystrophin, resulting in absent (or nl expectancy

Most common MD, especially in children 1/3000 live births

Asymptomatic but affected mother --> drastic increase in trinucleotide rpts

Autosomal dominant defect in ryanodine

Nl CK because not a lot of muscle degen/regen Histology? Central cores appear as central/ eccentric areas of muscle fibers w/o oxidative enzyme activity

none

Known association w/ malignant hyperthermia- fever, muscle rigidity/necrosis, lactic acidosis (excessive Ca release)

Histology? Abnormal deposits of glycogen Diagnosis needed to treat pts and avoid recurrent hospital admissions for renal failure

nl CK and EMG; dx requires direct measure of muscle CPT or genetic testing

M>F

Maternal transmission, extra-muscular manifestations (in tissues/organs w/ high met rates) Furrowed brow, high-arched eyebrows Mitochondrial myopathy

Histology? Ragged red fibers representing abnl excess mitochondria

Abnormal amounts of mitochondria Progressive External Opthalmoplegia (PEO) - ptosis, opthalmoparesis MELAS - stroke CD4+ T cell and B cell response --> ischemic muscle Complement mediated injury ischemic muscle injury

1/100,000

Elevated muscle enzymes Myositis specific Abs (Anti Jo-1- worse prognosis, Anti Mi-2 -better prognosis)

F>M Kids (more calcinosis) & adults

DM = DZ of body attacking blood vessels around muscle, SYMMETRIC WEAKNESS OF PROXIMAL MUSCLES (usually causing watershed inflammation around muscle. lower extremities first, then upper extremities)

Increased risk of malignancy in +/-4 yrs before/after dx corticosteroids Methotrexate, azathioprine (LT) IV immunoglobulins

Bx evidence? Necrosis, upregulation of MAC around photoprotection blood vessels, regeneration, varied fibers, inflammation around blood vessel (not in the muscle fibers) (CD4+ T/B cells) XR? Calcinosis MRI? Muscle inflammation

Polymyositis

Proximal muscle weakness, no rash (more of just ruling out other myopathies…)

Cell mediated immune response within the muscle (endomysial inflammation) involving T cells & macrophages

Histology? CD8+ T cell/mo infiltration in NORMAL looking muscle!

Inclusion body myopathy

Most common acquired myopathy >50y.o; Distal and asymmetric weakness of finger/wrist flexors, knee extensors, ankle dorsiflexors

?

Histology? Centrally-placed nuclei, red-rimmed vacuoles (fibers w/ holes in them)

Toxic Myopathy

Myopathy from following "toxins": Alcohol, Statins, Colchicine, Glucocorticoids, AZT

Myopathies from systemic dz

Myopathy associated with following systemic diseases: Hypokalemia, Hypophosphatemia, Critical illness myopathy, or endocrine disorders (thyroid dz, parathyroid dz, adrenal disorders, hypopituitarism, acromegaly)

Polymyalgia Rheumatica N/A (PR)

Dx critieria: Persistent proximal pain (>1m) involving (neck, shoulders, pelvic girdle- 2), >1h morning stiffness, abrupt onset of illness (50, Rapid response to low dose prednisone, elevated ESR, absence of other disorders (flu, hypothyroidism)

Polygenic (environment & genetics)

Genetic component (HLA-DR)

Activation of innate immune system leads to elevated levels of Genetic polymorphisms NE descent: TNF in adhesion molecules & 20-53/100,000 in pts TNF >50 (less in Italians)

Pain perception thresholds decreased (abnl neurochem)

Fibromyalgia (FM)

Soft tissue pain disorder

F>M Extremely unlikely in pts >M (10:1)

Elevated ESR/CRP Thrombocytosis (hi platelets) Nl CPK Anemia of chronic dz Negative ANA, RF

Corticosteroids

First degree relatives w/ FM (8x higher risk!) Mutations in serotonin gene

No anemia Nl CPK, aldolase Nl ESR/CRP Nl thyroid studies Negative ANA, RF

Pt education Anti-inflammatory/ analgesic meds (not better than placebo) AVOID NARCOTICS tricyclics (muscle relaxant, antidep) Serotonin reuptake inh Lyrica (decrease perception of pain) FITNESS TRAINING! (low impact aerobics and muscle strength)

Interstitial lung disease Diaphragm/ intercostal weakness --> resp arrest Cardiac rhythm disturbance

Disease

Clinical Variants

Defining Characteristics

increased angiogenesis to joint space, Hyperplastic synovia, hypertrophic synoviocytes, painful overgrown synovia (PANNUS) Morning stiffness (>1h), 3+ joint arthritis, hand joint arthritis, symmetric, rheumatoid nodules (extensor surfaces, pressure points), +RF, XR changes [4/7 criteria for 6+ wks to R/O inf]

Rheumatoid Arthritis

Fusiform swelling, SPARES THE DIP JOINT!

Pathogenesis

Etiologies

Epidemiology

Risk factors

Lab/Imaging Clinical exam? Prodrome malaise/fatigue, stiffness that improves w/ activity, non-reducable deformities (swanneck, boutonniere, trigger finger, MCP subluxation, ulnar dev, hammer toes)

Aberrant immune response in genetically predisposed person leads to synovial inflammation and destruction of the joint Genetic & environmental factors--> innate immunity->macrophages--> T cells through TNFa and osteoclasts through RANKL; when DCs get to lymphoid organs, they activate T/B cells that release inflammatory factors/antibodies into the joint. Cytokines, Proteinases, cathepsins responsible for joint destruction. RANKL increases osteoclasts causing bone erosion.

Prev? 1% of pop F>M (2.5:1) Peak onset? 35-50y.o. RA in men 2000 WBCs in joint fluid XR? periarticular osteopenia, uniform narrowing around joint, marginal erosions, C1-C2 subluxation, ulnar dev

Systemic sx (fever/malaise, poor energy, weight loss, tissue damage in other organs)

Treatment

NSAIDS DMARDS: -Immunosuppressants (MTX, leflunomide, azathioprine) - secondary agents (hydroxychloroquine, glucocorticoids) -TNFa antagonists (Etanercept, Infliximab, Adalimumab, Golimumab) -IL-1R Antagonists (Anakinra) -T cell costimulatory blockers (Abatacept) -Combo tx

W/ age, side chains in cartilage shrink and hold less water = less resilience & more dessication = stress fx & fissures

Osteoarthritis

Degenerative joint disease

Use-related pain, loss of ROM Morning stiffness shortened proteoglycans (less H2O retention)

Focal loss of articular cartilage followed by hypertrophism of underlying bone and formation of osteophytes at joint margin

Older individuals

Trauma Infection Crystsal dz Neuropathy

Nl ESR/CRP/platelets Nl hematocrit F (5:1)

Hyperuricemia --> tophi (uric acid deposition that are engulfed by granulocytes) --> inflammation (NALP3 inflammasome)--> lactate production & pH drop --> formation of more crystals --> more inflammatory cells recruited --> renal damage if deposited on tubules

Risk factors

>6.7mg/dL solubility of monosodium urate crystals Paget's, Psoriasis certain cancers excessive alcohol intake Co-infection of joint

Lab/Imaging

Complications

NSAIDs- Indomethacin (acute pain relief) ALWAYS TAP JOINT & CULTURE FLUID! (yellow parallel crystals) XR? Nl mineralization, punched out erosions w/ sclerotic borders, overhanging edges

Age onset? M 40-50; F postmenopause

Unclear but thought to be of 2 mechanisms: 1. Autoantibody-mediated inflammation (autoantibodies form immune complexes that drive complement consumption, Chronic inflammatory causing inflammation) F>M (9:1) systemic autoimmune Peak incidence ages 15dz characterized by anti40y.o. 2. Autoantibodies to phospholipids produce nuclear autoantibodies hypercoaguble state and clots (antiphospholipid syndrome thrombosis, pregnancy morbidity, anti-cardiolipin Abs, paradoxical prolonged PTT)

Treatment

Colchicine (acute pain relief, prophylactic w/ LT meds) Probenecid (chronic gout)

Initial tx for chronic gout can actually increase the severity/freq of acute attacks so take prophylactic colchicine simultaneously

Allopurinol (chronic gout)

Rashes? Topical steroids Joint pain? NSAIDs FH (mostly sporadic tho) Environmental factors (uv light, drugs, infections, smoking, silica) Positive ANA, anti-RNP, anti-Ro/La, positive direct Race - A.A., hispanics Coombs, low complement

Others? Antimalarials (hydroxychloroquine)

Accelerated atherosclerosis

Systemic corticosteroids for serious complications

Prev? 1/2000

Immunosuppressants for steroidresistance

Chronic fatigue! Raynaud's periungal erythema Cutaneous vasculitis (palpable purpura) Seen w/I first few months of life Neonatal lupus

Mom w/ lupus

erythematous pathces that form blanchable rings on head/neck

Drug-induced lupus

Lack skin findings, systemic arthalgias/inflammation

Thrombocytopenia Anti-rho antibodies

congenital heart block

Positive ANA

induced/triggered by procainaminde, hydralazine, quinidine

Scleroderma (SS)

Major organ involvement!

(General)

proximal scleroderma (hardening of skin) extensive fibrosis, sclerodactyly (skin tightening due to fibrotic changes --> ischemia & pitting of fingertips--> autoamputation) facial disfigurement (microstomia - pursed mouth, lip retraction, beaked nose) mat telangiectasias dilated capillary loops at proximal nail folds leukoderma (salt&pepper skin), calcinosis

Unclear but key features? Endothelial cell damage (vascular injury), inflammation precedes fibrosis, excess deposition of collagen by fibroblasts --> all lead to impaired fx of skin, lungs, affected organs Autoimmune mediated diffuse fibrosis of skin & internal organs

F>M Cell mediated and humoral immunity

Lung impairment (dyspnea on exertion, cough, pulmonary fibrosis)

Positive ANA, Anti-Scl-70 (nucleolar pattern ANA), Anticentromere

Onset age? 30-50y.o. (somewhat older than lupus)

XR? Bone resoprtion of digits, subcutaneous calcinosis

Widemouth diverticuli Watermelon stomach (telangiectases in stomach) pericarditis, arrythmias

Widespread skin involvement & rapid progression

Diffuse

Pulmonary fibrosis (caused by fibrosing alveolitis, pulmonary vasculopathy)- early onset

PFTs detect poor gas exchange XR? Interstitial fibrosis CT? ground glass opacities in lung

Crackles w/ inhalation Onset of skin changes w/I 1 year of Raynauds Truncal & acral skin involvement

SRC histology? Sheared RBCs, narrowing of lumen, wall fibrosis SRC - anti-RNA pol III

SRC? ACE inh GERD? PPIs MSK? NSAIDs, PT, low dose steroids (but watch renal!) Raynauds? Smoking cessation Lungs? Heavy immunosuppression

Anti-Scl-70 Ab

Dysphagia, GERD (from fibrotic esophagus) Scleroderma renal crisis (SRC) malignant hypertension, renal insufficiency, microangiopathic hemolytic anemia - tx ACE inh

Tendon friction rubs Localized skin involvement (distal/upper extremities), nail fold involvement, slower pace of progression Limited (CREST)

Anti-centromere Abs Calcinosis, Raynaud's (long duration), Esophageal dysmotility, Sclerodactyly, Telangiectases

Localized cutaneous SS

morphea (erythematous plaques that are proximal, skin discoloration/firmness/induration)

GERD? PPIs MSK? NSAIDs, PT, low dose steroids (but watch renal!) Raynaud's? Smoking cessation PAH? Oxygen, calcium channel blockers, prostacyclin derivatives

Pulmonary hypertension (no fibrosis) - later onset Dysphagia, GERD (from fibrotic esophagus)

Histology? Nl epidermis but extensive collagen deposition & loss of epidermal appendage structures

Scleroderma + one or more features of other connective tissue disease Overlap syndromes

Anti-RNP Abs Mixed connective tissue disease (MCTD) - SLE, SS, polymyositis, & positive anti-RNP NSAIDs & glucocortocoids for pain & inflammation Chronic inflammation causes bone formation and erosion --> fusion of joints (ossification of annulus fibrosus in vertebrae) Axial arthritis (bilateral sacroilitis, spondylitis), arthritis of girdle joints, acute anterior uveitis (inflamed iris), extraskeltal manifestations (aortic insufficiency, conduction abnl, decreased chest wall expansion, spinal cord compression, cauda equina syndrome)

Ankylosing Spondylitis

Loss of nl spine curvature & ability to flex Symptoms progress upwards (start in SI joint --> cervical spine)

Molecular mimicry impt- genetically susceptible person w/ HLAB27 is exposed to unkwn antigen that causes an immune response that exhibits cross-reactivity w/ self tissues, causing clinical expression of spondyloarthropathy (joint dz of vertebral column)

Immunosuppressants only help peripheral arthritis TNF inhibitors relieve axial arthritis

M>F Age onset? 20s

HLA-B27

XR? Fuzzy, hard to trace bone margins of SI joint, bamboo spine (syndesmophytes- new bone formed in inappropriate location cause fusion through T-spine)

HLA-B27

XR? Pencil and cup formation (peripheral phalynx whittled down to pencil joint and distally has extra bone formation to where it looks like a cup), erosion of entire bone in digit (telescoping), excess bone formation near where tendon would insert (enthesitis evidence)

High levels of TNFa in SI joints, peripheral joints, & serum of affected pts. Enthesitis = primary hallmark of Spondyloarthropathies; causes dz bc 1.Inflammation, 2. Deregulated osteoclast activity --> bone erosion, 3. dysregulated endochondral bone formation at sites of enthesopathy, causing syndesmophyte formation

Classic - DIP joints of hands & feet Arthritis mutilans w/ sacroilitis

Psoriatic Arthritis

Peripheral polyarthritis (symmetrical), asymmetrical sacroilitis & spondylitis, dactylitis (sausage digits- PIP swelling & inflammation), arthritis mutilans (teloscoping digitsjust skin bc bone has been eroded away), conjunctivitis, iritis, Asymmetric, pauciarticular (90%) Staging - 0 (tumor in epidermis), 1&2 (thicker but limited to skin), 3 (LN), 4 (metastatic, systemicmedian survival of 7.5m) Emphasize prevention (sunscreen, protective clothing, avoid mid-day sun, self-skin exams, TBSE, vit D supplemenation)

Need to talk to parents about how size of congenital nevi can affect risk for development of MM; surgical options (staged removals, grafting); monitor CHANGES in lesion

Screening / Education

Oral form of Mucus Membrane Pemphigoid has better prognosis (very little scarring)

Pretty good prognosis with treatment

Worrisome in diabetics or pts with autoimmune dz

Screening / Education

Prevention to avoid recurrenceAntibmicrobial washes, bleach bathes

Avoid gross hot tubs!

Prevention (bleach baths, treating chronic carrier state w/ nasal Ab creams)

Prevention (bleach baths, treating chronic carrier state w/ nasal Ab creams)

Examine (& possibly treat) home/school for infected contacts!

Screen for STDs in young adults

Avoid skin-skin contact during active outbreaks

Prevention with immunization w/ zoster in people > 50y.o.

GAS/GBS screening for women undergoing C/S

Screening / Education Adjustment of risk factors (excessive alcohol, sedentary lifestyle)

Prophylactic bisphosphonate treatment prior to surgery!!!

Screening / Education

Stay active!!

Screening / Education

Diagnosis is impt in case patient needs surgery ever- need to be aware of risk for malignant hyperthermia w/ anesthesia

age/gender appropriate cancer screening

Screening / Education

Screening / Education

Avoid sun exposure, use sunscreen!

Counsel on posture, stretching, spinal extension exercises high risk for traumatic fractures

Screening / Education

Disease

Clinical Variants

Defining Characteristics tachypnea, hypoxia hydrostatic pulm edema: fluid accumulates in low P, hi comp areas (perihilar interstitium, alv interstitium, alveolus); bronchospasm seen more commonly, sx of congestive heart failure, cardiac dysfxn, fluid overload, NO PREEXISTING ACUTE TRAUMA

Pathogenesis

Etiologies

Thickened membranes =  diffusion; LV heart failure (MI, chronic CHF), renal failure, Hydrostatic edema (most common): Increased hydrostatic IV fluids pressure (due to LV heart failure) injury to capillaries = Pulm edema --> backup of (free radicals, fluid into pulm vasculature --> chemicals) blood vessel distention by Jreceptors --> tachypnea Starlings law reasons for edema: Permeability edema (more  gradient btwn severe): direct injury to capillary & capillaries (ALI, ARDS) capillary leakage into interstitial interstitial hydrost permeability pulm pressure;  edema: diffuse leakage of space overflows the alveolus gradient btwn with proteinaceous fluid (can fluid (patchy, bilateral interstitial fluid & be caused by pneumonia, accumulation), aspiration, inhalation, sepsis, oncotic press,  gravitational gradient (more edema at base);  trauma, pancreatitis, transfusion) leakiness of capillaries;  protein leakage; acute lymphatic flow inf, no CHF

Pulmonary Edema

Obstructive lung disease

Emphysema, chronic bronchitis, asthma

Restrictive lung disease

Parenchymal lung reduced lung volumes disease (interstitial lung dz); nonparenchymal (chest wall disorder; muscular weakness; less shifted towards RV)

abnl accumulation of fluid in the lung outside of the vasculature

severe dynamic compression --> hyperinflation as a compensatory mechanism to get more air out allows increased lung recoil so lung can expel more air; destroyed alveoli--> decreased functional space & DLCO

Risk factors

Lab/Imaging

Hydrostatic: risk CXR: Hydrostatic: factors for heart bilat interstitial dz markings @ basal lung/ perihilar area; Kerly's B lines (horizontal lines towards edge of XR), enlarged heart; Permeability - patchy, asymm infiltrates, nl heart histology: Hydrostatic - alv spaces filled w/ pink edema, nl anatomy; permeability: dense liver appearance, abnl anatomy, heterogenous patchiness,RBCs/ WBCs, separation of interstitium w/ protein coat (pink hyaline membrane)

ability to move air out of lungs is impaired so takes longer

PFTs: FEV1/FVC70 FEV1/FVC; FVC, FEV, spirogram shows no late vol changes/ rapid upstroke, flow-volume has VC, volumes shift towards RV neuromuscular dz: somewhat higher RV, low IC PFTs: FVC nl/, FEV1 nl, FEV1/FVC nl, TLC nl/, RV nl, DLCO 

pulmonary vascular disorder

Central Airway Obstruction

Epidemiology

Extra-thoracic obstruction Plateau on inspiration; disease/ obstruction outside of the lung

Equal pressure point has variable migration depending on transmural pressure; reduced airflow during inspiration (-)P inside the airway sucks trachea walls in while Patm around trachea pulls airways closed)

Patm > Paw during inspiration reduces airflow and causes aw collapse; nl expiration

Tracheomalacia, PFT: Plateau in insp laryngeal limb paralysis, laryngeal edema, tracheal strictures from ET tube, tracheal stenosis, OBESITY

Treatment Resolution? Hydrostatic: intact alv epithelium pumps fluid out w/ Na/K ATPase; tx underlying cause;

Permeability: alv epithelium injured so takes longer to resolve; tx primary injury cause, manage fluid balance, supportive care

Complications increased hospital stay (leading to other comorbidities) and high mortality for permeability edema

Disease

Clinical Variants Intra-thoracic obstruction

Defining Characteristics Plateau on expiration

Pathogenesis

Etiologies

Equal pressure point has variable migration depending on transmural pressure; reduced airflow during expiration

Ppl > Paw during expiration reduces airflow and causes aw collapse; nl inspiration asthma

Epidemiology

Risk factors

Lab/Imaging

Tracheal lesions, PFT: plateau in exp tracheal tumors, limb tracheomalacia, tracheal inflammation, mediastinal lymph nodes

Treatment

Complications

Disease

Clinical Variants Fixed lesion

COPD

Emphysema (blow a balloon up and release it? No air flows out bc loss of elastic recoil)

Defining Characteristics Plateau on inspiration & expiration

Pathogenesis

Equal pressure point migrates independently of location/ pressure relationships Airflow limitation that is exposure to smoke = activation of alveolar macrophages = not fully reversible, release of chemotactic factors = progressive, and recruitment of D13 = release of associated w/ abnl inflammatory response proteases (presence of protease inhibitors less effective due to to noxious tobacco) = destruction of particles/gases alveolar wall hyperinflation of lungs (low diaphragm position, Alveoli destruction = VQ hyper-resonance, distant mismatch, alveolar ventilation, breath/heart sounds, tetherings that support airway = barrel chest), dypsnea or  dynamic airway acute chest illness compression = abnl (initially DOE but then enlargement of small airways starts to affect DALYs), (bullae = sac-like wheezing, prolonged abnormalities) expiratory time, Severe (pursed-lip breathing, problems with driving pressure accessory muscle use, (decreased elastic recoil) retraction of intercostal and/or airflow resistance spaces), tripod position

A1AT deficiency panacinar emphysema

DOE, cough, wheezing, early presentation

Chronic bronchitis

typically presented as overweight, cyanotic, edematous, productive cough, dyspnea at rest

Etiologies

Epidemiology

Risk factors

large tumor

Subglottic stenosis, goiter, tracheal stricture hyper capillary surface #4 mortality in responsiveness, area =  diffusion; world & USA lung growth, cell mediators? F>M exposure to Epithelial cells, tobacco smoke/ macrophages, middle aged occupational CD8+ (TH1), (~50y.o.) dusts & chems/ neutrophils infections/ SES SMOKING (USA) develops in about nutrition 15% of smokers Air pollution (global) decreased elastic recoil

A1AT def (protease inhibitor that most common prevents destruction of alveolar phenotype? PiZZ wall)--> loss of a1 globulin (Z allele is a single point mutation that causes severe dz)

exposure to smoke = activation SMOKING of alveolar macrophages = release of chemotactic factors = loss of elastic recruitment of neutrophils = recoil release of proteases (presence of protease inhibitors less chronic productive cough for 3 consecutive effective due to tobacco/infection) = mucus months for 2 hypersecretion consecutive years

Lab/Imaging

Complications

PFT: plateau in exp & insp limbs PFT: see obstructive dz; lung vol (TLC & RV, inspiratory capacity), DLCO all persons >45 y.o. w/ chronic cough/ sputum production & exposure/ risk factor hx should be tested for airflow limitation (even if no dyspnea) spirometry = gold std CXR:  retrosternal air space ( lucency), flat diaphragm, bullous changes, hyperinflation CT R/Os alt dx

alpha1antitrypsin deficiency, FH of A1AT def, smoke, dust, kerosine, PiSZ smokers

Treatment

management? Prevent dz progression, relieve sx, improve ex tolerance, improve health status, prevent/ treat exacerbations, reduce mortality drugs generally less effective Short acting bronchodilators (Bagonists - albuterol, levalbuterol, metaproterenol, pirbuterol; anticholinergics like ipatropium)

long acting bronchodilators (Bagonists - salmeterol, CXR: radiolucency in formoterol) base of lung (vs. diffuse sometimes emphysema in other phosphodiesterase variants) inhibitors (theophyline, roflumilast) PFT: see obstructive dz responds poorly to meds

anti-inflammatory inhaled steroids (fluticasone, budesonide, mometasone) home O2 if hypoxemic (prevents cor pulmonale)

hoarseness = common side effect of steroids Could require oxygen, pulmonary rehabilitation, lung volume reduction surgery, and/or lung transplantation cor pulmonale

Disease Asthma

Clinical Variants

Defining Characteristics

exercise-induced asthma Airflow obstruction (15-30min post exercise- (wheezing, prolong forced short sprints; vagal reflex) expiratory time), lung hyperinflation (low allergic asthma diaphragm position, hyperresonance, distant nocturnal asthma (vagal heart/breath sounds) reflex) severe disease? Accessory resp muscles, immediate Type I IgE retraction of intercostal mediated spaces bronchoconstriction chronic, inflammatory airway dz w/ recurrent sz (esp @ night, early AM; widespread/ varying obstruction;

Pathogenesis hygiene hypothesis: early exposure to infectious agents= TH1 response= suppression of TH2 activation=  allergy /asthma frequency; people less likely to be exposed to these infections today= TH2 cells mediate onset of asthma Airway remodeling occurs in pts w/ uncontrolled chronic asthma (older pts) morphological changes in asthma (hyperplastic mucus gland/goblet cells, infiltration of inflammatory cells, thick BM, edema, fibrosis, epithelial damage) = Smooth muscle hypertrophy = reversible bronchoconstriction, hyperresponsive airflow limitation

Etiologies inflammatory cell mediators? Epith cells, mast cells, CD4+ (TH2), eosin, IL4, IgE, Factors contributing to severity? Environmental (animal/insect/ mold/outdoor allergens), occupational exp, indoor/ outdoor pollutants, foods/ preservatives, certain meds, infections, immunotherapy cold= vagal reflex = ACh = bronchoconstriction

Epidemiology

Risk factors

Lab/Imaging

Treatment

PFT: exp arm has concavity; FEV1/FVC 1 exudative Cell types: Neutrophils? inf/symp causes; Lymphocytes? cancer, TB; RBCs: hemorrhagic (malignancy, TB, PE, trauma), hemothorax

decreased pleural pressure (atelectasis, trapped lung) - fluid moves into lung

Hepatic hydrothorax

Lab/Imaging

Collapse of alveoli or partial lung --> VQ mismatch hypoxemia (perfusion, low ventilation) OR R->L shunt hypoxemia

either spontaneously resolves or persists (if persists, leads to interstitial fibrosis) Pleural effusion

Risk factors

liver related pleural effusion due cirrhosis, liver to high portal pressure (from failure cirrhosis usually)

diuretics

do not attempt pleurodesis!!

Beta blocker to decrease portal pressure

ascites RUQ

transplant

Parapneumonic Effusions (PPE)

Exudative pleural effusion no bacteria or pus in pleural fluid

Pleural effusion ipsilaterally Pneumonias associated with underlying pneumonia; due to inflammed visceral fluid (inc fluid prod, less resorption) 3 stages: 1. exudative: inflammatory/ capillary leakage, tx w/ Abx 2. fibrinopurulent: loculations, requires chest tube drainage 3. organized: scarring, pleural peel formation, requires surgical decortication

40% of bacterial pneumonia develop PPE

Thickened visceral membrane (makes lung expansion difficult)

Antiobiotics for exudative stage; chest tube drainage for fibrinopurulent stage; decortication for organized stage

complicated bloody surgical procedure

Disease

Clinical Variants

Empyema

Malignant Pleural effusion

Defining Characteristics

Pathogenesis

Etiologies

Epidemiology

Exudative pleural effusion Infection (collection of pus) in pleural space

Exudative pleural effusion

Risk factors

Lab/Imaging

Treatment

Complications

CXR: distinguish from Drainage neoplasm (which always appears spherical) - empyema will look different based on viewing position

hematogenous metastases to parietal pleura

2nd most common cause for exudative effusion

cancer cells erode through visceral pleura

Thoracentesis: gross pus or positive gram stain, pleural fluid cultures (always low pleural fluid cytology

pleurodesis

positive in 60-80%

high recurrence rate, usually represent an advanced malignancy

possible pleural bx

cancer cells occlude lymphatics

Chylothorax

Exudative pleural effusion

disruption of thoracic duct or LN dissection; represents high lipid content in pleural space

trauma or CANCER!

turbid, milky white pleural effusion; does not smell (empyema), no pus

Pulmonary Arterial PAH Hypertension (PAH) (WHO Group 1)

mPAP >= 25 PWP M (2:1)

Treatment see PAH

natural hx? Pre-symptomatic (RV hypertrophy to compensate for increased PVR, allows CO to keep up), symptomatic (vascular remodeling causes decreased CO, while PAP & PVR continue to increase), declining (loss of PAP = declining CO & cor pulmonale)

shared similarities with PAH

venular proliferation on postleft-sided capillary side (left heart) leads to predominant dz narrowed lumen of small pulmonary veins --> development of pulmonary infiltrates, edema, severe hypoxemia

see PAH

mPAP >= 25 PWP > 15

increased mPAP and PVR due to vasomotor constriction or pulmonary vascular remodeling

no meds approved for this population

severely decreased DLCO

chronic hypoxemia leads to shunting of blood away from non-ventilated areas and increased backflow to RV (L-R shunt); increases vasoconstriction of pulmonary arteries

see PAH

DOE after asymptomatic period of months - years

uncommon, subacute manifestation of pulmonary embolic disease that evolves via proximal pulmonary artery obstruction from failed clot resolution --> remodeling to increase pressure backflow to RV

(WHO Group 1')

Pulmonary arterial hypertension from Left heart disease

Pathogenesis

(WHO Group 2)

Pulmonary arterial hypertension from lung disease/ hypoxia (WHO Group 3)

Chronic Thromboembolic Pulmonary HTN (CTEPH) (WHO Group 4)

COPD, ILD, mixed restrictive/ obstructive lung dzs, sleep apnea, alveolar hypoventilation disorders, chronic exposure to hi loss of pulmonary vasculature altitudes, (COPD) increases workload for developmental abnl remaining vessels

incidence of CTEPH happens w/I 2y of acute VTE

younger age, larger PE, idiopathic VTE, hx of previous PE

10% of pts have antiphospholipid antibody syndrome

only PAH that is curable!! (pulmonary thromboDx requires VQ scan endarterectomy) (shows areas of mechanically dissect mismatched flow) clot off the artery

Complications High mortality without treatment (median survival 2.8 yrs) - cor pulmonale

Disease

Clinical Variants

Defining Characteristics

Pulmonary arterial hypertension w/ unclear or multifactoral causes

Pathogenesis

Risk factors

Lab/Imaging

Treatment

Complications

Chronic myeloproliferative dz, splenectomy, sarcoidosis, LAM, pulmonary langerhans cell histiocytosis, glycogen storage diseases, hyper/ hypothyroidism, end stage renal dz

see PAH

Diffusion-perfusion impairment = overdistention of capillary = RBCs escape w.o oxygen traveling to other side (bc capillary is too wide) = R-L shunt hypoxemia (PVR is too low!!)

Liver disease (causes vasodilation & capillary overdistention)

supplemental oxygen can cause R-->L shunting w/ severe pulmonary vascular dilation

Hepatopulmonary syndrome

Secondary to liver disease

Hyperventilation / Hypocapnia

increased effective minute Brain: hypocapnia --> ventilation = PaCO2 < 35 vasoconstriction --> (hypocapnia) hyperexcitability of neurons and poor perfusion to brain --> seizures neuro signs (seizures, syncope, visual changes, demand, dizziness), CV signs (arrythmia, chest pain), O2 delivery = electrical increased work of abnormality --> arrythmia breathing, dypsnea, muscle weakness, Lung: hypocapnia --> smooth parasthesias, carpopedal muscle contraction and mucus spasm, tetany, NO edema (stiffer, more resistant) -> HEADACHES hyperventilation, dypsnea & work of breathing nl/ hi pO2, nl pCO2 w/ sleep-psych hypervent

decreased effective minute ventilation = PaCO2 > 45 (hypercapnia)

Epidemiology

miscellaneous diseases that all cause PAH

(WHO Group 5)

Hypoventilation / Hypercapnia

Etiologies

hypoventilation = acute CO2 = pH = O2

Physiologic causes? Hypoxia, acidosis, irritants (P.E., inhalants), CHF (J-receptors) Non-physiologic causes? Pain, anxiety, psychogenic

NOT related to RR

treat underlying disease, brown Diagnostics? paper bag Pregnancy test, ABG (increases blood (pH, pO2, HCO3-, CO2 because closed pCO2), kussmaul system), breathing (slow deep reassurance, breathing classic in sedation? acidosis)

sepsis, PE, pregnancy

Brain: congenital central hypoventilation (hirchsprung's dz), chronic hypercapnia? pH  w/ hypothyroid, time, kidney compensates w/ central alveolar HCO3;  RBCs (polycythemia), sedatives/narcotics hypoventilation? No  baroreceptor sensitivity (high / benzos, anesthesia, dypsnea, hypoxemia PCO2 causes less minute secondary to hypercapnia ventilation than expected); rely Ondine's curse; on secondary drive to breath muscle & PNS: ALS, MG, MD, neuromuscular (hypoxia) kyphoscoliosis, hypoventilation? obesity Orthopnea (loss of 2° consequences? -HCO3, hypoventilation diaphragm fx), cor cerebral vasodilation syndrome; lung: pulmonale (terminal (headaches), sleep arousal COPD, Asthma, event) (sleep disturbance, bronchiectasis, somnolence), Hb desaturation/ pulm fibrosis erythropoiesis (cyanosis, polycythemia), pulm common cause for vasoconstriction (pulm HTN, cor resp acidosis? pulmonale) DRUGS, stroke

Central cause? Nl PFT, nl muscle fx, impaired hypoxic drive (problems with unconscious breathing only) Neuromuscular cause? FEV1, FVC, TLC, RV (restrictive pattern), weak muscle fx (low pressure, forces, MVV), rapid shallow Lung dz cause? obst/rest pattern on PFT, nl muscle strength but low MVV/endurance; hypoxic drive alone w/ chronic hypercapnia

Respiratory acidosis? Correct w/ drug antagonist, intubate Central alveolar hypoventilation? Respiratory stimulants, diaphragmatic pacing, nocturnal ventilation neuromuscular? NO stimulants, tx underlying condition, nocturnal ventilation pulm? Treat underlying dz, careful O2 supplementation, nocturnal ventilation

do not give supplemental oxygen to patients with chronic hypercapnia (only drive to breathe is hypoxia!!)

Disease Hypoxemia

Clinical Variants

Defining Characteristics

Pathogenesis

FIO2; hypoventilation; diffusion impairment; VQ mismatch; shunt (RL), altitude induced hypoxemia

General

hypoventilation induced hypoxemia

Etiologies

PaCO2 > 45 mmHg; nl A- elevated PaCO2 means there is extra-pulmonary less amount of O2 in the causes a gradient, responds to alveolus = less O2 that will move increased FiO2 from alveoli to pulmonary capillary = hypoxemia; no abnormalities in gas exchange

VQ mismatch hypoxemia increased A-a gradient, nl PaCO2 (unless severe hypoxemia), respond to increased FiO2

disease process causes amplification of VQ mismatch, where composition of alveolar gas varies in different lung regions, causing hypoxemia

hi ventilation, low perfusion (PE)

Right to Left Shunt hypoxemia

blood moves from right side of heart to left side of heart without being oxygenated (extreme form of VQ mismatch)

anatomic shunt (intracardiac shunts, pulmonary AV malformations, hepatopulmonary syndrome)

severe hypoxemia that is not readily fixed with increased FiO2, increased A-a gradient, nl PaCO2

low ventilation, hi perfusion (pneumonia, PECHF, ALI/ARDS, atelectasis, pulmonary fibrosis, COPD)

physiologic shunt (atelectasis, pneumonia, ALI/ARDS) Diffusion limitation hypoxemia

increased A-a gradient, exercise-induced hypoxemia, usually responds to FiO2 increases

difficulty moving the oxygen out of the alveoli and into the pulmonary capillary exercise-induced hypoxemia? Blood moves faster during exercise, so not enough time for O2 to diffuse from alveoli to capillaries; nl there are compensation mechanisms (dilate cap surface area, increase alveolar O2 content) but in these patients, compensatory mechanisms are impaired

interstitial lung disease, pulmonary fibrosis

Epidemiology

Risk factors

Lab/Imaging

Treatment

Check A-A gradient

usually corrects with small doses of O2 (FiO2); correct with drug antagonist (opoid antidote)

patients respond to increased FiO2

Complications

Disease Acute respiratory failure (ARF)

Clinical Variants

Defining Characteristics

Acute lung injury (ALI) defining criteria? Acute respiratory distress syndrome (ARDS) Acute onset post "at risk" dx Bilat infiltrates on CXR PaO2/FiO2 respiratory load = No LA HTN (no evidence worse alv ventilation = lung of CHF) compliance (low compliance means more pressure required to make a change in vol)

Pulmonary hypertension

Pulmonary embolism

Pathogenesis

loss of capillary volume

chest pain, dyspnea, apprehension, syncope, cough, hemoptysis, sweats

Large clots increase the pressure of RV, which cannot compensate to acute changes in pressures --> enlargement of RV --> decreased preload & contraction of LV (can't fill anymore) --> decreased CO virchow's triad

Etiologies nl CXR? Possible causes = CNS event (stroke, drug OD, head injury), neuromusc dz, airway obst (asthma, COPD), PE abnl CXR? Possible causes = ALI/ARDS, aspiration, pneumonia, hydrostatic pulm edema, obst lung dz (nl/abnl CXR), PE (nl/abnl CXR), pneumothorax

Epidemiology

Risk factors

Lab/Imaging

at-risk dx? Direct lung injury (aspiration of GI contents, pulmonary contusion, pneumonia/ sepsis); indirect lung injury (nonpulm sepsis, abdominal trauma, multiple fx, hypertransfusion)

3003 pts = high risk (75% chance of DVT), 1-2 pts (moderate risk),