INFECTIOUS
Disease Image Agent Description/Distribution Risk Factors/Epidemiology Pathogenesis Lab Tests/Dx Tx
IMPETIGO
Staph Aureus OR Streptococcus pyogenes
• Superficial • Begins as pustule •HONEY-CRUSTED
• occurs around face esp around nares
•50–70% of cases are due to S. aureus, with the remainder being due to either S. pyogenes or a combination of these two organisms •Group B streptococci are associated with newborn impetigo
• predisposing factors: minor trauma, pre-existing skin disease, poor hygiene
• Streptococci may be early pathogen w/ staphylococci replacing streptococci as the lesion matures
• s. aureus: exotoxins and coagulase
• topical tx: bacitracin or mupirocin • be sure to treat around nares to prevent shedding
BULLOUS IMPETIGO
Staph Aureus • Of all impetigo 30% results in bullous impetigo.
• Blisters occur at site of infection of Group II phage type 71 Staph aureus
Exfoliative toxins (ETs): act as serine proteases and can cleave human desmoglein 1, an adhesion molecule in the skin -> causes blister and allows bacteria to spread under the skin -->
Phage typing
FOLLICULITIS
Staph Aureus, pseudomonas (hot tub folliculitis)
• superficial infection of hair follicles: erythematous follicular-based papules and pustules
• beard, post neck, occipital scalp, axillae
topical treatment with clindamycin 1% or erythromycin 2%, coupled with an antibacterial wash or soap
FURUNCULOSIS
Staph Aureus deeper follicular infection: acute, round, tender, circumscribed, perifollicular staphylococcal abscess that generally ends in central suppuration
pustule enlarge --> tender red nodule --> painful --> RUPTURE --> pain subsides
• Systemic anti-staphylococcal antibiotics
• small furuncles: warm compresses • large furuncles/carbuncles: incision and drainage
• MRSA: vancomycin
CARBUNCULOSIS
Staph Aureus • coalesced furuncles forming larger draining nodules, with separate heads. • back of neck, back, thighs • tender, painful, and have fever and malaise
ECTHYMA
staphylococcal or streptococcal pyoderma
•nearly always of the shins or dorsal feet • begins with a vesicle or vesicopustule, which enlarges and in a few days becomes thickly crusted
•underlying superficial saucer-shaped ulcer with a raw base and elevated edges remains
clean w/ soap and water, abx ointment
ERYSIPELAS
Group A streptococcal •infection of the skin involving superficial dermal lymphatics
•local redness, heat, swelling, and a highly characteristic raised, indurated border
• young children and elderly • risk factors: lymphedema, venous status, DM, trauma, alcoholism, obesity
B-hemolytic penicillin
CELLULITIS
s. aureus or strep pyogenes • infection extending to subcutis • more diffuse w/ ill defined borders and spreads rapidly
• constitutional sx, regional LAD, sometimes bacteremia
• risk factors: lymphedema, venous status, DM, trauma, alcoholism, obesit
• untreated --> bullous and necrotic --> abscess/fasciitis
• oral Abx: need broad spectrum • parenteral therapy for pts w/ extensive disesase, systemic sx, or
immunocompromised
• good hygiene, warm compresses, elevate affected limb
INFECTIOUS
NECROTIZING FASCIITIS Microaerophilic β-hemolytic streptococci, hemolytic staphylococcus, coliforms, enterococci, Pseudomonas, and Bacteroides•acute necrotizing infection involving the fascia and subcutaneous tissue •Within 24–48 h, redness, pain, and edema quickly progress to central patches of dusky blue discoloration, with or without serosanguineous blisters
•Anesthesia of the involved skin is very characteristic. By the fourth/fifth day, these purple areas become gangrenous • w/o tx --> fever, systemic toxicity, organ failure, shock, death
• may follow surgery- perforating trauma, or may occur de novo • predisposing factors: DM, cirrhosis, IV drug use
• CT or MRI: delineate extent of infection • biopsy, gram stain, culture to help identify organism
• early surgical
debridement/fasciotomy, sometimes amputation
• IV abx: gentamicin and clindamicin • supportive care
• can still have 70% mortality w/ treatment
BACILLARY ANGIOMATOSIS
bartonella toxin proliferates endothelium cells
SECONDARY SYPHILIS
treponema palldium lesions on palms/soles after systemic infection seeds into skin
• acquire virus through inhalation or exposure of mucous membranes • may go through several rounds of replication before skin manifestations • virus can stay localized if infect specific region
• exantheums --> virus transmitted via resp route but not contact w/ rash
MEASLES (Rubeola)
Measles virus • maculopapular lesion
• Koplik spots: gray spots on buccal mucosa
• prodrome: cough, conjunctivitis, high fever
• exanthem: hairline, face, neck --> trunks/extremities
• complications: pneumonia, encephalitis, SSPE
RUBELLA (aka German Measles)
• prodrome: mild constitutional sx • exanthem similar to measles • posterior cervical and auricular nodes involved
• complications: CONGENITAL rubella syndrome, teratogenic
ERYTHEMA INFECTIOSUM
(5th Disease)
Human Parvovirus B19: tiny naked ssDNA
• slapped cheek syndrome • prodrome: mild URI sx
• exanthem: slapped chekk --> trunk --> central clearing
• complications: aplastic anemia
ROSEOLA INFANTUM (6th
Disease)
Human Herpes Virus 6 (HHV6): large enveloped dsDNA
• prodrome: URI sx, abrupt-onset high fever that breaks
• fine macular rash on trunk --> extremities
• complications:pneumonia
INFECTIOUS
HERPES SIMPLEX
• Recurrent HSV-1 is the cause 95% or more of the time • HSV1 = orofacial • HSV2 = genital
•most frequent clinical manifestation of orolabial herpes is the “cold sore” or “fever blister.”
•typically presents as grouped blisters on an erythematous base
• HERPES LABIALIS: fever blisters • PRIMARY GENITAL INFECTION: erosive dermatitis on external genitalia • prodrome: pain, burning, itching
• infects mucosal surfaces • HSV multiplies in nucleus and surroundes themselves w/ nuclear membrane envelope
• HSV1: latent in trigeminal ganglion • HSV2: latent in sacral ganglion • reactivates from psychological or physical stress
• infectious via contact
• viral culture: confirms dx • direct fluorescent Ab: helpful but less specific • Tzanck smear: rapid dx but less sensitive
acyclovir
HERPES ZOSTER
Reactivation of Varicella Zoster Virus following primary infeciton or vaccination
• eruption initially presents as papules and plaques of erythema in the dermatome. Within hours, the plaques develop blisters • begins w/ pain/paresthesia in band like pattern
• post-herpetic neuralgia: continued pain after skin disease resolves
• dormant in sensory ganglia • reactivates from immunosuppression, emotional stress/trauma --> dermatomal dermatitis
• start early on prednisone • rest, analgesics, compresses, antiviral therapy
• disseminated/opthalmict ypes --> IV acyclovir
WARTS
more than 100 types of HPV •benign epidermal neoplasm: hyperplasia + hyperkeratosis
•elevated, rounded papules with a rough, grayish surface
•Tiny black dots may be visible, representing thrombosed, dilated capillaries
•Warts DO NOT have dermatoglyphics (fingerprint folds), as opposed to calluses • FLAT WARTS = verruca planar • PLANTAR WARTS
•Spontaneous resolution (10% stay) •Pare the lesion down: CPT code 11055 •Topicals: Salicyclic acid Pads (cut to fit). Hold on with duct tape; Aldara. Apply every night (cover with bandaid) •Liquid nitrogen: Location dependant 10-30sec twice
•Persistent treatment (every 2-4 weeks): Hemorrhagic Blister is Okay (good sign) •Tricks: Forceps and Q-tip
GENITAL WARTS
HPV 6, 11, 16, 18 •Risk of cervical cancer with Type 16, 18
• Incubation can be many months • CONDYLOMA ACUMINATUM
•MC Viral sexually transmitted disease
•30-50% Sexually Active adults have HPV
•5% clinical sxs
• sexually transmitted
• direct contact from break in skin --> wart appears 2-9 mo --> wart disrupt adjacent skin --> warts spread • infectious via contact
•Liquid Nitrogen: Location dependant usually 10sec
•Aldara: Apply every night as tolerated 6-12weeks
Sometimes every other night Wash off in the morning •Persistent treatment if needed •Not completely clear •Notify sexual partner(s)
INFECTIOUS
MOLLUSCUM CONTAGIOSUM
Poxvirus, MCV-1, 2, 3 or 4 •smooth-surfaced, firm, dome-shaped, pearly papules, averaging 3–5 mm in diameter may be up to 1.5 cm in diameter • central umbilication with central keratotic plug
• intertriginous sites, axillae, popliteal fossa, groin
3 groups are primarily affected: young children, sexually active adults, and immunosuppressed persons
• Virion is encased in a protective sac • transmission from direct skin or mucous membrane contact
• virus replicate in cytoplasm --> induce hyperplasia
• resolve spontaneously but can persist in immunocompromised pts • infectious via contact: atopic skin, shaving, bathers, wrestlers, sex
• Nothing: 6-8weeks individual; Auto inoculate up to a year
•Liquid nitrogen with q-tip for 5 seconds •Curettage (brutal !) don’t use! Leave scar
•Aldara: AAA qd or qod 3-4weeks
•Natural habitat is water, soil or decaying vegetation
•Only a few species are pathogenic for humans.
Cell Membrane and Wall Structure •They are eukaryotic cells.
• Cell membrane and wall similar to gram positive bacteria bc there’s a cell membrane surrounded by a cell wall • Fungal membrane contains ergosterol -> different than human cell membranes that have cholesterol
• Cell wall from inner most layer-out: Chitin -> glucan -> mannoproteins • Unlike bacteria it contains no peptidoglycan.
KOH Preparation • Skin is swabbed with 70% ETOH and allowed to air dry
• Surface is scraped to remove skin scales or hair that contain the fungus • Specimen is treated with 10% potassium hydroxide to destroy tissue elements, specifically keratin (thus KOH is a clearing agent.) • Look for branching hyphae or yeast cells. YEAST
Unicellular Reproduce by budding. Some also
produce pseudohyphae.
MOLD
Multicellular Produce hyphae Solid media: grow as
smooth colonies and look very much like bacteria
CANDIDIASIS
candida •involvement of folds and occurrence of many small erythematous desquamating “satellite” or “daughter” lesions scattered along the edges of the larger macules • CANDIDAL INTERTRIGO: intertriginous areas often affected bc inc warmth, moisture, and maceration, permitting organism to thrive --> becomes reddened plaques
• ORAL THRUSH = oropharyngeal candidiasis: easily scrapable nonadherent plaques, dysphagia
• PARONYCHIA: infection of nail w/ tender, edematous, erythematous nail folds w/ purulent discharge
• CANDIDAL VULVOVAGINITIS: acute inflammation of the perineum characterized by itchy, reddish, scaly vaginal mucosa; and creamy discharge. • BALANITIS: shiny reddish plaques on glans penis
immunocompromised, diabetes, elderly, pts on abx
usually on skin flora --> altered host env leads to proliferation
KOH prep: budding yeast, pseudohyphae
fluconazole 1x/week, stays in skin/hair/nails for 6-7 days no talcum --> irritating • CANDIDA INTERTRIGO, BALANITIS: topical antifungals (azoles) • THRUSH: nystatin or clotrimazole • PARONYCHIA: topical antifungal 2-3 mo, PO anti-staph abx
• VULVOVAGINITIS: fluconazole FUNGI
INFECTIOUS
PITYRIASIS VERSICOLA
Malassezia furfur hypo- or hyperpigmented coalescing scaly macules on the trunk and upper arms
• Heat and humidity • systemic corticosteroid use, cushing's, immunosuppression, malnutrition
• Dicarboxylic acids inhibit melanin production by inhibiting tyrosinase --> hypopigmentation
• griseofulvin and lamisil do not work --> more for dermatophytes
Sold media: produce filamentous colonies
ALL TINEA INFECTIONS
Survive on dead keratin Classified by body region
•KOH from scale at border •Get a culture
TINEA NIGRA
Hortae Werneckii dimorphic fungus •Strands of mycelium and
numerous spores called “spaghetti and meatballs” when viewed microscopically (KOH prep) •Wood's light exam acentuates pigment changes BLACK PIEDRA Piedra hortae WHITE PIEDRA Trichosporon beigelii
topical: terbinafine, clotrimazole, econazole
TINEA PEDIS aka Athlete's Foot
•Trichophyton rubrum •1 T. mentagrophytes •Epidermophyton floccosum
Affected skin is usually pruritic, with scaling plaques on the soles, extending to the lateral aspects of the feet and interdigital spaces often with maceration.
• Adolescents and young males • most common fungal infection in north america and europe
TINEA UNGUIUM
•T. rubrum •T. mentagrophytes
thickened yellow nails and hyperkeratotic subungual debris
TINEA CRURIS
•T. rurum •E. floccosum
• jock itch: in groin, upper/inner thighs but spares the groin
• scaling annular plaques
common in men
TINEA CORPORIS Caused by any dermatophyte • Ringworm infection • face, hands, body
Especially in children
TINEA MANUUM T. rubrum infection of palms of hand
ECTOthrix- caused by Microsporium audouinii, Microsporium canis and some trichophyton.
•hyphal elements and arthrospores SURROUND the hair shaft
•Hair breaks a few millimeters ABOVE the scalp
ENDOthrix- caused by Trichophyton tonsurans
•Arthrospores INSIDE the shaft itself •Hair breaks AT the scalp
TINEA BARBAE •T. mentagrophythes •T. verrucosum
infection of beard hair
infection of : scaly erythematous skin w/ hair less
Topicals: •Powders
•Domeboro solution 20min TID •Selenium sulfide for hair •Azoles creams: Some have antibiotic capabilities (spectazole)
•Lamisil or nafitine bid x 2-4weeks (fungicidal)
Oral
•Location (scalp and groin) and size dependant
•Griseofulvin 20-25mg/kg/d divided BID and Lamisil 2-6weeks
CUTANEOUS MYCOSES
AUTOIMMUNE/INFLAMMATORY
Disease Image Description/Distribution Risk Pathogenesis Lab Tests/Dx Tx
Wheals, many diff shapes and
sizes Type I hypersensitivity supportive
antihistamines: H1 blockers, H2 blockers, doxepin
steroids: long taper
avoid irritants/allergen barrier cream: zinc oxide antihistamines topical steroids patch testing red poorly defined plaques w/
scale and crust on cheeks
associated w/ asthma and allergic rhinitis
chronic pruritic inflammatory
skin disease MOISTURIZE
infants/toddlers: cheeks, forehead, EXTENSORS
most common in developed countries
genetics: fillagrin mutation --> cause transepidermal water
loss Avoid perfumes, soaps, hot water
older children/adolescents: flexural areas of neck, elbows,
wrists, ankles impaired immune response antihistamines
adults: FLEXURAL areas of wrists, ankles, feet, face
Topical steroids: OINTMENTS stronger, avoid use in intertriginous areas dry skin/xerosis
diaper area spared COMPLICATIONS:
Dennie-Morgan lines: double folds and lines under eyes from chronic edema
Lichenification: thick callous skin from chronic trauma
Horizontal nasal crease: from constantly scratching nose
Neurodermatitis: itch-scratch cycle, becomes subconscious from scratching
Scars
Infections: impetigo, warts, molloscum
Eczema herpeticum: HSV can use atopic dermatitis to invade and spread into skin comedome (pore) --> oil and keratin builds up --> ruptures hair follicle --> bacteria accumluates --> inflammatory response --> PUSTULES
Comedomes: topical retinoids, accutane
Bacteria: Abx, benzoyl peroxide Inflammation: Abx, benzoyl peroxide, hormonal therapy, accutane
Sebum production: hormonal therapy, accutane erythematous targetoid lesions
in palms or mucous membranes, B/L and symmetric
immune complex formation --> deposit in cutaneous
microvasculature work up: HSV titers, skin biopsy PO prednisone drugs: sulfonamides,
anticonvulsants
early histologic findings: vacuolar interface dermatitis, perivascular
lymphocytic infiltrate acyclovir 4x/day
infection: HSV, mycoplasma
idiopathic
from meds: abx, anti-epileptics, NSAIDs
death rate: 1-5%
initial sx: fever, stinging eyes, swallowing
true derm emergency --> high morbidity and poor prognosis severe, denudation (>30%
epidermal detachment), also
from meds death rate: 34-40% transfer to ICU/burn unit
CONTACT DERMATITIS
pruritic, erythematous oozing rash
contact to poison ivy, nickel, rubber, preservatives
Type IV hypersensitivty to IRRITANTS (larger than Ag/allergens) URTICARIA
can migrate chronic types: still can rarely
find a cause
eosinophils
ERYTHEMA
MULTIFORME 20-40 yo
late histologic findings: subepidermal bullae, full thickness necrosis
Abx: for skin infections but use sparingly
ACNE
4 factors: follicular hyperkertinization, excess sebum, bacteria, inflammation ATOPIC DERMATITIS
Pityriasis alba: small hypopigmented ill-defined patches on face from inhibition of melanin due to thicker skin
environment/stress
TOXIC EPIDERMAL NECROLYSIS STEVEN JOHNSON
SYNDROME
widespread blisters and purpuric macules. mucosa involvement and
AUTOIMMUNE/INFLAMMATORY
great loss of water/fluids --> need to go to burn unit
steroids controversial: can't fight off infection
increased risk for infection -->
die from SEPSIS IVIG: best tx but expensive
fat disorder on extensor surfaces of extremities, more common on ant shins
hypersensitivity rxn to: URI, infection, IBD, malignancies, sulfonamides, Ocs
supportive: NSAIDs, supersaturated solution of potassium iodide in orange juice, PO prednisone
prodrome: fever, joint pain, malaise
rash occurs for 1-3 wks then
resolves Abx for URI
well demarcated thick erythematous plaques w/ silver
scale on extensor surfaces clinical
Topical steroids (NOT ORAL): potent except for intertriginous areas
PLAQUE: silver scale and sharp demarcations, symmetric. Most common type
histology : acanthosis, elongated rete ridges, hyperkeratosis and
parakeratosis Calcipotrene: Vit D derivative INVERSE/FLEXURAL: bright red
plaques in skin folds with no scales (often misdiagnosed as
candidiasis) OTHER FINDINGS:
phototherapy: UVB, excimer laser, PUVA
GUTTATE: Rain-drop sized salmon-pink scaly papules on trunk or extremities. Usually after strep infection
Psoriatic Arthritis: Sausage digits, tenosynovitis, affects DIP joints or sacroiliitis
systemic (for psoriatic arthrits): MTX, cyclosporine, acitretin PUSTULAR: Sterile pustules in
cornified layers, on palms and soles. Often from withdrawal of corticosteroids --> AVOID ORAL STEROIDS FOR PSORIASIS
Nail changes: Pitting, oil spots, onychodystrophy
Biologics: TNF-a inhibitor, IL 12/23 blocker
Scalp involvement Geographic tongue: Plaque psoriasis on tongue, may have bad breath
high risk for CVD
purple, pruritic polygonal papules
widespread papulosquamous eruption
Flaccid blisters and erosions w/ frequent mucous involvement
IgG against Dsg 3 --> lose
normal adhesion histology: Nikolsky sign: intact epidermis
shearing away from dermis -->
leave moist surface behind suprabasilar acantholysis
intraepidermal bullae → blisters/separates within epidermal layer
“tombstone” row of basal layer keratinocytes
immunofluorescence: chicken wire/fish net pattern Flaccid bullae and localized or
generalized exfolication, rapidly denudes
intact bullae, erythematous papules, urticarial plaques involving skin and mucosa
histology: Subepidermal bulla with eosinophils or neutrophils can be in groin, axillae, trunk,
thighs immunofluorescence: linear
TOXIC EPIDERMAL
NECROLYSIS Nikolsky's sign: lateral pressure induce separation of epidermis from dermis
Auspitz sign: pinpoint bleeding after picking off scale, from vessels in dermal papillae
LICHEN PLANUS
histology: hyperkeratosis, acanthosis, saw-tooth elongation of rete ridges, lymphocytic infiltrate
ERYTHEMA NODOSUM
PSORIASIS
ERYTHRODERMIC: Bright red lesions involving full body w/ fevers/chills/malaise. Often from uncontrolled or untreated psoriasis --> need hospitalization
T cell mediated: releaseTNF-α and interleukin cytokines → body starts to produce skin at faster rate
histology: acanthosis, hyperkaratosis, hypergranulosis, elongated rete ridges, fibrosis of papillary dermis
PEMPHIGUS VULGARIS
Asboe-Hansen sign: put pressure on intact bullae → fluid spreads under adjacent skin and makes blister bigger
40-60 yo, M = F
intralesional kenalog injections
LICHEN SIMPLEX CHRONICUS from repetitive trauma/scratching BULLOUS PEMPHIGOID 60-80 yo, M=F
IgG against basement membrane /hemidesmosomes (BP230, BP180)
PEMPHIGUS FOLIACEUS
face, scalp, upper trunk
middle aged and
AUTOIMMUNE/INFLAMMATORY
Associated w/ gluten-sensitive enteropathy HLA-B8, HLA-DR3, HLA-DQw2 Type III hypersensitivity: granular IgA in papillary dermal tips non-scarring alopecia/balding in
round defined area
hair specific autoimmune
disease no tx: 90% clear within one year
asymptomatic: no scale, erythema, orLAD
Lymphocytic infiltrates sometimes around or within
hair bulb of anagen follicles Minoxidil (rogaine)
Topical steroids: if autoimmune, < 10 yo
intralesional steroid injections foreign body inflammatory rxn
to dark coarse curly hair stop shaving
shaving --> hair curls and dives back into skin --> brings in
bacteria use single blade/electric razor
retin-A: decrease hyperkeratosis topical corticosteroids oral or topical abx: for pustules/abscesses and reduce skin bacteria
laser hair removal: painful and only works short-term pustular --> short-course of abx hyperkeratosis --> retin-A gel, high potency topical steroids scar --> intralesional steroids TAC excision in stages
ALOPECIA AREATA
regrown hair can be white can be stress induced DERMATITIS
HERPETIFORMIS
Intensely pruritic papulovesicular eruption symmetrically on elbows, knees, buttocks
20-60 yo, males histology: neutrophils in subepidermal space
ACNE KELOIDALIS
NUCHAE chronic scarring folliculitis
chronic irritation: close haircuts, rubbing of head gear PSEUDOFOLLICULITIS
BARBAE
transfollicular or extrafollicular penetration of foreign bodies
bumps proliferate with more shaving
SYSTEMIC/CONNECTIVE TISSUE DISEASES
Disease Image Description/Distribution Pathogenesis Lab Tests/Dx Tx
systemic disease involving skin (malar rash, discoid rash), oral ulcers, heart, kidneys, joints, neuro, blood
type III hypersensitivity
Anti Ro/La (ssDNA) sun avoidance
suspect if have frequent miscarriages
cell rupture releases "garbage" DNA --> macrophages can't clear completely --> Ab made against DNA/histone proteins --> complexes deposit throughout body
ANA: main screening test --> 1:160 = positive. but have false positives (infection,
elderly, pregnant) topical steroids
ACUTE CUTANEOUS LE form: looks like SLE, photodistributed butterfly rash. No internal involvement
need 4 of 11 criteria: malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, renal disorder, neuro disorder, hematologic disorder, immunologic disorder, antinuclear Ab
plaquenil: dec immune system and reduce sun sensitivity but need optho exam before starting SUBACUTE LE: photodistributed
annular plaques, joint and vasculitis involvement
work up: blood work,
biopsy IL kenalog
CHRONIC/DISCOID LE:
photosensitivity atrophic plaques on scalp --> scarring alopecia. Rarely ANA positive
immunosuppressants: Imuran, MTX NEONATAL LUPUS: mother pass Ab to
kids --> kids get anti-Ro and heart block
DRUG INDUCED LE: from hydralazine, procainamide, isoniazid
proximal muscle weakness with cutaneous manifestation
Ab tests: ANA, Jo-A, SS-A
(ro), t-RNA synthetase topical steroids adult variant: associated w/ internal
malignancy --> SCREEN for cancers
muscle biopsy = gold
standard LOTS of oral prednisone child variant: calcinosis of skin
add steroid sparing agent w/in 2 months: MTX, imuran, celicept
heliotrope rash avoid sun
Gottron's papules: raised fleshy
colored lesions plaquenil
periungual erythema and telangiectasia: capillary loops in proximal nail bed thrombose/break shawl sign: violaceous scaling patches around shoulder
diffuse, hard immobile skin
chronic fibrosing systemic disease --> fibroblasts activated to make more
collagen MTX
SYSTEMIC SCLEROSIS: diffuse and CREST syndrome (calcinosis, raynaud's, esophageal involvement, sclerodactyly, telangiectasia)
systemic fibrosis: have resp (interstitial fibrosis, pulmonary HTN), CV, GI, kidney issues. Most die from
renal HTN diffuse: anti-scl70 Raynaud's --> calcium channel blocker
penicillamine ACE: renal protection morphea tx: IL Ken at leading age, topical CS, plaquenil
non-blanchable spots on trunks/legs
that are raised --> palpable purpura punch biopsy PO steroids and refer to derm GIANT CELL/TEMPORAL
ARTERITIS U/L headache near temples
need to dx quickly or else may turn BLIND
biopsy temporal artery HIGH DOSES of PO steroids pulseless disease: fever arthritis,
weak pulses in extremities
CONNECTIVE TISSUE DISEASES
SLE
VASCULITIS
TAKAYASU ARTERITIS DERMATOMYOSITIS
SCLERODERMA
LOCALIZED SCLEROSIS: morphea --> just involves skin. atrophic plaques (skin steps off) w/ telangiectasia. Middle aged females
SYSTEMIC/CONNECTIVE TISSUE DISEASES
young asian females
affects renal and visceral med-sized vessels associated w/ HBV in children HIGH FEVERS red conjunctiva circumoral palor red perianal rash lymphadenitis
peripheral desquamation granulomatous inflammation
of resp tract C-ANCA (anti-pr3) positive steroids + cyclophosphamide nasopharynx, lung, kidney
involvement
necrotizing vasculitis of
small-med sized vessels CXR: migratory infiltrates
second line: IVIG, cellcept, rituximab, azathioprine saddle nose deformities necrotizing
glomerulonephritis UA: RBC/casts fatal if not tx aggressively
friable erythematous gingiva: strawberry mouth
triggers: vaccine, LT-inhibitors, cocaine, azithromycin, rapid stop of
steroids P-ANCA (anti-MPO) positive steroids
lung and heart involvement
eosinophil-rich and granulomatous inflammation of resp tract
CBC: peripheral eosinophilia
cytoxan: if have cardiac disease
necrotizing vasculitis of small-med sized vessels heart disease = most common cause of death
SQ nodules: may ulcerate necrotizing vasculitis of small
vessels steroids 1 mg/kg/day to start
lung and kidney involvement necrotizing glomerulonephritis
cyclophosphamide or azathioprine: for severe renal or lung disease
prodrome: fever, arthalgia, myalgia,
weight loss pulmonary capillaritis IVIG
splinter hemorrhages, ulcers, necrotizing livedo
type III hypersensitivity: IgA dominant immune deposits
in small vessels need serial UA to track
kidney function self-limited affects kids
IF: IgA, C3 and fibrin deposition in affected vessel walls
Dapsone, Colchicine: dec duration of cutaneous lesions
skin, gut, kidney involvement systemic corticsteroids: for
arthrlagias and abd pain
palpable purpura in lower extremities
refer to nephrologist headache, joint pain (LE large joints),
hematuria, rash, abdominal pain waste basket dx
CRYOGLOBULINEMIC VASCULITIS
no signs of systemic disease or glomerulonephritis
cryoglobulin immune deposits in skin and glomeruli --> precipitate out w/ cold and occlude blood vessels
congenital capillary malformation: deficiency of SNS innervation of vessels color gets dark w/ crying, fever, overheating in < 1% of newborns can evolve to raised,
thickened plaque TAKAYASU ARTERITIS
POLYARTERITIS
NODOSA belly pain, skin erruption
PO steroids, cyclophosphamides
KAWASAKI DISEASE can get coronary artery
aneuryms IVIG, ASA, PO steroids
MICROSCOPIC POLYANGIITIS
HENOCH-SCHONLEIN PURPURA
P-ANCA positive
preceded by URI strep or other infectious triggers
usually clincial dx WEGNERS
GRANULOMATOSIS
CHURG-STRAUSS SYNDROME
associated allergic rhinitis, nasal polyps, asthma
CUTANEOUS MANIFESTATIONS OF INTERNAL DISEASE LEUKOCYTOCLASTIC
VASCULITIS from drugs, URI
NEVUS FLAMMEUS
port wine stain in head and neck: dermatomal, unilateral, variable blanching
SYSTEMIC/CONNECTIVE TISSUE DISEASES
ACANTHOSIS
NIGRICANS velvety hyperpigmented plaque
Nonspecific reaction pattern that may accompany obesity; diabetes; excess corticosteroids; pineal tumors; other endocrine disorders determine type of xanthoma measure fasting cholesterol, TAGs, HDL, VLDL, LDL primary hyperlipoproteinemia = dx of exclusion
congenital lesions of skin, CNS, bone, endocrine glands
autosomal dominant
congenital disease > 2 or more features = NF1
dx excise cutaneous tumors
> 6 café au lait spots NF1 gene
MRI: dx, management, and screening of family members
follow pt closely to detect malignant degeneration of neurofibromas
axillary freckling: earliest sign
genetic counseling cutaneous neurofibromas
Lisch nodules: iris hamartomas
bone lesion: sphenoid wing dysplasia or congenital bowing of long bones
bilateral acoustic neuroma autosomal dominant
1-2 café au lait spots
neurofibromas: less common than NF1
no lisch nodules or mental retardation/learning disabilities café au lait, low set ear, webbed neck short stature, pectus excavata pulmonic stenosis, cryptorchidism, hypogonadism
short, facies, low set ears
café au lait, cardiac defects
large segmental café au lait sporadic: GNAS1 mutation
bone lesions: polyostotic fibrous dysplasia
precocious puberty, hyperthyroidism
café noir spots: more black than creamy
XANTHOMAS build-up of lipids in tissue due to
dyslipidemia lipid abnormalities
NEUROFIBROMATOSIS 1 NF1 + juvenille xanthogranuloma = HUGE risk of juvenille CML NEUROFIBROMATOSIS 2 SCH gene: swannomin/merlin proteins defective MCCUNE ALBRIGHT SYNDROME
NOONAN SYNDROME autosomal dominant:
PTPN11 mutation
CARDIOFACIOCUTANEOU S SYNDROME
BRAF, MEK1, MEK2 mutations
SYSTEMIC/CONNECTIVE TISSUE DISEASES
EKG conduction defects, deafness, hypospadias/cryptorchidsm Multiple hamartomas (benign tumors) of the skin, central nervous system, kidneys, heart, retina, and other organs
autosomal dominant
MRI brain genetic counseling
epilepsy + angiofibromas + mental
retardation TSC1, TSC2 gene defect surgical excision of facial
lesion if cosmetic concern adenoma sebaceum inc chance of malignancy
shagreen patch: usually in lower trunks
white ash leaf macules: hypopigmented ellipitic macule. Earliest finding
periungual fibromas: tumors around nails that look like warts
brain lesions: glioneuronal hamartoma --> cause seizures, cognitive defects, autism, behavioral problems
heart: cardiac rhabdomyoma renal: angiomyolipoma, renal cell carcinoma
opthalmic: retinal hamartoma pulmonary:
lymphangioleiomyomatosis --> SOB and PTX
multiple hamartoma syndrome autosomal dominant: PTEN mutation
multiple facial trichilemmomas: looks like wart
oral mucosal papillomatosis < 10% have café au lait spots sebaceous gland tumor + > 1 internal malignancy
FAP + extraintestional manifestations
intestinal polyposis, epidermal cysts, multiple osteomas, desmoid tumors epidermal cysts on weird locations (legs)
fibrofolliculomas, achrochordons, trichodiscomas
LEOPARD SYNDROME PTPN11 mutation
TUBEROUS SCLEROSIS
COWDEN DISEASE
high incidence of malignant tumors of breast and/or thyroid gland
MUIR-TORRE
SYNDROME most common associated neoplasm =
colorectal cancer
autosomal dominant
BIRT-HOGG-DUBE
SYNDROME can get spontaneous PTX and renal
cancers
autosomal dominant GARDNER SYNDROME
BENIGN LESIONS
Disease Image Description/Distribution Pathogenesis Lab Tests/Dx Tx
benign neoplasm of melanocytes histology: MATURE melanocytes descending into dermis
JUNCTIONAL NEVUS (A): flat, at epidermal/dermal junction INTRADERMAL NEVIS (C): indurated, in dermis w/ no connection to epidermis
COMPOUND NEVUS (B): still connected to epidermis but growing down into dermis
brown pigmented lesion w/ hair present at birth --> monitor carefully b/c can become melanoma if large
BECKER'S NEVUS: common on men in lateral upper chest. Lots of hair associated
HALO NEVI immune rxn against mole from body can get vitiligo
benign juvenille melanoma: most common in children
hairless, red/brown dome-shaped papule
slightly elevated, round, regular nevus
pigment in dermis --> reflects blue light
LABIAL MELANOTIC
MACULE faint black spot on lower lip/mucosa
histology: atypical melanocytes w/ bridging of rete ridges
cutaneous hamartoma: contains surface epidermis and adnexal structures (sebaceous gland) linear, unilateral, wart-like, whorled follow Blashkos lines: where melanocytes travel in utero
ILVEN (inflammatory linear verrucous epidermal nevus): intensely erythematous, pruritic, inflammatory
usually scalp present at birth CONGENITAL NEVUS
serial excisions for prophylaxis before turns into melanoma MELANOCYTIC NEVUS
BLUE NEVUS
SPITZ NEVUS remove
DYSPLASTIC NEVUS
irregular pigmented macule w/ irregular border, smaller than melanoma
marker for inc risk for developing melanoma
remove mod and severe-graded atypia
EPIDERMAL NEVUS present at birth cryo, surgery, laser
BENIGN LESIONS
tumors can arise on top: need prophylactic surgical excision
common benign neoplasm = trichoblastoma common malignancy = BCC
raised discolored plaques on extremities or face w/ "stuck on"
appearance genetic predisposition:
rare if < 30 histology: horn cysts shave removal benign squamous proliferation sign of skin maturity -->
usually in elderly
well-circumscribed,
crumbles when picked curettage
doesn't occur on lips, palms, soles
raised and brown = okay, flat and black = problem
liquid nitrogen: be careful on dark skin --> can leave hypopigmentation IRRRITATED SK: often confused w/
BCC due to inflamed/swollen look
LESER-TRELAT SIGN: eruptive SK as sign of internal malignancy (usually gastric cancer)
STUCCO KERATOSES: papular warty lesions on lower legs, sign of dry skin
DERMATOSIS PAPULOSA NIGRA: multiple brown-black papules on african-americans. "morgan freeman" disease
silicone gel sheeting: doesn't work BCC MIMICS
NEVUS SEBACEOUS
linear --> cobblestoned
SYRINGOMA
multiple flesh-colored small papules around eyes, from eccrine glands around eyes
histology: comma-shaped groups of epithelial cells
TRICHOEPITHELIOMA small flesh-colored papules on face histology: pseudo-horn cysts
CYLINDROMA flesh-colored to reddish nodule on head, neck, scalp
“turban tumor” =
autosomal dominant histology: jigsaw-puzzle pattern
PILOMATRICOMA firm nodule in a child w/ erythematous surface
histology: basaloid cell nest, ghost cells (no nucleus), giant cells, bone cells and calcifications
KELOIDS scar that proliferates beyond margin of injury
SEBORRHEIC KERATOSIS
BENIGN LESIONS
intralesional steroid injections: large needle to inhibit collagen synthesis
more common in blacks
cryotherapy, compression, irradiation invagination of epidermis w/ black
punctum, very common
pore from old hair follicle invaginates into skin and grows keratin --> bacteria makes abscess around it
drain fluctant and inflamed cysts commonly on scrotum spontaneously ruptures --> need to destroy cyst wall
to prevent recurrence PILLAR CYST: form of EIC without
punctum, on scalp. Filled w/ hard
debris multiple EICs: suspect Gardner's syndorme
snip excision w/ iris scissors
large tag --> shave removal
cryotherapy: spray or forceps
surgical excision cryo doesn't work
asymptomatic to slightly itchy lesions more in females
dimple sign: lesion retract beneath skin when you compress and elevate w/ thumb and index finger
fibrous rxn to trauma, viral infection, insect bite multiple DFs seen in SLE inflamed cartilage
women: antihelix LN2
cut out cartilage donut pillow: relieve KELOIDS scar that proliferates beyond margin
of injury
tender, itches, grows fast
EPIDERMAL INCLUSION CYSTS
small punch biopsy over black punctum
ACROCHORDON skin tags: tiny, brown/skin colored and attached by short narrow stalk
from chronic irritation, rubbing, genetics, obesity
CUTANEOUS HORN hard conical projection made of keratin
a wart, actinic keratosis, or SCC excision: ellipitical or punch, depending on size CHRONDRODERMATITI S NODULARIS HELICIS
pain out of proportion if suspect AK men: helix DERMATOFIBROMA
pinkish papule w/ darker hyperpigmented ring, usually on leg
MALIGNANT LESIONS
Disease Image Subtypes Description/Distribution Risk Factors/Epidemiology Pathogenesis Lab Tests/Dx Tx
malignant neoplasm of
melanocytes • personal history of atypical moles, fam hx • congenital nevus • nonmelanoma skin cancer • immunosuppression • sunburn, PUVA, chronic tanning, white skinned • UVA >> UVB
Growth Phases • Radial growth: superficial and laterally
• Vertical growth: deeper into dermis
Pathogenesis
• familial melanoma: CDKN2A mutation --> Rb and p53 inactive
• MC1-R gene: increases risk Better Prognosis factors • young age • female • extremities
• skin metastasis better than visceral
ABCDE
• asymmetry, border irregularity, color, diameter • Color: dark, brown, or pale Metabolic Panel • +S100 • HMB45 • Melan A Histology
• Atypical cells in epidermis • Lack of maturation with descent
• Cytologic atypia & nuclear pleomorphism
• Nucleolar variability: often large & irregular
• Mitoses: deep dermal, often atypical
• Increased apoptosis
• biopsy depth > 1 mm: need sentinel LN biopsy • LN pos = metastatic --> dissect sentinel and surrounding LN • LN neg: remove primary tumor EXCISION • in situ: 0.5 cm margin • < 1 mm: 1 cm margin down to fascia • > 2 mm: 2 cm margin down to fascia Adjuvant Therapy • IFN-a: inc survival but not well tolerated
Metastatic disease • CT: chest, abd, pelvis • MRI brain • radiation Breslow Depth
• obtain skin biopsy for dx and staging
• predicts survival and prognosis
• measures top of granular layer to deepest point of invasion
• < 6mm: benign • > 0.76mm DEEP -> regional lymph node involvement so inc Melanoma in Situ • histology: atypical
melanocytes but basement membrane still intact
Superficial Spread •lower leg in female •back/trunk in males • In early states it may be small, then growth becomes irregular • horizontal superficial spread w/o much induration
MC type of MM in the white-skinned population – 70% of cases
• begins as flat lesion • can turn black, blue, red, white
Nodular • Trunk is a common site • Usually with a POOR prognosis • Black/brown nodule • Ulceration and bleeding are common
M>F • rapid growth
• vertical growth phase MELANOMA
MALIGNANT LESIONS
Lentigo Maligna Melanoma
• Mainly on face in elderly pt • grows on epidermal-dermal junction
• Elderly pts • May be many years before an invasive nodule develops • grows on sun damaged skin
Acral Lentiginous Melanoma
•Usually comprises a FLAT lentiginous area w. INVASIVE nodular component • POOR prognosis b/c usually identified too late --> on palms or soles
• Common in black people and Asian
• In white-skinned population accounting for 10% of MM
• KIT gene: overexpressed. possible gene association
• hutchinson's sign: pigment spreads under nail plate to proximal and lateral nail folds
Subungal Melanoma • Often diagnosed late • Confusion with benign subungal nevus, infections or trauma
Rare
Amelanocytic Melanoma• fleshy pink, indurated lesion • Diagnosis is often missed clinically so do bx • often mistaken for BCC or verruca
• Lack of pigmentation due to the rapid growth of tumor and differentiation of the malignant melanocytes
Desmoplastic Melanoma
• Usually found on head and neck region
• Usually amelanotic lesions • High chance for recurrence
Positive S-100 protein but are often negative to tyrosinase, Melan-A.
Conjunctival Melanoma• Markedly pigmented tumor in eye
Metastatic Melanoma • Satellitosis near the primary melanoma
• Sometimes distant metastases that appear as papules or plaques, not pigmented. MELANOMA
MALIGNANT LESIONS
Malignant Melanoma Invasive and may show lymph node invasion by tumor cells (pics on right)
Rate of Metastasis • pTis (in situ): 5 mm margin • pT1 (<1.0 mm): 1 cm margin • pT2 (1.0–2.0 mm): 1–2 cm margin • pT3 (2.0–4.0 mm): 1–2 cm margin • pT4 melanoma (>4.0 mm): 2 cm margin
• Derived from basal cell layer of epidermis
• Head & neck of elderly patients
• Slow, progressive growth • Locally destructive, recurs, rarely metastasizes • translucent, "pearly" nodule w/ telangiectasia
• high risk: micronodular, infiltrative, morpheaform, pigmented types
•MC type of skin CA • fair skin, blue eyes, fair hair
•Inability to tan •Exposure to UV radiation from sunlight or artificial tanning lamps •UV exposure pattern- intermittent, childhood sun exposure
• immunosuppression
• PTCH mutation: unchecked cell proliferation
• photocarcinogenesis: DNA damaged by UVB, ROS induces DNA damage, cell-mediated immunity suppressed, p53 mutates
• p53 mutation: can't trigger apoptosis
• indolent, low metastatic potential
• When washing face, crust comes off and lesion starts bleeding
• Almost always epidermal attachment
• Nests or lobules of hyperchromatic but uniform basaloid cells with PERIPHERAL PALISADING surrounded by loose stroma
• CLEFT-LIKE retraction spaces • May appear pigmented due to dermal melanophages
•New drug target PATCH called Vismodegib •ELECTRODESICCATION AND CURETTAGE (ED&C): great for small low risk BCC •Excision: large low risk (5 mm) or any high risk (10 mm) •MOHS micrographic surgery: microscopically controlled technique with real-time frozen tissue secitons to insure margin control; for high risk, large low risk, face, scalp, and neck, recurence •Radiation- adjunctive therapy if can't do surgery, or if have perineural invasion •Aldara- low cure rate
Nodular BCC low risk
Superficial BCC Erythematous plaques w/ +/- papules, scale, telangiectasia
low risk
Morpheaform BCC scar-like or white plaque w/ slight translucence. Looks like scar on nose
high risk
Cystic BCC well-marginated, red or flesh-coloured nodule with cystic centers. POPPING DOES NOT RESOLVE IT --> not just a simple cyst
Fibroepithelioma of Pinkus
smooth pink plaque on lower back. Very rare
histology: thin anastomosing strands and cords of tumor cells extending into dermis from epidermis surrounded by fibrous stroma MELANOMA BASAL CELL CARCINOMA • MOHS • excision w/ 4 mm margins • EDC • XRT • imiquimod • topical 5-FU • photodynamic therapy, cryosurgery
• combination therapy: EDC + imiquimod
MALIGNANT LESIONS
Gorlin Syndrome aka Basal Cell Nevus Syndrome
•Hundreds of Basal Cells that look like moles
•Also get calcification of falx cerebri, jaw cysts, bifid ribs
•Auto dom •PATCH gene mutation •Kids • Excellent prognosis • erythematous, keratotic papule or nodule • Metastases uncommon if tumor < 1.5 cm deep • 5% metastasize if 2 cm or more and definite dermal invasion
• metastasizes usually to lung
• Usually men • 2nd MC skin cancer • Very rare in blacks • UVB > UVA exposure • transplant pts: need frequent derm follow-up • other exposures: chronic ulceration/inflammation, scarring, arsenic from wells, smoking
• HPV 16/18
• risk factors for metastasis: ear/lip, impaired host, > 2 cm, depth > 4 mm, perineural invasion, poor differentiation
• Irregular border • Indurated with white/yellowish scale • Can see
hyperkeratosis/parakeratosis • Can see cells along the basal layer are mildly irregular, some are large w/ hyperchromatic nuclei
• Stay in bottom 1/3 of epidermis
• The dermis is bluish •keratin “pearls”
•Surgical excision with adequate margins •ELECTRODESICCATION AND CURETTAGE (ED&C) •Excision: high risk (10 mm), low risk (4 mm)
•MOHS
•Radiation-adjunctive therapy •Aldara-low cure rate • if palpable LN: fine needle/surgical biopsy
Keratoacanthoma • rapidly growing ulcerative keratotic nodules that looks like crater • GRYZBOWSKI SYNDROME: multiple nonregressing, generalized eruptive • FERGUSON SMITH SYNDROME: familial, spontaneously regressing • KERATOACANTHOMA CENTRIFUGUM MARGINATUM: solitary, expanding
erythematous plaque w/ central regression. looks like discoid
• elderly ~ 64 yo • more prevalent in Muir-Torre syndrome pts
• can spontaneously regress • surgical excision: if regress on own will heal w/ scarring • MTX injection, topical 5-FU, imiquimod
• radiation
Actinic Keratosis •Very Common, precursor to SCC that's confined to epidermis • mild erythema w/ imperceptible scale --> becomes more papular and obvious later • cutaneous horns can overlie AK
•Caused by long term UV exposure
• sun-damaged skin on balding scalp aka dermal solar elastosis •Worse in transplant patients
• solar elastosis: greyish areas in dermis
• dysplastic cells in lower epidermis, hyperkeratosis • need inspection and palpation to detect, may be imperceptible
•LN2 (cryotherapy) •topical chemo like 5-FU or Aldara •sunscreen • photodynamic therapy BASAL CELL CARCINOMA SQUAMOUS CELL CARCINOMA
MALIGNANT LESIONS
Actinic Cheilitis • diffuse AK/change of lip • loss of vermilion border • squamitization of mucosal tip • leukoplakia
SCC can arise from actinically damaged tip --> can metastasize in mouth and spread to throat
Marjolins ulcer • SCC coming from area of scar/chronic inflammation • ulcer that doesn't heal
incisional biopsy
Bowen's Disease aka SCC in Situ/ Erythrodysplasia of Queyrat
• Full thickness epidermal atypia but not into the dermis • larger size, induration, crusting, refractory to LN2 --> BOWEN'S
• can arise in non-sun exposed sites
• risk of progression to SCC
• NOT invasive bc BM is intact • Dysplastic throughout epidermis
LN2, topical chemo like 5-FU or Aldara, or surgery. If on genitalia, do MOHS
Leukoplakia MC premalignant lesion of the oral mucosa, treat like SC-Cis
• ddx = thrush, but this lesion NON-SCRAPABLE
KARPOSI'S SARCOMA
• Spindle-cell tumor derived from endothelium • Caused by Human Herpesvirus 8 (HHV8) aka KSHV • bluish-red or purple bumps on the skin (from vascular lesions from epithelium) • Epidemic, AIDS-related •Immunocompromised • Classic or sporadic • Endemic (African) • irregularly diliated anastomosing vascular channels
HPV associated large well-differentiated nests of eosinophilic keratinocyts w/ "pushing border" Oral florid papillomatosis mouth Giant condylomata of Buschke-Löwenstein on genitalia Epithelioma cuniculatum (plantar surface of the foot)
on plantar foot SQUAMOUS
CELL CARCINOMA
VERRUCOUS
CARCINOMA Surgery…DO NOT
Radiate…this will only piss them off and they will turn deeply invasive
MALIGNANT LESIONS
Mycosis Fungoides
(T-Cell) •Pts are commonly
misdiagnosed with eczema
• plaque stage: looks like eczema, but steroids don't work
• tumor stage: knee picture. Looks pretty bad Sezary Syndrome •Leukemic form of Mycosis
Fungoides •high mortality rate
Paget's of Breast •Extension of underlying ductal carcinoma to the skin including the nipple, and areola •Similar to Bowens dz
Surgery
Extramammary Paget's
•MC labia majora •Associated with underlying malignancy 20% of the time -> most common is rectal, bladder, renal, uterine
•If you see a lesion and its associated with an internal cancer, 50% have already metastasized
F>M
XERODERMA PIGMENTOSUM
early onset of disease states: 1000x risk of skin cancers
defect in nucleotide excision repair genes--> exaggerated response to UV
RECESSIVE DYSTROPHIC EB
basement membrane familial disease: skin sloughs off easily and SCC develops in scars or sites of chronic irritation
• collagen type VII defect • leading cause of death beyond childhood in pts w/ dystrophic EB --> septic • SCC occurs on extremities and metastasizes early BAZEX
SYNDROME
• early onset BCC • follicular atrophoderma • congenital hypotrichosis: loss of eyebrows and hair
ROMBO SYNDROME • early onset BCC • peripheral vasodilation w/ cyanosis • hypotrichosis • milium/cysts • blepharitis EPIDERMO-DYSPLASIA VERRUCIFORMIS
flat wart-like lesions in early
childhood --> acutally SCC HPV 3, 5, 8
OCULO-CUTANEOUS ALBINISM
pigment disorder of eyes, hair, skin no melanin --> no UV protection --> inc SCC, melanomas > BCC PRIMARY CUTANEOUS LYMPHOMAS PAGET DISEASE UV protection
