skin - pathophysiology
TRANSCRIPT
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Pathophysiology: Skin The Dermatologic Vocabulary ................................................................................................................................................. 2
Histopathology of the Skin ...................................................................................................................................................... 4
Acne & Rosacea ....................................................................................................................................................................... 6
Cutaneous Autoimmune Bullous Diseases: Pemphigus & Bullous Pemphigoid ..................................................................... 9
Psoriasis & Atopic Dermatitis ................................................................................................................................................ 11
Pigmented Lesions & Melanoma .......................................................................................................................................... 14
Non-Melanoma Skin Cancer ................................................................................................................................................. 17
Dermatology of Pigmented Skin ........................................................................................................................................... 19
Birthmarks in Babies ............................................................................................................................................................. 20
Drug Eruptions ...................................................................................................................................................................... 22
Cutaneous Manifestations of Internal Diseases ................................................................................................................... 25
Common Infections of the Skin ............................................................................................................................................. 27
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The Dermatologic Vocabulary
Lesion morphology: shape and relative size of the lesion(s)
1. MACULE non-palpable, circumscribed, color change <1 cm; (“macular” or “patch” are used to describe larger areas of the color change)
junctional nevus
2. PAPULE palpable, circumscribed lesion, < 1 cm molluscum contagiosum, intradermal nevus
3. PLAQUE palpable, circumscribed, relatively flat topped lesion, greater in surface area than in thickness, > 1 cm;
psoriasis, lichen simplex chronicus
4. NODULE palpable, circumscribed lesion, ≤ 1 cm and < 2 cm; melanoma, squamous cell carcinoma
5. TUMOR large nodular lesion,≥ 2 cm squamous cell carcinoma, basal cell carcinoma
6. VESICLE clear fluid –filled lesion (blister), < 0.5 cm herpes simplex and zoster infections, vesicular foot dermatitis
7. BULLA clear fluid-filled lesion (blister), > 0.5 cm bullous impetigo, toxic epidermal necrolysis, bullous pemphigoid
8. PUSTULE turbid fluid-filled lesion folliculitis, acne
9. CYST nodule filled with a semisolid or liquid substance epidermal inclusion cyst
10. WHEAL transient palpable lesion (hive) caused by an interstitial serous fluid accumulation in the upper dermis
11. COMEDONE plugged pilosebaceous opening acne comedone, solar elastosis with cysts and comedones (Favre-Racouchot syndrome)
12. BURROW short, linear, thread-like lesion caused by the scabies mite tracking through the stratum corneum
Secondary Changes in lesions are frequently seen and may result from the primary disease process, normal skin
repair, external manipulation, or infection. 1. SCALE accumulation of adherent stratum corneum psoriasis, tinea corporis
2. CRUST accumulation of serous, cellular, squamous, and bacterial debris over a damaged epidermis
impetigo, secondarily infected eczema
3. LICHENIFICATION accentuated skin markings due to thickening of the epidermis
lichen simplex chronicus
4. EROSION tissue loss confined to the epidermis candidiasis
5. EXCORIATION erosion clearly caused by external factors neurotic excoriations
6. ULCER tissue loss extending into the dermis venous stasis ulcer, ulcerated basal cell carcinoma
7. FISSURE crack in the epidermis extending into the dermis perleche
8. SCAR fibrous tissue replacing usual dermal tissue space scarring alopecia
9. ATROPHY loss of substance of the epidermis and/or dermis steroid induced atrophy, lupus erythematosus
10. HYPERKERATOTIC lesion with excessive “heaped-up” scale hypertrophic actinic keratosis, squamous cell carcinoma
11. VERRUCCOUS vegetating, wart-like surface verruca vulgaris
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Further description: COLOR
1. ERYTHEMATOUS Reddened skin
2. VIOLACEOUS Violet
3. PURPURIC Related to purpura (small hemorrhage in skin)
4. PIGMENTATION Hyperpigmented, hypopigmented, depigmented
DEFINITION Well-defined, Poorly defined
SHAPE
1. ANNULAR Shaped like / forming a ring (is there a difference between edge & center?)
2. ARCUATE Like an arc (annular, but not complete
3. UMBILICATED With a central depression (like umbilicus)
4. SYMMETRY Symmetric, asymmetric
5. EXOPHYTIC Growing outward
6. ENDOPHYTIC Growing inward
INDURATION Hardness
DESQUAMATION Epidermis peeling off
DISTRIBUTION
1. LINEAR
2. CONFLUENT Lesions merge / run together
3. ZOSTERIFORM Band-like distribution along dermatome (usually unilateral)
TELANGIECTASIA Visible small blood vessels near surface of skin
Primary Lesion 1. Macule / patch 2. Papule / plaque / nodule 3. Vesicle / bulla 4. Pustule
DEFINITION 1. Well-defined 2. Ill-defined
OTHER (color, shape,
distribution, etc.) 1. Scaly? Crusted?
Excoriated? 2. Linear? Annular?
Umbilicated?
3. Erythematous? Hyperpigmented? Hypopigmented? Purpuric?
4. Atrophic?
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Histopathology of the Skin Overview (Superficialdeep)
1. Epidermis 2. Dermis (papillary rete) 3. Subcutaneous tissue
Epidermis Layers: 1) Stratum corneum: anucleate; basket weave
appearance, thickness changes with anatomic site 2) Granular cell layer (stratum granulosum): thickness
varies with SC thickness; basophilic keratohyaline granules present
3) Stratum spinosum (spinous layer): 5-10 layers; flatter towards the top, connected by desmosomes (site of blistering problems in some conditions)
4) Basal layer: single layer ovoid cells; perpendicular to basement membrane zone, more basophilic, variable amounts of melanin
5) Basement membrane zone: bonds epidermis/dermis; PAS+; site of blistering disorder problems (structural abnormalities / inflammatory disruption)
Cell types: 1) Keratinocytes: most cells; mature as you go up 2) Melanocytes: about 1 out of 10 cells; in basal layer,
synthesize melanin, transfer to keratinocytes via dendritic processes
3) Langerhan’s cells (dendritic cells, antigen-presenting, have tennis-racquet-shaped Birbeck granules)
4) Merkel cells (sensory receptors)
Dermis Papillary dermis (pegs) Reticular dermis (underneath) Thicknesses depend on anatomical site Contains:
collagen, elastic fibers; GAGs
vessels/nerves
Mast cells (inflammation, etc.)
adnexal structures: o Hair follicles: note that hair shaft itself is multi-layered
Terminal anagen hairs: skin scalp (what we think of as hair) Vellus hair: nose, forehead (can’t really see). Male pattern baldness = transition from terminal
antigen to vellus hair on scalp o Smooth muscle (arrector pili goosebumps) o Eccrine units: dermal sweat glands, dump into ducts, merocrine secretion (exocytosed) o Apocrine glands:
from hair/epidermial germ;
SKIN COLOR Skin color depends NOT on the NUMBER of melanocytes you have but instead the amount of pigment they produce.
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duct enters at infundibulum; similar to eccrine duct but gland has apocrine secretion (secretion via budding of PM).
Mostly in axilla/anogenital region but also external ear canal (ceruminous), eyelids, breast (mamillary): few non-functional on face, scalp, abdomen; more prominent in acral skin
Anatomic variation Acral sites:
hyperkaratotic stratum corneum
nerve-end organs: o Pacini corpuscles (onion/shaped; palms/soles + some on nipples/anogenital, sense pressure) o Meissner’s corpuscles (ventral hands/feet; mediate sense of touch)
No hair follicles Mucosal sites: no granular cell layer or stratum corneum Scalp: increased anagen hair follicles Nipple/scrotum: increased smooth muscle bundles Periorbital/perioral/perinasal/neck: skeletal muscle (neck, orbicularis oculi, etc.) Nail unit: nail bed under nail plate; cuticle. Note that things under cuticle can leave marks as nail grows (diagnostic help)
Dermatopathology Pathologic conditions affecting skin and mucosal tissue
benign/malignant tumors, inflammatory conditions, deposition disorders, infections Diagnosis: clinical history is key! Exam + demographics + history, etc. Inflammatory skin conditions: Diagnosis
1. Look for epidermal alteration a. Thickening (acanthosis = diffuse epidermal hyperplasia; rete hyperplasia) b. Atrophy c. Spongiosis (fluid): typically due to eczema; white space between keratinocytes, serum in SC d. Dyskeratosis/lichenoid tissue reaction (being eaten away?) e. Blistering (separation of layers)
i. Fluid separation within/beneath epidermis ii. Can be from spongiosis, cytolysis of keratinocytes, acantholysis (loss of cell/cell contact); BMZ
destruction, liquefactive necrosis iii. Can be tense (subepidermal separation) or flaccid (transepidermic usually)
f. Stratum corneum alteration (hyperkeratosis, neutrophils in cornea) g. Cellular atypia (lymphoma, leukemia, breast cancer, melanoma, nevi)
2. Look for infiltrates a. Where is it? Dermal/epidermal junction, around vessels, interstitial, etc. b. What is it? Lymphocytes +/- eosinophils, granulomatous, etc.
i. Urticaria (hives): PMNs & eosinophils ii. Arthropod bite: lymphocytes & eosinophils in wedge shape
iii. Drug hypersensivity: spared epidermis; mostly perivascular lymphocytes in dermis
3. Miscellaneous findings a. Fat alteration (paniculitis)
i. erythema induratum = thickened septae; erythema nodosum: whole lobule + septae involved b. Amyloid deposition (yellowish, can pinch & produce purpura) c. Cysts d. Cancer/precancerous:
i. Actinic keratosis: precancerous, basal layers abnormal ii. Squamous cell carcinoma (in situ / invasive) basal cell carcinoma)
Acral: extremities of peripheral body parts
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Acne & Rosacea Things in bold, caps, underlined = things she said we should know
Acne Vulgaris: Pathogenesis Self-limited condition of the pilosebaceous unit (hair follicle + associated sebaceous gland) Sebaceous gland: all skin with hair follicles (all but palms/soles)
Sebocytes mature, accumulating more lipid secrete by holocrine (decapitation: cell dies & releases contents)
Sebum is secreted product o KEY: SQUALENE AND WAX ESTERS DISTINGUISH SEBUM FROM
LIPID IN INTERNAL ORGANS
Activity fluctuates with age (and men>women) o high at birth, quiescent 2-6yo, increases @ 7yo o peak in 20s, gradual decline with age (decrease per decade:
men < women)
Androgens explain fluctuation: o sebum production corresponds to adrenarche,
not puberty o DHEAS (weak androgen) is locally converted to
testosterone & DHT (stronger) to stimulate sebum production (DHEAS ↑ in adrenarche although systemic T & DHT not ↑ til puberty)
Comedogenesis (comedon = acne lesion)
Keratinization pattern altered inside hair follicle
Normal: loose organization; many lamellar granules, few keratohyaline granules)
Changes: ↑density, ↑structure, ↑keratinocyte turnover & ↓apoptosis
o Etiology unclear: ↓linoleic acid, ↑ IL-1α, ↑androgens?
Keratin shed, forms whorls, plugs follicle
Resident flora: Proprionibacterium acnes
P. acnes is GRAM NEGATIVE, NON-MOTILE, MOSTLY ANAEROBIC
No formal link between P. acnes & acne o Probably normal flora, protective role usually
(but ↑↑ in acne pts) Possible mechanism of pathogenesis:
1. P. acnes has lipases that break down sebum (+ proteases, hyaluronidases too)
2. Production of FFA + other molecules inflammation 3. cytokine (IL-1α, TNFα, IL-8 ) release by kera tinocytes & local inflammatory cells 4. chemotaxis of T-lymphocytes & neutrophils damage follicular epithelium 5. Hair follicle keeps dilating; sebaceous gland atrophies scarring
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Acne vulgaris Comedo/comedone = initial lesion
Closed comedone: slightly elevated, 1-4mm papule, mostly face (“whitehead”) o Has lamellated/whorled keratin; not inflammatory grossly but infiltrate on path
Open comedone: similar but communicates with surface of skin (“blackhead”)
o Color from melanin deposition
Papulopustle: after progression; more inflammatory (erythema + tenderness + induration)
Overlying pustule (pus blocks follicle) Nodulocystic acne: inflammation persists, becomes deeper; keratin shedding blocked (scarring imminent)
Acne Fulminans (“acute febrile ulcerative acne”) Severe form of nodulocystic acne accompanied by systemic symptoms & signs
Sudden onset, mainly in teenage boys o massive inflammatory, tender lesions on back + chest; rapidly ulcerate; heal
with scarring o Febrile, leukocytotic (10-30k WBC/mm3) o Polyarthralgias, myalgias, other systemic complaints; +/- lytic bone lesions in
tender bones o Often require hospitalization: can be a derm emergency!
Neonatal acne 20% newborns; 2-3 mo; spontaneous remission without scarring
Infection with Malassezia furfur (yeast)
Presentation: inflamed papules on cheek, across nose/forehead
Infantile acne 3-6mo, improves by 1yo but can persist for yrs
Hormonal imbalances are key o boys: LH/Testosterone; DHEAS in both from immature adrenal gland
Occupational acne A.k.a. “chloracne”; from occupational exposure (chlorinated aromatic hydrocarbons)
o Cutting oils, petroleum products, coal tar derivatives, electrical conductors/insulators, insecti/fungi/herbicides, etc
Classic: big nodules behind ear, on cheek/scrotum
o E.g. Victor Yushchenko post-dioxin poisoning attempt
Drug-induced acne Key clue: Monomorphic (all in same phase of evolution)
TONS of meds can cause it (EGFR inhibitors are newest but also anabolic steroids, lots more)
Endocrine acne Cystic acne in association with other signs of hyperandrogenism (hirsutism, irregular menses, infertility, obesity)
Polycystic ovary syndrome: #1 endocrine abnormality in US (5% women) o Diagnosis of exclusion (oligomenorrhea + clinical/biochemical hyerandrogenism)
High glycemic index of western diet might be involved in prevalence of acne in developed countries
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Rosacea Less well understood
Cutaneous reaction that initially presents with flushing of skin o Flares with remissions
Pathogenesis
Vascular dysfunction (blood flow ↑ vs regular skin, vessels dilated, blood/inflammatory substances extravasate)
Microorganisms (maybe?) – Demodex folliculorum (mite)?
Neurologic dysfunction: o Parkinson’s patients often develop o Hot drinks / emotions / alcohol can trigger flares!
Clinical manifestations (subtypes)
Vascular rosacea Earliest stage: recurrent blush, start of telangiectasia (nasal ala cheeks)
Degree: related to degree of sun damage
Edema + burning/stinging (when applying products to face, for instance
Inflammatory rosacea Small papules/pustules deep persistent nodules
Deeper red than acne; no comedones or follicular keratinization defects
Sebaceous hyperplasia & phymatous rosacea Overgrowth of sebaceous glands is prominent in some patients
Rhinophyma = nasal sebaceous hyperplasia o Swelling/smoothening of nose enlarging pores / lumpy fibrosis later (permanent) o Path: too many sebaceous glands!
Ocular rosacea > 50% of rosacea patients: “dryness / tired eyes”
Edema / tearing / pain / blurry vision / styes / chalazia (other features too, can be pretty severe)
Possibly due to meibomain impaction (glands that secrete lipids in tears) ↓lipid in tear film
Steroid-induced rosacea Prolonged use of topical steroids on face (or could be systemic)
Clues: lesions on UPPER LIP, EYELIDS, AROUND NOSE
Withdrawing steroid “ANGRY FACE” syndrome (initial flare, then recedes)
Epidemiology
Females > Males
30-50 yo usually
N. Europeans > Asians > Others
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Cutaneous Autoimmune Bullous Diseases: Pemphigus & Bullous Pemphigoid
Pemphigus Vulgaris Pemphigus (Greek: “Blister”)
Painful blisters of mucous membranes / skin o stratified squamous epithelium only (not respiratory
epithelium, etc.) o Large erosions, weeping, can recur explosively; flaccid vesicles o Intraepidermal blistering
Peak: 30-50 yo; natural history = 50% mortality @ 2yrs, 100% @ 5yrs
Oral lesions at first skin lesions later Pathology: no inflammatory cells but tons of antibodies (IgG fluorescence everywhere) Genetics: MHC Class II genes
DR4 (Ashkenazi Jews) or DQ1 (other populations)
Everybody with pemphigus has the mutation, but only 1:10,000 with the mutation develop pemphigus
Desmosomes are key
cell-cell junctions in epidermis, keratin filaments in cell desmosomal plaque desmogleins/desmocollins hemophilic interactions with next cell
Auto-antibodies against desmoglein proteins o Epitope expansion can occur over time (antibodies
against new desmoglein epitopes); corresponds with progression of disease
As long as Ab bind, cell detachment happens (see slide: mouse models tried to block other points).
Weird: cell adhesion is complex. Why would blocking just one component block adhesion? Nobody knows exactly why (complex cell signaling pathways)
Treatment Implications:
need drugs that reduce autoantibody synthesis
doesn’t help just to reduce inflammation
remission is slow (12-24mo) Treatment options:
Apherisis (too invasive)
IvIG (give lots of Ab, body starts chewing them up – including anti-Dsg autoAb)
Usually start with prednisone in high doses
Add purine synth inhibitors (azathioprine; block T/B cell synth), IvIG / Rituximab (anti-CD20 mAb), cyclophosphamide (alkylating agent), plasmapheresis, etc. as needed
Bullous pemphigoid
Elderly patients (60-80yo)
Large, dramatic, pruritic blisters on skin (not painful)
Presentation Auto-Ab against…
Pemphigus foliaceus Desmoglein 1 Pemphigus vulgaris (oral only) Desmoglein 3 Pemphigus vulgaris (oral + skin) Desmogleins 3 + 1
Paraneoplastic pemphigus Dsg 3,1 + plakin proteins + more
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o On base of large inflammatory process o mucosal lesions uncommon
Hemidesmosome antigen is target of IgG + complement
Antigen right near cell membrane (extracellular, in lamina lucida)
Subepidermal blistering (IgGs found in basement membrane zone) Blocking steps of cascade blocks blister formation (PMNs are critical) Treatment implications
Suppress inflammation & wait for remission
Bigger menu of drugs to choose from Treatment: Anti-inflammatory
Topical steroids sometimes; tetracycline / methotrexate/ niacinamide for mild cases; maybe dapsone for some
Can use prednisone in lower doses (purine synth / cyclophos / etc rarely, in lower doses)
PEMPHIGUS VULGARIS BULLOUS PEMPHIGOID
COMMON FEATURES
Rare
Antigen targets known
Auto-Ab are pathogenic (not just markers)
AGE OF PATIENT Middle-aged (30-50 yo) Elderly patients (60-80 yo)
BLISTERS: Painful Large erosions, weeping, can recur explosively; flaccid vesicles
Painless but pruritic Large, dramatic blisters on skin
MUCOUS MEMBRANES Involved (oral skin) Involvement uncommon
TARGET Desmosome Hemidesmosome
LEVEL OF SEPARATION Intraepidermal Subepidermal
INFLAMMATORY
REACTION None Big
BLOCKING STEPS OF
DETACHMENT CASCADE Blocking steps of cascade doesn’t help: Ab binding sufficient to cause blistering
PMNs are critical: if you block PMN activity, cascade stops (Ab binding insufficient by itself)
TREATMENT IDEA Block Ab synthesis; slow remission Reduce inflammation; wait for spontaneous remission
THERAPY OPTIONS High doses (immunosuppressive levels); few drugs available
Lower doses (anti-inflammatory levels), more options
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Psoriasis & Atopic Dermatitis Quick immunology review: Helper T-cells
Th1: key for clearance of intracellular pathogens; important in pathogenesis of autoimmune diseases
Th2: key for clearance of parasites & allergic reactions (IgE); important in pathogenesis of allergic diseases
Dendritic cell / T-cell Signaling (immunological synapse)
Dendritic / APC cell presents antigen on MHC
MHC + antigen binds complementary T-cell receptor on matching T-cell
Other costimulatory molecules are key: e.g. ICAM-1 (APC) / LFA-1 (T-cell), LFA-3 (APC) / CD2 (T-cell)
Combination of signals leads to T-cell activation
Psoriasis Chronic disorder; polygenic predisposition + triggering factors
Pathogenesis:
Th1 cells are key (cytokines: IFNγ, TNFα, IL-2): autoantigen in skin probably triggers Th1 rxn
Results: o Epithelial hyperproliferation, vascular proliferation o PMNs recruited + T-cell mediated immune reaction
Type Photo Description Other
Plaque psoriasis
Palpable plaques, silvery scale are classic Extensor surfaces (knee / elbow), sacral
Most common form; “Auspitz’s sign”= bleeding on removal of plaque.
Guttate psoriasis
Well-defined, smaller, discrete papules (still with silvery scale)
Younger patients (esp several weeks post strep infection)
Pustular psoriasis
Generalized, lakes of coalescing pustles on background of erythema Palmoplantar surfaces
Nail psoriasis
Onycholysis (distal lifting of nail bed); oil spots on nail bed, nail pits
Psoriatic arthritis
Mono / asymmetric arthritis (DIPs mostly) Arthritis mutilans severe disability Spondylitis/sacroilitis possible too
Can present like RA (symmetric polyarthritis) too
Other forms: Erythrodermic psoriasis (diffuse, all over the place), scalp psoriasis, inverse psoriasis (not classic with silvery scales but erythematous plaques instead)
Epidemiology of psoriasis
Males = females
30% develop dz < age 20
2% of general pop
10-30% pts psoriatic arthritis
Certain HLA subtypes associated (HLA Cw6 = 13x RR)
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Treatment: 1. Address triggers (trauma, infections, drugs that are exacerbating) 2. Topical treatment (corticosteroids are mainstay; vit D/retinoids/tar too) 3. Phototherapy (unless post-sunburn) 4. Systemic immunosuppresives if severe 5. Newer: TNFα antagonists, mABs, others
Atopic dermatitis Relapsing, pruritic skin disease Pathogenesis:
Th2 cells are key (cytokines: biphasic) o Acute atopic dermatitis: Th2-mediated (IL-4, IL-5, IL-13) o Chronic atopic dermatitis: Th2 and Th1 (IFNγ, IL-12) o T-cells, eosinophils, monocytes activated; IgE increased
Skin barrier defective: ↑ cutaneous superinfections; fewer lipids/FA in AD pts
Polygenic inheritance pattern (autosomal dominant) o 81% of kids with 2 AD parents will have AD; 60% adults with AD have kids with AD
o Stronger correlation between siblings with AD (environmental factors too)
“Atopic march”: associated with other atopic disorders
Food allergy (30% AD pts)
Asthma (30-60%)
Allergic rhinitis (60-80%)
Diagnostic criteria: Must have: Pruritis + Eczema (typical morphology / age specific patterns,
chronic/relapsing)
Most will have: Early age at onset + Atopy (personal/family Hx, IgE reactivity, xerosis = abnormal dryness of skin / mucous membranes)
May have other features too Signs:
Dennie-Morgan folds under eyes (secondary to edema)
hyperlinear palms, keratosis pilaris (spiny papules)
Ichthyosis (plate-like dark scales on skin) Progression
Location Quality
Infancy
Skin folds, face, scalp, cheeks Extensor surfaces (not diaper area)
Erythematous + exudative
Childhood
Flexor surfaces; pityriasis alba (post-inflammatory hypopigmentation)
Often generalized xerosis (dryness)
Adulthood
Hand dermatitis common More ill-defined Lichenification (thickened epidermis) more common
AD IS NOT THE SAME AS ECZEMA
Eczema is a reaction pattern
Erythematous patches/plaques with epidermal changes (Scale/crust)
Can result from many causes o atopic dermatitis, irritant dermatitis,
allergic contact dermatitis, venous stasis, etc.)
Epidemiology of AD
Prevalence doubled in last 30 yrs in industrialized countries o 15-30% children, 2-10% adults
Females < Males (1.3:1) Often begins in infancy, 85% before
5yo; 70% remit before adolescence; 50% recur in adulthood; can start in adulthood: late-onset AD
Atopy: from Gr. atopos, “Strange or unusual”
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Cutaneous infections are common with AD
Impetigo (90% AD pts S. aureus colonized) Eczema herpeticum (superinfection with HSV) – discrete, punched out ulcers on background of atopic derm
Eczema vaccinatum (severe widespread eruptin post-smallpox vax or exposure to vaccinated people, 1:25k-30k)
Treatment: 1. Avoid triggers (irritants/allergens/heat/stress/etc): especially food allergies in children, bacteria + environment 2. Moisturize! (ointment>cream>lotion) 3. Mild soaps (Dove) 4. Topical therapy: steroids for flare-up, calcineurin inhibitors 5. Antihistamines: sedating for sleep, nonsedating for day 6. Treat superinfections 7. Phototherapy 8. T-cell suppression (corticosteroids to sequester T-cells, induce apoptosis; macrolides to block early phase of activation,
immunosuppressive agents like methotrexate or purine synth inhibitors if recalcitrant)
Other random conditions (Ddx of AD)
Contact dermatitis: irritant or allergic; sudden onset; linear / geographic (“outside job”), very pruritic
Lichen simplex chronicus: “elephant skin” or “tree-bark-like” with accentuation of normal skin markings; more common in adults; chronic itch-scratch cycle (can see in AD, contact dermatitis, psoriasis), hard to treat
Nummular eczema: coin-shaped, 1 or several well-demarcated pink plaques, fall/winter, easy to tx
Seborrheic dermatitis: infants: “cradle cap” (scalp + skin folds); adults: pruritis + greasy white-yellow scales + erythema on scalp/eyebrows/ears/central chest (where sebaceous glands are)
Tinea Corporis: fungal; one or more annular & polycyclic plaques, use scrape + KOH to diagnose
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Pigmented Lesions & Melanoma
Melanocytes:
from neural crest cells; found within basal layer of epidermis (1 melanocyte: 4-10 keratinocytes)
dendritic processes with clear cytoplasm & small, dark nuclei (use special stain), solitary cells (no desmosomes)
make melanin in melanosomes (organelles) keratinocytes via phagocytosis o makes UV-absorbing “cap” to absorb radiation
Benign pigmented lesions Description Location Patient Histology Other
Ephelide (freckle)
small clusters of macules, tan-red to brown, well-circumscribed
Sun exposed areas: nose, cheeks, shoulders, dorsal hands, arm
Common in children
↑ pigmenentation; ↑ transfer to keratinocytes (not increased local # melanocytes)
direct relation to sun exposure; recur in summer & fade in winter
Solar lentigo (“age spots” / “liver spots”)
Irregular evenly pigmented macules, tend to coalesce
Sun-damaged skin (face, dorsal aspects of hands/arms)
Common, middle-aged & elderly
Elongate of rete; no increase in # melanocytes
Incidence increases with age
Nevocellular Nevi (melanocytic nevus / “mole”): benign melanocytic neoplasms
Proliferation of melanocytes cohesive nests & aggregates o (do see ↑# melanocytes)
Transformation: lose dendritic processes, become round/oval, nuclei uniform
Acquired nevi:
Adolescence/early adulthood; enlarge stable involute (maximum in 20s, regress/disappear by 70s-80s)
Progression: normally distributed on BMZ, proliferate on junction, descend to dermis, then lose melanocytes in junction 1. Junctional nevus (just at dermal/epidermal junction)
a. symmetric, sharply circumscribed, flat, uniform medium/dark brown color b. No melanocytes in dermis, no atypia, regular size/shape/spacing of nests @ tips of rete ridges
2. Compound nevus (junctional & dermal nests) a. Raised/dome shape (involvement of dermis); uniform light/medium brown color, can be hairy b. Dermal melanocytes mature with descent (deeper cells smaller/less pigmented/less nested); no atypia
3. Intradermal nevus (now in dermis) a. Raised lesions, light brown / flesh colored, can be hairy b. Dermal melanocytes maturing with descent like above but in nests/cords/sheets, pushing upwards
Clinical features of benign acquired nevi
Symmetrical
Regular borders
Uniform color
Small (<5mm) (Compare to melanoma, which
inexorably progress)
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Congenital nevocellular nevi
Present at birth, big variation in size (few mm “bathing trunk”)
Varied appearance (can be asymmetrical, geographic borders but with uniform pigmentation, +/- hair growth)
Increased risk of melanoma in affected areas
Singular melanocites with dendritic morphology in lower 2/3 dermis
Other acquired melanocytic lesions 1. Dermal melanocytosis (“Mongolian spot”)
o ill-defined patches, blue, Asian infants, birthfade by early childhood 2. Blue nevus
o Well-circumscribed, dome-shaped papules, small (<1cm), gray-blue/blue-black, o On dorsal hands/feet/face); present @ birth or any age o Mϕ chewing up melanin on path
Atypical (“dysplasitic”) nevi
Acquired, pigmented lesion on skin but with different clinical/histological features than nevi o Usually > 5 mm in diameter, symmetrical, regular but fuzzy borders, variations of pigmentation o Architecture: disordered (elongated/bridged rete “east-west” architecture) o Hyperplasia, cellular atypia (large nuclei, irregular nuclear membrane, etc) but not clonal
Some overlap with malignant melanoma o Abnormal ABCDE but clinically stable o Not necessarily precursor lesion but marker of ↑risk
50-100 dysplastic nevi = “atypical mole syndrome
Puberty can keep developing throughout life
Management: most don’t progress; follow with photos, biopsy for atypia; re-excise for severe atypia on biopsy
Melanoma Malignant growth of melanocytes
Location: skin/sun-exposed areas; can happen on mucosal too; can be de novo or from existing nevi
Pathophysiology: genetics, immune system (host); radiation, etc (environment) Histology: nests don’t mature; still make pigment as they go down; scattered throughout epidermis, diffuse atypia Risk factors
Increased episodic exposure of fair skin to sun (especially in childhood)
PMH or FHx melanoma; > 50 or irregular nevi, immunosuppressed pts too Familial atypical mole/melanoma syndrome(FAMM)
Melanoma in 1+ 1st/2nd degree relative, >50 moles, autosomal dominant condition
Develop melanomas at younger age, lifetime risk approaches 100% ABCDEs of Melanoma
Asymmetry: compare one half to another
Border: is it ragged/notched/blurred/irregular?
Color: is it uneven? (reflects histology)
Diameter: is it > 5mm?
Evolution: is it changing or evolving in size, shape, color, symptomatology? (use photos)
Epidemiology 8,400+deaths/yr, 60k cases/yr
5% skin cancers but >80% skin cancer deaths
1/75 lifetime risk in US (increasing)
53yo median age at dx
Most common cancer in women 25-29, 2nd
to breast cancer in 30-34yo women
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Progression / growth phases
Growth phases: radial (epidermis only) vertical (dives down)
Stratifying by subtype does not improve prognostic information
1. In situ: no potential to metastasize, confined by basement membrane, no access to lymph / vasculature, can cure with excisional surgery
2. Invasive lesions Type Frequency Location Growth pattern Other
Superficial spreading
Most common (70%)
Upper back (+ legs in women)
Variable radial phase vertical phase
Sometimes changes in pre-existing mole
Nodular
20% Legs + trunk No radial, immediately vertical & aggressive
Lentigo maligna
5% older (mean age = 65 yo)
Sun-exposed skin (head/neck)
Long radial phase vertical phase
Cumulative instead of intermittent sun exposure,
Acral lentinginous
5% Acral sites (palms/soles/nail beds)
Most common subtype in darkly pigmented pts
Diagnosis/Prognosis
Biopsy is key for both (depth of invasion, # mitoses, ulceration, vacular invasion, sparse lymphocytic response?)
Breslow’s tumor thickness: MOST IMPORTANT histologic determinant of prognosis o top of granular cell layer to base of ulcer @ deepest point of invasion, 90° to epidermis
Staging: T1-4 by Breslow depth, N by LNs, M by metastasis o 0: in situ I: small, N0M0 II: larger, N0M0 III: N ≥ 1 IV: M ≥ 1
Treatment:
surgery (need to Dx early) o bigger excision doesn’t mean better survival (current guidelines: about 1cm margin per mm tumor)
immune system might be key; no single systemic therapy proven to extend life; combo therapy maybe?
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Non-Melanoma Skin Cancer
Basal cell carcinoma and squamous cell carcinoma are most common (also Merkel cell carcinoma, others) Pathophysiology
Host: genetics (skin type, mutations in repair pathways, etc), immune system
Environment: solar radiation, viruses, ionizing radiation, chemicals/trauma Triggers
UV light is big one (90% cancers have signature UV mutations; on sun-exposed areas)
Immunosuppression (100x risk increase for transplant patients); viruses like HPV
Genetic mutations: p53 in SCC, Sonic Hedgehog pathway in BCC
Basal Cell Carcinoma Clinical features:
Waxy, pearly, translucent, persistent
Friable (bleeds easily), ulcerated, pink scaling plaques
90% on sun exposed areas (head neck, other areas depending on culture)
Locally aggressive: usually doesn’t spread/metastasize (instead infiltrates surrounding area & destroys tissue)
High cure rate but 20-40% chance of developing another case Pathophysiology: mutations in SONIC HEDGEHOG PATHWAYS
Genes encoding patched homolog (PTCH1), smoothened homolog (SMO) o Usually hedgehog stimulates patched, which inhibits smoothed, which sends a signal for growth if not inhibited
Results in unrestrained growth
Squamous Cell Carcinoma Clinical features
Keratotic/scaly plaques on erythematous base
Ulcerated / crater-like / friable
75% on head / neck / hands
Invades more than BCC (LN, lungs, etc): risk of metastasis 0.5-5% Pathophysiology: mutations in P53
Often 2 hits: one leads to dysplasia, second leads to invasiveness
Progression:
1. Actinic keratosis (precursor lesion, can be detected & cured)
a. Rough scaly spot on red, irritated base; can shed & recur b. Sandpaper texture (sometimes more easily felt than seen), can have more than 1 c. 90% go away on their own (immune system: transplant patients can’t clear)
2. SCC in situ 3. Invasive metastatic SCC
Random facts: SPF only tells you how good a sunscreen is against UVB radiation ABCDE doesn’t help so much with these cancers (more for melanoma)
Epidemiology:
#1 skin cancer (incidence) o 80% new skin cancer cases o Annual incidence 0.1-0.5%
4:1 BCC:SCC in clinic
Epidemiology:
#2 skin cancer in gen pop
300k/yr in US
#1 cancer in transplant pts
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Treatment BIOPSY BIOPSY BIOPSY BIOPSY BIOPSY BIOPSY BIOPSY BIOPSY…
Lots of treatment options One cool new treatment is Moh’s micrographic surgery: can check 100% of margin while pt waiting & take out more
Consider: tumor type, age, cosmetic results, #/size lesions, distinctness of borders, 1° vs recurrent, location
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Dermatology of Pigmented Skin
People have different colors of skin. A majority of Baltimore & soon the US will be people with skin of color.
Non-white ethnic groups tend to have poorer health care outcomes
Know the answers to these questions below
What determines skin pigmentation? AMOUNT OF MELANIN PRODUCED BY MELANOCYTES (melanosome activity) Number of melanocytes generally constant
Pigmentation differences from melanosome activity (#/size/composition/distribution)
Melanosomes: dendritic cells; produce/distribute melanin to keratinocytes, functions for photoprotection o Pheomelanin (red/yellow melanin): light/dark skin, especially red-heads, women>men
Can become carcinogenic when exposed to UV light o Eumelanin (brown/black): abundant in dark-skinned people
Epidermal-melanin unit: melanocyte + its 30-40 keratinocytes
What is the rate-limiting enzyme in melanin biosynthesis? TYROSINASE Melanosomes: organelles that contain melanin; exported to surrounding cells. Matrix proteins + enzymes
o 4 stages of development (1=no melanin, type 4 = lots of melanin) o Different skin types have different predominant melanosomal stages (dark skinned = has more stage IV)
Tyrosinase is rate-limiting (part of DOPA/etc pathway) – deficient in some albinism pts
Darker skin: more melanized melanosomes (later stages); bigger, more melanosomes/cell, slower degradation
Differences in epidermal structure: Melanosomes in black skin are larger, individually dispersed in keratinocytes WHITE BLACK ASIAN
Stratum corneum Thicker, fewer layers Thinner, more layers Stratum lucidum Swells with sun exposure No change with sun exposure Water barrier Higher Lower Lipids in SC Fewer More Melanosomes Smaller, grouped in KC, more
numberous in SC than basal layer
Larger, individually dispersed in KC, more numerous in basal layer
Grouped but individually dispersed in sun-exposed areas
Vitamin D production High Low Photodamage Big changes Less changes Big changes
Differences in dermal structure: More dilated blood/lymphatic vessels in Black skin (nobody knows why) Dermis = collagen + elastic fibers + interfibrillar matrix (GAGs & water)
Also: less solar elastosis, thicker/more compact than white skin
WHITE BLACK
Dermis Thinner / less compact Thick / compact Paipillary/reticular layers More distinct Less distinct Collagen fiber bundles Bigger Smaller, closely stacked Lymphatic vessels Moderate/dilated Many, dilated, empty Fibroblasts Fewer, some binucleate cells Many, many binucleated cells Elastic fibers More, more evidence of solar
elastosis Less, little evidence of solar elastosis (photodamage)
Superficial blood vessels Sparse / moderate More numerous, mostly dilated
Most derm diseases have WORSE PROGNOSES IN BLACK PATIENTS than in white patients Vitiligo (depigmented patches)
Sarcoidosis
Pseudofolliculitis barbae (Razor bumps)
Keloidosis (more common in AA/Asian pop, can lead to scarring / disability)
Traction alopecia from braids, etc.
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Birthmarks in Babies
Neurofibromatosis Type I (BROWN) Autosomal dominant, 50/50 spontaneous mutations & inherited, multisystem disorder, 1/3500 people, variable expression, nearly 100% penetrance by age 20
Diagnostic Criteria: NEED 2 OF 7 6+ café au lait macules (>5mm pre-puberty, >15mm post-puberty) 2+ neurofibromas of any type, or 1+ plexiform neurofibroma Freckling in axillae / groin (Crowe sign) Optic glioma 2+ Lisch nodules Dysplasia of sphenoid; dysplasia or thinning of long bone cortex 1st degree relative with NF1
Comprehensive screening finds mutations in >95% individuals – only indicated if they’re at risk Clinical findings
Finding Picture Description Age
Café au lait macules
Need 6+ (2 SD from mean) Increase in number throughout childhood
Skin fold freckling ( Crowe sign)
Most specific, nearly pathognomonic finding
90% adults have freckling
Neurofibromas
Hallmark sign; dome-shaped,
soft, fleshy, skin-colored to slightly hyperpigmented / firm / nodular; major source of morbidity (not painful though)
Onset at puberty Increase in size/# throughout adulthood Grow most in puberty & pregnancy
Plexiform neurofibromas
Feels like “bag of worms”; disfiguring, can threaten function of area, 8-12% develop malignant tumor
Usually congenital
Tuberous Sclerosis (WHITE) 1/6k-10k, autosomal dominant Can include seizures / multisystem hamartomas / brain/skin/heart/lungs/kidney, along with derm abnormalities Findings around infancy:
Cardiac rhabdomyomas (often detected on prenatal U/S) o 50-70% infants with TS have one; 96% infants with one will have TS! Often have several o Often Asx; in ventricular wall, can cause complications
Hypopigmented macules (“ash leaf spots” or more subtle “confetti macules”) at birth
Later findings
Seizures before age 1 (70-80%)
Angiofibromas (facial in adults, periungual, fibrous forehead plaques in ~20% kids)
Retinal (44% pts, call opthamology!) / pulmonary (bad prognosis) hamartomas
“Color-Coded” Birthmarks
Brown Neurofibromatosis type I White Tuberous Sclerosis Red Infantile Hemangiomas Yellow Nevus sebaceus
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Renal angiomyolipomas: 70-90% of adults, spontaneous hemorrhage is #1 complication o RENAL PROBLEMS ARE #1 CAUSE OF DEATH IN TS
Infantile Hemangiomas (RED) Vascular tumor, not malformation; COMMON (4-10% white infants)
Nearly all double in size in first 2 months, reach 80% size in 3-5 months, then regress 10%/yr (50% regress @ 5yr, etc)
Can complicate: big size, on face, segmental morphology is bad PHACE(S) Syndrome: need 2 of these Posterior fossa malformation Hemangiomas Arterial anomalies Coarctation of aorta Eye anomalies (S)ternal clefting +/- supraumbilical raphe
9:1 females:males, 20% of pts with facial segmental hemangioma are PHACE(S) Means a more complicated presentation: associated with structural brain & CV anomalies, 50% have neuro sequelae New therapy for severe hemangiomas: Propranolol (β-blocker) – nobody knows how it works
Nevus Sebaceous (YELLOW) 1/300 newborns; Definition:
small immature sebaceous glands with abortive hair follicules
Raised at birth (mom’s hormones) less warty with time flare up again in puberty
May need surgical intervention (scalp / central face) Risk of malignant change:
Formerly thought it was around 31% but most of these were benign growths
BCC in 0.8%, NO malignant tumors in children, (4 benign tumors) Nevus sebaceous syndrome: EXCEEDINGLY RARE; large nevus sebaceous + mental retardation / neuro signs. NOT IN NORMAL NS
Risk factors: KNOW THESE
Females (2-3:1)
White, non-Hispanic
Premature
LOW BIRTH WEIGHT is #1 (40% ↑/ 500g ↓in weight)
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Drug Eruptions Background: 2.2% - 13.6% inpts have drug rash, 75% from antibiotics, 94% exanthematous/morbiliform
Drug-induced Reaction Patterns: think of pattern for diagnosis! 1. Exanthemous / Morbilliform
Exanthemous drug eruption
Drug hypersensitivity syndrome
2. Erythema Red man syndrome
3. Urticarial Urticaria
Serum-sickness-like reaction
4. Blistering Fixed drug reaction
Drug-induced pemphigus, pemphigoid, linear IgA
Stevens-Johnson
Toxic epidermal necrolysis
5. Pustular Drug-induced acne
AGEP
Exanthemous / Morbilliform PICTURE DESCRIPTION OTHER
Exanthemous drug eruption exanthem: “bursting out”
Morbilliform (“maculopapular)
Pink / red / salmon
Macules/papules, can be confluent
Can spread symmetrically (headtrunk)
#1 drug eruption (94%)
Starts within 1wk of exposure (semi-synthetic PCNs > 1wk)
Resolve 1-2wk post cessation
Antibiotics are #1 cause (anti-convulsants too)
Management: stop offending agent, antihistamines, topical corticosteroids +/- systemic steroids as needed
Drug-induced hypersensitivity
Similar to exanthemous drug eruption + systemic
DRESS syndrome: Drug Rash with Eosinophilia and Systemic Sx
Fever/malaise / cervical LAD / eosinophilia
Skin eruption (exanthema / exfoliative dermatitis)
Internal organ involvement (Liver: hepatitis + jaundice, 50% elevated LFTs, renal, CNS, pulmonary)
Occurs after first exposure, 2-6wks afterwards
1 in 1k-10k taking anticonvulsants, sulfonamide abx
Allopurinol too
Mortality ~10%!
Management: MUST STOP offending agent; +/- corticosteroids, topical steroids & antihistamines for Sx
Erythema PICTURE DESCRIPTION OTHER
Red Man Syndrome
Pruritis
Erythema: face, neck torso
Related to Vancomycin exposure (rapid infusion; don’t see much anymore), others too
Within 10m initiation or completion of infusion
Histamine release involved
Management: antihistamines (incl. pretreatment); discontinue infusion
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Urticarial PICTURE DESCRIPTION OTHER
Urticaria
Red, erythematous, pruritic papules / plaques (wheals) with pale halo
2nd
most common drug eruption (5%)
Benign, transient
Type I / IgE-mediated hypersensitivity (think about anaphylaxis, watch BP if extensive rash)
PCN & derivatives #1 cause, also ACE inhibitors
Angioedema: subcutaneous fat / deep dermal tissue rxn
Management: discontinue drug, ± antihistamines, ± corticosteroids
Serum-sickness-like reaction (SSLR)
Urticaria & angioedema
Fever & arthralgias
Serpiginous / erythematous / purpuric eruption at lines of transgradiens on hands/feet (where plantar/palmar surfaces meet
Serum sickness: injection of “protein” that induces immune response, deposition of immune complexes in vessels, etc.
SSLR: from non-protein drugs, NOT associated with circulating immune complexes
1-3wks post exposure, after 2nd
-3rd
exposure, F>M
Cefaclor / buproprion are top 2 drugs
Blistering PICTURE DESCRIPTION OTHER
Fixed drug eruption (FDE)
Sharply demarcated, round, dusky, erythematous/edematous plaques
Happens at same anatomic site each time exposed (weird!)
Genetalia / lips / hands / feet
Resolves over 2-3wks, post-inflammatory hyperpigmentation
Tetracyclines & sulfonamides often, anticonvulsants too
Stevens-Johnson Syndrome
Fever, cough, malaise
Macula exanthema (can blister)
Mucous membrane erosions at 2+ sites
< 10% body surface area
Mortality 5% - EMERGENCY!
Histology: full thickness epidermial necrosis & blistering, no SC involvement (FAST)
Management(TEN too): ID/stop drug, IVF & supportive care, get to BURN UNIT
Toxic epidermal necrolysis (TEN)
Think of it like more severe SJS
Fever, pruritis, conjunctivitis (non-specific)
Painful skin (plaques, target lesions, erythema, sheet-like loss of epidermis, blisters spread with lateral pressure = nikolsky’s sign)
>30% body surface area
Mortality 30-50%: BIG EMERGENCY!
Histology, management like SJS – GET TO BURN UNIT
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Pustular PICTURE DESCRIPTION OTHER
Acute generalized exanthematous pustulosis (AGEP)
Acute pustular eruption but sterile (no bacteria)
Facial edema, fever + leuckocytosis, 100s of sterile pustules
Resolves 1-2 wks
Allopurinol, macrolides + PCN/derivatives (Abx + anticonvulsants)
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Cutaneous Manifestations of Internal Diseases
Oncology PICTURE DESCRIPTION OTHER ASSOCIATED DISEASES
Cutaneous Metastasis
Firm papules/nodules that are often bound down (“rubbery & connected”)
± ulceration
Side lighting can help
10% all metastasis, 75% skin metastasis is first sign of extranodal spread
Metastasis spreading upwards, invading dermis, chewing up everything, full of atypia
Breast / lung / GI / skin cancers
Leukemia Cutis
Small (2-5mm) pinkish, non-tender papules
Localized / diffuse skin infiltration by leukemic cells
Can be sign of leukemic cells in peripheral circulation
In dermis: epithelial structures /markings still intact
Leukemia
Paraneoplastic Pemphigus (PNP)
Severe mucosal ulceration and polymorphic eruptions associated with neoplasia
Erythema multifome-type lesions
Friable
Vermillion border involvement
Overlap with both pemphigus vulgaris & bullous pemphigoid
Intraepidermal split (like pemphigus)
Direct/indirect immunofluorescence like pemphigus
immunoprecipitation (+) on transitional epithelium of bladder: like bullous pemphigoid)
TONS of types of auto-AB – very polymorphic
very poor prognosis (doesn’t get better)
CLL/large cell lymphoma/NHL, Waldenstrom’s macroglobulinemia
Bullous Neutrophilic Dermatosis
Rapidly expanding, very painful, ulcerative lesions
Pus: sea of PMNs
Looks like bad infection but is aseptic process (can be superinfected though)
Violaceous hemorrhagic border
DEBRIDING BAD (if you traumatize lesion, it grows)
No antibiotics: want to immunosupress (prednisone, CSA)
Lymphoreticular system malignancies
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Gastroenterology PICTURE DESCRIPTION OTHER ASSOCIATED DISEASES
Peutz Jeghers
Early life: hyperpigmented macules (lips, buccal mucosa, palms/soles / periorifical)
Macules fade except on buccal mucosa (stay til adolescence)
Herditary polyposis (autosomal dominant, high penetrance)
GI: Hamatomatous polyps (mostly small bowel, low malignant potential, mostly recurrent pain)
Acrodermatitis Enteropathica
Infancy: acral dermatitis, alopecia, diarrhea
Dry, scaly, eczematous patches/plaques early, then evolve into vesiculobullous/erosive lesions
Autosomal recessive
Can be acquired (dietary Zn deficiency, failure of GI absorption, nephrotic syndrome, bypass surgery)
Lab: anemia, low serum/urine Zn
GI: Zinc absorption disorder
Glucagonoma Syndrome (migratory necrolytic erythema)
Edge-active skin lesions (blisters, crusting, scales)
Periorificial and intertriginous dermatitis / erythema
Glossitis (red tongue) + angular cheilitis (cracks at corner of mouth)
Lab: serum glucagon + abdominal CT
From excessive glucagon production (α-cell tumor of pancreas)
Endocrine / Metabolic
PICTURE DESCRIPTION OTHER
Necrobiosis Lipoidica Diabeticorum (NLD)
Well-demarcated, atrophic plaques
Yellow-brown color
Anterior / lateral surfaces of lower legs
Chronic, indolent, relatively asymptomatic
W>M (3:1)
2/3 with overt diabetes, rest have abnormal glucose tolerance
Pretibial Myxedema
Indurated (thick & firm) plaques/nodules
Flesh-colored
On pretibial areas of lower legs
Can be tender
Hyperthyroidism of Grave’s disease
/ recovering from thyroid storm
Acanthosis Nigricans
Diffuse, velvety thickening & hyperpigmentation
Axilla, other body folds, dorsum of hand
5 types
Hereditary
Endocrine (insulin resistance, acromegaly, Cushing’s, Addison’s)
Obesity
Drug-induced
Malignancy (usually GI adenocarc)
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Common Infections of the Skin New techniques: instead of growing bacteria (only see what you grow!) deep sequencing of rRNA with universal primers
Flora similar between people, different by site Skin is a defense organ
Physical barrier (SC) + constantly shedding
Chemical (low PH)
Immunologic (skin-associated lymphoid tissue)
Microbiological: normal skin flora occupy niche
Bacterial infections: Strep pyogenes and Staph aureus Streptococcus pyogenes (group A, β-hemolytic)
Not part of normal skin flora
Proteolytic enzymes: RAPID SPREAD through tissue planes; greater local invasion, lymph/vascular spread
Edema with scarce exudation
Impetigo, erysipelas, celulitis Staphylococcus aureus (coagulase positive)
Frequently found transitorily on skin
Coagulase abscess formation
Well-circumscribed, walled-off
Central fluctuation
Folliculitis, furuncles, carbuncles
Viral infections
Strep pyogenes skin infections (examples)
Impetigo Note golden crust
(dried serum)
Erysipelas Involves upper dermis, superficial lymphatics
Celulitis Involves deeper dermis and subcutaneous fat
Staph aureus skin infections (examples)
Folliculitis
Pilosebaceous unit Overlaps with acne
Furuncle (“boil”) Tense, pus-filled, tender,
drain eventually
DNA Viruses
Papova viruses HPV (warts / cancers) Poxviridae Molluscum contagiosum Herpes viruses HSV, VSV (note herpes zoster is VSV)
NORMAL SKIN FLORA
Cornyeforms (diptheroids) (GM+) o cornyebacterium, brevibacterium,
propionibacterium spp)
Staphylococci (coag neg) (GM+)
Micrococci (GM+)
Acinteobacter spp (GM-)
Proteus, pseudomonas,enterobacter (GM-)
M. furfur (yeast)
Demodex spp. (mite)
THE BIG PICTURE: SKIN INFECTIONS
Bacterial: homogeneous, tense red skin, or individual areas + pus (exudates, suppuration),dried pus/serum (crust)
Viral: can be diffuse immune rxn or localized with discrete areas of cytopathic damage
Fungal: often has leading edge activity with central clearing; often has scale
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HPV infection
WARTS (STI & otherwise)
Make sure to test for HIV & other STIs after Dx
100+ types, 30 infect anogenital mucosa, 12+ oncogenic o HPV-16 ≫ HPV-18,31,45 for oncogenicity
Cervical (+ anal, oropharyngeal, penile) cancers
Vaccine: gardasil (3 shots x 6 mo, 11-12 yo females)
Herpes simplex
2nd most common STD in US (after HPV)
HSV-1 > HSV-2
Most asymptomatic
Primary infection & recurrences (orolabial / genital)
o can reactivate with stress, UV light, etc
GROUPED ULCERS ON ERYTHEMATOUS BACKGROUND
Varicella Zoster Virus: Herpes Zoster (and chicken pox too)
latency in sensory dorsal root ganglion
outbreak with immunosuppression or age
PAINFUL erythematous papules and plaques in a dermatomal distribution
Vesicular / bullous within hours, neuralgia can persist for months
Molluscum contagiosum
Pox-virus
Patients: 1. Children (most common) 2. Sexually active adults 3. Immunosuppressed (HIV) 4. Atopic dermatitis
Smooth-surfaced, dome-shaped papules with characteristic umbilication
Custered around site of inoculation
Fungal infections Superficial infections: dermatophytoses (tinea corporis, cruris; onychmycosis, etc.) & candidiases
Deep fungal infections too
Use KOH prep for diagnosis
HSV infections
Generic HSV Grouped ulcers on
erythematous background
Orolabial Herpes “cold sore”
HSV-1 > 2
Genital Herpes HSV-2 > 1
HSV Epidemiology
75% population 15-49yo Subclinical infection:
15% gen pop, 23% HIV- MSM, 93% HIV+ MSM
Most infections: Asx and undiagnosed
Genital warts are just the tip of the iceberg
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Lesions: edge-active, scale, central sparing
Other answers to “test-type questions”
Which isn’t a common strep pyogenes infection?: (erysipelas, cellulitis, intertrigo, necrotizing fasciitis, impetigo)
Pox virus are DNA viruses
Infection Bug
Tinea versicolor Pityrosporum ovale (& M. furfur) Thrush Candida Albicans Superficial onychomycosis Trichophyton metagphraphes Distal subungual onchyomycosis Trychophyton rubrum
Fungal infections
Tinea Corporis
Microsporum canis, Trichophyton rubrum
Tinea Cruris Mostly men, inner/upper
thighs, “jock itch”
Tinea Capitis Mostly schoolchildren
T. rubrum, M. canis mostly (US)
Tinea Pedis / Manus Athlete’s foot: most common
T. rubrum mostly “sandal” distribution common
Onchyomycosis DSO, WSO, PSO
Tinea versicolor M. furfur
Name the infection
Intertrigo HPV Tinea Versicolor
Mostly schoolchildren T. rubrum, M. canis mostly (US)
Tinea Capitis
Molluscum Tinea Perleche
Basal Cell Carcinoma