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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