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

1
 The Dermatologic Vocabulary
Lesion morphology: shape and relative size of the lesion(s)
non-palpable, circumscribed, color change <1 cm; (“macular”
1. MACULE or “patch” are used to describe larger areas of the color junctional nevus
change)
molluscum contagiosum,
2. PAPULE palpable, circumscribed lesion, < 1 cm
intradermal nevus
palpable, circumscribed, relatively flat topped lesion, greater
3. PLAQUE psoriasis, lichen simplex chronicus
in surface area than in thickness, > 1 cm;
melanoma, squamous cell
4. NODULE palpable, circumscribed lesion, ≤ 1 cm and < 2 cm;
carcinoma
squamous cell carcinoma, basal cell
5. TUMOR large nodular lesion,≥ 2 cm
carcinoma
herpes simplex and zoster infections,
6. VESICLE clear fluid –filled lesion (blister), < 0.5 cm
vesicular foot dermatitis
bullous impetigo, toxic epidermal
7. BULLA clear fluid-filled lesion (blister), > 0.5 cm
necrolysis, bullous pemphigoid
8. PUSTULE turbid fluid-filled lesion folliculitis, acne
9. CYST nodule filled with a semisolid or liquid substance epidermal inclusion cyst
transient palpable lesion (hive) caused by an interstitial serous
10. WHEAL
fluid accumulation in the upper dermis
acne comedone, solar elastosis with
11. COMEDONE plugged pilosebaceous opening cysts and comedones (Favre-
Racouchot syndrome)
short, linear, thread-like lesion caused by the scabies mite
12. BURROW
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

accumulation of serous, cellular, squamous, and bacterial impetigo, secondarily infected

2. CRUST
debris over a damaged epidermis eczema

accentuated skin markings due to thickening of the

3. LICHENIFICATION lichen simplex chronicus
epidermis
4. EROSION tissue loss confined to the epidermis candidiasis

5. EXCORIATION erosion clearly caused by external factors neurotic excoriations

venous stasis ulcer, ulcerated basal
6. ULCER tissue loss extending into the dermis
cell carcinoma
7. FISSURE crack in the epidermis extending into the dermis perleche

8. SCAR fibrous tissue replacing usual dermal tissue space scarring alopecia
steroid induced atrophy, lupus
9. ATROPHY loss of substance of the epidermis and/or dermis
erythematosus
hypertrophic actinic keratosis,
10. HYPERKERATOTIC lesion with excessive “heaped-up” scale
squamous cell carcinoma
11. VERRUCCOUS vegetating, wart-like surface verruca vulgaris

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Further description:
COLOR Primary Lesion
1. ERYTHEMATOUS Reddened skin
1. Macule / patch
2. Papule / plaque / nodule
2. VIOLACEOUS Violet
3. Vesicle / bulla
Related to purpura (small hemorrhage in
3. PURPURIC 4. Pustule
skin)
Hyperpigmented, hypopigmented,
4. PIGMENTATION
depigmented
DEFINITION Well-defined, Poorly defined DEFINITION
SHAPE 1. Well-defined
1. ANNULAR
Shaped like / forming a ring (is there a 2. Ill-defined
difference between edge & center?)
2. ARCUATE Like an arc (annular, but not complete
3. UMBILICATED With a central depression (like umbilicus) OTHER
4. SYMMETRY Symmetric, asymmetric (color, shape,
5. EXOPHYTIC Growing outward distribution, etc.)
6. ENDOPHYTIC Growing inward 1. Scaly? Crusted?
INDURATION Hardness Excoriated?
DESQUAMATION Epidermis peeling off 2. Linear? Annular?
DISTRIBUTION Umbilicated?
1. LINEAR 3. Erythematous?
2. CONFLUENT Lesions merge / run together Hyperpigmented?
Band-like distribution along dermatome Hypopigmented?
3. ZOSTERIFORM
(usually unilateral) Purpuric?
Visible small blood vessels near surface of 4. Atrophic?
TELANGIECTASIA
skin

3
 Histopathology of the Skin
Overview (Superficialdeep)
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) SKIN COLOR
Skin color depends NOT on the
Dermis NUMBER of melanocytes you
Papillary dermis (pegs)  Reticular dermis (underneath) have but instead the amount of
Thicknesses depend on anatomical site pigment they produce.
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;
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  duct enters at infundibulum; similar to eccrine duct but gland has
apocrine secretion (secretion via budding of PM). Acral: extremities of
 Mostly in axilla/anogenital region but also external ear canal peripheral body parts
(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)

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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 Epidemiology
o Flares with remissions  Females > Males
 30-50 yo usually
Pathogenesis  N. Europeans > Asians > Others
 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)

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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 Presentation Auto-Ab against…
Pemphigus foliaceus Desmoglein 1
against new desmoglein epitopes); corresponds
Pemphigus vulgaris (oral only) Desmoglein 3
with progression of disease
Pemphigus vulgaris (oral + skin) Desmogleins 3 + 1
Dsg 3,1 + plakin
As long as Ab bind, cell detachment happens (see slide: mouse Paraneoplastic pemphigus
proteins + more
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)
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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

Rare
COMMON FEATURES Antigen targets known
Auto-Ab are pathogenic (not just markers)
AGE OF PATIENT Middle-aged (30-50 yo) Elderly patients (60-80 yo)
Painful Painless but pruritic
BLISTERS: Large erosions, weeping, can recur explosively; flaccid
Large, dramatic blisters on skin
vesicles

MUCOUS MEMBRANES Involved (oral  skin) Involvement uncommon

TARGET Desmosome Hemidesmosome
LEVEL OF SEPARATION Intraepidermal Subepidermal
INFLAMMATORY
None Big
REACTION

PMNs are critical: if you block PMN activity,

BLOCKING STEPS OF Blocking steps of cascade doesn’t help:
cascade stops (Ab binding insufficient by
DETACHMENT CASCADE Ab binding sufficient to cause blistering
itself)
Reduce inflammation; wait for spontaneous
TREATMENT IDEA Block Ab synthesis; slow remission
remission
High doses (immunosuppressive levels); few Lower doses (anti-inflammatory levels), more
THERAPY OPTIONS
drugs available 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
Epidemiology of psoriasis
Pathogenesis:  Males = females
 Th1 cells are key (cytokines: IFNγ, TNFα, IL-2): autoantigen in skin  30% develop dz < age 20
probably triggers Th1 rxn  2% of general pop
 Results:  10-30% pts  psoriatic arthritis
o Epithelial hyperproliferation, vascular proliferation  Certain HLA subtypes
o PMNs recruited + T-cell mediated immune reaction associated (HLA Cw6 = 13x RR)

Type Photo Description Other

Palpable plaques, silvery scale are classic Most common form;

Plaque psoriasis Extensor surfaces (knee / elbow), sacral “Auspitz’s sign”= bleeding
on removal of plaque.

Younger patients (esp

Guttate Well-defined, smaller, discrete papules
several weeks post strep
psoriasis (still with silvery scale)
infection)

Generalized, lakes of coalescing pustles on

Pustular
background of erythema
psoriasis
Palmoplantar surfaces

Onycholysis (distal lifting of nail bed); oil

Nail psoriasis
spots on nail bed, nail pits

Mono / asymmetric arthritis (DIPs mostly) Can present like RA

Psoriatic
Arthritis mutilans  severe disability (symmetric polyarthritis)
arthritis
Spondylitis/sacroilitis possible too too
Other forms: Erythrodermic psoriasis (diffuse, all over the place),
scalp psoriasis, inverse psoriasis (not classic with silvery scales but erythematous plaques instead)

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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
AD IS NOT THE SAME AS ECZEMA
 Eczema is a reaction pattern
Pathogenesis:
 Erythematous patches/plaques with
 Th2 cells are key (cytokines: biphasic)
epidermal changes (Scale/crust)
o Acute atopic dermatitis: Th2-mediated (IL-4, IL-5, IL-13)
o Chronic atopic dermatitis: Th2 and Th1 (IFNγ, IL-12)  Can result from many causes
o atopic dermatitis, irritant dermatitis,
o T-cells, eosinophils, monocytes activated; IgE increased allergic contact dermatitis, venous stasis,
 Skin barrier defective: ↑ cutaneous superinfections; fewer etc.)
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 Atopy: from Gr. atopos,
o Stronger correlation between siblings with AD “Strange or unusual”
(environmental factors too)

Epidemiology of AD
“Atopic march”: associated with other atopic disorders
 Prevalence doubled in last 30
 Food allergy (30% AD pts)
yrs in industrialized countries
 Asthma (30-60%)
o 15-30% children, 2-10% adults
 Allergic rhinitis (60-80%)
 Females < Males (1.3:1)
 Often begins in infancy, 85% before
Diagnostic criteria: 5yo; 70% remit before adolescence;
 Must have: Pruritis + Eczema (typical morphology / age specific patterns, 50% recur in adulthood; can start in
chronic/relapsing) adulthood: late-onset AD
 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

Skin folds, face, scalp, cheeks

Infancy Erythematous + exudative
Extensor surfaces (not diaper area)

Childhood Flexor surfaces; Often generalized xerosis (dryness)

pityriasis alba (post-inflammatory hypopigmentation)

More ill-defined
Adulthood Hand dermatitis common Lichenification (thickened
epidermis) more common

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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
direct relation to sun
small clusters of
Sun exposed areas: ↑ pigmenentation; exposure;
Ephelide macules, Common in
nose, cheeks, shoulders, ↑ transfer to keratinocytes (not recur in summer & fade in
(freckle) tan-red to brown, children
dorsal hands, arm increased local # melanocytes) winter
well-circumscribed

Solar lentigo Irregular evenly Sun-damaged skin (face, Common,

Elongate of rete; no increase in # Incidence increases with
(“age spots” / pigmented macules, dorsal aspects of middle-aged
melanocytes age
“liver spots”) tend to coalesce hands/arms) & elderly

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:
Clinical features
 Adolescence/early adulthood; enlarge  stable  involute (maximum in 20s, regress/disappear by 70s-80s) of benign acquired nevi
 Progression: normally distributed on BMZ, proliferate on junction, descend to dermis, then lose melanocytes in junction  Symmetrical
1. Junctional nevus (just at dermal/epidermal junction)
 Regular borders
a. symmetric, sharply circumscribed, flat, uniform medium/dark brown color
 Uniform color
b. No melanocytes in dermis, no atypia, regular size/shape/spacing of nests @ tips of rete ridges
2. Compound nevus (junctional & dermal nests)  Small (<5mm)
a. Raised/dome shape (involvement of dermis); uniform light/medium brown color, can be hairy
(Compare to melanoma, which
b. Dermal melanocytes mature with descent (deeper cells smaller/less pigmented/less nested); no atypia inexorably progress)
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

14
 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, birthfade 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
Epidemiology
 Location: skin/sun-exposed areas; can happen on mucosal too;  8,400+deaths/yr, 60k cases/yr
can be de novo or from existing nevi  5% skin cancers but >80% skin cancer deaths
 1/75 lifetime risk in US (increasing)
Pathophysiology: genetics, immune system (host); radiation, etc  53yo median age at dx
nd
(environment)  Most common cancer in women 25-29, 2 to
breast cancer in 30-34yo women

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)
15
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 Most common Upper back (+ legs in Variable radial phase  Sometimes changes in
spreading (70%) women) vertical phase pre-existing mole

No radial, immediately
Nodular 20% Legs + trunk
vertical & aggressive

5% Sun-exposed skin Cumulative instead of

Long radial phase 
Lentigo maligna older (mean (head/neck) intermittent sun
vertical phase
age = 65 yo) exposure,
Acral sites
Acral Most common subtype
5% (palms/soles/nail
lentinginous in darkly pigmented pts
beds)

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?

16
 Non-Melanoma Skin Cancer
 Basal cell carcinoma and squamous cell carcinoma are most common (also Merkel cell carcinoma, others)

Pathophysiology
Random facts:
 Host: genetics (skin type, mutations in repair pathways, etc), immune system SPF only tells you how
 Environment: solar radiation, viruses, ionizing radiation, chemicals/trauma good a sunscreen is
against UVB radiation
Triggers
 UV light is big one (90% cancers have signature UV mutations; on sun-exposed areas) ABCDE doesn’t help so
 Immunosuppression (100x risk increase for transplant patients); viruses like HPV much with these cancers
(more for melanoma)
 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)

Epidemiology:
 #1 skin cancer (incidence)
High cure rate but 20-40% chance of developing another case o 80% new skin cancer cases
o Annual incidence 0.1-0.5%
Pathophysiology: mutations in SONIC HEDGEHOG PATHWAYS  4:1 BCC:SCC in clinic
 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 Epidemiology:
 Ulcerated / crater-like / friable  #2 skin cancer in gen pop
 300k/yr in US
 75% on head / neck / hands  #1 cancer in transplant pts
 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
17
 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

18
 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 Larger, individually dispersed in Grouped but individually
numberous in SC than basal KC, more numerous in basal dispersed in sun-exposed areas
layer layer
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 Less, little evidence of solar elastosis (photodamage)
elastosis
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)  Keloidosis (more common in AA/Asian pop, can lead
 Sarcoidosis to scarring / disability)
 Pseudofolliculitis barbae (Razor bumps)  Traction alopecia from braids, etc.

19
 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
“Color-Coded” Birthmarks
 6+ café au lait macules (>5mm pre-puberty, >15mm post-puberty)
Brown Neurofibromatosis type I
 2+ neurofibromas of any type, or 1+ plexiform neurofibroma
White Tuberous Sclerosis
 Freckling in axillae / groin (Crowe sign)
Red Infantile Hemangiomas
 Optic glioma
Yellow Nevus sebaceus
 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 Most specific, nearly

90% adults have freckling
( Crowe sign) pathognomonic finding

Hallmark sign; dome-shaped, Onset at puberty

soft, fleshy, skin-colored to slightly
hyperpigmented / firm / nodular;
Increase in size/# throughout adulthood
Neurofibromas
major source of morbidity Grow most in puberty & pregnancy
(not painful though)
Feels like “bag of worms”;
Plexiform disfiguring, can threaten
Usually congenital
neurofibromas function of area, 8-12%
develop malignant tumor

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
20
  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) Risk factors: KNOW THESE
 Nearly all double in size in first 2 months, reach 80% size in 3-5  Females (2-3:1)
months, then regress 10%/yr (50% regress @ 5yr, etc)
 White, non-Hispanic
 Can complicate: big size, on face, segmental morphology is bad  Premature
 LOW BIRTH WEIGHT is #1
(40% ↑/ 500g ↓in weight)
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

21
 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 2. Erythema
 Exanthemous drug eruption  Red man syndrome
 Drug hypersensitivity syndrome 3. Urticarial
 Urticaria
 Serum-sickness-like reaction
4. Blistering 5. Pustular
 Fixed drug reaction  Drug-induced acne
 Drug-induced pemphigus, pemphigoid, linear IgA  AGEP
 Stevens-Johnson
 Toxic epidermal necrolysis

Exanthemous / Morbilliform
PICTURE DESCRIPTION OTHER
 #1 drug eruption (94%)
Exanthemous
 Morbilliform (“maculopapular)  Starts within 1wk of exposure (semi-synthetic PCNs > 1wk)
drug eruption
 Pink / red / salmon  Resolve 1-2wk post cessation
 Macules/papules, can be confluent  Antibiotics are #1 cause (anti-convulsants too)
exanthem:
“bursting out”  Can spread symmetrically (headtrunk)  Management: stop offending agent, antihistamines, topical
corticosteroids +/- systemic steroids as needed
 Occurs after first exposure, 2-6wks afterwards
 DRESS syndrome: Drug Rash with Eosinophilia and Systemic Sx
 1 in 1k-10k taking anticonvulsants, sulfonamide abx
Similar to  Fever/malaise / cervical LAD / eosinophilia
Drug-induced  Allopurinol too
exanthemous drug  Skin eruption (exanthema / exfoliative dermatitis)
hypersensitivity  Mortality ~10%!
eruption + systemic  Internal organ involvement (Liver: hepatitis + jaundice, 50%
 Management: MUST STOP offending agent; +/- corticosteroids,
elevated LFTs, renal, CNS, pulmonary)
topical steroids & antihistamines for Sx

Erythema
PICTURE DESCRIPTION OTHER
 Related to Vancomycin exposure (rapid infusion; don’t see
much anymore), others too
Red Man
 Pruritis  Within 10m initiation or completion of infusion
Syndrome
 Erythema: face, neck torso  Histamine release involved
 Management: antihistamines (incl. pretreatment);
discontinue infusion

22
 Urticarial
PICTURE DESCRIPTION OTHER

nd
2 most common drug eruption (5%)
 Benign, transient
 Red, erythematous, pruritic
Urticaria  Type I / IgE-mediated hypersensitivity (think about anaphylaxis, watch BP if extensive rash)
papules / plaques (wheals) with
 PCN & derivatives #1 cause, also ACE inhibitors
pale halo
 Angioedema: subcutaneous fat / deep dermal tissue rxn
 Management: discontinue drug, ± antihistamines, ± corticosteroids
 Urticaria & angioedema  Serum sickness: injection of “protein” that induces immune response, deposition of immune
 Fever & arthralgias complexes in vessels, etc.
Serum-sickness-
 Serpiginous / erythematous /  SSLR: from non-protein drugs, NOT associated with circulating immune complexes
like reaction
 1-3wks post exposure, after 2 -3 exposure, F>M
nd rd
purpuric eruption at lines of
(SSLR)
transgradiens on hands/feet (where  Cefaclor / buproprion are top 2 drugs
plantar/palmar surfaces meet

Blistering
PICTURE DESCRIPTION OTHER

 Resolves over 2-3wks, post-inflammatory

Fixed drug  Sharply demarcated, round, dusky, erythematous/edematous plaques
hyperpigmentation
eruption (FDE)  Happens at same anatomic site each time exposed (weird!)
 Tetracyclines & sulfonamides often, anticonvulsants
 Genetalia / lips / hands / feet
too

 Mortality 5% - EMERGENCY!
 Fever, cough, malaise  Histology: full thickness epidermial necrosis &
Stevens-Johnson  Macula exanthema (can blister) blistering, no SC involvement (FAST)
Syndrome  Mucous membrane erosions at 2+ sites  Management(TEN too): ID/stop drug, IVF &
 < 10% body surface area supportive care, get to BURN UNIT

 Think of it like more severe SJS

 Fever, pruritis, conjunctivitis (non-specific)
Toxic epidermal  Mortality 30-50%: BIG EMERGENCY!
 Painful skin (plaques, target lesions, erythema, sheet-like loss of epidermis,
necrolysis (TEN)  Histology, management like SJS – GET TO BURN UNIT
blisters spread with lateral pressure = nikolsky’s sign)
 >30% body surface area

23
 Pustular
PICTURE DESCRIPTION OTHER

Acute
generalized
 Resolves 1-2 wks
exanthematous  Acute pustular eruption but sterile (no bacteria)
 Allopurinol, macrolides + PCN/derivatives (Abx +
pustulosis  Facial edema, fever + leuckocytosis, 100s of sterile pustules
anticonvulsants)
(AGEP)

24
 Cutaneous Manifestations of Internal Diseases

Oncology
PICTURE DESCRIPTION OTHER ASSOCIATED DISEASES

 Firm papules/nodules that are often  10% all metastasis, 75% skin metastasis is first sign of
Cutaneous
bound down (“rubbery & connected”) extranodal spread  Breast / lung / GI
Metastasis
 ± ulceration  Metastasis spreading upwards, invading dermis, chewing / skin cancers
 Side lighting can help up everything, full of atypia

 Localized / diffuse skin infiltration by leukemic cells

 Small (2-5mm) pinkish, non-tender
Leukemia Cutis  Can be sign of leukemic cells in peripheral circulation  Leukemia
papules
 In dermis: epithelial structures /markings still intact

 Overlap with both pemphigus vulgaris & bullous

 Severe mucosal ulceration and
pemphigoid
polymorphic eruptions associated with  CLL/large cell
 Intraepidermal split (like pemphigus)
Paraneoplastic neoplasia lymphoma/NHL,
 Direct/indirect immunofluorescence like pemphigus
Pemphigus  Erythema multifome-type lesions Waldenstrom’s
 immunoprecipitation (+) on transitional epithelium
(PNP)  Friable macroglobuline
of bladder: like bullous pemphigoid)
 Vermillion border involvement mia
 TONS of types of auto-AB – very polymorphic
 very poor prognosis (doesn’t get better)

 Rapidly expanding, very painful,

ulcerative lesions
Bullous  Lymphoreticular
 Pus: sea of PMNs  DEBRIDING BAD (if you traumatize lesion, it grows)
Neutrophilic system
 Looks like bad infection but is aseptic  No antibiotics: want to immunosupress (prednisone, CSA)
Dermatosis malignancies
process (can be superinfected though)
 Violaceous hemorrhagic border

25
 Gastroenterology
PICTURE DESCRIPTION OTHER ASSOCIATED DISEASES
 GI: Hamatomatous
 Early life: hyperpigmented macules (lips, buccal mucosa, polyps (mostly small
 Herditary polyposis (autosomal
Peutz Jeghers palms/soles / periorifical)  bowel, low
dominant, high penetrance)
 Macules fade except on buccal mucosa (stay til adolescence) malignant potential,
mostly recurrent
pain)
 Autosomal recessive
 Infancy: acral dermatitis, alopecia, diarrhea  Can be acquired (dietary Zn
Acrodermatitis  GI: Zinc absorption
 Dry, scaly, eczematous patches/plaques early, then evolve into deficiency, failure of GI absorption,
Enteropathica disorder
vesiculobullous/erosive lesions nephrotic syndrome, bypass surgery)
 Lab: anemia, low serum/urine Zn
Glucagonoma  From excessive
Syndrome  Edge-active skin lesions (blisters, crusting, scales) glucagon production
 Lab: serum glucagon +
(migratory  Periorificial and intertriginous dermatitis / erythema (α-cell tumor of
abdominal CT
necrolytic  Glossitis (red tongue) + angular cheilitis (cracks at corner of mouth) pancreas)
erythema)

Endocrine / Metabolic
PICTURE DESCRIPTION OTHER
Necrobiosis
 Chronic, indolent, relatively
Lipoidica  Well-demarcated, atrophic plaques  2/3 with overt diabetes, rest have
asymptomatic
Diabeticorum  Yellow-brown color abnormal glucose tolerance
 W>M (3:1)
(NLD)  Anterior / lateral surfaces of lower legs

 Indurated (thick & firm) plaques/nodules

Pretibial  Flesh-colored  Hyperthyroidism of Grave’s disease
Myxedema  On pretibial areas of lower legs / recovering from thyroid storm
 Can be tender

5 types
 Hereditary
 Diffuse, velvety thickening & hyperpigmentation  Endocrine (insulin resistance,
Acanthosis
 Axilla, other body folds, dorsum of hand acromegaly, Cushing’s, Addison’s)
Nigricans
 Obesity
 Drug-induced
 Malignancy (usually GI adenocarc)

26
 Common Infections of the Skin
New techniques: instead of growing bacteria (only see what
you grow!) deep sequencing of rRNA with universal primers NORMAL SKIN FLORA
 Flora similar between people, different by site  Cornyeforms (diptheroids) (GM+)
o cornyebacterium, brevibacterium,
propionibacterium spp)
Skin is a defense organ
 Staphylococci (coag neg) (GM+)
 Physical barrier (SC) + constantly shedding
 Micrococci (GM+)
 Chemical (low PH)
 Acinteobacter spp (GM-)
 Immunologic (skin-associated lymphoid tissue)
 Proteus, pseudomonas,enterobacter (GM-)
 Microbiological: normal skin flora occupy niche
 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
Bacterial infections: Strep pyogenes and Staph aureus
Strep pyogenes skin infections (examples)
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
 Impetigo, erysipelas, celulitis Note golden crust Involves upper dermis, Involves deeper dermis
(dried serum) superficial lymphatics and subcutaneous fat

Staph aureus skin infections (examples)

Staphylococcus aureus
(coagulase positive)
 Frequently found transitorily on skin
 Coagulase  abscess formation
 Well-circumscribed, walled-off
 Central fluctuation
 Folliculitis, furuncles, carbuncles
Folliculitis Furuncle (“boil”)
Pilosebaceous unit Tense, pus-filled, tender,
Overlaps with acne drain eventually

Viral infections

DNA Viruses
Papova viruses HPV (warts / cancers)
Poxviridae Molluscum contagiosum
Herpes viruses HSV, VSV (note herpes zoster is VSV)

27
HPV infection HSV Epidemiology
 WARTS (STI & otherwise)  75% population 15-49yo
 Make sure to test for HIV & other STIs after Dx  Subclinical infection:
 100+ types, 30 infect anogenital mucosa, 12+ oncogenic 15% gen pop, 23% HIV- MSM,
o HPV-16 ≫ HPV-18,31,45 for oncogenicity 93% HIV+ MSM

 Cervical (+ anal, oropharyngeal, penile) cancers  Most infections: Asx and

undiagnosed
 Vaccine: gardasil (3 shots x 6 mo, 11-12 yo females)
Genital warts are just the
tip of the iceberg

Herpes simplex HSV infections

 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 Generic HSV Orolabial Herpes Genital Herpes
 GROUPED ULCERS ON Grouped ulcers on “cold sore” HSV-2 > 1
ERYTHEMATOUS BACKGROUND erythematous background HSV-1 > 2

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

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 Lesions: edge-active, scale, Fungal infections
central sparing

Tinea Corporis Tinea Cruris Tinea Capitis

Microsporum canis, Mostly men, inner/upper Mostly schoolchildren
Trichophyton rubrum thighs, “jock itch” T. rubrum, M. canis mostly (US)

Tinea Pedis / Manus

Athlete’s foot: most common Onchyomycosis Tinea versicolor
T. rubrum mostly DSO, WSO, PSO M. furfur
“sandal” distribution common

Other answers to “test-type questions”

Name the infection

Tinea Versicolor Tinea Capitis

Intertrigo HPV Mostly schoolchildren
T. rubrum, M. canis mostly (US)

Molluscum Basal Cell Carcinoma

Tinea Perleche

 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

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