Basement Membrane Zone (BZD) Genetic Protein EB Simplex (EBS) Keratin 5 Keratin14 Plectin

Mechanism AD: autosomal dominant Helix-initiation/terminiation region

Appearance Mechanobullous Pigment changes

Distribution Herpetiform Musocal Epidermal

Presentation

Treatment / Prognosis Heal with minimal scarring

Histology Epidermis (Basal layer)

+ Muscular dystrophy

Junctional EB

6 4 integrin BPAg2 Laminin 332

JEB (non-Herlitz)

Milder form

Mucosal Airway

+ Pyloric atresia

DermalEpidermal Junction (BZD) Severe: death

JEB (Herlitz) (does not adhere)

Most severeform

Systemic infection Airway obstruction High risk for sepsis More severe

Dystrophic EB

T7 collagen

Recessive (RDEB) = none Carriers normal

White papules Pruritis Mitten-sock Pseudosyndactyle

Scarring, Contracture, Deformity Squamous cell carcinoma (80%) Heals with scarring

Papillary Dermis (superficial)

Dominant (DDEB) = mutant Dominant negative effect Bullous Congenital IchthyosiformErythroderma (BCIE) Keratin 1 Keratin 2 Keratin 10 aka Epidermolytic Hyperkeratosis Blister Erythema Often inflamed (Extensive scaling) Appearance Vesicles / Bullae Tense Pruritus Urticarial base Can cross placenta into newborn! Vesicles / Bullae Tense Pruritus !!! Generalized Birth or early childhood

(Late childhood to adulthood) Distribution Extremities Axillae Groin Epidemiology Age > 60 Rarely in children Treatment Histology

Autoantibody Bullous pemphigoid (BP)

Protein BPAg1& BPAg2

Mechanism

Pemphigoidgestationis

BPAg2

Trunk

Pregnancy

Cicatricialpemphigoid

Laminin 332 ( 6 4 integrin) (BPAg2) T7 Collagen Bullae

Conjunctiva Oral mucosa Skin Heterogeneous Associated systemic diseases 1. IBS 2. RA 3. Multiple myeloma chronic bullous of childhood

Scarring

EpidermolysisBullosaAcquisita (EBA)

Scarring Millia

Linear IgA Bullous Dermatosis (LABD) Phemphigus Vulgaris

BPAg2

Linear deposition of IgA

Vesicle / Bullae

Annular Arcuate Epidermis Oral mucosa

Desmoglein 3

Autoimmune (antibody to desmosome protein)

Heal without scarring Systemic corticosteroids

Acantholysis (spinous layer) = abnormal attach

Lamellar Ichthyosis (NCIE) X-linked recessive Ichythosis BZD Summary Protein target BPAg2 6 4 integrin Laminin 332 Type VII collagen Epidermis

TG1 (keratinocyte transglutaminase) Steroid sulfatase

AR: autosomal recessive Defect in cornified cell envelope

Scales (plate-like) Erythema

Generalized

aka Non-Bullous CIE

Stratum corneum massively thickened (hyperkeratosis) Stratum corneum massively thickened (hyperkeratosis)

Enzyme deficiency ( cholesterol) Increased in keratinocyte lipids Decreased desquamation

Scales (plate-like) No erythema

Structural target Hemidesosome-anchoring filament complex Hemidesosome-anchoring filament complex Lamina lucida-lamina densa interface Anchoring fibrils

Genetic Disease Junctional EB,non-Herlitz Junctional EB with pyloric atresia Junctional EB, Herlitz Dystrophic EB

Autoimmune Disease Bullous pemphigoid Ocular cicatricialpemphigoid Cicatricialpemphigoid EB acquisita

*also known as BP180 or Type XVII collagen *EB = EpidermolysisBullosa

Protein Xerosis (dry skin)

Mechanism Less flexible stratum corneum 1. Decrease lipids 2. Uncoordinated desquamation 3. Dehydration Prone to microfissure 1. Histamine (inflammatory) 2. Invasion

Appearance Scaly Rough Pruritus

Presentation Common (most by 60) During low ambient humidity Factors 1. Arid environment 2. Wetting-drying 3. Detergent 4. Genetic 5. CKD, HypoT4, Malnutrition 6. Medications (statins)

Treatment / Prognosis Minimize exposure Emollient Keratolytics (urea or ammonium) Topical steroids Antihistamines

Histology

Dermis Protein Ehler-Danlos Syndrome (EDS) T5 Collagen T1 Collagen Mechanism (Type 1 and 2 EDS) Altered collagen fiber size & organization Skin Hyper-extensible Hypermobile joints Distribution Presentation Abnormal healing after trauma Gorlin sign (touch nose with tongue) Cigarette paper scars Vascular (aneurysms or rupture) Uterine rupture in pregnancy Swelling Papularurticaria Laxity Acral Bladder diverticula Hernias Corpulmonale Subsequent death can occur Corkscrew hairs Perifollicular hemorrhage Bleeding gums Loss of strength > collagen Loss of elasticity > elastin Summary Loss of strength > collagen

T3 Collagen

(Type 4: most severe)

Cutis Laxa

Elastin Acquired

In some families (AD) Acral localized acquired Generalized elastolysis Fragmentation &lost dermal elastic fibers

Scurvy

Vitamin C

Perifollicular hemorrhage b/c 1. Higher type 3 collagen in papillary dermis 2. More dependent on hydroxylation 3. Weaker in the absent of vitamin C Progressive fibrosis and vascular destruction Anti-fibrillin antibodies (Choctaw natives) Overstimulated fibroblast (cytokine, TGF, hypoxia) Microchimerism with fetal cells

Scleroderma

Unknown

Calcifications (dermis) Hardening Sclerodactyly Spotted pigmentation

Loss of compliance &elasticity >fibroblast

Skin Appendages Sebaceous Acne Vulgaris Type Comedomal Mechanism Comedo (keratin plug in hair follicle) Block sebaceous glands secretion (antimicrobial) Inflammatory papule (build-up) Bacterial growth in sebum Rupture and cyst formation Skin Black head (open) White head (closed) Erythema Antibacterial&Anti-inflammatory Hormonal Distribution Presentation Comedolytics (thin epitheliumearly shed) Antisebocyte (shrink secretion) Inflammatory Treatment Tretinoiin (Retin-A) Benzoyl Peroxide Isotretinoin (Accutane) Benzoyl Peroxide Clindamycin Doxycycline (sub-dose) Spironolactone (offlabel) OCP (estrogen) Treatment

Cystic

Hair Follicle Telogen Effluvium

Type Pregnancy

Mechanism Increased hair thickness during pregnancy All hair enters cycle at same time Hair loss due to hair growth (shedding) 5-DHT (5 -reductase converts from testosterone) Paradoxical increase in axilla, pubis, chest, face Unknown cause of irritation Autoimmune process (attack melanocytes)

Skin Alopecia (thinning)

Distribution

Presentation 3 months post-delivery

Androgenetic Alopecia

Male Pattern Selective

Alopecia

Finasteride (Propecia) -5AR inhibitor Areata (area) Totalis (scalp) Universalis (all) Distribution Axilla Anogenital Cerumen Breast Presentation Remove irritant Hair grows back usually

Alopecia Areata

Alopecia (selective)

Apocrine HidradenitisSuppurativa

Type Acne Inversa

Mechanism Plug of unknown origin within hair follicle 1. Blocks apocrine gland secretion 2. Aprocrine cell swelling 3. Hair loss 4. Increased size and involve neighbor follicles 5. Form continuous tract of pus Mechanism Forms isotonic (not hypotonic) excretion Overstimulation of SNS

Skin Abscess-like Linear scars (sinus tract)

Treatment Steroid injection

Eccrine Cystic Fibrosis Hyperhidrosis

Type CFTR

Skin

Distribution

Presentation Chloride sweat test

Treatment

Excess sweating

Palm Soles Distribution Presentation

Nail Onychomycosis

Type

Mechanism Mechanical Trauma (manicure) Fungal infection (Trichophytonrubrum) Cuticle infection

Skin Detachment

Botulinum Toxin A (Botox): inhibit mAChR Treatment

Paronychia

Skin Immune System Immune Allergic Contact Dermatitis (ACD) Stimulus Allergen (mild chemical) Hapten (binds proteins to make antigenic) Chemical Mechanism Delayed-Type Hypersensitivity 1. Histamine 2. Th1 predominance 3. Sensitization(LC and CLA-T) 4. Elicitation (Memory T) 5. Proliferate in situ (re-exposure) Direct cellular injury No immunologic memory Appearance Vesicles Papule/Plaques Erythema Edema Pruritus Distribution Geometric! Linear (ivy) Nickel jewel Generalized Presentation Often no reaction at first exposure Delayed reaction Severe: general cutaneous reaction Treatment / Prognosis Histology Spongiolysis (Epidermis) = fluid accumulation

Irritant Contact Dermatitis (ICD) Atopic Dermatitis (AD)

Local

Reaction at first exposure Immediate (minutes to hours) Dose related

Spongiolysis (Epidermis)

Often inherited: filaggrin eczema itch that rashes

Th2 predominant (IgE, eosinophils) Staphylococcusaureus 1. Superantigens stimulate T cells 2. Toxic shock toxin (TSST-1) 3. Cytokine overproduction Loss of barrier defense

Xerosis (dry skin) Crust (infection) Pruritis Vesicular Lichenification Pigment

Symmetric Skin folds (antecubital) (popliteal) Flexures Face Elbow Knee Scalp Trunk

Atopic Triad (associated with) 1. Asthma 2. Allergic rhinitis Common onset in childhood Higher risk of cutaneous infection (HSV, molluscumcontagiosum) 2% world population Nail involvement common Arthritis in 5% Other:guttate/pustular/erythroderma Constitutionally ill Leonine facies Immigrants to U.S. Armadillos in the South Often indolent Early CD8+ antitumor response CD3, CD4, CLA, CD45RO+,CD8Th2: IL-4, IL-5, IL-10

Systemic immunosuppressants Calcineurin Inhibitors 1. Tacrolimus, Pimecrolimus 2. Block T cells 3. No atrophy

Spongiolysis (Epidermis)

Psoriasis

Minor trauma (Koebner)

Th17 1. IL-22: keratinocyte proliferation 2. IL-23: self-proliferation Streptococcus A infection

Plaques Scale (hyperkeratotic) Salmon-color Erythema Demarcated

Ustekinumab ( IL-23 receptor) Cyclosporine BMT for other reason (curative)

Acanthosis (Epidermis) Parakeratosis (hyperkeratosis) Bacilli in dermis Foamy macrophages

Leprosy (Hansens)

M. leprae Intracellular MHC I

Lepromatous: Th2 (antibodies)

Widespread Face Few

Tuberculoid: Th1 (cell-mediated)

Resistance

Cutaneous T-Cell Lymphoma (CTCL) Graft vs. Host (GVHD) Drug Eruption

Tumor (CD4+ Th2)

Mycosis fungiodes (classic) Sezary syndrome (erythrodermic) De novo (tumor only stage)

Patch-Plaque-Tumor Red Scale Pruritus Macule / Papule Blistering Erythema Papular Erythema Purpura White patches Irregular shape Wheal Erythema Edema Pruritus

Progression Diffuse

High CD8/CD4 better prognosis (CD8 has antitumor effect)

Monoclonal T cells Abnormal lymphocyte Epidermotropism

Transplant

Donor CLA+ T cells

Cyclosporine

Polyclonal T cells Normal lymphocyte

Many

Erythema multiforme (EM) Toxic epidermal necrolysis Cutaneous vasculitis Melanocytes destroyed

Generalized Trauma area

Vitiligo

Autoimmune

Urticaria (hives)

Mast cell

Mast cell degranulation Histamine release

Lasts less than 24 hours

Non-cellular infiltrate Dermis

Infections Fungal Tineacorporis Organism Dermatophyte Mechanism Keratinases for invasion Manninsdecrease desquamation Appearance Pink-Red-brown Scaly Annular Demarcated Distribution Pedis (feet) Cruris (groin) Scalp Face Presentation Complex toe-web space infection Treatment / Prognosis Topical or systemic antifungal Histology Hyphae on KOH

Tineaversicolor

Malassezia furfur

Hypo/Hyperpigment Papules / Plaques White scale (scrape) Erythema Plaque Beefy red Satellite pustules Mechanism Appearance Red Hot Tender Un-raised Poor demarcation Red Plaque Raised-Indurated Warmth Edema Demarcated Altered cool dry surface Red-Brown Plaque Face Leg Distribution

Often in the summer Can be hypopigmented afterwards (substance that bleaches melanin)

Topical ketoconazole Topical selenium

SpaghettiMeatball on KOH

Cutaneous Candidiasis

Candida spp.

Topical or systemic antifungal

Yeast / Buds Pseudohyphae

Bacterial Cellulitis

Organism Staph. aureus Strep. pyogenes (GAS)

Presentation Fever Lymphadenopathy

Treatment / Prognosis Systemic antibiotics

Histology Deep: Dermis / Fat

Erysipelas

Strep. pyogenes (GAS) + other strep species

Peaudorange Fever Lymphadenopathy

Systemic antibiotics Recurrence (destroyed lymphatics)

Superficial dermis

Erythrasma

Corynebacterium

Groin

Coral-red fluorescence (Wood lamp) Odor

Topical antibiotics (erythromycin)

TrichomycosisAxillaris

Underarm hair MicrococcusKyptococcus Altered cool dry surface +sweat: methane thiol (CH3 SH) Unimpressive host response Direct toxicity Interfere with blood flow Tissue breakdown Toxin cleaves desmoglian 1 Infection at distant site Toxin cleaves desmoglian-1 Exfoliative dermatitis Pits Sulci / Erosions Sole (foot) Rule out tinea with KOH prep Odor Topical antibiotics (clindamycin)

Pitted Keratolysis

Necrotizing Fasciitis

Strep. pyogenes (GAS) MRSA

Erythema Vesicles / Bullae Purpura Eschar Bullae Erythema Desquamatization

Rapid progression and spread Systemic symptoms Febrile Shock Also produces staph scalded skin Fever Usually infants and young childrenRarely adults with renal disease

Antibiotics Surgical debridement High mortality (20%)

Subcutaneous tissue

Bullous Impetigo Scalded Skin

Staph.aureus Staph.aureus

Not scarring

Abscess

MRSA

Nodules

Viral Herpes simplex Eczema Herpeticum

Organism HSV-1/-2

Mechanism

Appearance Vesicles Erythematous base

Distribution Grouped

Presentation Pain

Treatment / Prognosis Anti-virals (acyclovir)

Histology Acantholysis

Defects in antimicrobial defense due to eczema allow rapid spread of herpes Drug (Common) HSV M. pneumonia Herpes Zoster Poxvirus (MCV) Papules Umbilicated Erythema Dermatome Genitals Trunk Common in children Destructive therapies Inclusion bodies (gram-stain) Acanthosis akaStevens-Johnson Syndrome

Erythema multiforme

Shingles Molluscum

Warts

HPV *thrombosed capillaries

Papules / Plaques Verrycous Black dots *

Biopsy to rule out cancer Destructive therapies

Acanthosis

Pigmentation Migration Dermal Melanocytosis Mutation (Mongolian spot) Mechanism Arrested melanocyte migration Stuck in dermis AD: autosomal dominant Stem cell factor receptor Critical in melanocyte migration Melanoblast proliferation Melanoblast migration Appearance Blue/Black Hyperpigmentation Distribution Lumbosacral Presentation At birth African and Native American (90%) Can be confused with bruising White forelock of hair (85-90%) At birth Treatment / Prognosis Lighten and disappear with age Histology

Piebaldism

C-Kit gene

White Depigmentation

Skin Hair

Persist and unchanged with age

Waardenburg Syndrome

Pax 3 MITF Sox 10

Depigmentation

Deaf Heterochromic eyes White forelock Associated with Hirschprung disease Distribution Skin Eyes Hair Presentation Nystagmus Photophobia Diminished visual acuity Increased risk of skin cancer Mental deficiency Epileptic seizures Presentation Immunodeficiency Tyrosine rich diet Low phenylalanine diet Treatment / Prognosis Histology Treatment / Prognosis Histology

Production Oculo-cutaneous Albinism (OCA)

Mutation I: Tyrosinase II: P-protein III: TRP-1

Mechanism

Appearance No Pigment

AR: autosomal recessive Lack or reduction of pigment AR: autosomal recessive Lower tyrosine Lower melanin Mechanism AR: autosomal recessive Impaired melanosome transport Fumbled transfer Engulfed by melanophages Mechanism Decreased melanin production Decreased glucocorticoids Adrenal insufficiency Pituitary overcompensation Melanin synthesis increased By estrogen and progesterone Mechanism Autoimmune Destruction of melanocytes

Reduced Pigment Minimal Pigment Pale skin Blue eyes Blond-white hair Appearance Hypopigmentation Silvery hair Hyperpigmentation

Phenyl-ketonuria (PKU) Transfer Griscelli Syndrome

Phenylalanine hydroxylase Mutation Myosin-Va gene RAB27A Inflammation (secondary) Mutation MSH ACTH MSH ACTH Pregnancy

Skin Eyes Hair Distribution Diffuse

Post-Inflammatory

(e.g. acne)

Hormonal Pan-HypoPituitarism Addisons Disease

Appearance Chalky-white Hypopigmentation Bronze Hyperpigmentataion

Distribution

Presentation Secondary adrenal insufficiency

Treatment / Prognosis

Histology

Diffuse

Melasma

Destruction Vitiligo

Mutation

Appearance White to pink Depigmentation Appearance Silver-Blue

Distribution Patchy

Presentation Mouth/Eye/Nose/Hands/Genitals Associated with thyroid disorders Presentation

Treatment / Prognosis Light (UV)

Histology

External Argyria

Mutation Silver

Mechanism Ingestion of silver

Distribution

Treatment / Prognosis

Histology Around eccrine glands

Minocycline

Antibiotic

Tetracycline antibiotic

Blue-Black

Scars

Black thyroid, bones, teeth, sclera

Disease Sunburn

Mutation UVB

Mechanism Weak epidermal attachment Vessel dilationand permeability 1. Cytokines (IL-1, TNF ) 2. Histamine, NO, Kinins 3. Eicosanoids Direct effect on vessels Immediate (Meirowsky) 1. Photo-oxidation 2. Redistribution of melanin Delayed (Main) 1. Melanosome number 2. Melanin synthesis (new) 3. MSH Alteration of elastin Reduced collagen Increased T3:T1 collagen Essential for calcium metabolism Mechanism Accumulate and diffuse in dermis Photoactivated by UV AR: autosomal recessive DNA nuclear excision repair

Appearance Redness Swelling Pain Blisters

Distribution

Presentation

Treatment / Prognosis Aspirin Indomethacin

Histology Necrotic keratinocyte Epidermis

UVA Tanning UVA

Hyperpigmentation

Occurs within minutes

UVB

Thickening

48-72 hours

Photo-aging

UVA

Tough-Leathery Wrinkles Pigmentation Risk in elderly, darker, altitude Associated colon, prostate, breast CA Presentation

Retinoic acid can inhibit MMP (prevent and reversal of aging)

Rickets Osteomalacia Photosensitive Porphyria

Vitamin D Deficiency Mutation Porphyrin

Appearance Blisters

Distribution Subepidermal

Treatment / Prognosis

Histology

XerodermaPigmentosa

UV

Nodules Tumors Sun spots Photo-aging

Skin cancer

Exogenous

UV absorption

Sulfonamide Thiazide Lime Lupus CTD Rosacea HSV Polymorphous light eruptions Solar urticaria Vitiligo Albinism Skin Type: I always burns, never tans VI never burns, tans deeply

Photo-aggravated

Idiopathic

Pigmentation

Skin Cancers Cancer Basal Cell Carcinoma Precursor lesion None Precursor Cell Progenitor cells 1. Hair follicle 2. Interfollicularepithelium Appearance Pearly papule Telangiectasia Ulcerated-Crusted Pigmented Pink, scaly White, ill-defined Distribution (classic) Presentation Most common (80%) 1. Slight M > F 2. Median age 68 3. Risk in organ transplant (decreased immunity andHPV) Locally destructive Very low metastasis risk Mortality rare Palmar / plantar pits Skeletal abnormalities Calcification of falxcerebri Precursor Cancer Second common (20%) 1. Primarily in Caucasians 2. Risk in organ transplant (decreased immunity and HPV) Low risk of metastasis (5-30%) Malignant Melanoma Multiple (de novo, nevi) CDKN2A(INK4A) -p16 -p14ARF Melanocyte A: asymmetry B: border irregularity C: color varied D: diameter large E: evolving Amelanotic melanoma Risk of metastasis Survival 99% if early diagnosis Survival 15% if metastasis Third common (3.5%) 1. Most common cancer in 25-29 2. Risk in fair skin, red hair, light 3. Risk if many nevi 4. Risk in family history 5. Heavy UV exposure Excision GDC-0449 (in trial) PTCH (tumor suppressor) Treatment / Prognosis Excision Curettage Radiation Histology

(ulceration) (pigmented) (superficial) (subtle)

Basal Cell nevus syndrome Squamous Cell Carcinoma

PTCH

AD: autosomal dominant

BCCs

Actinic keratosis

Keratinocyte

Pink, scaly patch Indurated nodule

Excision Curettage Radiation

Crowding Precancerous Full thickness atypia