Keratohyalin granules Form keratin filaments

Anucleated cells Filled with keratin filaments

Connective tissue Blood vessels

Thickening of stratum corneum Excess quantity of keratin Seen in psoriasis and callus

Hyperkeratosis + retained nuclei in stratum corneum Indicates hyperproliferation Seen in skin diseases (psoriasis) and malignancies

Increased thickness of stratum granulosum Classic finding in lichen planus

Fluid accumulation (edema) of epidermis Seen in eczema, many other skin disorders

Loss of connections between keratinocyte Often loss of desmosomes “Rounded” keratinocytes Detached, floating freely in epidermis

Directly caused by disease process Macules, papules, vesicles, bulla

Flat lesions (not raised) Macule: 1cm

DERMATOLOGY: BOARDS AND BEYOND Flashcards by Karla Chavez

It contains STEM cells that are capable of regenerating keratinocytes in the epidermis.

Stratum basalis

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Order of the layers of the epidermis.

Stratum basale
Stratum spinosum
Stratum granulosum
Stratum lucidum
Stratum corneum

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Meant to be the tough outer layer of the skin that protects your body.

Stratum corneum

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Processes that cause leaky vessels are going to tend to swell the ?, not the epider

Dermis

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Acantholysis means a loss of connections between keratinocytes it’s often a loss of desmosomes that significantly affects the

Stratum spinosum

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The classic malignancy, in which to see acanthosis nigricans is

Gastric adenocarcinoma

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Erosion is a wider lesion that involves the epidermis and an ? is similar to an erosion, but it’s deeper and involves both the epidermis and the dermis.

Ulcer

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Epidermis: keratinocytes (squamous epithelial cells)
Dermis: connective tissue, vessels
Subcutaneous fat (also called hypodermis or subcutis)

Layers of the skin

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Stratum Basalis

Stem cells

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Stratum Spinosum

Desmosomes form spines

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Stratum Granulosum

Keratohyalin granules
Form keratin filaments

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Stratum Lucidum

Clear layer of dead skin cells

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Stratum Corneum

Anucleated cells
Filled with keratin filaments

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Dermis

Connective tissue
Blood vessels

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Hyperkeratosis

Thickening of stratum corneum
Excess quantity of keratin
Seen in psoriasis and callus

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Parakeratosis

Hyperkeratosis + retained nuclei in stratum corneum
Indicates hyperproliferation
Seen in skin diseases (psoriasis) and malignancies

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Hypergranulosis

Increased thickness of stratum granulosum
Classic finding in lichen planus

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Spongiosis

Fluid accumulation (edema) of epidermis
Seen in eczema, many other skin disorders

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Acantholysis

Loss of connections between keratinocyte
Often loss of desmosomes
“Rounded” keratinocytes
Detached, floating freely in epidermis

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Key feature of pemphigus vulgaris

Acantholysis

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Diffuse epidermal hyperplasia
Elongated rete ridges
Spinous layer thickening

Acanthosis

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Nigricans = darkened
Hyperpigmented (dark) plaques on skin
Intertriginous sites (folds)
Classically neck and axillae
***Hyperkeratosis
Mild acanthosis
Associated with insulin resistance
Rarely associated with malignancy

Acanthosis Nigricans

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Primary skin Lesions

Directly caused by disease process
Macules, papules, vesicles, bulla

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Macules and Patches

Flat lesions (not raised)
Macule: <1cm
Patch: >1cm

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Secondary skin lesions

* Modification of primary lesion * Or caused by trauma, external factors * Scale, crust, erosion, fissure, ulcer

Papules and Plaques

* Raised lesions * Papule: <1cm * Plaque: >1cm

Mole/nevus

Papule

Psoriasis

Plaque

Maculopapular Rash

* Collection of small skin lesions * Some flat (macules) * Some raised (papules) * “Morbilliform” – looks like measles - Common in many disorders * Drug rash * Scarlet fever * Syphilis * Rubella

Vesicles and Bulla

* Fluid-filled lesions (blisters) * Vesicle: <1cm * Bulla (plural = bullae): >1cm

Bulla

Bullous pemphigoid

Vesicle

Chickenpox

* Pus-filled vesicle * White center

Pustule

* Smooth, elevated papule or plaque * Surrounded by erythema (redness) * Itchy * Caused by dermal edema * Component of urticaria (allergic reaction)

Wheal

* Secondary lesion * Peeling/flaking of stratum corneum

Scale

* Secondary lesion * Dried exudate of skin lesion Impetigo

Crust

Characteristic histopathologic findings include hyperkeratosis (thickening of the stratum corneum), enlarged dermal papillae, and increased pigmentation of the basal cell layer.

Acanthosis nigricans

Urticaria is characterized by ?: transient, itchy, raised lesions that arise from edema in the dermis. ? are pale to red (often with pale centers and red borders) and blanch with pressure. This boy’s reaction is an immediate type 1 hypersensitivity reaction triggered by egg antigens binding to IgE antibodies on mast cells. Activated mast cells release granules of histamine and other vasoactive mediators that promote vasodilation, dermal edema, and inflammation.

Wheals

Staphylococcal scalded skin syndrome (SSSS), a skin disorder caused by strains of Staphylococcus aureus that produce exfoliative toxins. These exfoliative toxins cleave desmosomes (attachments between keratinocytes) in the stratum granulosum, causing ?.

Acantholysis (loss of connections between keratinocytes)

Histologically, acantholytic keratinocytes appear

Rounded and detached

Acantholysis can lead to

Fragile blisters, skin exfoliation, and a positive Nikolsky’s sign where gentle stroking of intact skin causes exfoliation of the top layer.

Nikolsky’s sign is not specific to SSSS and can also be seen in other skin disorders like

Pemphigus vulgaris and toxic epidermal necrolysis

Plaque psoriasis, a chronic inflammatory skin disorder characterized by well-demarcated pink plaques with a silver white scale. These plaques commonly affect the extensor surfaces of the knees and elbows. Psoriasis leads to

Acanthosis: diffuse epidermal hyperplasia (thickening) with thickening of the stratum spinosum and elongated rete ridges.

Other common histological findings in psoriasis include

Parakeratosis (retained nuclei in the stratum corneum) and neutrophils within the stratum corneum (Munro microabscesses).

Psoriasis leads to

Hypogranulosis (thinning of the stratum granulosum).

Pemphigus vulgaris

An autoimmune blistering disorder where antibodies are formed against desmoglein proteins in the skin and mucosa. Desmogleins form an important component of the desmosomes that attach keratinocytes together in the epidermis.

The histologic hallmark of pemphigus vulgaris is

Acantholysis (loss of intercellular attachments between keratinocytes) above the stratum basale (suprabasal). The stratum basale is intact, and the separation of the blister occurs above it in the stratum spinosum.

* Fibrous, extracellular matrix of proteins * Anchors epithelial cells to connective tissue

Basement Membrane

Pemphigus vulgaris leads to ? on the skin and mucosa that are fragile and usually already ruptured on examination. Oral lesions especially are rarely intact and often precede skin lesions by months when pemphigus vulgaris first develops. The oral lesions are usually irregular, ill-defined erosions and ulcers that are slow to heal. Immunosuppressants are the mainstay of treatment.

Flaccid blisters and bullae (large blisters)

2 LAYERS: - Basal lamina * Extracellular matrix secreted by epithelial cells * Contains laminin proteins * Type IV collagen (Goodpasture’s/Alport syndrome) - Reticular lamina (reticular connective tissue) * Reticular = like a net * Anchors basal lamina to connective tissue

Basement Membrane

* Sheets of epithelial cells bind together * Different functions for each side of cell (“polarized”)

Cell Polarity

Side facing cavity/lumen: * Lumen of blood vessel * Lumen of GI tract * Lumen of nephron * Outside of body

Apical membrane

Side away from cavity/lumen:

Basolateral membrane

* Join plasma membranes of adjacent cells - Four types: * Tight junctions * Adherens junctions * Gap junctions * Desmosomes

Epithelial Cell Junctions

* Seals two cell membranes together * Barrier to paracellular movement between cells * Found near apical membrane * Most apical adhesion between cells Built from key proteins: * Occludin * Claudin

Tight Junctions (Occluding Junctions or Zonula Occludens)

* Found below tight junctions * Anchors cells to one another * Forms belt around cells Cadherin - Cell membrane glycoprotein - Attach to actin filaments in cells

Adherens Junctions (Belt Desmosomes or Zonula Adherens)

* Calcium-dependent adhesion (CAD) proteins * Glycoproteins * Many subtypes

Cadherin

Lost in some forms of breast cancer

E-cadherin

* Macula = Latin for spot * “Spots” of cell-cell attachment (not belts) * Common in the skin * Attached to intermediate filaments - Made of keratin and found in cell cytoplasm, Linked by cadherins.

Desmosomes (Spot Desmosome or Macula Adherens)

Keratins

* Tough, fibrous structural proteins * Found in hair, skin * Also horns, claws, hooves * Keratin monomers assemble intermediate filaments

* Similar to desmosomes * Contain intermediate filaments of keratin * Linked by integrins * Attach epithelial cells to basement membrane (Laminin (basal lamina), collagen)

Hemidesmosomes

* Channel connections (electrolytes) * Connexins: protein molecules * Form structure called connexon * Allow small molecules to pass * Too small for proteins, nucleic acids

Gap Junctions

Autoantibodies to desmosomes

Pemphigus vulgaris

Autoantibodies to hemidesmosomes

Bullous pemphigoid

Air sacs of lungs and the lining of the heart, blood vessels, and lymphatic vessels

Simple squamous epithelium

Allows materials to pass through by diffusion and filtration, and secreates lubricating substance

Simple squamous epithelium

Secreates and absorbs

Simple cuboidal epithelium

In ducts and secretory portions of small glands and in kidney tubules

Simple cuboidal epithelium

Ciliated tissues are in bronchi, uterine tubes, and uterus; smooth (nonciliated tissues) are in the digestive tract, bladder

Simple columnar epithelium

Absorbs; it also secreates mucuos and enzymes.

Simple columnar epithelium

Cilliated tissue lines the trachea and much of the upper respiratory tract

Pseudostratified columnar epithelium

Lines the esophagus, mouth and vagina

Stratified squamous epithelium

Secretes mucus; ciliated tissue moves mucus

Pseudostratified columnar epithelium

Protects against abrasion

Stratified squamous epithelium

Protective tissue

Stratified cuboidal epithelium

The male urethra and the ducts of some glands

Stratified columnar epithelium

Sweat glands, salivary glands and the mammary glands

Stratified cuboidal epithelium

Secrets and protects

Stratified columnar epithelium

Lines the bladder, urethra and the ureters

Transitional epithelium

Allows the urinary organs to expand and stretch

Transitional epithelium

Is an inflammatory bowel disease associated with increased permeability of the intestinal wall. Tight junctions between intestinal epithelial cells form a barrier that regulates the paracellular (between cell) uptake of water, electrolytes, and nutrients, like glucose. Tight junctions vary in their selective permeability based on environmental stimuli and location within the intestine.

Crohn’s disease

The intestinal inflammation in Crohn’s disease is associated with ?, which increases intestinal permeability.

Tight junction dysfunction and changes in the expression of tight junction proteins

Changes in the expression of the tight junction proteins ? are thought to be an important part of the barrier dysfunction seen in inflammatory bowel disease. Inflammatory cytokines can affect the expression of ? to make the intestinal wall more permeable. In addition, some evidence suggests that dysregulated tight junction proteins and the subsequently impaired epithelial barrier may even precede and promote the intestinal inflammation seen in inflammatory bowel disease.

Claudin and occludin

These are important in the heart, where they allow depolarization to spread from one myocyte to another.

Gap junctions

Pemphigus vulgaris, an autoimmune blistering disorder where antibodies are formed against ?, a major component of desmosomes.

Desmoglein

Desmosomes form attachments between keratinocytes, and their destruction leads to

Acantholysis (loss of attachments between keratinocytes).

Acantholysis and blister formation occur predominantly in the stratum spinosum, while the underlying stratum basale remains intact.

Pemphigus vulgaris

Bullous pemphigoid, an autoimmune blistering disorder in which antibodies target ? important components of hemidesmosomes. Hemidesmosomes attach keratinocytes to the basement membrane between the dermis and epidermis. Destruction of these hemidesmosomes leads to blisters at the dermo-epidermal junction (where the epidermis and dermis meet).

Bullous pemphigoid antigens (BPAG1 and BPAG2),

Bullous pemphigoid usually affects people over the age of 70. Blisters in bullous pemphigoid are

Itchy, tense, and do not rupture easily. Commonly-affected areas include the trunk, upper arms, and thighs. Rubbing the skin usually does not cause exfoliation of the top layer of skin (a negative Nikolsky’s sign).

A genetic disorder in which defective type IV collagen leads to progressive kidney disease, hearing loss, and eye abnormalities.

Alport syndrome

Eighty-five percent of patients with Alport syndrome inherit an

X-linked mutation in the alpha-5 chain of Type IV collagen.

Is an important component of the basement membrane in renal glomeruli, the inner ear, and the eye.

Type IV collagen is

The only symptom at birth may be microscopic hematuria, but progressive kidney disease eventually leads to gross hematuria, proteinuria, and, ultimately, end-stage renal disease by middle age. Sensorineural hearing loss can start in late childhood and progress to deafness by age 40. Vision is often normal, but eye abnormalities can include lenticonus (an abnormal conical shape to the lens), corneal opacities, and macular thinning.

Alport syndrome

Inflammation of hair follicles and sebaceous glands * Exocrine glands in skin in dermis * Secrete oily substance called sebum * Often contain hair follicles (“Pilosebaceous unit”) * Complex, multifactorial etiology

Acne

Acne: Sebaceous glands enlarge at puberty * ↑ androgens → ↑ sebum * Adolescent acne: men > women

* Men with androgen insensitivity: no acne * Women with excess androgens (PCOS): acne

* Comedo: debris blocking sebaceous duct (bumps on face) * Comedone: plural of comedo * Microcomedo: microscopic comedo (not visible) * Lipid-rich environment for bacterial growth * Bacteria use triglycerides in sebum as fuel

ACNE: Comedones allow bacterial growth

* Propionibacterium acnes (cutibacterium acnes) * Anaerobic bacterium * Normal skin flora * Inflammation from bacterial proliferation

ACNE: Sebum: growth medium for bacteria

Increased sebum and keratin * Keratinocytes line hair shafts → keratin * Blocks ducts * Bacterial growth behind blockage

Acne

Face, neck, chest, upper back

Acne: Affects most hormone-responsive glands

* Open comedos: blackheads * Closed comedos (by skin): whiteheads * Inflammatory lesions (papules/pustules) * Scarring and hyperpigmentation may occur

Acne: Multiple lesion types

* Benzoyl peroxide (topical) - Breakdown keratin, unblocks pores (comedolytic) - Bactericidal to P. acnes * Antibiotics - Decrease P. acnes colonization of skin - Clindamycin and erythromycin * Retinoids (vitamin A derivatives)

Acne: Treatment

* 13-cis-retinoic acid * Metabolites bind to nuclear receptors - Retinoic acid receptors (RAR) - Retinoid X receptors (RXR) * Decreases keratin production in follicles * Less follicular occlusion * Highly teratogenic * OCP and/or pregnancy test prior to Rx

Isotretinoin Accutane

* Red plaques with scale (flaky skin) * Occurs on face and scalp (areas with lots of sebaceous glands) * Poorly understood pathogenesis * No inflammation of sebaceous glands * Associated with fungal infection by Malassezia

Seborrheic dermatitis

Topical antifungals and corticosteroids

Treatment of seborrheic dermatitis

* Benign neoplasm of melanocytes * Tan/brown pigmented lesions * Uniform color * Often round or oval shape * Usually <6mm

Melanocytic Nevus (Moles)

* Present at birth * Often have hairs growing from lesion

Melanocytic Nevus Moles (congenital)

* Appear in childhood * Increase in number during adolescence * Peak count in 30s * Regress with age

Melanocytic Nevus Moles (acquired)

* Rarely develop dysplasia → melanoma * Atypical features may warrant biopsy/removal * Not removed prophylactically for prevention

Melanocytic Nevus Moles

* Junctional nevi - Growth along dermal-epidermal junction - Often found in children * Compound nevi - Growth extends into dermis * Intradermal nevi - Loss of junctional lesion - Found only in dermis - Common in adults

Acquired Nevi

* Chronic inflammatory skin disorder * Well-demarcated plaques * Pink or salmon colored * Silver-white scale * Most commonly on extensor surfaces (Knees and elbows)

Psoriasis

* Inflammation from trapped hairs * Associated with shaving * Entrapment of recently cut, very short hairs * Firm papules/pustules in area of beard growth * Common in black men (up to 80%) * 3% white men

Pseudofolliculitis barbae (Razor bumps, shave bumps)

* Pathogenesis poorly understood * Combination of genetic and environmental factors * Believed to be autoimmune * Strong association with HLA-C

Psoriasis

Acanthosis (thickening of epidermis) Parakeratotic scaling * Retained nuclei in stratum corneum * Indicates hyperproliferation Stratum spinosum * Increased in size Stratum granulosum * Thinned or absent Munro microabscesses * Neutrophils in stratum corneum (munro absceses)

Psoriasis

Psoriasis: Dermis blood vessels close to surface Scale breaks →

Bleeding (Auspitz sign)

Psoriasis: most common type

Plaque psoriasis

* Guttate psoriasis * Pustular psoriasis * Erythrodermic psoriasis * Inverse psoriasis

Psoriasis (Multiple other less common subtypes)

Commonly involves nails * Nail pitting * Onycholysis (separation of nail from nailbed) About 1/3 of patients develop psoriatic arthritis * Seronegative spondyloarthritis * More common in patients with nail findings

Psoriasis

* Common skin disorder (3% population) * Affects adults > 30 * Celtics and Northern Europeans: greatest risk * Affects light-skinned individuals

Rosacea

* Inflammatory skin condition * Complex, poorly understood pathology * Chronic redness of nose and cheeks * Papules and pustules * May look similar to acne but no comedones

Rosacea

Facial flushing * Often triggered by environmental stimuli * Cold, heat, sun, hot drinks, spicy foods, alcohol Phymatous rosacea * Skin hypertrophy * Thickened skin * Most commonly on nose (rhinophyma)

Rosacea

* Common benign tumors * Proliferation of immature keratinocytes * Occurs in older patients (>50) * Arise spontaneously * Commonly on trunk

Seborrheic keratosis

* Flat * Well-demarcated * Round or oval * Dark, velvety surface * “Stuck on”

Seborrheic keratosis

* Dark cells similar to basal skin cells * Keratin-filled cysts (“horn cysts”)

Seborrheic keratosis

* “Explosive onset” of multiple itchy SK lesions * Probably caused by cytokines * Associated with malignancies (gastric adenocarcinoma most common)

Leser-Trelat Sign

* Warts * Cellular proliferation caused by HPV * Many types - Verruca vulgaris (skin - most common) - Verruca plana (skin - flat wart) - Condyloma acuminatum (venereal warts)

Verrucae

* Most common manifestation of HPV infection * Transmitted by contact with virus * Common on hands * Epidermal hyperplasia * Koilocytosis (cytoplasmic clearing (“halos”) around nucleus)

Verruca Vulgaris (cutaneous Warts)

Pre-malignant lesions

Actinic keratoses

Blocking pilosebaceous follicles in that area and causing comedones to form. This occlusion can happen with tight gear like headbands and helmets (“acne mechanica”) or with oily cosmetics and hair products (“pomade acne”).

Acne

Sign of Leser-Trélat, the explosive onset of seborrheic keratoses associated with internal malignancy, most commonly gastrointestinal adenocarcinomas. Seborrheic keratoses are typically round or oval lesions that are well-circumscribed and hyperpigmented with a “stuck on” appearance. Their proliferation with internal malignancy is likely due to ?. The velvety, hyperpigmented (dark) plaque on his neck is acanthosis nigricans, which is also commonly associated with the Leser-Trélat sign.

Cytokines produced by the neoplasm.

Acquired immune deficiency syndrome (AIDS) can be associated with cutaneous findings such as fungal, bacterial, and viral infections of the skin, as well as skin malignancies such as Kaposi sarcoma. AIDS can also be associated with ? which consists of red, scaly skin on the face and scalp.

Seborrheic dermatitis

Can cause a diffuse, maculopapular, erythematous (red) rash that may involve the back as well as the palms and soles.

Secondary syphilis

Which is caused by human papillomavirus (HPV) infection of epidermal cells. Histologic findings include epidermal hyperplasia (thickening of the epidermal skin layer) and a thickened stratum granulosum with koilocytes – epithelial cells with perinuclear cytoplasmic clearing, causing “halos” around the nucleus.

Verruca vulgaris, or common warts

? (collections of neutrophils in the stratum corneum) and a thinned stratum granulosum are findings in psoriasis.

Munro microabscesses

Isotretinoin (13-cis-retinoic acid) is a retinoid, meaning a compound similar to vitamin A. It is converted to metabolites that activate retinoic acid receptors (RAR) and retinoid X receptors (RXR) located in the

Nucleus (“nuclear receptors”)

When a retinoid binds to its nuclear receptor, the retinoid-receptor complex becomes active and binds to a segment of DNA to promote

Gene transcription

Is used to treat severe acne and works by reducing the size of sebaceous glands and decreasing sebum production, inhibiting the sebum-dependent bacteria Cutibacterium acnes (formerly Propionibacterium acnes). It also reduces follicular hyperkeratinization (excess keratin deposition), leading to fewer comedones.

Oral isotretinoin

Histologic findings in psoriasis include

Epidermal hyperplasia (thickening of the epidermis) with parakeratosis (keratinocytes that do not mature normally and retain nuclei in the stratum corneum).

Clinically, parakeratosis causes the ? on psoriatic plaques and pits in the nails: clusters of parakeratotic cells in the nail plate slough off and leave depressions in the remaining nail.

Typical scale

Psoriasis causes a thinned or absent stratum granulosum

Psoriasis causes a thickened stratum spinosum.

* Infection (most commonly Strep) * Crohn’s disease (may precede flare) * Sarcoidosis * Coccidioidomycosi

Triggers of erythema nodosum

* Type IV hypersensitivity reaction * Panniculitis * Inflammation of subcutaneous fat * Often idiopathic

Erythema Nodosum

* Painful, red nodules * Most commonly on shins

Erythema Nodosum

“Septal panniculitis” * Inflammation of septa of fat between dermis and fascia * Contrast with “lobular”: inflammation of fat lobules

Erythema Nodosum: Pathology Findings

* Rare, chronic inflammatory skin disorder * “Lichen” = tree moss * “Planus” = flat * Occurs in adults * Unknown pathogenesis * Resolves spontaneously over years

Lichen Planus

Associated with hepatitis C

Lichen planus

Pruritic Purple Polygonal Planar Papules Plaques

Lichen planus: * 6Ps

* Itchy (often intense) * Purple flat lesions * Multiple, symmetric usually on arms/legs/wrists * Wrists, ankles are common sites

Lichen planus

* Mucosal involvement (Mouth, tongue, Glans penis)

Lichen Planus

Wickham striae: white dots/lines * Caused by hypergranulosis (classic feature of ?) * Best seen on oral lesions

Lichen Planus

* Lymphocytes at dermal-epidermal junction * Hyperkeratosis * Hypergranulosis * “Sawtooth” pattern of rete ridges

Lichen Planus

* Acute, self-limited skin rash * Eruption of skin lesions * Self-limited * Resolves 2-3 months * Usually no treatment required * Cause unknown (possibly viral)

Pityriasis Rosea

Begins with “herald patch” * Single red/salmon-colored lesion * Round or oval * Well demarcated * Chest, neck, or back

Pityriasis Rosea

Days later: Multiple lesions on trunk * Multiple similar, smaller lesions * Groups of lesions * Follow skin lines on back * “Christmas tree distribution”

Pityriasis Rosea

Superficial, Epidermis

Burns: 1st

Superficial partial thickness, Epidermis, some dermis Deep partial thickness Epidermis, most dermis

Burns: 2nd

Full thickness, Epidermis and dermis

Burns: 3rd

4th degree, Underlying tissue

Burns: 4th

* Epidermis only * Painful, red, blanch with pressure * Looks like sunburn * No blisters * Heal within 7 days * Minimal treatment required

Superficial Burn (1st Degree Burn)

* 2nd degree * Epidermis and some dermis * Often form blisters * Painful, red * Blanch with pressure * Heal within 7 to 21 days

Superficial Partial Thickness

* 2nd degree * Epidermis, most dermis * Erythematous, yellow or white * Almost always blister * Easily unroofed (tissue moves) ***Painful to pressure only *** Do not blanch * Usually > 21 days to heal * Heal with scarring

Deep Partial Thickness

* 3rd or 4th degree * Entire epidermis and dermis * Can involve underlying tissue (4th degree) * Fat, fascia or muscle * Scarring with wound contracture

Full Thickness (painless)

* Delayed inflammatory response of skin * Caused by ultraviolet radiation (UVR) * Two forms UV radiation * UVB radiation: wavelength 280 to 320 nm * UVA radiation: wavelength 320 to 400 nm * Both may cause sunburn

Sunburn

* Damage to epidermis and dermis * UV radiation → DNA damage → apoptosis * “Sunburn cells”: keratinocytes undergoing apoptosis * Vasodilation * Release inflammatory mediators * Self-limited

Sunburn

Range most effective at causing sunburn

UVB (280 a 320 nm)

This type of burn is usually red, moist, painful, blistered, and blanches with pressure. It usually heals within 7 to 21 days. Children under age 5 and adults over age 55 are more susceptible to deeper burns because they have thinner skin.

Second-degree, superficial partial-thickness burn

Sunburn cells are ? in the epidermis caused primarily by ultraviolet B (UVB) radiation.

Apoptotic keratinocytes

Pityriasis rosea, most likely triggered by a viral infection. Can sometimes be associated with prodromal symptoms, as suggested by this man’s headache and fatigue. Some studies support ? as the most likely etiology.

Human herpesvirus 7 virus reactivation

It leads to red, tender nodules on the bilateral shins. Each nodule is usually 2 to 5 cm, but they can sometimes coalesce into larger lesions. EN affects women three to six times more often than men. While it can be idiopathic, common triggers include infection, malignancy, and autoimmune disease. This woman’s recent throat infection and elevated anti-streptolysin O titer suggest that her trigger was streptococcal infection, which is the most common infectious trigger for EN.

Erythema nodosum (EN),

Commonly causes skin infections including impetigo, erysipelas, and cellulitis

Streptococcus

Primarily affects the epidermis and usually causes pustules that break down to form a golden crust.

Impetigo

Erysipelas (affecting the top dermis) and cellulitis

(affecting the deeper dermis and subcutaneous tissue) do not present as discrete nodules.

Usually also causes generalized signs of infection, like fever and chills.

Erysipelas

In lichen planus, a band of ?obscures the dermal-epidermal junction.

Lymphocytes

* Black/brown pigment * Gives color to skin and hair * Protects from ultraviolet radiation * Formed from amino acid tyrosine

Melanin

Synthesized in melanocytes - Specialized secretory cells - Derived from neural crest * Found in basal layer of epidermis * Synthesize melanin in melanosomes * Melanosomes transferred to keratinocytes Mik

Melanin

* Small brown/dark macules (flat) * Can darken on exposure to sun * Increased amounts of melanin * Normal melanocyte number/density

Freckles

* Family of genetic disorders * Autosomal recessive * Absent/reduced melanin synthesis in melanocytes * Normal number of melanocytes * Most common forms: ↓ activity tyrosinase

Albinism (Oculocutaneous Albinism (OCA))

* Hypopigmentation of hair, skin, eyes * White hair, pink skin color, blue eyes * ↑ risk of sunburns * ↑ risk of skin cancer * No UV light protection * Basal cell carcinoma * Squamous cell carcinoma * Melanoma

Albinism (OCA)

* Acquired hyperpigmentation * Irregular areas of tan/dark macules on face * Often symmetrical * Sun-exposed areas of face * Most common in women with dark complexions

Melasma

* Triggered by UV light in susceptible woman * ↑ melanin synthesis * Onset often with pregnancy or OCP - ↑ estrogen - “Mask of pregnancy” - May resolve after pregnancy * Cosmetic problem

Melasma

* Sun protection * Skin lighteners: Hydroquinone (inhibits tyrosinase)

Treatment of melasma

* Acquired, localized pigment disorder * Autoimmune destruction of melanocytes * Asymptomatic depigmented (white) macules/patches * No clinical signs of inflammation (warmth)

Vitiligo

steroids, immunosuppressants

Treatment of vitiligo

* Dark skinned individuals - Obvious areas of depigmentation * Light skinned individuals - Failure to tan in localized region

Vitiligo

Oculocutaneous albinism (OCA) caused by a defect in the enzyme ?, which converts tyrosine to dopaquinone, a precursor of the pigment melanin. Defects in tyrosinase cause absent or reduced melanin production, which results in pale skin, white hair, and blue irises. A lack of melanin in the retina leads to decreased visual acuity, nystagmus, and photophobia.

Tyrosinase

People with OCA are at increased risk for skin cancer due to ?. OCA is usually inherited in an autosomal recessive pattern.

Increased absorption of ultraviolet radiation

Other types of OCA can lead to ?. These other types of OCA are associated with defects in genes that affect melanin synthesis or melanin transfer to keratinocytes. Some of those genes affect the function of melanosomes, the organelles within melanocytes that produce melanin. This boy has the most severe type of OCA (OCA type 1) associated with no pigment in the hair, and caused by defects in tyrosinase.

Pale yellow, red, or brown hair and a range of eye colors

This girl’s freckles are due to sun exposure that promotes increased melanin synthesis in melanocytes, the cells that produce the pigment melanin. Melanocytes are located within ?, the lowest layer of the epidermis. Melanin is transferred to adjacent basal keratinocytes to produce freckles.

The stratum basale

Pigmented nevi (moles) are formed by

Clusters of melanocytes

Red hair, freckles, pale skin, and increased sun sensitivity are associated with mutations in the MC1R gene, which encodes the

Melanocortin 1 receptor

Melanocytes make two kinds of melanin: pheomelanin and eumelanin. A defective melanocortin 1 receptor causes melanocytes to make more pheomelanin than eumelanin. Pheomelanin is

A redder pigment that does not protect against ultraviolet radiation as well as eumelanin, a brown pigment.

Vitiligo, an autoimmune skin disorder caused by ?, leading to depigmented (white) patches in the skin. Vitiligo is associated with many other autoimmune disorders.

T-cell attack of melanocytes

The strongest association is with thyroid disease, but vitiligo is also associated with an increased risk of

Alopecia areata, psoriasis, pernicious anemia, and type 1 diabetes mellitus.

Patients with vitiligo are commonly screened for thyroid disease because ? of these patients also have an autoimmune thyroid condition.

20%

The average age of onset for vitiligo is ?. The patches are depigmented (white) and well-demarcated. While these patches can occur anywhere on the body, they occur most commonly in a symmetric pattern on the distal extremities and around orifices like the eyes, nose, and mouth. Depigmented areas often enlarge over time.

20 years old

Treatment includes topical steroids and phototherapy, which can improve the appearance of lesions but does not provide a cure.

Vitiligo

Is a genetic disorder that leads to excess iron deposition in the body. Excess deposition of iron in the skin leads to hyperpigmentation (darkening of the skin).

Hereditary hemochromatosis

Is associated with vitiligo.

The autoimmune disease type 1 diabetes mellitus

Melasma

Patches of hyperpigmentation (darker skin) that usually appear symmetrically on the face. Genetic, environmental, and hormonal factors can contribute to melasma, but the most common triggers are hormonal and related to pregnancy or oral contraceptive use. Estrogen stimulation of melanocortin 1 receptors on melanocytes (cells that produce the pigment melanin) is believed to stimulate production of melanin, leading to dark spots on the face. Sun exposure can also trigger or worsen melasma.

Tinea versicolor is a fungal infection of the skin caused by the ?. This fungus induces enlarged melanosomes (organelles that make melanin) within melanocytes that cause the skin to have a brown discoloration.

Fungus Malassezia

Oral contraceptives are a much more common trigger for

Melasma

* Traumatic bleeding in dermis * Intact epidermis * Many vascular tumors look similar

Blood Blister

* Rare tumor of blood or lymph vessels - Sarcoma = tumor of mesenchyme origin - Angio = blood vessel (endothelial origin) - Lymphangiosarcoma = derived from lymph endothelium - Hemangiosarcoma = derived from vascular endothelium * Hemangioma = benign version * Purple nodules or plaques * Poor prognosis

Angiosarcoma

* Occur in liver - Associated with vinyl chloride exposure * Occur in breast - Often following radiation therapy - Often in setting of lymphedema after mastectomy

Angiosarcoma

* Usually head and neck (sun exposed areas) * Often scalp or face * Arise from dermis * Older, white males * Median age: 65 to 70 * Male to female ratio: 2:1

Angiosarcoma: Occur beneath skin

* Zoonotic infection by Bartonella - Bartonella quintana and Bartonella henselae * End-stage HIV and AIDS patients * Systemic infection → blood vessels in skin * Presents as numerous red/purple nodules * Similar appearance to Kaposi sarcoma

Bacillary Angiomatosis

* Common in HIV/AIDS * Angioproliferation * HHV-8 (Human Herpesvirus-8) * Key differences from bacillary angiomatosis

Kaposi Sarcoma

* Kaposi Sarcoma: Lymphocytes

* BA: Neutrophils/lymphocytes

* Benign vascular tumor * Blood vessel hyperplasia due to growth stimuli * Most often on skin (Trunk, arms, legs, head, neck) * Can be mucosal: lips, gums * Classic stimuli: pregnancy and trauma * Often bleed profusely * Surgically removed

Pyogenic Granuloma (Lobular capillary hemangioma)

* Benign capillary proliferations * Common in middle-aged or elderly * Develop with aging * Usually multiple * Classically on the trunk * May bleed from trauma

Cherry Hemangioma

* Congenital malformation (newborns) * Large cyst containing lymph (benign) - Caused by obstruction of lymph drainage * Classically develops on neck

Cystic Hygroma

* Often identified on prenatal ultrasound * Increased risk of fetal aneuploidy and malformations - Trisomy 21 (Down) and Turner syndrome (XO) - Cardiac and skeletal malformations * Increased risk of miscarriage or fetal death * Often found together with nuchal translucency

Cystic Hygroma

* Structure in dermis of skin * Most numerous in fingers and toes * Contains modified smooth muscle cells * Regulates skin temperature * Shunts blood away from surface in cold * Preserves heat

Glomus body

* Benign growth of modified smooth muscle cells * Occurs in fingers and toes * Usually at tips/ends - “Subungual” = under nailbed * Pink/purple papule or nodule * Painful especially when exposed to cold - “Paroxysms of pain” - “Cold sensitivity

Glomus tumor

* Benign hemangioma (Excess proliferation of blood vessels) * Appear in newborns - Common: Up to 10% Caucasian babies in some studies - Usually a single lesion - Usually not present at birth - Usually identified first few days/months after birth * Involute within few years

Strawberry Hemangioma

* Capillary malformation (not a tumor) * Common on eyelids or back (nape) of neck * “Birthmark” * Pink-red macule * Up to 60 percent of infants * Fade first few years of life

Nevus Simplex (Stork bite/Salmon Patch)

* Malformation of dermal capillaries and venules * Slow/low blood flow * Pink/red patches * Often unilateral * Blanch when pressed * Do not regress * Grow as child grows

Nevus Flammeus (Port Wine Stain)

Associated with Sturge-Weber syndrome

Nevus Flammeus (Port Wine Stain)

Usually comes from lices or cats

Bartonella

Due to exposure to vinyl chloride monomer (VCM), a colorless gas used in the production of polyvinyl chloride (PVC). VCM is absorbed by the lungs and metabolized in the liver, where it is linked to an increased risk of liver ?.

Angiosarcoma

Liver angiosarcoma is derived from endothelial cells. Diagnosis is often delayed due to lack of symptoms until late-stage disease. Symptoms may be nonspecific, including ? Overall prognosis is poor.

Abdominal pain, fatigue, and weight loss.

Kaposi’s sarcoma (KS), a neoplasm of endothelial cells seen most often in immunocompromised patients. KS is caused by infection with ?, also known as Kaposi’s sarcoma-associated herpesvirus (KSHV).

Human herpesvirus 8

Biopsy shows tumor cells with a characteristic spindle shape that stain positive for latency-associated nuclear antigen (LANA), a protein in KSHV.

Kaposi’s sarcoma (KS),

EBV can cause ?, characterized by a white patch on the side of the tongue, in patients with HIV.

Oral hairy leukoplakia

Disseminated VZV infections in patients with HIV cause

Widespread blisters.

* Superficial skin infection * Neutrophils collect beneath stratum corneum * Macules → papules → rupture → erosions * Dried sebum → “Honey-colored” crust * Highly contagious

Impetigo

* Traditional, most common form * Face and extremities * Caused by S. aureus * Also “Beta-hemolytic step” – mostly S. Pyogenes (group A) * Honey crusted lesions

Impetigo contagiosa (non-bullous)

* Seen in children * Trunk commonly involved * S. aureus

Bullous impetigo

* Destroys keratinocyte attachments * Cleaves desmoglein 1 complex * Desmosome protein * Links keratinocytes together * Affects stratum granulosum * Leads to bullous impetigo

S. Aureus Exfoliative Toxin (Exfolatin)

* Newborn disease * Colonization of skin with S. Aureus * Diffuse exfoliative toxin * Classically occurs 3 to 7 days of age * Fever, diffuse erythema * Sloughing of skin * Damage intraepidermal * Heals completely with no scar * Nikolsky’s sign: skin slips off with gentle tug * Treatment: antibiotics

Scalded Skin Syndrome

* Bacterial skin infections that often overlap * Differ mainly by layer of skin involvement * Skin break/trauma → bacterial entry * Redness, warmth * Sometimes fever * Usually unilateral * Most common on legs (lower extremities) * Erysipelas also on face

Erysipelas and Cellulitis

* Superficial dermis * Young children and older adults * Usually Group A strep (S. Pyogenes) * Acute onset: fevers, chills, rash * Clear demarcation rash/normal skin

Erysipelas

* Deep dermis * Subcutaneous fat * Middle-aged and elderly (rarely children) * Group A strep (S. Pyogenes) or S. Aureus * Slower onset * Rash, focal pain, warmth over days * Ill-defined, spreading border

Cellulitis

* Collection of pus (neutrophils, bacteria) * Walled-off in dermis or subcutaneous space * Usually S. aureus * Red, painful nodule * Tense, raised skin * May complicate cellulitis/erysipelas * Usually requires incision and drainage

Skin Abscess

* Infection of fascia * Involves muscle fascia and subcutaneous fat * Destruction (necrosis) of tissue above fascia

Necrotizing Fasciitis

* Skin color changes: red-purple-blue-gray-black * Bullae * Pain and tenderness - May be “out of proportion to exam” - Apparently minor rash with exquisite tenderness - Patient may mistake infection for muscle injury - Eventually pain stops (anesthesia) from nerve destruction

Necrotizing Fasciitis

* Crackling sound when skin is pressed * From gas under skin * Methane and CO2 from bacteria

Necrotizing Fasciitis: Crepitus

* Often fulminant and deadly * Infection spreads along muscle fascia * Poor blood supply → uncontrolled spread * Requires urgent surgical debridement

Necrotizing Fasciitis

* Polymicrobial * Often anaerobes (Bacteroides, Clostridium, etc.) * Strep, staph, others * Occurs in diabetics, immunocompromised, vascular disease * Usually occurs following surgery

Necrotizing Fasciitis, Type 1:

* Group A strep (sometimes Staph) * Occurs in otherwise healthy people after skin injury

Necrotizing Fasciitis, Type 2:

* Minor skin trauma * Or diabetic/immunocompromised after surgery * Redness/warmth (can be confused with cellulitis) * Pain out of proportion to exam * Fever, hypotension

Necrotizing Fasciitis, classic case:

Necrotizing fasciitis (NF), a rapidly progressive infection of the fascia that causes necrosis of skin, subcutaneous tissue, and muscle. Her vital signs (fever, tachycardia, tachypnea, and hypotension) suggest ? and her leg has evidence of necrosis, including black skin. This woman’s chronic foot ulcer is due to peripheral vascular disease and ischemia. Diabetes and peripheral vascular disease are associated with increased risk for NF. This type of infection is often polymicrobial and includes aerobes and anaerobes that proliferate in the poorly-perfused, low-oxygen environment of the fascial tissues. Even with aggressive surgical debridement and broad-spectrum antibiotics, necrotizing fasciitis carries a high mortality rate.

Septic shock

.Crepitus arises when gases in subcutaneous tissues are compressed as pressure is applied. Bacteria causing her infection produce gases including ?, leading to crepitus on exam.

Hydrogen, nitrogen, hydrogen sulfide, and methane

Impetigo, a superficial epidermal infection that leads to collections of ?under the stratum corneum (the outermost layer of the epidermis).

Neutrophils

Are seen in herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections.

Epithelial multinucleated giant cells (or Tzanck cells)

S. aureus are the most common bacterial cause of skin abscesses, collections of pus in the dermis or subcutaneous tissue. In particular, ? is an increasingly common cause of skin abscesses.

Methicillin-resistant S. aureus (MRSA)

Due to their ability to stick to artificial surfaces, these bacteria more commonly cause infections of artificial devices like central venous catheters.

Staphylococcus epidermidis and Staphylococcus haemolyticus

Caused by strains of Staphylococcus aureus that produce exfoliative toxins A or B. These toxins are enzymes that cleave desmoglein-1, a desmosome protein that attaches keratinocytes to one another in the stratum granulosum. Cleavage of desmoglein-1 causes the granular layer to slough off, leading to blisters and skin exfoliation. The basal layer (located below the granular layer) is unaffected and remains intact to regenerate the epidermis once the infection has resolved.

Staphylococcal scalded skin syndrome (SSSS)

If neonates are treated appropriately with penicillinase-resistant anti-staphylococcal antibiotics (such as nafcillin or oxacillin), prognosis is excellent. Usually resolves completely with no scarring within 10 days. However, the prognosis is worse in rare cases when adults develop SSSS. These patients usually have an underlying immunocompromised state or renal disease.

SSSS

Since staphylococcal exfoliative toxins are cleared by the kidneys, ? (whether via kidney disease or via immature kidney function in neonates) is a risk factor for SSSS.

Impaired kidney function

Is an autoimmune blistering disorder characterized by antibodies against desmoglein-3.

Mucosal dominant pemphigus vulgaris

The stimulation of CD8+ T cells to kill keratinocytes is the proposed mechanism behind the blistering disorder

Toxic epidermal necrolysis (TEN)

TEN most commonly affects older adults after being triggered by a medication. Although SSSS and TEN can both cause extensive skin blistering, TEN also affects ?, which are unaffected in SSSS.

Mucosal membranes (such as the oral mucosa)

SSSS only affects the stratum granulosum, whereas TEN causes

Necrosis of the entire epidermis and separation of the epidermis from the dermis.

* Fluid-filled skin lesions - Separation of skin layers - Space filled with fluid * May rupture * Vesicle: <1cm * Bulla (plural = bullae): >1cm * Many causes * Burns * Friction

Blisters

* Pemphig: from Greek word for blister - Loss of connections between keratinocytes * Involve mucous membranes (mouth) and skin

Pemphigus

Hallmark of Pemphigus

Acantholysis

- Pemphigus vulgaris (most common) - Pemphigus foliaceus - IgA pemphigus - Paraneoplastic pemphigus

Subtypes of pemphigus

* Loss of connections between keratinocytes * Often loss of desmosomes * “Rounded” keratinocytes * Detached, floating freely in epidermis * Key feature of pemphigus vulgaris

Acantholysis

* Autoantibodies against desmoglein - Component of desmosomes - Type II hypersensitivity reaction * Disrupts connections in stratum spinosum - Fluid collects above basal layer * Occurs mostly in adults (30 to 60) * Nikolsky’s sign - Skin slips off with gentle tug - Also seen in Staph Scalded Skin (child) - Also seen in Stevens-Johnson syndrome

Pemphigus vulgaris

* Large, flaccid bullae that easily burst (not tense) * Often few intact bullae, most rupture and scabbed * Often presents first with oral bullae and ulcerations - Painful chewing/swelling

Pemphigus vulgaris

(+) immunofluorescence for IgG

Classic finding of Pemphigus vulgaris

Like a net

“Reticular” pattern of Pemphigus vulgaris

Immunosuppressants

Treatment of Pemphigus vulgaris

Infection, side effects of Rx

Increased mortality of Pemphigus vulgaris

Bullous pemphigoid

* “Pemphigoid”: looks like pemphigus * Autoantibodies against hemidesmosomes * Bullous pemphigoid antigens (proteins) * BP180, BP230 * Attach epithelial cells to the basement membrane

Bullous pemphigoid

* Bullae are subepidermal, nonacantholytic * Less fragile (flaccid) than pemphigus vulgaris * Numerous intact, tense bullae * Less ruptured bullae with scabs

Eosinophils and lymphocytes

Bullous pemphigoid: Biopsy

Line at base of epidermis

Bullous pemphigoid: Immunofluorescence

* Occurs in the elderly (median age 80 in one study) * Rarely involves mouth * Absent Nikolsky's sign * Treatment: immunosuppressants * Also increased mortality - Less than pemphigus - Less bullae rupture → less chance of infection

Bullous pemphigoid

* Skin condition associated with celiac disease * Herpes-like lesions on skin - Papules/vesicles in bilateral groups ("herpetiform") ***Pruritic (itchy) * Classically on extensors: elbows, knees

Dermatitis Herpetiformis

* IgA deposition in dermal papillae - Numerous, small lesions at tips of dermal papillae

Dermatitis Herpetiformis

* Occurs in individuals with genetic gluten sensitivity * Antibodies triggered by gluten cross-react at skin * Biopsy: microabscesses (spaces) at tips of papillae * Neutrophils

Dermatitis Herpetiformis

IgA Deposition at tips of dermal papillae on IF

Dermatitis Herpetiformis

Antibodies: IgG

Pemphigus, Bullous Pemphigoid

Antibodies: IgA

Dermatitis Herpetiformis

Target: Desmosomes Location: Stratus Spinosum

Pemphigus

Target: Hemidesmosomes Location: Basement Membrane

Bullous Pemphigoid

Target: (Gluten-related) Location: Dermal papillae

Dermatitis Herpetiformis

Causes inflammation of the small intestine, often leading to malabsorption of nutrients, diarrhea, abdominal pain, weight loss, and anemia.

Celiac disease

In celiac disease, antibodies formed against the protein ? can also affect the skin, causing dermatitis herpetiformis.

Transglutaminase

Is an itchy, red rash with papules and vesicles, most commonly affecting the elbows, knees, trunk, and buttocks.

Dermatitis herpetiformis

The best long-term treatment for both celiac disease and dermatitis herpetiformis is a

Strict, gluten-free diet

Dermatitis herpetiforme: Skin biopsy shows ?: collections of neutrophils at the tips of the dermal papillae.

Piérard microabscesses

The classic histological finding for an infection with HSV or varicella-zoster virus is

Multinucleated giant cells

The gold standard for diagnosis is direct immunofluorescence that shows immunoglobulin-A deposition at the tips of the dermal papillae.

Dermatitis herpetiforme

The characteristic histological finding is blisters that contain eosinophils and extend to below the epidermis (subepidermal). Immunofluorescence highlights a line of immunoglobulin G along the basement membrane.

Bullous pemphigoid

Bullous pemphigoid is most common in people over the age of 70. The initial rash in bullous pemphigoid is variable and can first appear as hives or red patches, but eventually develops into blisters. Common sites affected are

The trunk, upper arms, and thighs.

The blisters are large, tense and do not rupture easily. Rubbing the skin usually does not cause exfoliation of the top layer of skin (negative Nikolsky’s sign).

Bullous pemphigoid

Is a characteristic finding of psoriasis.

Munro’s microabscesses (collections of neutrophils) in the stratum corneum

Psoriasis usually causes

Pink plaques with a silvery scale, not blisters.

* Urticaria = hives * Urticaria = pruritic, raised wheals and angioedema * Angioedema = deep mucocutaneous swelling

Allergic Skin Reactions

* Allergic skin reaction * Usually caused by mast cell degranulation - Type I hypersensitivity reaction - Antigen binding to IgE antibodies on mast cells - Histamine release * No changes to epidermis * Dermal edema * Dilation of lymph vessels for fluid drainage

Urticaria

* Usually acute and self-limited * Resolves within days/weeks * May be treated with antihistamines and steroids

Urticaria

* May be a component of anaphylaxis - Wheezing - Mucosal swelling (lips/tongue) - Hypotension - Syncope

Urticaria

* Chronic disorder with flares/remission * Also a hypersensitivity disorder - Complex, incompletely understood pathogenesis - T-cells, cytokines * Usually “extrinsic”: reaction to environmental antigens - Less common form: intrinsic * Usually occurs in children * Red, pruritic (itchy) rash

Atopic Dermatitis, Eczema

Over 80% patients: ↑ serum IgE levels

Atopic Dermatitis, Eczema

70% of patients: family history of atopic diseases * Commonly co-occurs with allergic rhinitis/asthma * “Atopic march”

Atopic Dermatitis, Eczema

* Protein of stratum corneum * Filaggrin deficiency impairs skin barrier * Filaggrin gene mutations → increased risk of eczema * Skin dry and scaly * Easy entry of allergens

Filaggrin (Atopic dermatitis)

* Babies: face (cheeks) and scalp * Children/adults: * Thickened (“lichenified”) plaques * Skin flexures * Antecubital and popliteal fossae

Atopic Dermatitis, Eczema

* Similar clinical features to eczema * Localized to area of skin contact with allergen * Type IV hypersensitivity disorder

Contact Dermatitis

* Similar clinical features to eczema * Localized to area of skin contact with allergen * Type IV hypersensitivity disorder

Contact Dermatitis

* Poison ivy * Nickel (jewelry) * Laundry detergents

Contact Dermatitis, classic causes (irritants):

* “Non-immediate” reaction to drug * Often seen with some penicillin antibiotics * Maculopapular * Itchy or may be non-pruritic * Absence of fever, wheezing, joint pain * Days or weeks after starting drug * Type-IV (T-cell-mediated) mechanism

Drug Rash

* Remove irritant * Steroids

Contact Dermatitis, treatment:

* Severe skin reaction * Type IV hypersensitivity disorder * May also involve mucous membranes * Usually triggered by drugs * Nikolsky sign - Skin slips off with gentle tug - Also seen in Staph Scalded Skin (child) - Also seen in Pemphigus vulgaris

Stevens-Johnson Syndrome

Necrosis of the epidermis

Hallmark of Stevens-Johnson Syndrome

* 1-3 days before skin findings * Fever * Flu-like malaise

Stevens-Johnson Syndrome, prodrome:

* Lesions start on face/chest * Spread symmetrically * Red, tender skin * Progresses to vesicles/bullae * Sloughing of skin * Mucosal lesions: 90% cases

Stevens-Johnson Syndrome

* Toxic epidermal necrolysis - Severe form SJS (>30% skin) * High mortality - SJS 1-5%; TEN 25-35%

Stevens-Johnson Syndrome

* Skin disorder associated with infections (90% cases) - Herpes simplex virus (most common) - Mycoplasma pneumoniae (often in children) * Also associated with some drugs - Sulfa drugs - NSAIDs - Phenytoin * Also some cancers and autoimmune diseases

Erythema multiforme

* Pathogenesis unclear * Most data from HSV-related cases * Cell-mediated (type IV) autoimmune * Triggered by viral antigens in keratinocytes

Erythema multiforme

Hallmark: “Target lesion” * Dark/dusky central area * Surrounding red rings

Erythema multiforme

* Symmetrical distribution * Starts on “extensor surfaces of acral extremities” - Backs of hands, feet - Contrast with SJS: face * Spreads to center (“centripetal spread”) * May involve mucous membranes - Mouth, eye, genitals - Erythema - Erosions (painful) - Bullae

Erythema multiforme

* Oral or genital HSV eruption (or other trigger) * EM skin eruption occurs few days to 2 weeks later * Lesions evolve over 3-5 days * Resolve within 2 weeks (no treatment) * Rarely severe cases require steroids or other Rx

Erythema multiforme, typical case:

Urushiol, an oily substance within the sap of poison ivy, poison oak, and poison sumac. Urushiol causes a ? 12 to 48 hours after exposure to the sap. This leads to red, itchy, and painful papules and vesicles. The linear pattern of the rash. This occurs due to the way this man brushed against the poison oak as he walked by it. While not always present in contact dermatitis, well-demarcated or geometric patterns like these lines can be helpful in determining the etiology and distinguishing contact dermatitis from other types of skin rash.

Type IV hypersensitivity reaction

Peanut ingestion may cause a rash as part of a type I hypersensitivity reaction. Type I reactions are ? and occur within minutes to hours of ingestion. They may cause a skin reaction consisting of urticarial wheals. This man had papules and vesicles that began the days after his hike.

Immunoglobulin E-mediated

This girl had urticaria due to a peanut allergy, but urticaria can also be triggered by

Infection, physical stimuli like cold, medications, and other substances like bee venom.

Examples of disorders caused by type IV hypersensitivity reactions include

Contact dermatitis, Stevens-Johnson syndrome, multiple sclerosis and erythema multiforme

A self-limited skin disorder caused by a cell-mediated (type IV), delayed-type hypersensitivity reaction to infections or drugs. This type of hypersensitivity is due to activated T-lymphocytes.

Erythema multiforme (EM)

A common trigger for EM is ?, which causes cold sores, as occurred preceding the rash in this man. The rash in EM can include multiform macules, papules, vesicles, and bullae that usually start on the extremities and spread centrally.

Herpes simplex virus

The classic “target lesion” of EM has a center that is ? . EM is usually a self-limited condition that resolves on its own within two weeks.

Dark, vesicular, or eroded, with a surrounding red or purple ring

Stevens-Johnson syndrome (SJS), a type IV hypersensitivity reaction that causes keratinocyte necrosis in the epidermis and subsequent exfoliation. This type of reaction is mediated by ? that cause keratinocyte necrosis through a complex, poorly-understood mechanism.

CD8+ T-lymphocytes

Is a severe form of SJS that affects greater than 30% of the body surface area

Toxic epidermal necrolysis (TEN)

* Premalignant skin lesions * Caused by sun exposure * Growth of atypical epidermal keratinocytes * Can lead to squamous cell carcinoma - Increasing degrees of dysplasia → malignancy

Actinic Keratosis (Solar keratosis)

* Round, red/brown papules or plaques * Sun exposed areas * Biopsy: Hyperkeratosis, epidermal cell dysplasia * Parakeratosis: retained nuclei in stratum corneum

Actinic Keratosis (Solar keratosis)

* 2nd most common skin cancer * Arises from squamous cells in epidermis * Occurs in sun-exposed areas - Face, lip, ears, hands - DNA damage by UV light * Occurs in older patients - Rare <45 years old - Common > 75 years old * Less than 5% metastasize to regional nodes * Rarely metastasize beyond nodes

Squamous Cell Carcinoma

* Red, scaling plaques with sharp borders * More advanced lesions: ulcerate, keratin production * May crust or bleed

Squamous Cell Carcinoma

* Sun exposure * Chronic immunosuppression (Organ transplant, HIV, long term glucocorticoids) * Chronic skin inflammation (Burns, chronic ulcers, draining sinus tracts) * Arsenic exposure (found in contaminated drinking water)

Risk Factors for Squamous Cell Carcinoma

Classic finding: keratin pearls

Pathology of the Squamous Cell Carcinoma

* Variant of SCC (“squamoproliferative tumor”) * Usually benign, self-resolving * “Dome-shaped” nodule with central hyperkeratosis * Classic feature: rapid growth (weeks) → regression * Removed surgically or followed for regression

Keratoacanthoma

* Squamous cell carcinoma in situ * Well-demarcated, scaly patch or plaque

Bowen’s Disease

* Most common skin cancer * Slow growing * Rarely metastasize * Most found early and excised * Occur in sun-exposed areas * Lowest potential for recurrence or metastases * Basal < squamous < melanoma

Basal Cell Carcinoma

* “Pearly” papules or nodules - May have telangiectasias on surface - Dilated blood vessels * May ulcerate with crust in center * Borders may be “rolled” (rounded, thickened)

Basal Cell Carcinoma

Nests of “basaloid” dark cells in dermis

Basal Cell Carcinoma

* “Palisading nuclei” * Cells at periphery of nests line up in parallel

Basal Cell Carcinoma

* Special variant of BCC (~30% of BCCs) * Light red to pink plaque * Slight scale * Most commonly occur on the trunk

Superficial BCC

* Surgical excision * Cryotherapy * Electrosurgery * Radiation therapy * Topical chemotherapy * High risk lesions excised - Larger lesions - Recurrent lesions - Lesions in specific locations - Immunosuppressed patients (SCC)

Treatment SCC and BCC

* Highly malignant form of skin cancer * ABCDE - Asymmetrical - Irregular border - Color variation - Diameter > 6mm - Evolving over time

Melanoma

* Genetic disorders of skin, nerves and eye - Other structures sometimes involved (bones, kidneys) * Structures derived from ectoderm * Neurofibromatosis * Tuberous Sclerosis * Sturge-Weber syndrome * von Hippel-Lindau disease

Neurocutaneous Disorders (Phakomatoses)

* Familial cancer syndrome * Genetic disorder * Autosomal dominant * Mutations in NF1 or NF2 genes - NF1: Most common type * Nerve tumors with skin and eye findings

Neurofibromatosis

* Mutation of NF1 - Tumor suppressor gene on chromosome 17 - Encodes for neurofibromin (tumor suppressor protein) - Restricts RAS function - Mutation → RAS overactivity → uncontrolled growth * Autosomal dominant with 100% penetrance - All gene carriers have disease - Children of affected individuals → 50% chance of disease * Variable expressivity - Some patients: mild features - Other patients: severe features