DERMATOLOGY: BOARDS AND BEYOND Flashcards
It contains STEM cells that are capable of regenerating keratinocytes in the epidermis.
Stratum basalis
Order of the layers of the epidermis.
- Stratum basale
- Stratum spinosum
- Stratum granulosum
- Stratum lucidum
- Stratum corneum
Meant to be the tough outer layer of the skin that protects your body.
Stratum corneum
Processes that cause leaky vessels are going to tend to swell the ?, not the epider
Dermis
Acantholysis means a loss of connections between keratinocytes it’s often a loss of desmosomes that significantly affects the
Stratum spinosum
The classic malignancy, in which to see acanthosis nigricans is
Gastric adenocarcinoma
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
- Epidermis: keratinocytes (squamous epithelial cells)
- Dermis: connective tissue, vessels
- Subcutaneous fat (also called hypodermis or subcutis)
Layers of the skin
Stratum Basalis
Stem cells
Stratum Spinosum
Desmosomes form spines
Stratum Granulosum
- Keratohyalin granules
- Form keratin filaments
Stratum Lucidum
- Clear layer of dead skin cells
Stratum Corneum
- Anucleated cells
- Filled with keratin filaments
Dermis
- Connective tissue
- Blood vessels
Hyperkeratosis
- Thickening of stratum corneum
- Excess quantity of keratin
Seen in psoriasis and callus
Parakeratosis
- Hyperkeratosis + retained nuclei in stratum corneum
- Indicates hyperproliferation
- Seen in skin diseases (psoriasis) and malignancies
Hypergranulosis
- Increased thickness of stratum granulosum
- Classic finding in lichen planus
Spongiosis
- Fluid accumulation (edema) of epidermis
- Seen in eczema, many other skin disorders
Acantholysis
- Loss of connections between keratinocyte
- Often loss of desmosomes
- “Rounded” keratinocytes
- Detached, floating freely in epidermis
Key feature of pemphigus vulgaris
Acantholysis
- Diffuse epidermal hyperplasia
- Elongated rete ridges
- Spinous layer thickening
Acanthosis
- 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
Primary skin Lesions
- Directly caused by disease process
- Macules, papules, vesicles, bulla
Macules and Patches
- Flat lesions (not raised)
- Macule: <1cm
- Patch: >1cm
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
Neurofibromatosis 1 (NF1/von Recklinghausen disease)
Neurofibromas
* Benign tumors
* Develop on nerves
* Often cutaneous nerves
Neurofibromatosis 1 (NF1/von Recklinghausen disease)
Lisch nodules
* Brown spots on iris
Neurofibromatosis 1 (NF1/von Recklinghausen disease)
- Café-au-lait spots
- “Coffee with milk”
- Light brown macules
- Freckles
- Not random
- Clusters in skin folds
- Axilla and groin
Neurofibromatosis 1 (NF1/von Recklinghausen disease)
- Optic gliomas
- Usually develop by 3 years of age
- Bone abnormalities
- Curvature of long bones
- Facial deformity of eye socket
- Scoliosis
- Intellectual impairment
Neurofibromatosis 1 (NF1/von Recklinghausen disease)
- Hypertension
- Renal artery stenosis
- Rarely pheochromocytoma
- Malignant tumors
- Some neurofibroma become malignant
- Usually not skin lesions
- Peripheral nerve sheath tumors
- Occurs in adolescence or adulthood
- Presents as pain or sudden growth of neurofibroma
Neurofibromatosis 1 (NF1/von Recklinghausen disease)
- Six or more café-au-lait spots
- Two or more neurofibromas
- Freckles in axilla or groin
- Optic glioma
- Two or more Lisch nodules
- Bone lesions
- 1st degree relative with NF1
Diagnostic criteria of NF1
- Birth to 2 years
- Café-au-lait spots
- Bone abnormalities
- Optic gliomas
- Age 2 to 6
- Lisch nodules
- Developmental delay
- Adolescence (puberty)
- Cutaneous neurofibromas
NF1
- Less common than NF1
- Also autosomal dominant
- Mutation of NF2 gene
- Major features: CNS tumors
- Bilateral schwannomas
- “Acoustic neuromas”
- Occur in almost all patients
- Meningiomas
Neurofibromatosis 2
- Schwann cells: Glial (non neurons) of PNS
- Classically located to CN VIII
- Hearing loss, tinnitus, ataxia
Schwannoma
- Familial cancer syndrome
- Hallmark: hamartomas
- Benign malformation of cells/tissue
- Resembles tissue of origin (skin, lung, spleen)
- Main clinical feature: seizures
- CNS hamartomas
Tuberous Sclerosis
- Autosomal dominant with variable expressivity
- De novo mutations: 80% cases (no family history)
- Mutation in TSC1 or TSC2 gene
- TSC1: Hamartin
- TSC2: Tuberin
- Proteins inhibit mTOR
- Mechanistic target of rapamycin
- Kinase
- Mutation → mTOR overactivity → cell growth
- Especially cell size
Tuberous Sclerosis
- Widespread tumor formation
- Involves MULTIPLE organ systems
- Numerous hamartomas and other neoplasms
- Classic features
- Seizures– most common presenting feature
- “Ash leaf spots”: Pale, hypopigmented skin lesions
- Facial skin spots (angiofibromas)
- Intellectual impairment
Tuberous Sclerosis
- Cortical tubers
- Distorted cortex
- Seizures
- Subependymal nodules
- Ependyma = lining of ventricles
Tuberous Sclerosis: CNS Tumors
- Low grade astrocytoma
- Usually occur at interventricular foramen
- May obstruct ventricles → hydrocephalus
Tuberous Sclerosis: Subependymal giant cell astrocytomas
Fibrous papules usually on face
Tuberous Sclerosis: Angiofibromas
- Hypopigmented macules
- Usually oval or elliptical
Tuberous Sclerosis: Ash Leaf Spots
- Connective tissue hamartoma
- Usually found on lower back
- “Orange peel” or “leathery” texture
Tuberous Sclerosis: Shagreen patches
Fibromas beneath nailbeds
Tuberous Sclerosis: Ungual fibromas
- Tumors of muscle cells
- Benign (do not metastasize)
- Classic cardiac feature of TS (90% cases)
- Sometimes detected prenatal
- Tumor embedded in ventricular wall
- Rare symptoms from obstruction, arrhythmia
Tuberous Sclerosis: Rhabdomyomas
- Most frequent renal manifestation
- Multiple/bilateral
- Proliferation of epithelioid cells around vessels
- Growth and hemorrhage → pain
- May cause renin-dependent hypertension
- Risk of chronic kidney disease
- Compression of normal renal tissue
Tuberous Sclerosis: Renal Angiomyolipomas
- Congenital vascular disorder of capillaries
- Spontaneous gene mutation in early development
- Not inherited
- Three classic features
- Port-wine stain on face (birthmark)
- Leptomeningeal angioma (brain tumor)
- Increased ocular pressure (glaucoma)
Sturge-Weber Syndrome
- Child/infant
- Seizures
- Ash-leaf spots
- Angiofibromas
Tuberous Sclerosis: Classic Case
- Spontaneous mutation in GNAQ gene
- Occurs after fertilization (somatic mutation)
- Mosaicism (some cells normal, some mutated)
- Abnormal capillary formation/growth
Sturge-Weber Syndrome: Genetics
- Malformation of dermal capillaries and venules
- Occurs on face in SWS
- Unilateral
- 1st/2nd trigeminal area
- Slow/low blood flow
- Pink/red patches
- Apparent at birth
- Does not regress
- Grows as child grows
Sturge-Weber Syndrome: Port-Wine Stain/Nevus Flammeus
- Leptomeninges: pia mater and arachnoid
- Angioma: capillary-venous malformation
- Occurs on same side as port-wine stain
- May cause seizures (80% patients)
- Often begin first 2 years of life
- May cause hemiparesis, headaches
Sturge-Weber Syndrome: Leptomeningeal angioma
- In infancy or early adulthood
- Exact mechanism unclear
- Abnormalities anterior chamber angle
- Elevated venous pressure in episclera
- Choroidal hemangiomas
- Causes vision impairment
Sturge-Weber Syndrome: Glaucoma
- Newborn with port wine stain
- Seizures
- Glaucoma
Sturge-Weber Syndrome: Classic Case
- Genetic cancer syndrome
- Multiple benign/malignant tumors
- von Hippel-Lindau (VHL) gene
- Chromosome 3
- Codes for VHL tumor suppressor protein
- Ubiquitination of hypoxia-inducible factor
- Post-translational modification
- Addition of ubiquitin to proteins (small protein)
- Tags proteins for destruction in proteasome
- Cells behave as if hypoxic → blood vessel growth
Von Hippel-Lindau Disease
Multiple hemangioblastomas
* Clumps of capillaries (“angiomatosis”)
* Bright red on gross examination
* Well-circumscribed, benign
* No invasion or metastasis
* Symptoms: compression of other structures, hemorrhage
Von Hippel-Lindau Disease
- Occur in CNS
- Rarely occur sporadically outside VHL
- Classic locations: cerebellum, spinal cord, retina
Von Hippel-Lindau Disease
- Renal cysts
- Renal cell carcinomas (bilateral)
- Pheochromocytomas
Von Hippel-Lindau Disease
Requires “two hits”
* One abnormal gene inherited (germline mutation)
* Second spontaneous mutation → disease
* Similar to retinoblastoma, Li-Fraumeni, FAP
* “Autosomal dominant”
Onset usually late childhood to young adulthood (takes years for second hit to occur)
Von Hippel-Lindau Disease
A neurocutaneous disorder caused by a sporadic mutation of the GNAQ gene in an ectodermal cell early in fetal development. Although SWS is caused by a gene mutation, it cannot be passed from a parent to a child. The mutation occurs in a somatic (not reproductive) ectodermal cell in early development after conception. Only some of this woman’s cells carry this mutation, a pattern called somatic mosaicism. Since her ova, which are germ cells and not of ectodermal origin, do not carry this mutation, there is no risk of passing SWS to her child.
Sturge-Weber syndrome (SWS)
SWS also leads to ipsilateral glaucoma and ipsilateral leptomeningeal angiomas (capillary venous malformations in the innermost meningeal membranes surrounding the brain). In addition, SWS is associated with
Intellectual disability and focal seizures that affect the side of the body opposite from the port-wine stain.
Neurofibromatosis type 1 (NF1), a neurocutaneous disorder characterized by café-au-lait (light brown) macules, axillary and/or inguinal freckling, neurofibromas (nerve sheath tumors), Lisch nodules (small brown tumors that form on the irises), and bone abnormalities. About 20% of patients with NF1 will also develop
Optic nerve gliomas
NF1 is an autosomal dominant disorder with variable expressivity, meaning that one copy of the mutated gene is enough to cause the disease, but severity varies among different individuals. Signs of NF1 usually develop over time. Café-au-lait macules, an early sign of NF1, often get bigger and more numerous during childhood. Axillary or inguinal freckling and Lisch nodules develop in childhood. Cutaneous neurofibromas usually do not develop until
Adolescence.
Hypopigmented macules (ash-leaf spots), thickened skin with a leathery “orange peel” texture on the lower back (Shagreen patches), and periungual fibromas (fibromas near the nailbed, known as ? are cutaneous findings associated with tuberous sclerosis,
Koenen tumors
Bilateral vestibular schwannomas are tumors that arise from the myelin sheath of the eighth cranial nerve. These tumors are commonly seen in
Neurofibromatosis type 2
Optic nerve gliomas are associated with
Neurofibromatosis type 1
Are seen in Sturge-Weber syndrome, along with glaucoma and port-wine stains on the face.
Leptomeningeal angiomas (capillary-venous malformations of the innermost meningeal membranes)
Are seen in von Hippel-Lindau disease
Hemangioblastomas
A neurocutaneous disorder that causes tumors in many organ systems, including the brain, skin, eyes, heart, and kidneys.
Tuberous sclerosis (TS)
Brain tumors associated with TS include ?. Subependymal tumors and nodules occur beneath the ependyma, which is the lining of the ventricles. Cortical tubers, which are benign growths (hamartomas) of the cortex, and cortical dysplasia are especially common in TS, leading to seizures from an early age, as occurred in this girl. Subependymal tumors can sometimes obstruct the ventricles, causing hydrocephalus and increased intracranial pressure. In addition, intellectual disability and autism spectrum disorder are common in people with TS.
Subependymal giant cell astrocytomas, subependymal nodules, and cortical tubers.
Von Hippel-Lindau (VHL) disease, a genetic disorder that causes tumors in multiple organ systems, including ?. In VHL, a genetic mutation in the VHL gene promotes the transcription of hypoxia inducible genes, leading to excessive cellular growth
Central nervous system hemangioblastomas, retinal angiomas, pheochromocytomas, and renal-cell carcinomas
In absence of a mutation, a normal pVHL (von Hippel-Lindau protein, the product of the VHL gene) binds to the protein HIF1α and adds ?, marking HIF1α for destruction by proteasomes. During periods of hypoxia, pVHL does not bind to HIF1α, promoting the transcription of hypoxia inducible genes.
Ubiquitin
In VHL disease, a mutation in the VHL gene creates an abnormal pVHL that is unable to ?. As a result, hypoxia inducible genes are continuously transcribed regardless of whether hypoxia is present or not.
Add ubiquitin to HIF1α.
Although VHL disease is inherited in an autosomal dominant pattern, it may not be expressed until later in life. One normal copy of the VHL gene is sufficient to prevent tumor formation, but ?of people with one mutated VHL gene will eventually also develop a sporadic mutation in their second normal VHL gene, causing tumor formation. This woman’s VHL gene mutation caused her cerebellar hemangioblastoma, which led to her headaches and ataxia (difficulty coordinating voluntary movements like walking). In VHL disease, hemangioblastomas are most common in the cerebellum, spine, and retina.
90%
Neurofibromatosis type 2 (NF2), a genetic disorder associated with bilateral vestibular schwannomas. Schwannomas are tumors comprised of Schwann cells, a type of
Glial cell
Schwannomas can also occur in other parts of the nervous system, but the most common schwannoma in NF2 is the
Vestibular schwannoma
NF2 has an autosomal dominant inheritance pattern. Since this woman’s father was diagnosed with NF2, she has a 50% chance of inheriting the disease-causing gene. Her hearing loss at a young age suggests that she has inherited the NF2 gene and developed bilateral vestibular schwannomas. These tumors usually develop in adolescence or early adulthood before the age of 30. Vestibular schwannomas damage the eighth cranial nerve (the vestibulocochlear nerve) responsible for hearing and balance. Vestibular schwannomas can cause
Hearing loss, tinnitus (ringing in the ears), and ataxia
NF2 does not cause proliferation of nerve cells (neurons). The vestibular schwannomas seen in NF2 surround the eighth cranial nerve, and are comprised of Schwann cells,
Not sensory nerve cells.
Squamous cell carcinoma (SCC), a type of skin cancer derived from ?. Keratin pearls are made of keratinized concentric layers of abnormal squamous epithelial cells.
Keratinocytes (squamous epithelial cells) of the epidermis
Are not always present in SCC, but when present they are helpful for making the diagnosis of SCC.
Keratin pearls
SCC is the second most common type of skin cancer, usually occurring in sun-exposed areas like the face, ears, and back of the hands. Risk factors for developing SCC include sun exposure, immunosuppression, chronic inflammation of the skin, and exposure to arsenic. This man reports a ? that may have been an actinic keratosis, a premalignant lesion that can develop into SCC. SCC often appears as a red, scaly plaque. Advanced lesions may ulcerate, as seen in this man. Metastasis is rare.
Previous red spot on his nose
Basal cell carcinomas do not form keratin pearls, and the tumor cells are
Basophilic
A rare type of melanoma that affects the palms of the hands, soles of the feet, and underneath the nails.
Acral lentiginous melanoma (ALM)
Acral means peripheral, indicating that this tumor occurs on the hands or feet rather than the face or trunk. Lentiginous means dark, indicating these tumors tend to be very dark. Unlike other types of melanoma, sun exposure is not a risk factor for developing ALM. Although ALM makes up less than 5% of all melanomas, it is the most common type of melanoma seen in ? who have a lower risk of sun-related forms of melanoma. This woman’s melanoma is a form of ALM called a “subungual melanoma” which arises from the nail bed. It can present as a dark band in the fingernail or toenail.
Darker-skinned individuals
ALMs on the palms and soles can be recognized by the same criteria used to identify melanomas on other cutaneous sites: asymmetry, irregular borders, varied colors, diameter greater than 6 mm, and changes over time. Subungual melanomas often have a streak. ALM carries a poorer prognosis compared to other types of melanoma primarily because ALMs tend to be diagnosed at a more advanced stage. It is important to recognize that this type of melanoma can occur
Regardless of sun exposure.
Lentigo maligna occurs in areas of chronic sun exposure among older individuals. These lesions grow
Slowly over years.
Amelanotic melanoma is a rare subtype of melanoma where lesions are pink or red and often have
Well-defined borders.
Actinic keratoses, premalignant skin lesions caused by abnormal growth of epidermal keratinocytes. Actinic keratoses exhibit
Clinically, they appear brown or red with a rough, sandpaper texture. The main risk factor for developing actinic keratoses is chronic sun exposure. Most people who develop actinic keratoses have multiple lesions in sun-exposed areas like the hands and face rather than a single lesion.
Hyperkeratosis (thickening of the stratum corneum), parakeratosis (retained nuclei in the stratum corneum), and epidermal dysplasia.
Actinic keratoses are premalignant lesions with the potential to develop into
Squamous cell carcinomas.
This woman has a melanoma, a type of skin cancer derived from melanocytes. Sixty percent of melanomas contain activating mutations in BRAF, a gene that activates ? and promotes cell proliferation.
RAS signaling
Comprises 90% of melanomas with a BRAF mutation.
The V600E mutation (substitution of glutamic acid for valine at position 600)
Pharmaceutical BRAF inhibitors like ?have been shown to increase survival rates in patients with melanomas that carry this genetic mutation.
Vemurafenib
Risk factors for developing melanoma include sun exposure (especially severe sunburns early in life) and fair skin. Melanoma often presents as a pigmented lesion greater than 6 mm in size with asymmetric, irregular borders, and different colors that change over time.
Although most melanomas are asymptomatic, the development of pain or itching in a previously benign nevus can occur in melanomas.
Are seen in nevoid basal cell carcinoma syndrome, also known as Gorlin syndrome, which leads to many tumors and bone abnormalities at an early age. PTCH gene mutations are also seen in 30% of sporadic basal cell carcinomas. PTCH gene mutations are not associated with melanoma.
PTCH gene mutations
Are seen in Cowden syndrome, a genetic disorder associated with benign skin tumors (trichilemmomas), as well as an increased risk of breast, endometrial, and thyroid cancer. PTEN gene mutations are seen in a small percentage of sporadic melanomas, but BRAF mutations are much more common in melanoma.
PTEN gene mutations
The XPA gene is important for nucleotide excision repair. Mutations in the XPA gene can cause the disorder ?, which leads to extreme sensitivity of the skin to ultraviolet light and the development of melanomas, basal cell carcinomas, and squamous cell carcinomas early in life.
Xeroderma pigmentosum
Basal cell carcinoma (BCC), a type of skin cancer thought to derive from the basal cells that normally form the bottom layer of the epidermis. Microscopically, BCCs tend to form nests of atypical basaloid cells, with the peripheral cells arranged with their long axes in parallel (?). The BCC in this man shows the classic appearance of a translucent pearly nodule with telangiectasias (dilated subepidermal blood vessels). The nodules in BCC can also have rolled (thickened) edges with an ulcerated center.
Palisading nuclei
