Dermatologic Disease Flashcards
Stratum Germinativum
(epidermis basal layer)
Single layer of dividing cells that give rise to all epithelial cells
Stratum Spinosum
(epidermis squamous layer)
Layer of keratinocytes that mature and acquire keratin as they are pushed toward the surface
Stratum Granulosum
(epidermis granular layer)
Thin layer that acquires large basophilic granules called keratohyalin
Stratum Corneum
(epidermis)
Composed of orthokeratin (w/o nuclei)
Rete Ridges
(epidermis)
Epithelial projections that anchor epithelium to underlying CT
Basement Membrane
(dermis)
Reticulum fibers that act as a scaffold for epidermis
Papillary Dermis
(dermis)
Loose collagen and elastin directly below the rete ridges
Reticular Dermis
(dermis)
Dense structural collagen
Hair follicles
(adnexal structures (next to/joined with) skin)
All locations except palms and soles
Sebaceous glands
(adnexal structures (next to/joined with) skin)
Oil glands accompanying each hair follicle and in other locations w/o hair (mucosa) - lubricates hair and antibacterial
Arrector pili muscles
(adnexal structures (next to/joined with) skin)
Smooth muscles that attaches to hair follicle
Eccrine sweat glands
(adnexal structures (next to/joined with) skin)
All locations - thermoregulators
Apocrine sweat glands
(adnexal structures (next to/joined with) skin)
Under arms
Epidermal melanocytes
Clear cells living in the basal layer
Dermal melanocytes
Spindly cells living in papillary dermis
Langerhans cells
Dendritic histiocytic antigen processing cells living in stratum spinosum
Merkel cells
Receptors for light touch - live in the basal layer
List the types of flat lesions
Macule
Patch
List the types of raised (exophytic) lesions
-Plaque
-Papule
-Nodule
-Tumor/mass
-Vesicle
-Bulla
-Postule
-Sessile
-Pedunculated
-Papillary
Macule
any change in shape or color that is <1.0cm
Patch
any change in shape or color that is >1.0cm
Plaque
Slightly elevated lesion with large area
Papule
solid, <0.5cm
Nodule
solid, >0.5cm (sessile vs. pedunculated)
Tumor/mass
non-specific for any large, solid lesion
Vesicle
fluid-filled elevation <0.5cm
Bulla
fluid-filled elevation >0.5cm
Postule
pus-filled elevation of any size (yellow fluid)
Sessile
arising on a broad base
Pedunculated
arising on a stalk or pedicle that is narrower than the lesion
Papillary
lesion composed of multiple fronds or projections (may be sessile or pedunculated)
List the types of depressed lesions
-Fissure
-Atrophy
-Erosion
-Ulcer
-Scar
Fissure
linear cleavage of mucosa
Atrophy
thinning of the mucosa (red)
Erosion
depressed lesion, incomplete loss of mucosa (red)
Ulcer
complete loss of mucosa (dark yellowish)
Scar
result of injury causing mucosal atrophy or hypertrophy with increased underlying collagen
Hyperparakeratosis
thickened parakeratin
Hyperorthokeratosis
thickened orthokeratin
Hypergranulosis
thickened granular cell layer (accompanies hyperorthokeratosis, never parakeratosis)
Acanthosis
thickening or hyperplasia of stratum spinosum
Acantholysis
loss of intercellular bridges and cohesion of cells of stratum spinosum
Spongiosis
edema of stratum spinosum, widened intercellular bridges
Papillomatosis
Hyperplasia of papillary dermis, resulting in multiple surface elevations
Dyskeratosis
abnormal formation of keratin below surface
Exocytosis
Infiltration of epidermis by inflammatory cells
Describe the duration, histology, and course of Acute Inflammatory Dermatoses
Duration: days to several weeks
Histology: inflammation, edema often marked by mononuclear infiltrate instead of neutrophils
Course: may be self-limited or become chronic
Urticaria (Hives)
-Usually type 1 hypersensitivity rxn - localized mast cell degranulation, which leads to dermal microvascular hyperpermeability resulting in erythematous, edematous, and pruritic plaques are termed wheals
-Localized or generalized, small, pruritic papules to large erythematous plaques
-Usually develops and fades within hours, but can persist for days to months
-Tx: antihistamines, leukotriene, antagonists (block IgE) or steroids
Eczema
Group of conditions showing pruritic, erythematous papules, and possible vesicles which ooze and crust and later coalesce into raised scaly plaques
Etiology: allergen (delayed hypersensitivity), defect in keratinocyte barrier, drug hypersensitivity, UV light, physical/chemical irritant
Ex: allergic contact dermatitis (e.g. poison ivy)
-environmental agent that reacts with self-proteins creating neoantigens that sensitizes T cells
-on re-exposure, memory CD4 T cells are activated and release cytokines that recruit inflammatory cells and cause epidermal damage
Erythema Multiforme (EM)
-Severe, self-limited hypersensitivity response to infections (HSV, mycoplasma) and drugs
-Skin and mucous membrane injury mediated by CD8+ cytotoxic T lymphocytes
-Medication rxns may progress to more serious eruptions (Stevens-Johnson Sx or toxic epidermal necrolysis) causing massive sloughing which leads to fluid loss and infection
Describe the clinical features of Erythema Multiforme (EM)
-Red macules, papules, vesicles, erosions, ulcers “targetoid”, blood-crusted labial slough
-Palmar/plantar rash
-EM major (skin and severe mucosal disease): oral, ocular/genital mucosa
Describe Chronic Inflammatory Dermatoses
-Features become most apparent over many months to years
-Skin can appear rough due to thick scale and shedding (desquamation)
Psoriasis
-1-2% of US population is affected (common)
-Increased risk for heart attack and stroke and affects 10% of arthritis pts
-Autoimmune, T-cell mediated inflammatory disease - self and environmental antigens involved
-**T cells secrete cytokines (TNF is a major mediator) and growth factors inducing keratinocyte hyperproliferation
Describe the clinical presentation of Psoriasis
-Well-demarcated, pink to salmon-colored plaque covered by loosely adherent silver-white scale
-Skin of the elbows, knees, scalp, etc. (oral lesions extremely rare)
-Psoriatic arthritis is a severe complication of this disease
What is the diagnosis and tx for Psoriasis?
Diagnosis:
-Auspitz sign - pinpoint bleeding upon scratching scale off lesions
-Koebnerization - creation of lesions by scratching
Tx:
-Coal tar derivatives
-Sunlight
-TNF antagonists
-Vit A and D derivatives
-Methotrexate for severe cases
Lichen Planus
-Cutaneous and mucosal disease: CD8+ T-cell mediated cutaneous and mucosal cytotoxic response against antigens in the basal cell layer and the dermoepidermal junction
-Etiology: unknown
-Pruritic, purple, polygonal, planar papules, and plaques with Wickham striae
-Koebner phenomenon (Koebnerization): local trauma inducing lesion formation. Also occurs in psoriasis
Describe interface dermatitis
-Inflammatory infiltrate obscuring the dermoepidermal junction
-Necrotic or apoptotic keratinocytes (colloid or Civatte bodies)
-Lichenoid infiltrate: dense, continuous band of lymphocytes along the dermoepidermal junction
Oral Lichen Planus
-Bilateral buccal mucosa, tongue- white striae
-Other variants: red/white atrophic, erosive or ulcerative lesions
-White atrophic plaques (dorsal tongue)
-Desquamative gingivitis
-Can resemble other conditions clinically and microscopically (i.e. lichenoid reactions)
*drug induced
*lupus erythematosus - will cover in other lecture
*graft vs host disease
*contact reaction to dental material or oral flavoring agents
Tinea capitis
(Superficial Fungal Infection (Dermatophytes))
Head; causes focal alopecia
Tinea barbae
(Superficial Fungal Infection (Dermatophytes))
Beard area of men
Tinea corporis
(Superficial Fungal Infection (Dermatophytes))
Body; caused by heat and humidity and exposure to animals
-ringworm
Tinea pedis
(Superficial Fungal Infection (Dermatophytes))
Athlete’s foot fungus with superimposed bacterial infection
Candida
(Superficial Fungal Infection (Dermatophytes))
A yeast that infects intertriginous zones
-Ubiquitous opportunist when resistance is low due to:
*local causes: intertriginous zones (areas on skin that stay moist)
*systemic causes: steroids, antibiotics, diabetes, immunosuppression (HIV, Chemotherapy/radiation)
List the Blistering (Vesiculobullous) Disorders
-Pemphigus
-Paraneoplastic pemphigus
-Mucous membrane pemphigoid
-Bullous pemphigoid
-Dermatitis herpetiformis
Mucocutaneous disease/disorder involves….
mucous membranes (oral, genital etc) and skin
-The cause can be infectious, genetic or immune-mediated in nature
-Immune-mediated diseases include those that are caused by autoantibodies (autoimmune) and those that don’t have an antibody mediated pathogenesis
Vesiculobullous diseases may also be referred to as…
Vesiculoerosive or vesiculoulcerative b/c of the clinical lesions they cause
Pemphigus Vulgaris (PV)
An autoimmune vesiculobullous disease of adults over age 30
Describe the clinical presentation of Pemphigus Vulgaris (PV)
-Delicate blisters that quickly rupture quickly leaving flaccid, weeping and crusting sores
-Positive Nikolsky sign - non-lesional skin forms vesicle when rubbed
-Begins in mouth in 50%; involves mouth in 100%; mouth lesions most difficult to treat (first to show; last to go). Ragged erosions/ulcerations
-Treated with systemic steroid. Fatal if untreated. Death due to fluid and electrolyte loss and infection and sepsis
What is the pathogenesis of Pemphigus Vulgaris (PV)
Type II reaction (antibody mediated cellular dysfunction; IgG or IgM against the desmosomes (desmosomes 1 & 3) but not hemidesmosomes causing cell bridges to fall apart
Describe the histology and diagnosis of Pemphigus Vulgaris (PV)
Histology:
-Suprabasilar clefting of epithelium (basal cells stay with connective tissue)
-Loss of cohesion of keratinocytes causing them to separate (acantholysis) and float free within a vesicle (Tzanck cells)
Diagnosis:
-Biopsy (both H&E and immunoflourescence) is diagnostic
-Direct immunoflouresence - shows IgG forming a net surrounding each cells
-Indirect immunoflourescence) shows circulating autoantibodies
Paraneoplastic Pemphigus (PNP)
-Uncommon, serious vesiculobullous disease
-Occurs in patients with a history of leukemia or lymphoma
-Often confused with infection and can have overlapping features with pemphigus, EM major, lichen planus, or pemphigoid
-Any cutaneous or mucosal surface may be affected
-Tx: immunosuppression
-Poor prognosis: immune suppression causes risk for infection and recurrence of underlying malignancy
Mucous Membrane Pemphigoid (MMP)
-Clinically resembles pemphigus due to blister formation but about 5x more common than pemphigus
-Affects older adults: average age = 60 years
-May affect any mucosal surface; occasionally skin
-“Cicatricial” b/c can cause scarring with conjunctival (symblepharon) and cutaneous lesions
-Gingiva is most commonly affected: desquamative gingivitis
-May see intact blisters intraorally
-Biopsy shows subepithelial cleft- separation of the epithelium from the CT at the BMZ
-Target = hemidesmosome, positive DIF: linear deposition of antibodies (IgG, C3) at the BMZ
-Negative IIF
What is the tx for Mucous Membrane Pemphigoid (MMP)?
-Depends on extent of involvement
-Oral lesions alone - topical steroids, tetracycline/niacinamide or dapsone may be sufficient
-If ocular involvement is present (mandatory referral to ophthalmologist to evaluate), systemic immunosuppressive therapy is indicated
Bullous Pemphigoid (BP)
-Usually older population affected
-Cutaneous lesions are seen primarily - only 20% will have oral involvement. Tense bullae that do not rupture easily
-Pruritus is common initial complaint, followed by cutaneous blisters
Describe the histology of Bullous Pemphigoid (BP)
-Subepithelial cleft similar to mucous membrane pemphigoid
-Positive DIF and IIF, with antibodies deposited at the BMZ
-Management similar to mucous membrane pemphigoid, but most BP cases resolve spontaneously in 1-2yrs with steroid therapy
Dermatitis Herpetiformis
A rare autoimmune skin disease that produces crops of extremely pruritic papules and vesicles on a red base, resembling herpes
Clinical:
-In addition to skin lesions, patients have aphthous oral ulcers
-80% of patients have celiac disease (gluten/gliadin allergy)
Describe the histology, pathogenesis, and treatment for Dermatitis Herpetiformis
Histology:
-Tiny microabscesses of fibrin and neutrophils and at the tips of dermal papillae which coalesce and produce subepidermal vesicles
-Granular IgA deposits at tips of papillae
Pathogenesis: Certain HLA types predispose to IgA being produced against gliadin (in gluten), which cross reacts with reticulin, which anchors basement membrane to papillary dermis
Tx: Responds to a gluten-free diet
Seborrheic Keratosis
-Very common, skin of face and trunk, >40yrs
-Often multiple, tan-brown to black, well-demarcated plaques
-“Stuck on”, “dirty candle way”, “dried mud on brick wall” appearance
-Composed of basal cells that produce keratin inclusions
-No treatment necessary, removed for cosmetic purposes
Notes:
-Varient: dermatosis papulosa nigra –> multiple small dark papules (SKs) that develop in 3-% of AA >20yrs on facial skin
-If hundreds appear suddenly (sign of Leser-Trelat) = paraneoplastic syndrome - may have internal malignancy
Verruca Vulgaris
-Common warts- epithelial proliferation caused by direct contact or autoinoculation with low-risk HPV subtypes
-Any skin surface, especially hands, periungal
-Gray-white to tan, flat to convex, <1cm papule/nodule with rough, pebbly surface
-Tx: many options but disease is self-limited, often regress within 6mo-2yrs
Actinic Keratosis (AK)
-Premalignant skin lesion caused by chronic sun (UV-light) exposure
-Common on facial skin and vermilion zone (actinic cheilosis) of the lips in fair-skinned persons over 40yrs of age
-Average person presents with 6-8 lesions
-Scaly plaque with sandpaper texture
Describe the histology of Actinic Keratosis
-Hyperkeratosis, usually parakeratin
-Some degree of epithelial dysplasia
-Solar Elastosis - degeneration of connective tissue from UV damage with increased elastic fibers
What is the tx and prognosis for Actinic Keratosis?
Tx:
-Cryotherapy, surgical excision, laser ablation, photodynamic therapy
-5-flourouracil (Effudex), imiquimod 5% cream, diclofenac 3% gel
Prognosis:
-1/4 may regress with reduced sun exposure
-~8% risk of malignant progression with ~1% over 2yrs
-Average time to progression is about 2yrs
-Monitor pts for progression and new lesions
Squamous Cell Carninoma
-Sun-induced cancer usually in existing actinic keratosis (field-effect - large exposed area causes transformation of multiple cells over time)
-Slowly developing (months-years) and slow growing lesion
-Clinical: fleshy, firm nodule with a keratinized, crusty or ulcerated surface
-Tx: surgery or radiation; curable if not late stage
Basal Cell Carcinoma
-Arises from the basal cells of the epidermis or germ cells in hair follicles
-Most common skin cancer
-800,000 cases diagnosed annually in the US
-Affected pts are typically over 40yrs of age, have fair complexion and a history of chronic sun exposure
-Most develop in the middle third of the face
What are the two main subtypes of Basal Cell Carcinoma?
Noduloulcerative (most common): umbilicated papule that may show central ulceration/hemorrhage, rolled pearly white border, lack of adnexal skin structures (hair); may be referred to as a “rodent ulcer”
Sclerosing (morpheaform): mimics scar tissue
Describe Basal Cell Carcinoma histology
-Basaloid cells that appear to “drop off” of the basal cell layer of the epidermis
-Nodulo-ulcerative - large lobules of tumor cells are characteristic
-May show some similarity to ameloblastoma
What is the tx and prognosis of Basal Cell Carcinoma?
Tx: Excision, electrodessication, curettage; Mohs surgery for planes of fusion (nasolabial fold, eye)
Prognosis:
-Excellent, rare metastasis, >95% of patients cured after first treatment
-Larger, recurrent or tumors in embryonic planes of fusion are more aggressive and require Mohs surgery
-F/up important: 44% chance of 2nd BCC and 6% chance of SCC w/in 3 yrs
Ephelis/ephelides (freckles)
Benign Melanocytic Skin Lesion
-Brown macule, increased pigment with sun exposure but normal numbers of melanocytes
Actinic Lentigo
Benign Melanocytic Skin Lesion
-Brown macule common on dorsal hand and face- shows a linear increase of melanocytes in the basal layer
Melanocytic Nevi
Nevus = any congenital skin leasion; Melanocytic nevus = any benign congenital or acquired neoplasm of melanocytes
Acquired Melanocytic Nevi
-Benign neoplasms caused by mutation in BRAP or RAS
-Develop early in life (average caucasian has about 20); rare intraorally
-Well defined, <6mm in diameter
-Progression: Begin as flat lesions with a uniform color (dark brown or black) that elevate and fade with aging
-Tx: none, unless in an area of repeated trauma or a cosmetic concern
-Prognosis: Excellent, malignant transformation is extremely rare
Dysplastic Nevi
-Can be sporadic or familial (familial dysplastic nevus syndrome - strong association with melanoma)
-RAS or BRAF mutations are common
-Larger than acquired nevi (>5mm) and may have hundreds
-Sun-exposed and not sun-exposed skin
->10+ dysplastic nevi = increased risk for melanoma (marker for melanoma risk)
-Macule or plaques with pebbly surface, often variable pigmentation and irregular borders
Melanoma
-Malignancy of melanocytic differentiation
-Most are cutaneous (>90%); third most common in skin cancer; dramatic increased incidence in recent decades
-<5% of skin cancers, 75% of deaths due to skin cancer
What is the Etiology of Melanoma
-UV light, especially intense intermittent exposure at early age
-Non-UV melanomas have KIT mutations
-5-10% have hereditary predisposition
-Germ-line mutations in CDKN2A gene which encodes:
>p16 - keeps RB functional
>p14 - auguments p53 activity
Melanoma: Pathogenesis/Phases of Development
-UV-induced melanomas
-UV light induces RAS/BRAF mutation –> telomerase activation which prevents senescence –> p16 inactivation (vertical growth) –> p53 mutation (metastasis)
-Non-UV melanomas (nodular, acral-lentiginous, mucosal) are activated by different mutations (i.e. KIT oncogene)
Superficial spreading melanoma
-Most common type
-BANS: back, arm, neck, scalp
-Months to few years radial phase (plaque) before vertical phase (nodule forms)
Lentigo Maligna Melanoma
-Malar skin of elderly fair complexioned people with chronic sun exposure
-Flat brown macule that slowly expands radially over 10-15 years before entering vertical growth stage
Acral lentiginous melanoma
-Unrelated to sun exposure; main type in blacks and asians
-Very short radial growth phases (months) before invading; poor prognosis
-Most mucosal melanomas are this type (including oral)
Nodular melanoma
-Elevated, fast-growing mass
-Unrelated to sun exposure
-No radial growth, starts as vertical growth
-Worst prognosis
Melanoma clinical diagnosis
ABCDE’s
-asymmetry
-border irregularity
-color variegation (multiple colors)
-diameter greater than 6mm
-evolving - lesions that have change over time
Other Warning Signs:
-any new nevus over age 20
-any pigmented lesion on palms, soles, nail beds, genitalia (acral lentigenous)
-itching, pain, crusting, redness, ulceration, bleeding
Melanoma Tx
-Surgery with wide margins
-Sentinal lymph node biopsy
-Histologic assessment to determine type, depth of invasion and stage
-Drugs that inhibit BRAF or KIT
-For metastatic disease: immunotherapy (checkpoint inhibitors)
