Chapter 16: Dermatologic diseases Flashcards
Ectodermal dysplasia
-‐ Condition in which 2+ ectodermal structures fail to develop (skin, hair, nails, teeth, sweat glds)
-‐ Hypohidrotic ectodermal dysplasia: chromosome xq12 (x-‐linked; most men)
-‐ HED: reduced sweat glands, heat intolerance, sparse hair, xerostomia, periocular hyperpigmentation, midface hypoplasia (with protuberant lips)
-‐ A/Oligo/hypodontia and teeth have typical shape (incisor with tapered crown, reduced molar)
-‐ Odonto-‐onychodermal dysplasia: involves all 4 ectodermal structures
-‐ Histo: skin shows decreased number of sweat glands and hair follicles.
White sponge nevus
-‐ AD, mutation in keratin 4 or 13 (expressed in spinal layer of epithelium).
-‐ White plaques cheeks, genital, nasal, anal mucosa
-‐ Histo: prominent hyperparak, acanthosis, clearing of cytoplasm of cells in spinous layer (~ leukoedema and HBID)
-‐ Perinuclear eosinophilic condensation: represents tangled masses of keratin tonofilaments
Hereditary benign intraepithelial dyskeratosis
-‐ AD, descendants of a triracial isolate from North Carolina
-‐ Oral lesions (~WSN) + eye lesions (thick plaques).
-‐ Prominent dyskeratosis, cell-‐within-‐a-‐cell phenomenon.
Pachyonychia congenita
-‐ Nails are lifted because of accumulation of keratin in bed. Nail loss eventually occurs.
-‐ Also palmar-‐plantar keratosis with callus formation, hyperhidrosis, blisters in soles of the feet
-‐ Type 1 (Jadassohn-‐Lewandowsky): oral white plaques (esp tongue); keratin 6a or 16 mut
-‐ Type 2 (Jackson-‐Lawler): neonatal teeth; keratin 6b or 17 mut. No oral white lesions.
-‐ Histo: hyperpara and acanthosis with perinuclear clearing of epithelial cells
Dyskeratosis congenita (Zinsser-‐Cole-‐Engman syndrome)
-‐ X-‐linked (mostly males). DKC1 mutation (disrupts telomerase).
-‐ Skin pigmentation with reticular pattern, dysplastic nails
-‐ Oral: bullae on tongue and buccal mucosa, which are followed by erosions and leukoplakias
-‐ Thrombocytopenia develops, followed by aplastic anemia
-‐ Tongue and cheek leukoplakias (30% SCC transformation in 10-‐30 years)
Xeroderma pigmentosum
-‐ AR trait, DNA-‐repair gene defect. Many cutaneous malignancies at a very early age (1000x ).
-‐ Actinic keratosis -‐> BCC -‐> SCC; melanoma in 5%
-‐ Oral SCC: lips, tip of tongue (very rare site)
Hereditary mucoepithelial dysplasia
-‐ AD trait. Epithelial cells do not develop normally (but no dysplasia is seen).
-‐ Alopecia (eyebrows and eyelashes), cataracts in childhood, impaired vision
-‐ Oral: striking fiery-‐red erythema of hard palate, and less on gingiva and tongue.
-‐ Nasal, conjunctival, vaginal and other mucosas also have fiery red apperance
-‐ Histo: epithelium with disorganized maturation. Cytoplasmic vacuoles (grayish inclusions)
Incontinentia pigmenti (Block-‐Sulzberger syndrome)
-‐ 37:1 F:M. Nemo gene mutation (x28). Lethal in males. Those who survive have klinefelter syndrome or mosaicism for NEMO (two populations of cell with different phenotype).
-‐ Eyes, skin, CNS
-‐ Stages: vesicular (4 mths-‐bullae on skin), verrucous (6 mths-‐plaques in limbs), hyperpigmentation (until puberty-‐swirling macules), and atrophy and depigmentation
-‐ Oral: oligodontia (hypodontia), delayed eruption, small and cone shaped teeth
Darier’s disease (keratosis follicularis, dyskeratosis follicularis, Darier-‐White disease)
-‐ Mutation in calcium pump. Lack of cohesion of epithelial cells.
-‐ Papules on trunk/scalp, excess keratin with foul odor, palmo-‐plantar keratosis, nail changes.
-‐ Oral: multiple papules on hard palate and alv mucosa that can coaslesce and give cobblestone.
-‐ Palate lesions ddx: inflammatory papillary hyperplasia and nicotine stomatitis
-‐ Histo: dyskeratosis, keratin plug overlying epithelium with a suprabasilar cleft.
-‐ Test tube rete ridges. Two types of dyskeratotic cells (corps rounds and grains)
Warty dyskeratoma (focal acantholytic dyskeratosis, follicular dyskeratoma, isolated Darier’s)
-‐ Solitary lesion, same location (oral) and histology as Darier’s (but otherwise unrelated)
-‐ Corps round or grains not prominent
Peutz-‐Jeghers syndrome
-‐ STK11 (LKB1) gene mutation on chromosome 19
-‐ Lesions involve periorificial areas (mouth, nose, anus, genital)
-‐ Intestinal obstruction due to intussusceptions (proximal segment “telescopes” into distal part)
-‐ Freckles in hands, perioral skin and oral mucosa; intestinal polyps (are not premalignant)
-‐ GI, breast; also pancreas, female genital tract, ovary cancer
Hereditary hemorrhagic telangiectasia (Osler-‐Weber-‐Rendu syndrome)
-‐ HHT1: ENG (endoglin) mutation, lung involvement (arteriovenus fistulas)
-‐ HHT2: ALK1 (ACVRL1) mutation, liver involvement (arteriovenus fistulas)
-‐ Oral telangiectasias: most vermillion lips, tongue, buccal mucosa
-‐ Dx (at least 3): recurrent spontaneous epistaxis; telangiectasias of mucosa and skin; AV malformations of lungs liver or CNS; family history HHT
-‐ DDx: CREST (positive for serum anticentromere antibodies)
Ehlers-‐Danlos syndrome
-‐ Ehlers-‐Danlos syndrome: production of abnormal collagen (collagen type 5 most common).
-‐ Joint laxity, easy bruising, marked skin elasticity and papyraceous scarring of skin
-‐ 7 types: classical-‐80% (severe/mild), hypermobility (no scarring), vascular (ecchymotic-‐ extensive bruising), kyphoscoliosis, arthrochalasis, dermatosparaxis, and other
-‐ Metenier sign: easy eversion of the upper eyelid in Ehlers-‐Danlos syndrome
-‐ Sapyraceous scarring: similar to crumpled cigarette paper, unusual healing upon minor injury
-‐ Type VIII: marked periodontal disease at young age
-‐ Gorlin sign: 50% patients can touch tip of nose with tongue (normal pop 10%)
Tuberous sclerosis (Epiloia, Bourneville-‐Pringle syndrome)
-‐ TSC1/2 mutation (chr 9/16). Mental retardation, seizures and facial angiofibromas.
-‐ Facial angiofibromas: multiple papules, most in nasolabial fold area
-‐ Ungual (periungual) fibromas: similar to angiofibromas, around or under margins of nails
-‐ Shagreen patches: hamartomas on skin of trunk
-‐ Ash-‐leaf spots: ovoid hypopigmentation (best seen with UV light) (3+)
-‐ “Tubers”: potato-‐like hamartomas of CNS (best seen in MRI)
-‐ Cardiac rhabdomyomas, angiomyolipomas of kidney, retinal hamartomas (major features)
-‐ Minor features: multiple enamel pits, gingival fibromas, desmoplastic fibromas, renal cysts and hamartomatous rectal polyps (minor features)
-‐ TS DX: 2 major or 1 major+2 minor findings
Multiple hamartomas syndrome (Cowden syndrome, PTEN-‐hamartoma tumor syndrome)
-‐ PTEN mutation (chromosome 10). High incidence of malignancies.
-‐ Similar findings in Proteus-‐like, Bannayan-‐Riley-‐Ruvalcaba and Lhermitte-‐Duclos syndromes
-‐ Skin trichilemmomas (aroud mouth, nose and ears), acral keratosis (warty growth on dorsal hand), palmar-‐plantar keratosis and cutaneous hemangiomas/neuromas/lipomas/xanthomas
-‐ Thyroid disease (follicular adenoma/ca), fibrocystic breast, breast CA, benign GI polyps
-‐ Oral: multiple fibromas on gingiva, dorsal tongue and buccal mucosa
-‐ Dx: 2 of trichilemmomas, oral papules, and acral keratosis
Epidermolysis bullosa
-‐ Defect in attachment of epithelial cells (to each other or underlying CT)
-‐ Simplex (keratin 5/14 mut), junctional (laminin mut, dental findings, death at birth), dystrophic
(collagen VII, oral lesions), and hemidesmossomal (attachment proteins mut)
-‐ Dominant dystrophic: bullae on areas with mild trauma, scarring.
-‐ Oral: gingival eryhtema and recession, scarring of vestibule
-‐ Recessive dystrophic: very severe. Fusion of hand fingers (mittenlike deformity). SCC
-‐ Oral: scarring causes microstomia and ankyloglossia
-‐ Histo: junctional shows subepithelial clefting at the level of lamina lucida (EM gold standard)
Pemphigus
-‐ Vulgaris (fogo selvagem), vegetans (may be a variant of PV), erythematous and foliaceous
-‐ Desmoglein 3 expressed in skin and mouth. If auto-‐ab are present, pt develops PV
-‐ Desmoglein 1 expressed on skin only. If auto-‐ab are present, pt develops PE or PF
-‐ Hailey-‐Hailey (chronic benign familial pemphigus): genetic; oral lesions rare
-‐ M=F; 50+ yo; Mediterranean, South Asian and Jewish heritage
-‐ Oral + skin lesions (flaccid bullae that rupture quickly leaving an erythematous area)
-‐ Tzanck cells (rounded acantholytic epithelial cells) can be seen on exfoliative cytology
-‐ Direct IF shows IgG, IgM, and C3 in intercellular areas between epithelial cells
-‐ Indirect IF shows circulating Ab in the pt’s serum (correlates with disease activity)
Paraneoplastic pemphigus
-‐ In pts with leukemia or lymphoma. Also Castleman’s and thymoma.
-‐ Often precedes tumor identification.
-‐ Tumor produces IL-‐6, which stimulates production of auto-‐ab. Also, T cells may be involved.
-‐ Lip crusting like EM, skin lesions like LP, conjunctival scarring like pemphigoid;
-‐ Histology varies (most cases intra or subepithelial cleft)
-‐ Direct IF: weak IgG/complement intercellularly or linear deposition at BM
-‐ Indirect IF: must use transitional epithelim (rat bladder). Ab in intercellular zones
-‐ IP is gold standard: + desmoplakin, envoplakin, periplakin, desmoglein 1/3
Mucous membrane pemphigoid (cicatricial pemphigoid)
-‐ Auto-‐ab against various BM components
-‐ F>M; 50-‐60yo; oral + conjunctival, nasal, laryngeal, vaginal, skin lesions.
-‐ Blisters can be seen in mouth (blister roof is thicker than in pemphigus)
-‐ Ocular scarring and symblepharons: adhesion of bulbar and palpebral conjunctive
-‐ Entropion: scarring causing eyelid to turn inward
-‐ Trichiasis: eyelashes rub against cornea and globe
-‐ Dyspareumia: pain during intercourse due to vaginal lesions
-‐ Direct IF + as a linear band at BM against laminin 5
-‐ Indirect IF does not work well (low levels of circulating ab)
-‐ Linear IgA bullous dermatosis: IgA deposits in BM. Skin lesions only, in childhood
-‐ Angina bullosa hemorrhagica: blood-‐filled vesicles in soft palate, hx of trauma or corticoid
-‐ Epidermolysis bullosa acquisita: auto-‐ab against collagen type 7. Oral and skin lesions. Skin incubated in salt solution forms artificial bulla, and IgG IHC is positive on connective tissue side of bulla (vs MMP + in roof)
Bullous pemphigoid
-‐ Most common autoimmune blistering condition.
-‐ Mostly in skin, limited clinical course ( from MMP). Auto-‐ab against BM component
-‐ Direct IF: IgG and C3 in continuous linear band at BM: BP1 (180) and BP2 (230)
-‐ Indirect IF positive (unlike PV, unrelated to disease activity)
Erythema multiforme
-‐ 50% preceded by infection (herpes or pneumonia) or drugs (antibiotics/analgesics)
-‐ Types: EM minor, EM major (Stevens-‐Johnson) and toxic epidermal necrolysis (Lyell’s disease)
-‐ Direct and indirect IF non specific
-‐ M>F; 20-‐30 yo, self-‐limited 2-‐6 wks (20% recurrent). Target-‐like skin lesion 50% of cases.
-‐ EM minor: Infection-‐induced. Diffuse oral ulcerations. Hemorrhagic crusting of lips.
-‐ EM major: Drug-‐induced. EM minor + ocular or genital lesions; symblepharon ~MMP.
-‐ TEN: drug-‐induced. Almost entire skin ulcerated (pts seems scalded). Older people (F>M)
-‐ Histo: sub or intraepithelial vesicle with necrotic basal cells. Mixed inflammation (perivasc)
-‐ Direct IF not helpful (but granular C3 around blood vessels highly suggestive)
-‐ Tx: corticoidis (except TEN). Removal of causing agent. Antivirals if recurrent.
Erythema migrans
-‐ Assoc with fissured tongue.
-‐ Histo: psoriasiform mucositis with Munroe abscesses (collections of neutrophils in epith)
-‐ Psoaris pts have more erythema migrans: HLA-‐Cw6 seen in both
Reactive arthritis (Reiter’s syndrome)
-‐ Triad: nongonococcal urethritis, arthritis, and conjunctivitis (can’t see, pee, bend knee).
-‐ Seen in HIV+. HLA-‐B27. Triggered by dysentery or STD. 9:1 M:F
-‐ Balanitis circinata: lesion of glans penis similar to erythema migrans in Reiter’s
-‐ Psoriasiform lesions of the skin
-‐ Oral: varied (papules, painless ulcers, geographic tongue)
-‐ Histo: ~ psoriasis (with munroe abscesses)
Lichen planus
-‐ Skin: 4P’s-‐> purple, pruritic, polygonal papules (flexor surfaces of extremities)
-‐ Histo ddx: lichenoid drug reaction, lichenoid amalgam reaction, GVHD, lupus, CUS and cinnamon
-‐ Hydropic degeneration (destruction of basal cells in LP) + infiltrate of T cells
-‐ Civatte (colloid, cytoid, hyaline) bodies: degenerating keratinocytes in epith/CT interface
-‐ Direct IF: deposition of fibrinogen in BM; indirect IF negative (both nonspecific)
Lichen sclerosus et atrophicus
-‐ Unknown cause; can be associated with thyroid disease
-‐ Results in white patches on the skin, which may cause scarring on and around genital skin
-‐ 10:1 F:M, esp after menopause
-‐ Lichenoid infiltrate, sclerosis of connective tissue (~ amyloidosis or scleroderma), edema of upper dermis, hydropic degeneration of cells and atrophy of epithelium
Chronic ulcerative stomatitis
-‐ Auto-‐ab against p63-‐like protein. Smilar to ELP, but no striae (keratosis may be seen though).
-‐ Does not respond to corticoids, responds to anti-‐malarial drugs (hydroxychloroquine)
-‐ Direct IF: speckled, finely granular IgG in nuclei of basal and parabasal cells (basal 1/3)
-‐ Indirect IF: SES-‐ANA+ in basal and parabasal (in SLE and scleroderma ANA are positive, but in entire epithelium)
Dermatitis herpetiformis (Duhring-‐Brocq diseae)
-‐ AI blistering disorder; 90% of pts have a gluten-‐sensitive enteropathy
-‐ 15-‐25% of pts with celiac disease develop dermatitis herpetiformis
-‐ Shows grouped excoriations; erythematous, urticarial plaques; and papules with vesicles
-‐ Histo: neutrophils in the dermal papillae, with fibrin deposition and edema. Papillary microabscesses form and progress to subepidermal vacuolization and vesicle formation
-‐ Direct IF: IgA in a granular pattern in the upper papillary dermis
Graft-‐versus-‐host disease
-‐ Recipients of BMT (for leukemia, lymphoma, MM, aplastic anemia, thalassemia and sickle cell anemia).
-‐ Engrafted cells attack the host, even with the use of immunosuppressive drugs (cell mediated).
-‐ Cyclosporine acts primarily on T cells; is a natural fungal metabolite; inhibits cell-‐mediated immunity
-‐ Nonmyeloablative allogenic hematopoietic cell transplantation: not all WBC’s are destroyed
-‐ Acute (<100 days; ~ TEN) and chronic (100+ days; ~ SLE, SS or cirrhosis)
-‐ Oral GVHD: ~ LP. May form ulcers (r/o HSV, SCC). Xerostomia.
-‐ Antibody against CD52 used in prevention (depletes T lymphocytes)
Psoriasis
-‐ Increased prolif of keratinocytes. T lymphocytes and genetics also important.
-‐ Symmetric erythematous plaques with silvery scale on scalp, elbows and knees
-‐ Psoriatic arthritis: complication seen in 10% of pts, including in TMJ
-‐ Auspitz sign: small pinpoint bleeding sites observed when psoriatic scales are removed
Lupus erythematosus
-‐ Most common collagen vascular or connective tissue disease in US
-‐ Systemic, chronic cutaneous (discoid), and subacute cutaneous.
-‐ SLE: 10x females (30y). Butterfly rash over malar and nose (ddx: erysypela, melasma)
-‐ Kidney failure most significant aspect of SLE (most common cause of death)
-‐ Libman-‐Sacks endocarditis: warty lesions of valves, due to accum of immune complex and mononuclear cells. Only rarely causes emboli.
-‐ Oral SLE: similar to ELP, non specific and granulomatous
-‐ Lupus cheilitis: involvement of vermillion lower lip
-‐ Signs: systemic (fatigue, weight loss), musculoskeletal (arthalgia), skin (rashes, oral lesions), and hematologic (anemia, leucopenia)
-‐ CCLE: limited to skin or mucosa. Erythematous patches areas in sun exposed skin that heal with scarring and hypopigmentation and then migrate (discoid LE).
-‐ Oral CCLE: identical to ELP, however rarely occur in the absence of skin lesions
-‐ Subacute LE: intermediate between SLE and CCLE. Skin lesions in sun-‐exposed areas w/o scarring or pigmentation. No renal damage. May be triggered by medications
-‐ Skin histo: keratin in hair follicles (follicular plugging). Degeneration of basal layer. Aggregates of inflammaton in CT, perivascular in deeper CT
-‐ Oral histo: ~LP, but has PAS+ material in BM, subepithelial edema (may form vesicle) and more diffuse, deep inflammatory infiltrate (often perivascular)
-‐ Direct IF: IgM, IgG, C3 in shaggy or granular band at BM.
-‐ Positive lupus band test: normal skin, which shows DIF+ (but also seen in RA, SS and scleroderma). Not seen in all patients.
-‐ Indirect IF: 95% ANA+ (>640) (sensitive but not specific), dsDNA+ and Sm (specific SLE)
Systemic sclerosis (scleroderma, Hide-‐Bound disease)
-‐ Dense collagen deposited in excessive amounts in tissues. 5x females.
-‐ Raynaud’s phenomenon: vasocontriction triggered by stress or cold (not specific)
-‐ Acro-‐osteolysis: resorption of terminal phalanges and contracture, giving claw-‐like fingers.
-‐ Ulceration of finger tips
-‐ Mask-‐like facies (stiff skin) or mouse facies (atrophy of nasal alae)
-‐ Pulmonar fibrosis: lung HT and heart failure, leading to death
-‐ GE reflux
-‐ Oral: microstomia (lip rigidity), purse-‐string appearance, gingival recession, xerostomia, SG enlargement and dysphagia (collagen deposition produces firm, hypomobile tongue)
-‐ X-‐ray: diffuse widening of PDL, resorption of bone (post MD, coronoid process, condyle and chin) from collagen deposits pressure. Also tooth resorption may occur.
-‐ Localized scleroderma (morphea): affects only a single patch of skin (en coup de sabre scar)
-‐ Histo: diffuse collagen deposition (ddx: amyloidosis and plasminogen deficiency)
-‐ Dx: anti-‐sc170 (topoisomerase) ab for systemic.
-‐ No optimal tx. Penicillamine to inhibit collagen often used.
CREST syndrome (limited scleroderma)
-‐ Calcinosis cutis: deposition of calcium salts subcutaneously, multiple nodules
-‐ Raynaud’s phenomenon: when hands/feet are exposed to cold, they become white (vasospasm), bluish (venous stasis), the dusky-‐red (return of blood). May be painful.
-‐ Esophageal dysfunction: abnormal collagen deposition in mucosa
-‐ Sclerodactyly: stiff, smooth fingers, claw-‐like appearance (abnormal collagen in dermis)
-‐ Telangiectasia: facial skin and lips. Similar to HHT
-‐ Dx: anticentromere ab (if only telangiectasias are present, w/o other signs or clear hx)
-‐ Risk of developing pulmonary HT and cirrhosis
Acanthosis nigricans
-‐ Forms: benign (w/o cancer), malignant (GI adenoca, usually simult) or pseudo (seen in obese)
-‐ Benign assoc w/ diabetes, Addison’s, hypoTHY, acromegaly, Crouzon, corticoids, contraceptives
-‐ Both forms show lesions usually in flexural areas (leathery texture)
-‐ Oral: esp. in malignant form. Diffuse finely papillary areas often in tongue and upper lip
-‐ Histo: hyperorthokeratosia and papillomatosis. Skin lesions have melanin but little acanthosis.
Oral have acanthosis but little melanin.
