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64 Cards in this Set
- Front
- Back
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What is the IF pattern, and target Ag of pemphigus vulgaris?
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Intercellular IgG, IgM
Desmoglein 3 (desmosome) |
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What is the IF pattern, and target Ag of pemphigus foliaceus?
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Intercellular IgG
Desmoglein 1 (desmosome) |
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What is the IF pattern, and target Ag of bullous pemphigoid?
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Linear IgG at BMZ
BP230/BP180 (BP Ag1/2) (hemidesmosomes) *Same as pemphigoid gestationis |
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What is the IF pattern, and target Ag of pemphigoid gestationis?
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Linear IgG at BMZ
BP230/BP180 (BP Ag1/2) (hemidesmosomes) *Same as bullous pemphigoid |
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What is the IF pattern, and target Ag of dermatitis herpetiformis?
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Granular IgA in dermis
Transglutaminase (subepidermal) |
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What is the IF pattern, and target Ag of linear IgA dermatosis?
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Linear IgA at BMZ
BP180 (BPAg2) (hemidesmosome) Note: BP180 also in B. pemphigoid, P. gestationis |
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Keratinocytes express MHCII proteins and secrete cytokines that mediate inflammation
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Langerhans cells migrate to dermis after stimulation by proinflammatory cytokines, and subsequently to nodes
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Epidermal lymphocytes (only about 2% of skin lymphocytes) are predominantly CD8+; they express a restricted set of antigen receptors than other T-cells; majority express an effector phenotype
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Dermal:epidermal junction: Lamina lucida - includes extracellular portion of hemidesmosomes; Lamina densa - includes collagen IV, laminin network; Sublamina densa - includes anchoring fibrils (collagen VII)
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Fibroblasts live in dermis - synthesize and degrade ECM proteins, collagen, elastic fibers; secrete mediators (eg, eotaxin when stimulated by IL-4, as well as IL-1, IL-6)
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Mast cells live in dermis - have tryptase, chymase; devo depends on c-KIT receptor and ligand SCF
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Macrophages in dermis express CD68
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Dermal DCs stain with Factor 13a, express DC-SIGN/CD209, CD1b/c/d; involved in Ag presentation
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Dermal T-cells are perivascular; express memory phenotype markers; express CLA-1 which helps them home to the skin
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MCtc cells: skin, conjunctiva, heart, gut submucosa; MCt cells: alveolar wall, respiratory epithelium, gut mucosa
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Filaggrin mutations seen in ichtyosis vulgaris, atopic eczema
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Skin homing of MEMORY, EFFECTOR, Treg LYMPHOCYTES (CLA+) are programmed by skin-derived DCs via cytokines like CCR4/CCL17 and CCR10/CCL27 (LOOK UP)
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In suspected bullous skin dz, get bx of lesion (for H&E) and perilesional skin (for direct IF; IF may not be positive in lesion)
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REVIEW PAGES 176-177 - IMMUNOBULLOUS SKIN DZ
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Defensins: cysteine-rich peptides in skin; abundant in neutrophil granules; broad-spectrum against bacteria/fungi; increased in presence of proinflammatory cytokines (eg IL-1/TNFa)
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MUST KNOW PV, BP and DH for boards!!
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Envt, bacterial stimuli cause Th2 bias in eczema.
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>50% of patients with AD will develop asthma; even more will develop allergies
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Increased numbers of IgE+ langerhans cells in both active AD and active asthma suggest the allergic dz may be controlled systemically
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AD often presents by 2-6 months of age; 90% of patients have onset prior to age 5; consider other dx in adults, esp if no h/o childhood atopy
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DDx of adult presenting with new-onset eczema, no h/o childhood eczema/asthma/AR: cutaneous T-cell lymphoma (need bx for dx)
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High levels of FcERI-expressing, IgE+ langerhans cells in ACTIVE AD, asthma, AR
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IgE to S. aureus toxins is produced by patients wtih both EXTRINSIC and INTRINSIC AD
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Langerhans cells and inflammatory dendritic epidermal cells (IDEC) upregulate FcERI to catch skin-infiltrating allergens
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Cutaneous T-cell attracting chemokine (CTACK/CCL27) and thymus-activating regulating cytokine (TARC) levels are specific for AD; INCREASED levels seen in ACUTE sx; DECREASED levels seen with IMPROVEMENT of sx
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SUPERANTIGEN stimulation causes CD4+/CD25+ Tregs to LOSE immunosuppressive activity
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DECREASE/ABSENCE of antimicrobial peptides (BETA-DEFENSINS 2/3, CATHELICIDIN 37) results in INCREASED RISK of infections
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DEFICIENCY of H-beta-DEFENSIN-3 results in IMPAIRED S. aureus killing
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AD skin is susceptible to infection; may be due to DOWNREGULATION of antimicrobial genes d/t UPREGULATION of TH2 cytokines
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TLR2 gene polymorphism resulting in impaired TLR2 is linked to SEVERE AD with frequent infections
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Loss of function of FILAGGRIN predisposes to EARLIER onset, more SEVERE, PERSISTENT AD
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Cytokines in ACUTE AD: IL-4, IL-13; Cytokines in CHRONIC AD: IL-5, IL-12, IFN-y
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T-cells in AD: CD3/CD4/CD45RO/CD25/HLA-DR+ (acute), also CLA+ (E-selectin ligand)
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Langerhans cells in AD: Express FcERI, but LACK BETA CHAIN**
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IDECs in AD: stimulate naive T-cells to become IFNy-producting T-cells (chronic phenotype); DO NOT contain Birbeck granules
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REVIEW PICTURE of ACUTE vs CHRONIC AD (cytokines, cells, etc)
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Intrinsic = non-atopic eczema (20-30% pts); Extrinsic = atopic eczema (70-80%, a/w IgE sensitization, increased IL-4/13)
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INFANTS = EXTENSOR AD (plus neck, trunk, face); CHILDREN/ADULTS = FLEXOR AD (plus hands, feet)
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In pts with suspected AD who DO NOT RESPOND TO STEROIDS, obtain skin BX
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Increased risk of colonization of/infection with: STAPH AUREUS, HERPES SIMPLEX, MOLLUSCUM, M. FURFUR, P. OVALE
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Complications of AD: INFECTION, AKC (bilateral intense pruritus, burning, tearing, copious thick ropy discharge, may result w/vision loss, anterior subcapsular cataracts); ECZEMA VACCINATUM (rxn to smallpox vaccine)
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25-35% of patients with moderate/severe AD can have flares with foods (all big 8 except shellfish); elimination diet helps sx, results in decreased spontaneous basophil histamine release
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Envt control measures for +SPT result in clinical AD improvement
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Increased S. AUREUS colonization a/w decreased BETA-DEFENSINS, CATHELICIDINS by keratinocytes
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AD patients can make specific IgE Ab's against skin toxins; disease SEVERITY correlates with PRESENCE of Ab's
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Nummular eczema: lesions more on EXTREMITIES than trunk
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Lichen simplex chronicus: cutaneous response to repeated scratching; common in neck/ear folds; resembles TREE BARK
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Vitamin B6 deficiency/Niacin deficiency: Seizures, irritability, cheilitis
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Multiple carboxylase deficiency: rash, alopecia, lethargy
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Histiocytosis: Rash (resembles seborrhea), cytopenias, LAD, histiocytic infiltrates of organs/skin
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URTICARIA occurs in SUPERFICIAL DERMIS; ANGIOEDEMA occurs in DEEP DERMIS/SUBCUTANEOUS TISSUE
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Acute urticaria: <6 weeks; occurs in 20% of population; a/w drug, food, allergy, infection
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Chronic urticaria: >6 weeks; 0.5% of population affected; 99% of patients with CIU have idiopathic disease, 30-40% may have associated autoantibodies to FcERI (IgG/IgM); less commonly pts may have anti-IgE antibodies
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Antigen binds IgE on mast cells, basophils: release of HISTAMINE, PGD2, LTC4, LTD4, PAF, C3a/C4a/C5a, BRADYKININ occurs
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COLD URTICARIA: occurs on cold-exposed areas; systemic rxns can occur with large BSA exposure; dx with ICE CUBE TEST; rx CYPROHEPTADINE (C for cold); most idiopathic; can txfr by serum
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ICE CUBE TEST may be NEGATIVE in: COLD-INDUCED CHOLINERGIC URTICARIA, SYSTEMIC COLD URTICARIA, COLD-DEPENDENT DERMOGRAPHISM
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CHOLINERGIC URTICARIA: small pruritic macules and papules occur in response to HEAT, EXERCISE, STRESS; occurs in TEENS; SPT to own sweat may be positive; rx HYDROXYZINE (H for Heat)
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CHOLINERGIC URTICARIA will result in anaphylaxis with PASSIVE HEATING, while EXERCISE-INDUCED URTICARIA will not
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DERMATOGRAPHISM: affects 2-5% of population; results in linear wheal (lasts up to 30 minutes); may be transfered via serum
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SOLAR URTICARIA: rare, brief sun exposure causes urticaria within 1-3 MINUTES; often affects 20-30y old pts; may be transferred via serum
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AQUAGENIC URTICARIA: wheals after contact with water of any temperature
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Thyroid autoAb's present in >20% patients with CIU; Anti-TPO>Anti-TG
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VIBRATORY URTICARIA: dx with vortex for FOUR MINUTES
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Test for heat-induced/cholinergic urticaria using 111F water
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URTICARIAL VASCULITIS: lesions last >24h, less pruritus, painful/burning sensation, may see purpura/pigment after lesions resolve; bx shows LEUKOCYTOCLASTIC VASCULITIS
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HYPOCOMPLEMENTEMIC URTICARIAL VASCULITIS SYNDROME: Urticaria with hypocomplementemia, a/w ANGIOEDEMA, OBSTRUCTIVE LUNG DISEASE, UVEITIS/EPISCLERITIS; low C3, C4, C1q (VERY LOW), elevated ESR; DX TEST: ANTI-C1q ANTIBODIES (PRESENT IN 100% PATIENTS)
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Contact Dermatitis: Type IV hypersensitivity mediated by CD4 Th1, Th17 and CD8 T-cells; onset is DELAYED 24-72 hours; dx made by PATCH TEST (read at 72 hours, 5d)
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Allergic contact derm: most common on HANDS, GENERALIZED, FACE; a/w PRURITUS, ERYTHEMA, +/- VESICLES (on testing)
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Irritant contact dermatitis: Direct chemical-induced inflammation; more common on FINGERTIPS, less pruritic than ACD
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ACD versus ICD: indistinguishable clinically, histologically; a/w LYMPHOCYTIC INFILTRATION, SPONGIOSIS; must determine CLINICAL RELEVANCE of patch tests
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10 most common ACD allergens: NICKEL, BALSAM OF PERU, NEOMYCIN, COBALT, FRAGRANCE MIX, POTASSIUM DICHROMATE, BACITRACIN, THIMEROSAL, FORMALDEHYDE, GLUTARALDEHYDE
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Potassium dichromate: stainless steel, chrome plating of other metals, tanned leather
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Chromates: wet CEMENT, textiles, tanned leather
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Cobalt dichloride (uncommon): dental implants, artificial joints, engines/rockets (aeronautics)
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Nickel: jewelry, DIMETHYLGLYOXIME TEST (PINK = POSITIVE)
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Plants: Toxicodendrom (POISON IVY/OAK/SUMAC) is most common ACD; d/t URUSHIOL found in sap; usually occurs after several exposures; approximately 85% of exposed will develop rxn; 10-15% is highly susceptible to P ivy/oak, and develop SYSTEMIC sx including rash/edema of face/arms/genitalia; CROSS-REACTS with MANGO PEELS**
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Other plants a/w ACD: Ragweed - sesquiterpene lactones; PRIMROSE = PRIMIN (Most common ACD in EUROPE); Chrysanthemums/daisies/tulips = test actual plant
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Sensitizing substances in PLANTS are present in OLEORESIN FRACTION; most must be crushed to release antigenic chemicals
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In US, PERUVIAN LILY (Astroemeria) is most common cause of HAND DERMATITIS in flower workers
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Cosmetics in ACD: fragrances (Balsam of Peru - cross-reacts with cinnamon, vanillin); Preservatives (formaldehyde/other - most fabrics contain formaldehyde; QUATERNIUM 15 is most commonly implicated preservative in US; PARABENS are UNCOMMON cause of ACD); hair products (#2 in cosmetics; PARAPHENYLENEDIAMINE - HAIRDRESSERS); Acrylics (ETHYLACRYLATE in salons/spas - nails or eyes/face)
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SUNSCREENS are common cause of PHOTOALLERGIC ACD; dx with PHOTOPATCH testing (patch plus UVA exposure)
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Test for ACD if rash worsens after using: LANOLIN, PABA, "CAINES", ABX, ANTIHISTAMINES, STEROIDS
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Topical steroids cause ACD in up to 5% of pts; risks include REFRACTORY AD, LEG ULCERS, STASIS DERMATITIS
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If suspect topical steroid-induced ACD, read patch test at 3, 5 AND 7 DAYS LATER bc false negatives common early on d/t immunosuppressant nature of steroids
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Most common screening agents for topical steroid ACD are BUDESONIDE and TIXOCORTOL PIVALATE 1%
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Four major classes of sensitizing steroids: A: hydrocortisone type; B: triamcinolone type; C: betamethasone type; D: hydrocortisone-17-butyrate type (TEST FOR DIFFERENT SENSITIZATIONS BETWEEN CATEGORIES)
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Resins: ACD may occur to UNCURED resin or hardener, but NOT to EPOXY; COLOPHONY is made from pine trees - testing difficult bc differences in trees, may x-react with BofP; ETHYLENEDIAMINE DIHYDROCHLORIDE is in topical creams, AMINOPHYLLINE and generic nystatin, but does not x-react with EDTA - if sensitized, AVOID NYSTATIN, AMINOPHYLLINE, MECLIZINE/CYCLIZINE; PARAPHENYLENEDIAMINE is common in henna tattoos (not henna allergy); TOPICAL ABX (bacitracin, neomycin) common, have risk of delayed anaphylaxis - if sensitized AVOID BACITRACIN, GENTAMICIN, KANAMYCIN, STREPTOMYCIN, TOBRAMYCIN
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Allergic contact cheilitis: lip balm, dental devices, nail polish, cigarettes, etc
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Criteria for dx of surgical implant dermatitis: appears after implant surgery; persistent despite appropriate rx; + patch test to metallic component or acrylic glues; resolution after removal of implant
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SYSTEMIC CONTACT DERMATITIS: GENERALIZED ACD RASH after systemic admin of rx, chemical or food to which pt previously had ACD (ex: Benadryl cream-allergic pt gets rash after systemic diphenhydramine); INDURATED EDEMA may preferentially affect GROIN
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PEMPHIGUS a/w DESMOGLEINS 1, 3 in DESMOSOMES
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PEMPHIGOID, LINEAR IgA BULLOUS DERMATITIS = BP180/230 in HEMIDESMOSOMES
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PEMPHIGUS = FLACCID bullae; IgG/C3 on EPITHELIAL SURFACE; target DESMOGLEIN-3/DESMOSOME; rx STEROIDS
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PEMPHIGUS FOLIACEUS = DESMOGLEIN-1
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IgA PEMPHIGUS = IgA on EPI SURFACE; target is DESMOGLEIN-1/DESMOSOME
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PEMPHIGOID = TENSE bullae; URTICARIAL base; FLEXURAL areas; PRURITUS common; IgG to BMZ/EPIDERMIS; target BP180/230/HEMIDESMOSOME; Linear BMZ IgG/C3 (BP=BP)
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HERPES GESTATIONIS = URTICARIA/BLISTERING in PERIUMBILICAL AREA; C'-FIXING BMZ Ab's against BP180, also 230; linear BMZ C3 IF PATTERN
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EPIDERMOLYSIS BULLOSA ACQUISITA; sites of TRAUMA or ORAL MUCOSA; target TYPE VII COLLAGEN/anchoring fibrils; LINEAR BMZ IgG/C3, may have linear IgA/IgM
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DH = small HERPETIFORM bullae, SYMMETRIC on EXTENSOR SURFACES; a/w CELIAC DZ; increased risk of LYMPHOMA as in Celiac; MARKEDLY PRURITIC; IgA TTG correlates w/disease activity, gluten free diet compliance; target is EPIDERMAL TTG; GRANULAR BMZ IgA seen on IF
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SLE = GRANULAR BMZ IgM=C3>IgG>IgA (2 or more required); DEPOSITS in both INVOLVED and UNINVOLVED SKIN; No Ab's in discoid variant;
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Patients with AD have decreased H20 binding capacity d/t decreased ceramide levels in skin
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Water content is lowest in topical ointments
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30g of ointment covers the entire body of an average-sized adult
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Adverse effects of topical steroids: SKIN THINNING, TELANGIECTASIAS, BRUISING, HYPOPIGMENTATION, ACNE, STRIAE, INFECTION
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Topical calcineurin inhibitors: Tacrolimus 0.03%, 0.1%, Pimecrolimus 1%; DO NOT USE IN <2y; AVOID OCCLUSIVE DRESSINGS; SE's include burning/stinging
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TAR preparations INHIBIT influx of PROINFLAMMATORY cells, expression of adhesion molecules in response to allergen; AVOID on acutely INFLAMED skin; SE's include PHOTOSENSITIVITY, PUSTULAR FOLLICULITIS
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Wet dressings cool skin and act as barrier to trauma; IMPROVE PENETRATION of TOPICAL STEROIDS; SE's include chilling, maceration of skin, secondary infection
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Abx for AD includes PCN-based rx, 1st/2nd gen cephalosporins; avoid maintenance rx; topical abx ok for localized infection; MUPIROCIN good for intranasal STAPH CARRIAGE; ORAL ACYCLOVIR for DISSEMINATED EH; can use ppx acyclovir for recurrent cutaneous HSV
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DOXEPIN has both H1 and H2 receptor binding activity, long T1/2; AVOID TOPICAL ANTIHISTAMINES/anesthetics - RISK OF SENSITIZATION
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CSA results in decreased transcription of proinflammatory cytokines; RISK of NEPHROTOXICITY (may be irreversible) with extended use
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PHOTOTX (UVB, narrow-band UVB, high dose UVA1) DECREASES ACTIVATION MARKERS ON CLA+ T-cells; High dose UVA1 decreases dermal IgE-binding cells (mast cells, DCs) and downregulates proinflammatory cytokines and induces apoptosis of skin-infiltrating CD4s
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Recombinant human IFNy suppresses IgE synthesis, inhibits Th2 differentiation; results in REDUCED clinical severity, DECREASED circulating eosinophil counts in AD
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Low potency steroids: HC, desonide
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Medium potency steroids: Betamethasone valerate, Fluticasone propionate, mometasone furoate, triamcinolone acetate
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High potency steroids: Fluocinonide, Halcinonide
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Very high potency steroids: Betamethasone dipropionate, clobetasol propionate, halobetasol propionate
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