Autoimmune bullous diseases nRare diseases, severe forms are lethal nSkin and mucous membranes n nTwo groups according to the level of cleavage nIntraepidermal – Pemphigus and variants nSubepidermal – pemphigoid group, DHD, EBA n nAutoantibodies IgG/IgA against antigens in the epidermis and junctional zone n 111-1160_IMG Diagnostics – Tzanck test, histology, immunofluorescence direct & indirect, ELISA, immunoblot Pemphigus - desmosomes Pemphigoid - hemidesmosomes Pemphigus nSuprabasal (Dsg 3,1, IgG) npemphigus vulgaris n vegetans nSuperficial (Dsg 1, IgG) n pemphigus foliaceus n fogo selvagem (Brazil) n drug induced (thiols, phenols, penicilamin, captopril) n pemphigus erythematosus Senear Usher – fotosensitivity, ANA antibodies nParaneoplastic Pemphigus – lichenoid, EEM features, bronchiolitis nIgA pemphigus n n pemph-fol-jedl-fitc-igk-40x--saveim 129-2942_IMG Pemphigus nSuprabasal acantholysis H+E nDirect IF – pemphigus foliaceus nAnti IgG/C3 nIndirect IF – monkey esophagus nICS anti IgG Pemphigus vulgaris nRare bullous disorder with autoantibody-induced intraepidermal blisters (desmosomes - acantholysis) nIncidence 5/ 1 million inhabitants nChronic disease, can be lethal nAverage age 30-60 years nEtiopathogenesis nGenetic factors (HLADR4) nDrug induced, infections, phenols nAntibodies against desmoglein 1,3 n pemphigus-vulgaris-zada pemphigus-vulgaris-obl1-u pemphigus-vulg-detail pemfigus-vulgaris-hyzde Obsah obrázku oči, maska, zavřít, sousto Popis byl vytvořen automaticky Nikolsky sign Pemphigus vegetans n pv-klis-axila pemphigus -veg-trislo Pvegnavel pemphvegpust pemphigus-erythematosus-zada Pemphigus foliaceus pemph-fol-jedl-fitc-igk-40x--saveim Pemphigus therapy nCorticosteroids (Prednisone 1-1,5mg/kg/d) n...taper to 15 -20 mg/d nImmunosuppresives - corticosteroid sparing agents nMycophenolate mofetil 2g/d nAzathioprine – cave TPMT deficiency nMTX 10-20mg per week n (Cyclophosphamide – toxic) n - nRituximab anti CD20 antibody –risk of infections nDapsone nIVIG 1-2g/kg pulse every 6 weeks nImmunoadsorption IgG nLong term therapy, 2 years minimum, often life long Subepidermal autoimmune bullous dermatoses nRare disorders with autoantibody-induced subepidermal blisters (basement membrane – hemidesmosomes) n nBullous Pemphigoid - BP nPemphigoid gestations ( variant of BP) nCicatricial Pemphigoid – mucous membrane pemphigoid nEpidermolysis bullosa acquisita (association diabetes, bowel disease) nIgA linear dermatosis – typically childhood, in adults drug induced – vankomycin nDermatitis herpetiformis Duhring Obsah obrázku dort, vsedě, hledání, osvětlené Popis byl vytvořen automaticky Obsah obrázku dort Popis byl vytvořen automaticky https://www.euroimmun.com/documents/Indications/Autoimmunity/Dermatology/Desmoglein/EA_1490_I_U - Internet Explorer Obsah obrázku fialová Popis byl vytvořen automaticky BP – subepidermal blister - eosinophils Direct IF line on BM IgG/C3 Salt split skin blister roof in BP Pemphigoid bullosus nElder people – over 70 years nMany concomitant diseases nParaneoplastic disease (13%) prostate, breast cancer nDrug induced (PNC, enalapril, furosemid, gliptins) nNeurodegenerative diseases! nCerebral stroke + paresis, Parkinson disease, dementia n(BP expression in neuronal tissue) n1 year survival 60% patients orságBPtělo šustBP BP tense hemorrhagic blisters, infiltrated skin Tissue and blood eosinophilia, strong pruritus 123-2328_IMG pemphigoid-bullosus-paze BP in paretic limb Urticarial lesions in BP Pemphigoid bullosus therapy nCorticosteroids (Prednisone 0,5-0,7mg/kg) nor nPotent topical corticosteroids (clobetasol) nImmunosuppresives ( azathioprine, methotrexate, mycophenolate) nDapsone nTTC – antiinflammatory effect Cicatricial Pemphigoid MMP nIncidence 1/million inhabitants n60 years of age nParaneoplasia (stomach cancer), topicals for glaucoma nMucose membranes stenosis, scarring nConjunctiva - entropion, symblepharon, trichiasis blindness nPharynx, larynx, nGenital area nSkin – minor disease Brunsting Perry Pemphigoid n nTherapy – as in pemphigus jizvící-pemfigoid-buk-sliz jizvici-pemfigoid-gingivitis 122-2264_IMG Obsah obrázku zavřít Popis byl vytvořen automaticky Obsah obrázku modrá, zavřít, oči, brýle Popis byl vytvořen automaticky Pictures from Praktická dermatologie Dermatitis herpetiformis Duhring §rare disease – incidence 3/1 million inhabitants §gluten sensitive entheropathy – coeliakia §IgA antibodies against endomysium (tissue transglutaminase) §cross reaction with eTG on reticulin fibers in dermal papilae §sensitivity to gluten, iodine n Dermatitis herpetiformis Duhring nChildren rarely nYoung adults nHLA DQ2, DQ8 association nPredilection sites – elbows, knees, sacrum, hairline n nTherapy nGluten free diet nDapsone nTopical corticosteroids n n n Obsah obrázku barevné Popis byl vytvořen automaticky dhd-detail dermatitis-herpetiformis-hyzde