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 - n1. line! Rituximab 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 Connective tissue disorders nLupus erythematosus nScleroderma nDermatomyositis, polymyositis nOverlap syndromes Lupus erythematosus nsystemic lupus erythematosus - SLE nchronic cutaneous lupus erythematosus – CCLE nsubacute cutaneous lupus erythematosus – SCLE nneonatal LE ndrug induced ( hydralazine, sulfonamides) n n Systemic lupus erythematosus - SLE nARA criteria: nmalar rash ndiscoid lesions nphotosensitivity noral lesions narthritis nserositis nneurologic disorders nrenal disorders ( proteinuria 0,5g/d) nhematologic disorders nimmunologic disorders ( LE cells, ANA , dsDNA, Sm) ANAhom http://image.slidesharecdn.com/vaishali-140929111755-phpapp01/95/case-of-sle-10-638.jpg?cb=14119896 39 sle-cde-oblicej sle-motylek-muz SLE gangrena-diabeticorum kytlicova20080526_0008 128-2850_IMG Chronic cutaneous lupus erythematosus - CCLE ndiscoid lesions - CDE nhypertrophic lesions nlupus panniculitis nANA low titers or none nno systemic disease n nsymptom of systemic disease 122-2298_IMG cde-oblicej cde-oblicej-zena cde-oblicej-muz n IMG_5655 tomanova Subacute cutaneous lupus erythematosus - SCLE nannular lesions npapulosquamous lesions nphotosensitivity nANA, anti Ro/ SSA, La/SSB nmild systemic disease nneonatal LE scle-trup-celek-zena 110-1079_IMG xxx xxx n henčlova 20080401_0015 20071109_0003 Lupus erythematosus nTherapy: nantimalarial drugs (hydroxychlorochine) ncorticosteroids nimmunosuppresives (cyclophosphamide) nantiinflammatory drugs nUVA, UVB sunscreens nplasmapheresis, pulse therapy etc. nBelimumab (BAFF) Scleroderma nvascular changes n nchanges in collagen synthesis n nimmunological changes – n humoral (anti Scl70, ANA ) n cellular Plné kosočtverce Systemic sclerosis nARA criteria: nproximal scleroderma nbilateral lung interstitial fibrosis nfingertip changes, digital ulcers nsclerodactyly nother signs: nRaynaud ´s phenomenon nesophageal changes nrenal disease npulmonary hypertension npericardial effusion sclerodermia-diffusa-sklerodatylie sclerodermia-diffusa-obl sklerodermie-difusni-oblicej-zena-u akrocyanoza-ss CREST syndrome nC alcinosis nR aynaud nE sophageal changes nS cleroderma nT eleangiectasias nanti centromere antibody Scleroderma nTherapy: ncorticosteroids n immunosuppresives nendotelin receptor antagonist– bosentan – nphosphodiesterase 5 antagonists– sildenafil - DUC nd-penicillamine, penicillin nvasoactive and rheological drugs (pentoxiphylline) ncalcium antagonists – amlodipine nACE inhibitors - kidneys nprokinetic drugs, antacids nphysiotherapy Circumscribed scleroderma nmorphea nguttate nlinear ngeneralized nsubcutaneous nANA in low titers or none nno systemic disease nInfections – Lyme disease nTx MTX, CS, penicillin, UVA1 phototherapy, topical CS morfea-bok-zena morfea-detail-lilac-ring morphea-kriz sklerodermie-linearni-stehno Dermatomyositis, polymyositis njuvenile - association with infections nadult - association with tumours nheliotrophic rash, Gottron´s sign, poikilodermatitis, erythemas nEMG nANA, anti Jo-1 nCPK, LDH, GOT, ALD, AST, ALT, myoglobine nHistology – muscle, skin dmkrut-celo dmkrut-hrud dmkrut-ruce dmkrut-prsty n foto klinika 06 07 014 118-1847_IMG 118-1821_IMG Dermatomyositis - therapy nCorticosteroids nImmunosuppresives - MTX, azathioprine, cyclosporin nIVIG nJAK inhibitors