Autoimmune diseases
Cutaneous autoimmune disorders Andrea Szegedi Department of Dermatology Autoimmune diseases Are characterized by an immune reaction against a self antigen. This reaction has direct clinical, morphological and functional consequences. These alterations can’t be explained with other etiological factors. Autoimmune skin diseases Lupus erythematosus group Scleroderma group Dermatomyositis Autoimmune bullous diseases Autoimmune chronic urticaria Vitiligo Alopecia areata Vasculitides Lupus erythematosus disease group Systemic involvement CCLE Skin signs SCLE SLE Chronic Cutaneous LE – Discoid LE DLE - Discoid Lupus Erythematosus It belongs to the CCLE group Coin-shaped, indurated, erythematosus lesions Adherent scale, follicular plugging Peripheral spreading Central hypopigmentation and atrophy Telangiectasia, alopecia Female: male ratio 2-3:1 Transformation of DLE to SLE - 5% DLE - Treatment Basic therapy: Sunscreens Topical and intralesional glucocorticoids, Antimalarial drugs (chloroqiune, hydroxychloroquine) Refractory cases: Retinoids Vitamin E Oral glucocorticoids Azathioprine, cyclosporin A, Methotrexate Main features of Subacute Cutaneous LE (SCLE) Characteristic clinical picture (annular-polycyclic lesions or psoriasiform-papulosquamous lesions) Photoaggravated lesions (100%) Musculoskeletal complaints Frequent presence of anti-Ro antibodies (60%) Association with HLA-B8 and DR3 antigens Transformation of SCLE to SLE - 40% SCLE - Clinical picture Clinical findings which differ SCLE from DLE Follicular plugging is generally absent in SCLE Scale is less adherent in SCLE Lack of atrophy and scarring in SCLE Less indurated lesions in SCLE SCLE - Treatment Sunscreens + topical steroids Antimalarial drugs Systemic steroids Retinoids, dapsone Azathioprine, cyclophosphamide, methotrexate Plasmapheresis, interferon-gamma ARA criteria of Systemic Lupus Erythematosus Malar rash Discoid lesions, atrophic scarring Photosensitivity Ulcerations in the mouth or rhinopharynx Arthritis Serositis Renal disorders Neurological disorders Hematological disorders Immunological disorders Antinuclear antibodies Systemic lupus erythematosus 4 or more criteria of the ARA Female: male ratio - 9:1 Pathogenesis Skin symptoms: LE-specific and LE-nonspecific lesions LE-specific skin lesions Acute Cutaneous LE Subacute Cutaneous LE Localized ACLE (malar rash, butterfly rash) Generalized ACLE (lupus rash) Annular-plycyclic SCLE Papulosquamous SCLE Chronic Cutaneous LE Localized DLE Generalized DLE LE-specific skin disease Butterfly rash Malar rash Acute cutaneous LE LE-specific skin disease Butterfly rash Malar rash Acute cutaneous LE Skin signs of LE disease group (Gilliam classification) II. LE non-specific skin signs A. Cutaneous vascular diseases F. LE non specific bullous lesions 1. Vasculitis 2. vasculopathy G. Urticaria, urticaria vasculitis 3. periungual teleangiectasia H. Papulo-nodular mucinosis 4. livedo reticularis I. Cutis laxa 5. Thrombophlebitis J. Acanthosis nigricans 6. Raynaud syndrome B. Non scarring alopecia K. Erythema multiforme (Rowell) C. L. Sclerodactyly D. Rheumatoid nodules E. Calcinosis cutis Ulcus cruris M. Lichen planus Lupus non-specifis skin lesions of SLE Raynaud’s phenomenon Lupus non-specific skin lesions of SLE Lupus non-specific skin lesions of SLE SLE - Treatment Skin lesions as in DLE or SCLE: Local: Corticosteroid ointment, sunscreens Systemic: Antimalarial agents Internal involvement: High dose systemic corticosteroids and azathioprine, methotrexate, cyclophosphamide, cyclosporine A IVIG Sclerodermas I. Localized or circumscribed scleroderma - Morphea II. Systemic sclerosis: 1. Limited form 2. Diffuse form Systemic sclerosis - pathomechanism Immune mechanisms Vascular damage Altered collagen metabolism Systemic sclerosis Masked or sclerotic facies Difficult to wrinkle the forehead Difficult to whistle Pointed nose Small mouth, narrow lips Telangiectasia Systemic sclerosis -Acrosclerosis Claw-like flexion of the fingers Fingertip atrophy Nail bed telangiectasia Distal ulcerations, mutilation Systemic sclerosis - internal involvement Eyes: cataract Tongue, oral mucosa: sclerotic, fixed Larynx: hoarseness Esophagus: dysphagia, reflux Lungs: fibrosis Heart: myocardial fibrosis pericarditis Stomach: anacidity Kidney: glomerulosclerosis Systemic sclerosis Esophagus: dysphagia Lungs: fibrosis Systemic sclerosis - Treatment Anti-inflammatory, immunosuppressive agents (steroids, cyclophosphamide, methotrexate, thyrosine kinase blockersImatinib and antiCD20 monoclonal ab – rituximab is under investigations) Vasoactive agents ( calcium channel blockers, angiotensinconverting enzyme inhibitors, phosphodiesterase blockers /sildenafil/, pentoxyphillin, prostacycline derivates /iloprost/, angiotensin receptor blockers, endothelin receptor antagonist /bosentan, sitaxsertan/ ) Substances that influence collagen metabolism (UVA1, PUVA, extracorporal photopheresis, INF-γ, TGFβ blocker, D-penicillamin) Supportive therapy, physiotherapy Localized scleroderma - Morphea Female: male ratio - 2:1-3:1 Younger age group (20-40 years) Unknown etiology: genetic, immunological, hormonal, viral, toxic, neurogenic or vascular factors Borrelia burgdorferi ??? Clinical forms of Morphea Guttate Generalized Linear Nodular Subcutaneous Morphea -Treatment Antimalarial agents Vitamin E Topical steroids PUVA Methotrexat Classification of the idiopathic inflammatory myopathies in adults and children Dermatomyositis Polymyositis Overlap myositis Inclusion body myositis Cancer-associated myositis Dermatomyositis sine myositis Skin lesions of Dermatomyositis Heliotrope rash Gottron’s sign and Gottron’s papules Poikiloderma and erythema on the extensor surfaces of extremities Seborrheic eczema like erythema on the scalp Dermatomyositis - Treatment High dose systemic steroid Azathioprine Methotrexate Cyclophosphamide Cyclosporine A IVIG Autoimmune bullous diseases Intraepidermal autoimmune bullous diseases (pemphigus vulgaris, pemphigus vegetans, pemphigus foliaceus) Subepidermal autoimmune bullous diseases (bullous pemphigoid, cicatrical pemhigoid, herpes gestationis, epidermolysis bullosa acquisita) Dermatitis herpetiformis Duhring Pemphigus vulgaris The most common form in pemphigus disease group 40-50 years old, male:female = 1:1 Flaccid bullae and erosions on the skin and mucosa Progressive, it is fatal without therapy Mortaly: 5-10 % Pemphigus vulgaris - Pathogenesis In the serum and in the altered skin autoantibodies against the epidermis can be detected Pathogen antigens Pemphigus vulgaris antigen: Desmoglein 1 and 3 – these are desmosomal proteins Desmoglein 3 - mucosal lesions Desmoglein 1 and 3 - mucosal and skin lesions Mechanism Desmosome complex Pemphigus vulgaris-routine histology Pemphigus vulgaris – Immunflourescent staining Tzanck cells Pemphigus vulgaris - Diagnosis Clinical picture Tzanck cell Routine histology -intraepidermal acantholysis, vesicule formation Direct IF (DIF)+ Indirect IF (IIF) + Immunoblot technique ELISA technique Other members of the Pemphigus group pemphigus vulgaris - pemphigus vegetans pemphigus foliaceus - pemphigus erythematosus fogo selvagem drug induced pemphigus paraneoplastic pemphigus Other members of the Pemphigus group pemphigus vulgaris - pemphigus vegetans pemphigus foliaceus - pemphigus erythematosus fogo selvagem drug induced pemphigus paraneoplastic pemphigus Other members of the Pemphigus group pemphigus vulgaris - pemphigus vegetans pemphigus foliaceus - pemphigus erythematosus fogo selvagem drug induced pemphigus paraneoplastic pemphigus Pemphigus - Therapy Systemic corticosteroid therapy (1-2 mg/bkg) Azathioprine Cyclophosphamide Cyclosporin-A, mycophenolate mofetil IVIG Plasmapheresis Rituximab (anti-CD20 monoclonal antibody) Local therapy Attention, regular controls PEMPHIGOID GROUP Heterogenous disease group, with subepidermal blistering, characterized immunohistologically by subepidermal IgG deposition, and autoantibodies targeted toward the hemidesmosomal proteins. Bullous pemhigoid The most common autoimmune bullous disease Elderly patients Tense vesiculae and bullae with hyperaemic milieu Mucosal lesions are rare Bullous pemphigoid - Pathogenesis Autoantibodies against the hemidesmosomal antigens in the skin and serum Bullous pemphigoid antigen 1 - 230 kDa Bullous pemphigoid antigen 2 - 180 kDa Mechanism Hemidesmosome Histology of bullous pemphigoid Immunhistological staining of bullous pemphigoid Bullous pemphigoid- immunhistology Bullous pemphigoid - Therapy Systemic corticosteroid therapy (0,5 mg/bkg) Mild case: dapsone, tetracyclin Severe case: steroid and azathioprine Local therapy Attention, regular controls Dermatitis herpetiformis Childhood and young adults Groupped papules, weals, small vesicules Very itchy Above bony surfaces Association with gluten sensitive enteropathy Antibodies against tissue transglutaminase and epidermal transglutaminase in the skin Dermatitis herpetiformis - Histology Dermatitis Herpetiformis DIF Anti-human IgA Dermatitis herpetiformis - Therapy Gluten free diet Dapson Attention
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