Cutaneous autoimmune disorders
Andrea Szegedi
Department of Dermatology
Autoimmune diseases
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Are characterized by an immune reaction against a
self antigen.
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This reaction has direct clinical, morphological and
functional consequences.
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These alterations can’t be explained with other
etiological factors.
Autoimmune skin diseases
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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
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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
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Basic therapy:
Sunscreens
Topical and intralesional glucocorticoids,
Antimalarial drugs (chloroqiune, hydroxychloroquine)
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Refractory cases:
Retinoids
Vitamin E
Oral glucocorticoids
Azathioprine, cyclosporin A, Methotrexate
Main features of Subacute Cutaneous LE (SCLE)
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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
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Follicular plugging is generally absent in SCLE
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Scale is less adherent in SCLE
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Lack of atrophy and scarring in SCLE
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Less indurated lesions in SCLE
SCLE - Treatment
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Sunscreens + topical steroids
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Antimalarial drugs
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Systemic steroids
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Retinoids, dapsone
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Azathioprine, cyclophosphamide, methotrexate
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Plasmapheresis, interferon-gamma
ARA criteria of Systemic Lupus Erythematosus
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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
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4 or more criteria of the ARA
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Female: male ratio - 9:1
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Pathogenesis
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Skin symptoms: LE-specific and LE-nonspecific lesions
LE-specific skin lesions
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Acute Cutaneous LE
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Subacute Cutaneous LE
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Localized ACLE (malar rash, butterfly rash)
Generalized ACLE (lupus rash)
Annular-plycyclic SCLE
Papulosquamous SCLE
Chronic Cutaneous LE
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Localized DLE
Generalized DLE
LE-specific skin disease
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Butterfly rash
Malar rash
Acute cutaneous LE
LE-specific skin disease
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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
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periungual teleangiectasia
H. Papulo-nodular mucinosis
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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
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Raynaud’s phenomenon
Lupus non-specific skin lesions of SLE
Lupus non-specific skin lesions of SLE
SLE - Treatment
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Skin lesions as in DLE or SCLE:
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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
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Immune mechanisms
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Vascular damage
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Altered collagen metabolism
Systemic sclerosis
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Masked or sclerotic facies
Difficult to wrinkle the
forehead
Difficult to whistle
Pointed nose
Small mouth, narrow lips
Telangiectasia
Systemic sclerosis -Acrosclerosis
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Claw-like flexion of the fingers
Fingertip atrophy
Nail bed telangiectasia
Distal ulcerations, mutilation
Systemic sclerosis - internal involvement
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Eyes: cataract
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Tongue, oral mucosa:
sclerotic, fixed
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Larynx: hoarseness
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Esophagus: dysphagia, reflux
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Lungs: fibrosis
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Heart: myocardial fibrosis
pericarditis
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Stomach: anacidity
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Kidney: glomerulosclerosis
Systemic sclerosis
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Esophagus: dysphagia
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Lungs: fibrosis
Systemic sclerosis - Treatment
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Anti-inflammatory, immunosuppressive agents (steroids,
cyclophosphamide, methotrexate, thyrosine kinase blockersImatinib and antiCD20 monoclonal ab – rituximab is under
investigations)
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Vasoactive agents ( calcium channel blockers, angiotensinconverting enzyme inhibitors, phosphodiesterase blockers
/sildenafil/, pentoxyphillin, prostacycline derivates /iloprost/,
angiotensin receptor blockers, endothelin receptor antagonist
/bosentan, sitaxsertan/ )
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Substances that influence collagen metabolism (UVA1, PUVA,
extracorporal photopheresis, INF-γ, TGFβ blocker, D-penicillamin)
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Supportive therapy, physiotherapy
Localized scleroderma - Morphea
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Female: male ratio - 2:1-3:1
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Younger age group (20-40 years)
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Unknown etiology: genetic, immunological,
hormonal, viral, toxic, neurogenic or vascular factors
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Borrelia burgdorferi ???
Clinical forms of Morphea
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Guttate
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Generalized
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Linear
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Nodular
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Subcutaneous
Morphea -Treatment
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Antimalarial agents
Vitamin E
Topical steroids
PUVA
Methotrexat
Classification of the idiopathic inflammatory
myopathies in adults and children
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Dermatomyositis
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Polymyositis
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Overlap myositis
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Inclusion body myositis
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Cancer-associated myositis
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Dermatomyositis sine myositis
Skin lesions of Dermatomyositis
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Heliotrope rash
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Gottron’s sign and Gottron’s papules
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Poikiloderma and erythema on the extensor surfaces
of extremities
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Seborrheic eczema like erythema on the scalp
Dermatomyositis - Treatment
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High dose systemic steroid
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Azathioprine
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Methotrexate
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Cyclophosphamide
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Cyclosporine A
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IVIG
Autoimmune bullous diseases
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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
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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
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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
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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
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Other members of the Pemphigus group
pemphigus vulgaris - pemphigus vegetans
 pemphigus foliaceus - pemphigus
erythematosus
 fogo selvagem
 drug induced pemphigus
 paraneoplastic pemphigus
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Other members of the Pemphigus group
pemphigus vulgaris - pemphigus vegetans
 pemphigus foliaceus - pemphigus
erythematosus
 fogo selvagem
 drug induced pemphigus
 paraneoplastic pemphigus
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Pemphigus - Therapy
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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
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The most common autoimmune bullous disease
Elderly patients
Tense vesiculae and bullae with hyperaemic milieu
Mucosal lesions are rare
Bullous pemphigoid - Pathogenesis
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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
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Systemic corticosteroid therapy (0,5 mg/bkg)
Mild case: dapsone, tetracyclin
Severe case: steroid and azathioprine
Local therapy
Attention, regular controls
Dermatitis herpetiformis
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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
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Gluten free diet
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Dapson
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Attention