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1 lå Blåsdermatoser Bo Nilsson

2 Cutaneous lupus erythematosus (LE) Pemphigus Pemphigoid Dermatitis herpetiformis (DH)

3 Samples 1.Biopsy 2.Serum

4 The biopsy 1H 1. How should ldthe biopsy be taken? tk Lesional Non-lesional 2. How should the biopsy be transported? 2. How should the biopsy be transported? In special preservation medium (Histicon eller Michel s)

5 Skin anatomy Stratum corneum Epidermis Keratinocytes Basal membrane Basal membrane Dermis

6 Direct immunofluorescence, biopsy py Antibodies to immunoglobulins li and complement UV microscope Skin biopsy from a patient

7 Indirect immunofluorescence, Serum antibodies Antibodies to human IgG Serum from the patient UV microscope Monkey oesophagus

8 ELISA Blot

9 Ct Cutaneous lupus erythematosus t Acute cutaneous LE (ACLE) - Papillar exantema Subacute cutaneous LE (SCLE) Chronic cutaneous LE (CCLE) - Discoid LE (DLE)

10 20-60% of all SLE patients UV, infections HLA ACLE

11 SCLE Ro /SSA-positive up to 90% 50% SLE Ca 30% DLE HLA Light sensitivity Drugs Stress- triggering or amplifying factor Malignencies

12 CCLE - discoid LE (DLE) 5 10% d l SLE 5-10% develope SLE SLE debut UV related 50% Scar alopecia 30% Mucosa 25%

13 Neonatal LE in a child with Ro /SSA-positive mother

14 Cutaneous LE Lichenoid tissue reaction with signs of apoptosis Can be experimentally reproduced dby exposure to UVB, UVA up to visible light

15 UV-Radiation PGE2, NO Reactive oxygen Cytokines Keratinocyte Apoptosis Autoantigen ti modulation D-E Junction

16 UVB Keratinocyte C1q Apoptotic Keratinocyte Cytoplasmic Bleb: Ro (52kD>60kD) Ribosomal antigens

17 Lupus band test (LBT) UV

18 Lupus band IgG, IgA, IgM, C3 Sensitivity: approx 60-80%

19 Cutaneous lupus erythematosus Biopsy Light microscopy Immunofluorescence Detection of serum autoantibodies ANA Anti-DNA Antibodies to SSA, SSB, RNP, Sm etc Complement analyses

20 Laboratory o findings in cutaneous lupus ACLE SCLE CCLE LBT Lesional Non-lesional ANA Anti-SSA Anti-dsDNA Complement activation

21 Pemphigus Pemfix = blister Intraepidermal blisters, antibodies to cadherins Various forms due to the location of the antigen in epidermis Genus similarity, middle age Genetics ( DR4, DRw6, populationhlas) Assocition with other autoimmune diseases, thymoma

22 Pemphigus vulgaris Mucosal lesions in all patients; first sign in 50-70% Scalp, face, skin folds Nikolski ssign ki i

23 Pemphigus Vulgaris Antibodies to cadherins: desmoglein 1 and 3 in desmosomes (= intercellularsubstans ) Histology: Suprabasal akantolysis

24 Desmosomes Keratinocyte Keratins Plaque Plakins Desmoglein 1, 3 Keratinocyte

25 Pemphigus vulgaris Anti-desmoglein 1 Anti-desmoglein 3

26 Pemphigus folliaceus Anti-desmoglein 1

27 Paraneoplastic pemphigus Anti-desmoglein 3 Anti-plakins

28 Pemphigus autoantibodies Desmoglein 1 PV PF NP + + (+) Desmoglein 3 + Plakins

29 Pemphigus, biopsy IgG, C3 Sensitivity: approx 100%

30 Pemphigus, biopsy Blister

31 Pemphigus, serum Ab IgG Sensitivity: approx 80-90%; associated with disease activity

32 Pemphigus Biopsy Light microscopy Immunofluorescence Detection of serum autoantibodies Immunofluorescence ELISA, blotting

33 Bullous Pemphigoid The most common blister dermatosis in western Europe Male > female, > 60 year Prodromal stadium. Itch! Though fluid-filled blisters

34 Pemphigoid gestationis Distinctive form i pregnant women in the last month of pregnancy. Itch and tough liquid-filled blisters combined with figure-forming erythema Better prognosis than PV

35 Bullous pemphigoid Histology: subepidermal blister formations Eosinophils Antibodies to BP230 and BP180 which are associated with hemidesmosoms (antikroppar against the basal membrane )

36 Hemidesmosomes Basal keratinocyte e Keratins Plaque Basal lamina BP230 BP180 Collagen XVII Anchoring fibres

37 Bullous pemphigoid Pregnancy pemphigoid Anti-BP230 Anti-BP180 C3a C5a C3a C5a

38 Bullous pemphigoid, biopsy IgG, C3 Sensitivity: approx 100%(C3)

39 Pregnancy pemphigoid, biopsy (IgG), C3 Sensitivity: approx 100%(C3)

40 Bullous pemphigoid, p serum Ab IgG Sensitivity: approx 70%

41 Linear IgA Dermatosis Distinctive form in children and elderly IgA antibodies Antigens: fragments of BP180 and BP230 Knees, elbow, buttocks and sometimes mucous membranes Itch and tough liquid-filled blisters

42 Bullous pemphigoid Pregnancy ypemphigoidp Biopsy Light microscopy (subepidermal blister) Immunofluorescence (BM) Detection of serum autoantibodies Immunofluorescence ELISA, Western blotting

43 Dermatitis Herpetiformis Symetrical on extensor surfaces and back. Elbows, knees, sacrum Ti Triggeredby gluten (90% GSE), iodine, fish, see food Chronic Other autoimmune diseases (thyroidea, DM) Lymphoma (diet protects)

44 Dermatitis Herpetiformis i Uncommon, itching, chronic blister dermatosis Underlying glutenenteropathy, may be without symptoms and signs Family history in 10% All ages Male > female

45 Dermatitis Herpetiformis Papillitis i (micro abscesss) Subepidermal blister formations IgA/epidermal TG3 complexes

46 Dermatitis herpetiformis IgA, C3

47 Dermatitis herpetiformis Biopsy Light microscopy Immunofluorescence Detection of serum autoantibodies Anti-gliadin Anti-endomysium Anti-transglutaminase (TG2)

48 c Lupus band

49

50 Läkemedelsutlöst SCLE Beh Plaquenil i 6 veckor Snart 80-årig man med mild ulcerös kolit, gallgångsförträngning Hudtyp III, ej soleksem Aug -04 utslag i flinten steroidlösning Sept bronchit, Doxyferm PAD: toxicodermatit närmast erythema multiforme Lab: ANA 200, anti-ro/ssa och anti-la/ssb

51 Kutan vaskulit Nekrotiserande vaskulit i små kärl (arteriolae, venulae). Oftast primärt/endast i huden Immunkomplexmedierad Typexempel Henoch- Sh Schönleins li purpura IgA immunkomplex (typ III) Kutan Leukocytoklastisk vaskulit Läkemedel, RA, ulcerös kolit, infektion, malignitet?

52 Kutan vaskulit 18-årig tidigare frisk man Sedan 2 veckor magsmärtor,diarre Förkyld med halsont före det Gastro-koloskopi visar Crohn? även vaskulitbild Utslag på fötter och underben

53 Hudmanifestationer av leukocytoklastisk vaskulit: Palpabel purpura Urticaria Ulcerationer Infarkter Noduli Livedo retikularis Vikitgast: ORGANENGAGEMANG? U-sticka!! Kutan vaskulit

54

55 Systemisk Vaskulit Polyarteritis Nodosa, hudsymptom hos 25% Små och medelstora artärer Läkemedel, ede hepatit, streptokocker oc e kan utlösa Infiltrat, noduli, bullae, livedo retikularis

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