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Autoimmune Bullous Diseases

Autoimmune Bullous Diseases. Dr. Abdullah ALAKEEL Assistant P rofessor & Consultant Department of Dermatology KKUH. Circumscribed skin lesions containing fluid (If the size ≤ 5mm = vesicle If the size > 5mm = bulla). Classification Of Vesiculobullous Diseases:.

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Autoimmune Bullous Diseases

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  1. Autoimmune BullousDiseases Dr. Abdullah ALAKEEL Assistant Professor & Consultant Department of Dermatology KKUH

  2. Circumscribed skin lesions containing fluid (If the size ≤ 5mm = vesicle If the size > 5mm = bulla)

  3. Classification Of Vesiculobullous Diseases:

  4. Autoimmune bullousdiseases • A- Loss of intraepidermal adhesion: Pemphigus group : • 1- Pemphigus vulgaris (PV) with subtypes • a- Classic • b- Pemphigus vegetans 2- Pemphigus foliaceus with subtypes: a- Classic - Fogoselvagum - Pemphigus erythematosus ( Senear-Usher) b- Paraneoplastic pemphigus c- Drug induced pemphigus d- IgA pemphigus

  5. Autoimmune bullousdiseases B- Loss of subepidermal adhesion : 1- Pemphigoid a- Bullous pemphigoid b- Pemphigoidgestationis c- Cicatricialpemphigoid 2- Linear IgA disease - of childhood - Adult form 3- Epidermolysisbullosaacquisita 4- Dermatitis herpetiformis

  6. Autoimmune bullousdiseases • Pemphigus Group : • A group of disorders with loss of intraepidermal adhesion due to autoantibodies directed against proteins of the desmosomal complex that hold keratinocytes together. The desmosome is a complex structure, with many of its components targets for autoantibodies.

  7. PV • Pemphigus vulgaris (PV): • Definition : severe, potentially fatal disease with intraepidermal blister formation on skin and mucosa caused by autoantibodies against desmogleins. • Epidemiology : 0.1-0.5/ 100000 yearly, most patients middle aged.

  8. PV • Pathogenesis: • - Genetic predisposition: HLA-DRQ402- DQ0505 • - Antibodies against desmoglein 3 (Dsg 3) and later desmoglein 1 (Dsg 1 ). The bound antibodies activate proteases that damage the desmosome, leading to acantholysis. • - Serum antibody titer usually correlates with severity of disease and course.

  9. PV - Agents containing sulfhydryl groups (penicillamine, captopril, piroxicam) are more likely to cause PV. - Those without sulfhydryl groups tend to cause PV ( beta-blockers, cephalosporins, penicillins, & rifampicin) . • Note : drugs from either group can cause either type of pemphigus.

  10. PV • Clinical features: • Sites: oral mucosa, scalp , face, mechanicallystressedareas,nailfold, intertriginous areas. • Bliters are NOT stable, epidermisfallsapart, erosions & crusts are common • Oral involvement: 70%, anti-Dsg3 (Dsg 3 is the main desmoglein on mucosa) • Additionallocalizeddisease; scalp • Note:always check scalp whenconfrontedwithunexplained oral erosions.

  11. PV • Generalizeddisease due to development of antibodiesagainst Dsg1 whichispresent in skin alongwith Dsg3. • Pruritusisuncommon. • Histology: acantholysis, retention of basal layer keratinocytes (tombstoneeffect), milddermalperivascularinfiltrates.

  12. PV • Diagnostic approach: • Clinical evaluation • Nikolskysign • Pseudo-Nikolskysign (Asboe-Hansen sign), lessspecific

  13. PV • Histology: • DIF: perilesional shows a net-likeintracellulardepositionof IgG (100%), C3 (80%) • Indirect IF (IIF) performedusingmonkeyesophagus • ELISA: to identify anti-Dsg3,1

  14. PV • Differentialdiagnosis: • When skin isinvolved: • Bullousimpetigo, dyskeratoticacanthoyticdisorders ( Hailey-Hailey, Groverdisease) • When oral mucosaisinvolved: • Denture intolerance • Erosive candidiasis • Chronicrecurrentaphthae • Erythema multiforme • Erosive lichen planus • Herpeticginigivitis

  15. PV • Therapy : • 1- Systemiccorticoisteroids • The main cause of morbidity & mortality in patients is CS sideeffects, have to combine withsteroid-sparing agent, check for osteoporosis and latent TB • A- combination pulse therapy: prednisolone 1g + cyclophosphamide 7.5-10 mg/kg every 3-4 weeks • Withcyclophosphamide in interval 1-2mg/kg daily.

  16. PV • Prednisolone- azathioprinetherapy • Alternative immunosuppressive agents: cyclosporine, mycophenolatemofetil, chlorambucil • Topicalmeasures: local anesthetic gels • Therapyresistant course: IVIG

  17. Pemphigus vegetans • Unusual variant of PV withhyperkeratoticverruciformreaction (vegetans) • Clinical features : • Originallytypical PV, thendevelopment of white macerated plaques in involved areas • (pyodermite végétante) : limited to intertriginous areas, starts as pustules thatevolveintovegetatinglesions.

  18. Pemphigus vegetans • Diagnostic approach: as for PV • DDx: if mild and localizedcanbeconfusedwithHailey-Hailey • Therapy : see PV

  19. Pemphigus Foliaceus • Form of pemphigus withsuperficial blisters caused by anti-Dsg1 • Pathogenesis: • Anti-Dsg1, the main desmoglein on the upperepidermis. • More oftendruginducedthanPV,usuallysulfhydryl groups : captopril, penicillamine, peroxicam • Maybecaused by sunburn or paraneoplasticsign

  20. PF • Clinical features: • Scalp, face, chest and back, canprogress to involve large areas with diffuse scale and erosions. • Diagnostic approach: • Clinical • Biopsy ? Not helpful • DIF: superficialdeposition of IgG • ELISA: revealsIgGantibodiesagainst Dsg1 • Medicationhistory • Therapy:sameapproach as PV, but usually more responsive to therapy. Dapsonemaybehelpful

  21. Pemphigus eryhthematosus • Uncommonfeature of pemphigus foliaceuswithadditionalfeatures of lupus erythematosus. • More likely to betriggered by sunlight or medicationsthanotherforms of PF

  22. IgA Pemphigus • PustularacantholyticdermatosiswithintercellularIgAdeposition in epidermis. • Can beassociatedwithgammopathy • Clinical features: • Subcornealpustulardermatosis (Sneddon-Wilkinson disease): broad, annularerythematous patches withperipheralflaccid pustules and central crusting, favours flexures and trunk, nevermouth, pruritic

  23. IgA Pemphigus • Intradermalneutrophilicdermatosis (Huff syndrome): clinicallysimilar, sunflowerlesions • Diagnostic approach: • DIF; showingIgAdirectedagainstkeratinocytes • Therapy : most cases are responsive to dapsone, if not , corticosteroids & other immunosuppressive agents

  24. Paraneoplastic Pemphigus • Most oftenassociatedwithlymphoma, leukemia, thymoma, Castlemantumor. • Not with SCC or adenocarcinoms • Clinical: severe persistent painfulstomatitisextendingfromlips to pharynx, larynx and esophagus, conjunctivalinvolvementmay lead to blindness. • Cutaneous changes are polymorphic

  25. Paraneoplastic Pemphigus • Note: if patient issick and has lesionsresemblingerythema multiforme, lichen planus and a blisteringdisease , behighlysuspicious of paraneoplastic pemphigus. • Histology israrelyhelpful. • Therapy : treat the underlyingtumour , prognosiscorrelateswith the response • No consensus on what immunosuppressive regimen. Good successwith ant-CD20 (rituximab)

  26. Pemphigoid Group • Bullouspemphigoid(BP): • Subepidermalblisteringdiseasecaused by autoantibodies to components of hemidesmosomes in the basement membrane zone (BMZ). • Most commonautoiummunebullousdisease, 1/100000, favourselderly male<female.

  27. BP • Pathogenesis : • Autoantibodiesdirectedagainst 2 hemidesmosomalproteins: • - BP 230 • - BP 180 • BP 180 ismostlikely to be more involved in the initial immune response, sinceitistransmembranous.

  28. BP • Lesscommon causes includedrugs ( benzodiazepine, furosemide, penicillin, sulfasalazine), sunlight, and ionizing radiation. • Clinical : • before blisters develop, pruritus, urticariallesionsmaybepresent, blisters tend to develop in these areas. • Note:alwayskeep BP in mindwhenconfrontedwith an elderly patient with persistent « urticaria ». • Blisters are stable and tense. • Oral mucosalinvolvement in <20%.

  29. BP • Histology : • Prebullouslesions: presence of unexpectedeosinophilsis a good clue. • Latersubepidermal blister formation. • Diagnostic approach: • Labs: elevated ESR, eosinophils, and increasedIgE in 60%. • DIF: best takenfromerythematous area atperiphery, not blister itself; band of IgG & C3 along BMZ. • Indirect IF: usingNaCL split skin • ELISA: identifies ab againstboth BP 230 & 180 in 60-80% of pts.

  30. BP • Therapy: • Steroids ? • Methotrexate 15-20 mg weekly • Mostlywidelyusedsteroid-sparing agents, azathiporine & mycophenolatemofetil.

  31. Cicatricial Pemphigoid • Chronicsubepidermalblisteringdiseasefavoring mucus membrane especiallymouth and eyes. • Patients > 65 years. Women > men

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