bullous dermatosis in dermatology part 2.pptx

Bullous dermatosis

1. VESICULOBULLOUS DISEASES-II By Dr Neetu Chaudhary PG II nd Year PCMS and RC

2. OVERVIEW PEMPHIGOID DISORDERS INTRODUCTION CLASSIFICATION PATHOGENESIS LAB DIAGNOSIS TREATMENT

3. INTRODUCTION Pemphigoid means “like pemphigus “ however no acantholysis is seen , blister formation is subepidermal Defined as a group of immune mediated sub-epidermal blistering disorders Mostly IgG mediated, but IgA mediated forms have been described .

4. Introduction

5. PEMPHIGOID CLASSIFICATION IgG mediated Connective tissue AI disease IgA mediated Bullous Pemphigoid (BP) Gestational Pemphigoid / Herpes gestationis ) Cicatricial Pemphigoid ( CP) or (mucous membrane pemphigoid ) Lichen Planus Pemphigoides Epidermolysis Bullosa Acquisita Anti-p105-pemphigoid Anti-p200 Pemphigoid Anti-p450-pemphigoid IgA Pemphigoid ( Linear IgA Disease and CBDC)

6. BULLOUS PEMPHIGOID INTRODUCTION : Most common Ai blistering disorder seen typically in older age group <60yrs CLINICAL FEATURES : Classic form is characterized by large , pruritic tense fluid filled (serous/hemorrhagic) blisters arising on normal skin or on an urticarial or erythematous base. Site : flexural surface of lower abdomen, thighs Nikolsky sign : Negative Asboe hansen sign: Negative 2 phases : Non bullous phase : lesions could be eczematous , urticarial , serpiginous , targetoid Bullous phase

7. Non Bullous Phase Presentations :

8. Atypical Presentations Dyshidrosiform pemphigoid : Pemphigoid vegetans : intertrigenous Large erosive TEN like Prurigo Nodularis like Vesicular pemphigoid : DH like Erythrodermic Lichen planus pemphigoides Localized Childhood Bullous Pemphigoid

9. Atypical Presentations

10. PATHOGENESIS ANTIGENS : BPAG1 ( BP230 ) and BPAG2(BP180)/XVII Collagen

11. Pathophysiology of Subepidermal blister BP demonstrates circulating and tissue bound autoantibodies against BP180 and BP230. IgG predominates followed by IgE (anti-BP180 ) Serum anti-BP180-NC16A IgG correlates well with disease activity in BP Other conditions such as pemphigoid gestationalis , ciciatricial pemphigoid ,linear IgA bullous dermatosis , Lichen planus pemphigoides show similar Ai response to BP180

12. Pathogenesis

13. Bullous Pemphigoid Etiology: Genetic : HLA-DQB1 0301 allele has been associated with BP Neurologic disease: studies show patients with Dementia , Stroke , Parkinson’s disease have higher risk Malignancy : conflicting data , recent studies suggest link b/w BP and hematologic malignancies Histopathology : Bullous lesion/small vesicle : Intense to sparse ,Superficial dermal infliltrate of eosinophils , neutrophils ,lymphocytes, monocytes and macrophages . Urticarial lesion : Superficial dermal inflitrate of Lymphocytes , monocytes , macrophages , eosinophils and eosinophilic spongiosis

14. Bullous Pemphigoid IMMUNOFLUORESCENSE DIRECT I/F : SHOWS LINEAR IgG and C3 along BMZ INDIRECT I/F : More sensitive for detecting anti BMZ antibodies Use of 1M salt split skin: Helps to differentiate b/w EBA ( Ab bind dermal side )and BP ( Ab bind epidermal side )

15. IMMUNOFLUORESCENSE BullousPemphigoid

16. BULLOUS PEMPHIGOID DIFFERENTIAL DIAGNOSIS : IMMUNE MEDIATED : Linear IgA disease , DH , PG , MMP, EBA, Pemphigus NON IMMUNE : EM, TEN , ACD, SSSS, BULLOUS IMPETIGO, FRICTION BLISTERS, HAILEY HAILEY Ds CLINICAL COURSE AND PROGNOSIS : Waxing and waning course Occasional spontaneous remission

17. Treatment Of Bullous Pemphigoid MILD/LOCALIZED DISEASE: First line : Superpotent corticosteroids Second line : Oral corticosteroids Minocycline , Doxycycline or tetracycline alone or in combination with nicotinamide Erythromycin Dapsone Topical immunomodulators ( tacrolimus ) Extensive/Persistent Cutaneous lesions FIRST LINE : Superpotent topical corticosteroids Oral corticosteroids 2. SECOND LINE Azathioprine (0.5-2.5mg/kg) Mycophenolate Mofetil (15-3g/day) Methotrexate (7.5-15mg/wk) Chlorambucil (2-4mg/kg) Cyclophosphamide IvIg (in steroid resistant cases) Plasmapheresis Omalizumab Rituximab ( in combi with corticosteroids)

18. MUCOUS MEMBRANE PEMPHIGOID INTRODUCTION: ALSO K/N AS CICATRICIAL Pemphigoid Rare chronic subepidermal immunobullous disease characterized by erosive lesions of mucous membranes and skin ,might result in scarring Etiology and Pathogenesis : Female gender, advanced age , HLA DQB1 0301 allele , rarely provoked by prescription drugs, trauma. Pathogenesis : MMP is a disease phenotype associated with heterogenicity in antigens . BP180, BP230 , integrinB4 and alpha 6, Laminin 332 , Type VII collagen

19. MMP: CLINICAL FEATURES ORAL CAVITY : In over 85% patients , often 1 st to be affected , self limitimg Desquamative gingivitis, erosions , ulcerations of buccal mucosa , palate , gingiva , lips tongue resulting in delicate pattern of reticulate scarring Psuedomembrane Pain , bleeding inability to eat certain food Gingival recession and loss Mild scarring or atrophy , intraoral adhesions , loss of teeth ( rare ) OCULAR : (in 65% of patients)  106 Nonspecific conjunctivitis , Erosions , corneal damage Photophobia and photosensitivity, dryness Progressive process leading to scarring, s ymblepharon , ankyloblepharon , trichiasis,entropion , Blindness in close to 15% of patients Skin : 25–30% of patients Localized erythematous plaque near affected mucosal surfaces, generalized bullous eruption particularly on the head and upper body, or vegetating lesions occasionally  Scarring , cicatricial alopecia on the scalp 

20. MMP: CLINICAL FEATURES NOSE : In 20–40% of patients Discharge, erosion, excessive crust , Scarring Breathing difficulty Larynx : In 5–15% of patients Sore throat, hoarseness Scarring, stenosis of airway Breathing difficulty Oesophagus : In 5–15% of patients Dysphagia , odynophagia , esophageal reflux Stricture formation , Disability in eating , Death Anogenital area : In 20% of patients Erosion and ulceration , Bleeding Pain , Dysuria , Sexual dysfunction

21. MMP : DIAGNOSIS Histopathology: demonstrates the subepithelial split with an inflammatory infiltrate of eosinophils , lymphocytes and neutrophils Direct Immunofluorcense : shows a continuous, linear deposition of IgG and/or C3, and sometimes IgA along the BMZ Indirect immunofluorescence (IIF) Autoantibodies to BPAg2 and integrin subunits α6/β4 bind the epidermal side (upper lamina lucida ), Autoantibodies to epiligrin and type VII collagen bind to the dermal side on salt-split tissue (lower lamina lucida ).

22. TREATMENT MILD INVOLVEMENT MOUTH Topical corticosteroids , Topical calcineurin inhibitors ,I/L steroids NOSE Saline irrigation,Topical corticosteroids and lubricants ANOGENITAL Topical corticosteroids , Topical calcineurin inhibitors SKIN Topical corticosteroids , Topical calcineurin inhibitors MODERATE INVOLVEMENT Local care measures as above Dapsone 50-200mg OD alone or in conjunction with Prednisolone 20-60mg OD

23. Treatment SEVERE INVOLVEMENT Local care measures Prednisone 1–2 mg/kg/day; or dexamethasone 100 mg/day for 3 days (pulse therapy ) Mycophenolate mofetil : 35–45 mg/kg/day  Azathioprine Intravenous immunoglobulins : 2 mg/kg/cycle every 4 weeks Cyclophosphamide : 1–2 mg/kg/d for progressive, organ- or life-threatening patients  Methotrexate : 12.5–22.5 mg/wk Cyclosporine: 100–250 mg/day  TNF α antagonist ( etanercept ) CD-20 monoclonal antibody ( rituximab

24. Treatment

25. PEMPHIGOID GESTATIONIS Introduction:  Also known as gestational pemphigoid /Herpes gestationis is a rare pregnancy-associated autoimmune skin disorder Occurs in 2 nd 3 rd trimesters and postpartum period associated with premature delivery and a risk of  low birth weight , maternal prognosis is good Pathogenesis : Immunologically mediated, and linear deposition of C3, with or without immunoglobulin ( Ig ) G,  is found at the dermal­epidermal junction Target antigens are BP180 (main) and BP230

26. PEMPHIGOID GESTATIONIS Clinical Features : presents with urticarial lesions followed by vesicular lesions  on the trunk and extremities PG  includes periumbilical skin(unlike PUPP) Diagnosis : DIF with C3 in a linear  band at the dermal­epidermal junction is pathognomonic for PG

27. MANAGEMENT OF PEMPHIGOID GESTATIONIS FIRST LINE : Topical steroids and  a systemic antihistamine. First-generation antihistamines Systemic corticosteroids Plasmapheresis or IV immunoglobulin (in cases where prolonged treatment with corticosteroids is contraindicated )

28. Epidermolysis Bullosa Acquisita INTRODUCTION : EBA is a rare, acquired,subepidermal bullous disease associated with autoimmunity ( IgG antibodies )to type VII collagen present in anchoring fibrils usually occurs in adult patients, pediatric cases have been  reported. Cutaneous manifestations are heterogeneous : 5 clinical  presentations Non-inflammatory forms ( eg classic form/ mechanobullous form) and inflammatory forms( eg BP like EBA ) have been identified No family history of a bullous disorder

29. Epidermolysis Bullosa Acquisita CLINICAL FEATURES : CLASSIC FORM /MECHANOBULLOUS FORM :   Most common N on-inflammatory bullous disease with an acral distribution that heals with scarring and milia formation.  Resembles porphyria cutanea   tarda (PCT) Scarring alopecia and some degree of nail dystrophy  BULLOUS PEMPHIGOID LIKE PRESENTATION widespread, inflammatory vesiculobullous eruption involving the trunk, central body, and skin folds , extremities surrounded by inflamed or urticarial skin

30. Epidermolysis Bullosa Acquisita MUCOUS MEMBRANE  PEMPHIGOID LIKE : erosions and scars of mouth,  upper esophagus,conjunctiva , anus, or vagina with or  without similar lesions on the glabrous skin. BRUNSTING PERRY  PEMPHIGOID LIKE   localized to the head and  neck and characterized by residual scars, subepidermal bullae , IgG deposits at the DEJ, and minimal or  no mucosal involvement. IMMUNOGLOBULIN A  BULLOUS DERMATOSIS LIKE manifested by a subepidermal bullous eruption, a  neutrophilic infiltrate, and linear IgA deposits at the  BMZ

31. HISTOPATHOLOGY : shows a subepidermal   blister and a clean separation between the epidermis  and dermis. INDIRECT SALT SPLIT I/F : If the antibody labels  the dermal side of the separation, the patient usually  has either EBA or bullous SLE and not BP DIRECT SALT SPLIT SKIN i /f effectively  places EBA antigen  (and any associated immune deposits) on the dermal  floor of the separation IMMUNOELECTRON  MICROSCOPY : “gold standard” :immune deposits within the  sublamina densa zone of the cutaneous BMZ

32. TREATMENT OF EBA Colchicine 0.6-3.0 mg/d Cyclosporine A (6 mg/kg/d ) Dapsone (100-300 mg/d) Cytoxan 50-200 mg/d Prednisone 1.0-1.5 mg/kg Intravenous immunoglobulin 3 g/kg divided over 5 d Infiximab 5 mg/kg at 0, 2, 4, and 6 wk Rituximab

33. LINEAR IgA DISEASE & CHRONIC BULLOUS DISEASE OF CHILDHOOD INTRODUCTION: Also known as IgA pemphigoid . LABD has a bimodal peak of age distribution. Linear IgA Dermatosis   is a rare blistering disease with onset typically after  fourth decade of life. CBDC are blistering disorder of childhood presenting  predominantly in children younger than 5 years  of age Drug induced Linear IgA disease : associated with Vancomycin

34.   LINEAR IgA DERMATOSIS   EPIDEMIOLOGY : adults  at the 4th  decade of life; slight female  predominance CLINICAL FEATURES :Similar to DH ;annular or grouped  papules, vesicles,  and bullae on  extensors, including elbows, knees,  and buttocks; pruritus is less severe MUCOSAL INVOLVEMENT : in up  to 70% of  patients DISEASE ASSOCIATIONS  AND TRIGGERS : ulcerative  colitis; ultraviolet  light is the chief  physical trigger COURSE : Unpredictable

35. Drug-induced  linear IgA Dermatosis EPIDEMIOLOGY : Adults Clinical Features : Vary from erythema   multiforme­like ,  to toxic epidermal  necrolysis­like   with widespread  bullae ; Koebner   phenomenon may  be present Mucosal  involvement :less  prominent  Association and Triggers: Vancomycin most  commonly implicated; interferon- α,  influenza vaccine,  lithium, phenytoin ,  TMP-SMX , furosemide , atorvastatin ,  captopril,diclofenac ,  ketoprofen , and  infiximab Course : Rechallenge   of drug may  not result in  recurrence

36. Chronic  Bullous   Disease of  Childhood EPIDEMIOLOGY :< 5 years of age;  slight female  predominance CLINICAL FEATURES : Tense bullae in a  “cluster-of-jewels”  appearance;  collarette of blisters may be present Mucosal  involvement : noted,  but less  Association and Triggers: infectious  mononucleosis and  Paecilomyces lung  infection in the setting of chronic granulomatous disease COURSE :Self-limited;  remission  within 2 years  of onset

37. INVESTIGATIONS HISTOPATHOLOGY : subepidermal bulla with collections of neutrophils along the basement membrane , often at the papillary tips DIF : homogenous band of IgA is present at DEJ Linear IgA : 40% have C3, 24% have IgG , all have IgA Drug Induced IgA : all have IgA CBDC : 9% have IgG , may have C3, all have IgA

38. PATHOGENESIS AND DIAGNOSTIC CRITERIA The target antigen of the IgA autoantibodies is a 120-kd secreted portion of the BP180 antigen There have been reports of cases where other antigens with molecular weights of 285, 230, 180, 145, 100, and 97 kd DIAGNSOTIC CRITERIA OF LABD 1 ) a vesicular or bullous eruption of skin and occasionally mucous membranes 2) a subepidermal vesicle with a predominantly neutrophilic infiltrate on histologic examination 3) basement membrane zone–specific IgA antibody deposited in a linear pattern

39. TREATMENT   LINEAR IgA Disease Dapsone , sulfapyridine ; response  within 24-48 h L ow-dose prednisone may  suppress blister  formation  Drug-induced  linear IgA : Discontinuation of  causative drug sometimes  initiation of dapsone is helpful Chronic  bullous   disease of  childhood Dapsone , sulfapyridine small doses  of prednisone  may be of use. mycophenolate   mofetil as a  steroid-sparing  agent topical  tacrolimus

40. Lichen P lanus Pemphigoides Introduction Coexistense of Bullous Pemphigoid with Lichen Planus Also k/n as Bullous LP Middle age individuals Clinical features : benign, tense blisters and lesions of lichen planus (usually persistent) on top of lichen planus lesions or on clinically normal skin. Predilection sites: the extremities, trunk and oral mucosa Immunofluorescence : Linear deposits of IgG at the DEJ

41. Anti-p200 P emphigoid Often resembles BP, could resemble dermatitis herpetiformis , linear IgA disease or EBA. Could involve mucous membranes. Often coexisting psoriasis. (rapid response to treatment) Linear IgG and C3 at the dermal-epidermal junction. IDIF : Ab bind Dermal side ,n-serrated

42. OTHER RARE PEMPHIGOID DISORDERS Anti-p105-pemphigoid Bullae and erosions on mucous membrane and skin, resembling toxic epidermal necrolysis or pemphigus vulgaris Linear IgG and C3 deposition at the BMZ Indirect Immunofluroscense : Ab bind Dermal side Anti-p450-pemphigoid : only 1 case described in literature

43. Bullous Pemphigoid MMP Pemphigoid Gestationis LP Pemphigoides Epidermolysis Bullosa Acquisita MMP MMP LOCATION OF ANTIGENS IN PEMPHIGOID DISORDERS IN BMZ

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