HISTOPATHOLOGY OF IMMUNOBULLOUS DISORDERS

1. HISTOPATHOLOGY OF IMMUNOBULLOUS DISORDERS DR.SHUBHA

2. INTRAEPIDERMAL BULLOUS DISORDERS

3. TARGET ANTIGENS • Located in the desmosomes the most prominent adhesion junction in stratified squamous epithelium. • Desmosome complex contains desmogleins and desmocollins as transmembrane components and desmoplakins , phakoglobins as intracellular components.

5. PEMPHIGUS VULGARIS • Autoimmune disease characterised by large flaccid blisters ;primarily in older individuals . • Scalp, face, flexures, groin and pressure points. • Lesions characteristically involves the oral mucosa. • It is important that early blisters preferably smaller ones are selected for biopsy.

6. Greek pemphix-blister or bubble • Disruption of intercelular cementing substance • Most common 80% • Fourth to sixth decade • 50-70% mucosal lesions • Bullae rupture spontaneously, no tendency to heal spontaneously • Nikolsky’s sign (Asboe-Hansen sign)

9. HISTOPATHOLOGY • Target antigen is desmoglein 3 which is 130 kD localised in spinous layer and in mucus membrane.Early blisters; smaller in size selected. • Earliest change – spongiosis in lower epidermis. Acantholysis is suprabasal ,may extend into the adenexa. • Basal keratinocytes though seperated from one another remain attached to the basement membrane ;”Row of tombstones appearance”.

15. IMMUNOFLOURESCENCE • DIF -Edge of the blister with intact sorrounding skin is selected; transported in michael’s medium. • Very sensitive and reliable test esp. in oral lesions. • Squamous intercellular or cell surface IgG deposition seen in 95 % of cases. • IDF – IgG antibodies in 80 % of cases using monkey oesophagus as substrate.

17. PEMPHIGUS VEGETANS • Rare variant of pemphigus vulgaris . • Vegetating lesions in flexures. • Initially bullae or pustule • Two types – Neumann and Hallopeau. • Antibodies against Pemphigus vulgaris antigens – 130 KDa.

19. HISTOPATHOLOGY Vegetating lesions are acanthotic , hyperkeratotic and papillomatous. Suprabasal clefts contain acantholytic cells and eosinophils. Intraepidermal eosinophilic abscesses seen in older lesions. Hallopeau lesions – pustules on normal skin with acantholysis and small suprabasal clefts. Dermis – heavy infiltrate of lymphocytes and eosinophils with few neutrophils.

21. IMMUNOFLOURESCENCE • DIRECT -Intercellular deposition of IgG in all reported cases. • INDIRECT -Positive in most of the patients. • Differential diagnosis – Pyoderma vegetans ; seen in association with inflammatory bowel disease. Neutrophils are more common . Eosinophilic abscesses and acantholytic cells are rare.Mimicks pemphigus vegetans clinically and histologically.

22. PEMPHIGUS FOLIACEOUS • Subcorneal blister • Ig G antibodies against desmoglein 1 • Les severe, crusted moist, scaly lesions in seborrheic distribution • Very transient • Better prognosis

23. Early lesions – Vacoulation in intracellular spaces in the upper level of epidermis which coalesce to form clefts and bullae in granular layer or immediately beneath the stratum corneum. • Bullae contain fibrin , acantholytic cells and neutrophils. • Dyskeratotic cells in granular layer important. • Dermis shows mixed infiltrate of eosinophils and neutrophils .

28. IMMUNOFLOURESCENCE • DIRECT - Intercellular IgG and C3 deposition throughout the epidermis or restricted to upper part of epidermis. • INDIRECT– Positive in 85 % of sera. • Pemphigus foliaceous antibody DESMOGLEIN 1 is expressed more in the upper layers of epidermis. • Staphylococcal scalded skin syndrome

29. DIFFERENTIAL DIAGNOSIS • Marked dyskeratosis distinguishes pemphigus foliaceous from p.vulgaris.ultrastructurally , there is early loss of intercellular cement substance in lower half of epidermis, perinuclear homogenisation of tonofilaments in mid epidermis. • Impetigo • Subcorneal pustular dermatosis • SSSS.

30. PEMPHIGUS ERYTHEMATOSUS • Senear Usher syndrome • Variant of pemphigus foliaceous. • Clinically resembles lupus erythematosus ; erythematous plaques and patches in butterfly distribution . • HPE – Light microscpic changes similar to P. foliaceous. Rarely interface dermatitis in older lesions. • Direct immunoflourescence – squamous intercellular deposition of IgG , granular IgG and IgM at dermoepidermal junction.ANA positive in 30 – 80 % of cases.

31. IgA pemphigus • Pruritic pustular eruption in middle aged and elderly characterised by intercellular IgA deposition and intraepidermal neutrophils. • Two types –1. Subcorneal pustular dermatosis type – subcorneal vesicles and pustules with minimal acantholysis.2. intraepidermal neutrophilic dermatosis • Antibodies against Desmocollin -1 in SCPD type and Desmoglein 2 in latter type.

33. PARANEOPLASTIC PEMPHIGUS • Most common neoplasm – Nonhodgkins lymphoma , CLL , castlemans tumour ,thymomas and sarcomas. • Histological pitcure depends on various clinical presentations – unique combination of erythema multiforme like , lichen planus like , pemphigus vulgaris like and pemphigoid like features.

35. HISTOPATHOLOGY • Suprabasal acantholysis. • Basal apoptosis • Interface dermatitis (erythema multiforme like ) • With or without lichenoid inflammation. • desmoplakin

36. IMMUNOFLOURESCENCE • DIRECT – Squamous intercellular deposition of IgG in perilesional skin ; At dermoepidermal junction linear deposition of C3 and IgG seen. • IgG antibodies directed against desmoplakins , envoplakins and desmogleins.

37. Endemic P.Foliaceous • Bite of black fly • Drug • Penicillamine,captopril, penicillin,rifampicin • Neonatal pemphigus • Transplacental transfer, resolves in 2 weeks

38. Treatment • Systemic steroids • DCP • Dapsone • Methotrexate • Azathioprine • Ciclosporine • plasmapheresis

39. SUBEPIDERMAL BLISTERING DISORDERS • BULLOUS PEMPHIGOID – • Elderly • Preceded by pruritis by 2-3 weeks • Tense bullae on flexures • Face and scalp relatively spared • Heals spontaneously with PIH • Nikolsky negative • Mucosa rare

40. Underlying malignancy-gastric carcinoma • DM, RA, psoriasis • Better prognosis than pemphigus • Topical and systemic steroids

41. Antibodies react with two antigens ; 230 –kD(BPAg1) , 180kD (BPAg2). • Blister is subepidermal with intact and often viable epidermis forming the roof. • Early lesions show papillary edema with cell rich or cell poor perivascular lymphocytes and eosinophilic infiltrate. Eosinophilic spongiosis or microabscesses may be seen. • Blister lumen contains inflammatory cells .

46. IMMUNOFLOURESCENCE • Direct -Linear C3 deposition at dermo – epidermal junction in 100 % of cases and IgG in 65 – 95 % .IgG is located within lamina lucida and specifically bound to hemidesmosomes. • Salt split technique – IgG at roofor floor of artificially induced blister. • Indirect – circulating IgG antibodies to basement membrane zone in 70 – 80 %.

50. MUCUS MEMBRANE PEMPHIGOID • Subepidermal blister that may extend down the adenexa. • Neutrophils , lymphocytes and histiocytes predominate in the infiltrate with less eosinophils. • Late lesions –Lamellar fibrosis is the hallmark. • Mucosal lesions show cell rich lichenoid infiltrate.