1 / 80

HISTOPATHOLOGY OF IMMUNOBULLOUS DISORDERS

HISTOPATHOLOGY OF IMMUNOBULLOUS DISORDERS. DR.SHUBHA. INTRAEPIDERMAL BULLOUS DISORDERS. TARGET ANTIGENS. Located in the desmosomes the most prominent adhesion junction in stratified squamous epithelium.

fidels
Download Presentation

HISTOPATHOLOGY OF IMMUNOBULLOUS DISORDERS

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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.

  4. 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.

  5. 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)

  6. 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”.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

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

  12. 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 .

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

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

  19. 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.

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

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

  22. 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

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

  24. 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 .

  25. 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 %.

  26. 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.

More Related