Vesiculobullous disease

1. Vesiculobullous disease

9. Pemphigus groups

10. Classification Pemphigus vulgaris : Pemphigus vegetans : Localized Drug-induced Pemphigus foliaceus Pemphigus erythematosus : Localized Fogo selvagem : Endemic Drug-induced

11. Classification Paraneoplastic pemphigus IgA pemphigus : Sub-corneal pustular dermatosis Intraepidermal neutrophilic IgA dermatosis

12. Pemphigus Two major types: Vulgaris and foliaceus. Pemphigus vulgaris: Erosions on mucous membranes and skin; flaccid blisters on skin Pemphigus foliaceus: Crusted, scaly skin lesions Pathology. Pemphigus vulgaris: Suprabasilar acantholysis Pemphigus foliaceus: Sub-corneal acantholysis

13. Causes Common causes : Pemphigus is an autoimmune disease Caused by autoantibodies against keratinocyte proteins desmoglein-1 and desmoglein-3

15. Causes Rare causes : Penicillamine: 9% of rheumatoid arthritis patients develop pemphigus Captopril, rifampin, and meprobromate have been associated with pemphigus

16. Contributory or predisposing factors Pemphigus can occur in association with myasthenia gravis Certain human leukocyte antigen (HLA) types predispose: HLA DR4, DR6, and A10

17. Age 40-60 years Rare in children Gender Occurs in equal numbers in men and women. Race More common in Ashkenazi Jews and in people of Mediterranean decent. Genetics Associated with HLA DR4, DR6, and A10.

18. Symptom Painful blisters in the mouth appear first, and may lead to weight loss Blisters occur on the skin and mucosal areas, especially where trauma and pressure applied Large areas of affected skin seep and crustation Fever and malaise Pruritus normally absent

19. Signs Skin or mucosae can just shear off leaving widespread painful erosions Nikolsky's sign - epidermis is easily detached from underlying skin

20. Flaccid bullae of various sizes Bullae arise from 'healthy' skin, rupture, and leave crusting and denuded skin Any area of stratified epithelium can be affected

21. Signs Lesions often appear first in the mouth prior to skin involvement Extent of skin and mucosal involvement varies Eyes, nasal mucosa, and genitalia may be affected Lesions may occur in oropharynx and upper esophagus Pyrexia and systemic features common Secondary infection is common

22. Skin biopsy Acantholysis and intraepidermal separation of keratinocytes, is likely to have pemphigus vulgaris. Diagnosis is confirmed by direct or indirect immunofluorescence.

26. Don't miss! Pemphigus vulgaris should be suspected in any bullous or chronic mucosal ulceration Widespread skin involvement with erosions and bullae requires urgent hospitalization and systemic treatment as morbidity and mortality are high

27. Don't miss! Severe oral ulceration spreading past the vermilion border should raise suspicion of paraneoplastic pemphigus

28. Tzanck test Acantholytic cells Cause of abnormal result Pemphigus vulgaris Other bullous skin diseases

29. Skin biopsy Intraepidermal separation of keratinocytes, forming a split between lower and upper portions of epidermis Acantholysis - separation of individual epidermal cells from surrounding cells Mild or absent inflammatory infiltrate

30. DIF Direct immunofluorescence shows immunoglobulin G (IgG) on the keratinocyte cell surface of the patient's skin Direct detection of tissue-bound antikeratinocyte (desmoglein) antibodies on perilesional skin of the patient Antihuman IgG and C3 binding detected at epidermal cell surfaces; no deposition along basement membrane

32. IIF Indirect immunofluorescence shows IgG in patient's serum that binds the cell surface of normal keratinocytes. Autoantigens are desmogleins (transmembrane desmosomal adhesion molecules)

35. Cause of abnormal result Pemphigus vulgaris. Other pemphigus variants can yield a positive test

36. Treatment

37. Goals Prevent new lesions forming Prevent scarring Prevent secondary infections Minimize effects of disease on patient's lifestyle

38. Immediate action Patients with widespread disease should be referred for hospitalization and immediate treatment, as morbidity and mortality are high If secondary skin infection is suspected, immediate antimicrobial treatment should be commenced Fluid and electrolyte normalization should be achieved

39. Aim of treatment is to prevent eruption of new lesions

40. Specific therapy depends on the extent and severity of the disease Corticosteroids: topical steroids such as triamcinolone, clobetasol propionate, and fluticasone propionate can be used in mild disease But most patients require systemic steroids, which have adverse effects

41. Nonalkylating agents (e.g. azathioprine, mycophenolic acid, cyclosporine) are steroid-sparing agents

42. Alkylating agents (e.g. cyclophosphamide, chlorambucil) are steroid-sparing agents Antibiotics (e.g. tetracycline) have been used in pemphigus, usually in combination with other agents

43. Local antiseptics and analgesics can give symptomatic relief Anti-inflammatory drugs, such as gold or dapsone, are disease-modifying drugs for severe cases of pemphigus vulgaris

44. Other therapies include plasmapheresis, an inpatient procedure performed by a specialist. It is used only for refractory cases and results are variable

46. Coexisting disease Thymoma, carcinoma,Myasthenia gravis The presence of lymphoproliferative disorder should heighten suspicion of paraneoplastic pemphigus

47. Coexisting medication Certain medications can cause pemphigus and should be stopped immediately; most likely is penicillamine for rheumatoid arthritis Most patients with drug-induced pemphigus go into remission after they stop taking the offending medication

52. Bullous pemphigoid

54. Pathology

60. Treatment Topical steroid Systemic steroid Methotrexate Azathioprine Cyclophosphamide Dapsone IVIG Plasmapheresis