Autoimmune Blistering Diseases

1. Autoimmune Blistering Diseases Idiopathic, chronic blistering diseases are included here.

2. Pemphigus Pemphigus patients have IgG autoantibodies against intercellular material (cell membrane?) Antigen is a 130 kd polypeptide linked to plakoglobulin on binding sites Patients have both of circulating antibodies (in serum) and deposited antibodies (in epidermis)

3. Antibody titration Circulating antibody titration is correlated with disease activity. When disease improves titration decreases and when disease worsens titration increases.

4. IgG immunoglobulins are deposited in Stratum spinosum, above stratum basale (suprabasal) or in stratum granulosum (subcorneal).

5. Acantholysis Intercellular material dissolves after antigen-antibody reaction. Desmosomes try to bind keratinocytes weakly in this phase. But first trauma leads to disrupt of desmosomes and keratinocytes becomes free. This entity is called acantholysis.

6. Space, between keratinocytes is filled by fluid and blister formation occurs. Blister is situated in epidermis (intraepidermal blister). The roof of the blister consists of some superficial epidermal strata, so, roof of the blister is easily disrupted and blister opens. Secondary elementary lesion of the pemphigus blister is erosion. Erosion heals without scarring.

7. Clinical Types of Pemphigus Pemphigus vulgaris (Suprabasal) Pemphigus vegetans (Suprabasal) Pemphigus foliaceus (Subcorneal) Pemphigus erythematosus (seborrheicus) (Subcorneal)

8. Pemphigus vulgaris Disease generally begins in adolescent ages. Male/female ratio is equal. Initial lesions are almost always in the mouth. Mouth blisters easily open and remain painful erosions.

9. Pemphigus vulgaris The erosion can be differentiated from other diseases by the lack of spontaneous healing. The localized phase lasts 2-3 months. During this period the patient is seen by specialists interested in oral area and is frequently misdiagnosed.

10. Pemphigus vulgaris Later, blisters form on the skin due to trauma. These open and become erosions. Generally erosions dominate the whole body.

11. Pemphigus vulgaris There are no subjective symptoms on the skin. Intact blisters can be seen on non-traumatized skin. Blisters typically appear on normal skin without erythema and are fragile, slack and shrivel up.

12. Pemphigus vulgaris Wide areas of erosions are seen in a severe case.

13. Pemphigus vulgaris The skin around the blister has normal appearance macroscopically, but intercellular material has dissolved there and desmosomes are only binding structure.

14. Pemphigus vulgaris • When one press at the top of the blister, desmosomes disrupt by blister fluid pressure. So, blister widens through the normal skin (1). • After hours of a frictional trauma on perilesional skin, a blister occurs on the trauma site (2). • One can easily pull the blister roof along the normal skin, like a peach peeling (3).

15. Pemphigus vulgaris These three entities are called as "Nikolsky phenomenon" and shows acantholysis.

16. Pemphigus vulgaris Smear material taken from the blister floor is mounted on a slide and stained by Giemsa (Tzanck smear). One can see a typical keratinocytes with large and dark stained nucleus and narrowed cytoplasm. These cells are also called as "Tzanck cells" or "acantholytic cells". This phenomenon shows acantholysis.

17. Pemphigus vulgaris Definitive diagnosis should be made by intraepidermal blister formation and acantholysis.

18. Pemphigus vulgaris Pemphigus vulgaris have the worst prognosis in pemphigus group. Patients die in one year if they do not treat. Recent mortality rate is 25-40% and mortality causes are the side effects of high dose of corticosteroids mainly. %25-40

19. Pemphigus vegetans Initial features are the same with pemphigus vulgaris as blisters and erosions in the mouth and skin. But pemphigus vegetans patients develop vegetating masses on inguinal and axillary folds. Prognosis is severe, but milder than pemphigus vulgaris.

20. Pemphigus foliaceus There are generalized subcorneal blisters. The blister roof consists only stratum corneum, so blister roof is very thin. Blister fluid is easily reabsorbed and blister roof is desquamated. Blisters appear on an erythematous base. In the scaly phase pemphigus mimics an erythemato-squamous disease or an erythroderma. Practically mouth is not involved.

21. Pemphigus erythematosus (seborrheicus) Subcorneal blisters are localized on seborrheic areas as face, midline of the chest and back. The lesions mimic seborrheic dermatitis, but scales are not as greasy as seborrheic dermatitis.

22. Paraneoplastic pemphigus Develops due to an underlying malignancy. It is most frequently seen with hematologic malignancies such as non-Hodgkin lymphoma, chronic lymphocytic leukemia.

23. Paraneoplastic pemphigus The most important clinical sign is hemorrhagic painful oral erosions. Skin lesions are polymorphic and diagnosis may be difficult.

24. Paraneoplastic pemphigus • It is similar to erythema multiforme due to the polymorphic symptoms. The other similar diagnosis is bullous pemphigoid. This disease is characterized by marked pruritus. • This type of pemphigus does not respond well to treatment.

25. Drug Induced Pemphigus • Develops due to drugs such as D-penicillamine, captopril. • Skin lesions are similar to pemphigus foliaceus. Rarely, lesions of pemphigus vulgaris may be seen. • Prognosis is well in cases due to drugs containing sulphydril group. Resolution occurs when the drug is discontinued.

26. Treatment of Pemphigus Systemic corticosteroids are given to pemphigus patients. Initial dose must be at least 120 mg/day prednisolone or equivalent dose of another steroid. Dose may be increased until healing of the erosions and ceasing of the blister crops. After the control of the disease dose should be slowly decreased to maintenance dose prevents the exacerbations. Classically patient must use corticosteroid lifelong.

27. Treatment of Pemphigus • Drugs that can be combined with steroids: • Azathioprine: 50-200 mg/day (Safe) • Cyclophosphamide: 50-200 mg/day(Toxic) • Methotrexate: 15-30 mg/week • Mycophenolate mofetil (In trial phase) These drugs are not used alone but combined with steroids. Such combination proves smaller corticosteroid doses. In combined therapy both of the drugs are decreased together. At the last cytostatic is stopped and steroid in the maintenance dose is used lifelong.

28. Pemphigoid Linear IgG is deposited on the junction between epidermis and dermis. Epidermis detaches from dermis and subepidermal blister occurs. (Subepidermal blister)

29. Pemphigoid • The roof of the blister is made by whole epidermis. So, the blister is not easily open and tight, can reach to very large diameters.

30. Bullous pemphigoid Especially people above 70 years old are involved. Provoking factors are drugs such as furocemide, 5-fluorouracil and penicilline, and malignancies.

31. Bullous pemphigoid Firstly erythema, papule with edema, vesicles or blisters appear on a scar belongs a vaccine or burn, or on umbilicus as a localized phase. Wrong diagnosis may be eczema, urticaria, erythema multiforme at this phase because of the existence of pruritus.

32. Bullous pemphigoid • After several months the disease turn into generalized phase. Solitary or grouped large blisters arranged as a circle on body and/or extremities.

33. Bullous pemphigoid Prognosis is better than pemphigus and 40 mg/day prednisolone is useful and sufficient for the patients above 70 years old. Steroids may be used higher doses for the patient younger than 70 years old.

34. Cicatricial pemphigoid Females are involved frequently. Mainly orifices and around of orifices are involved. The disease is mainly localized to head. Attacks and remissions while remain scars after attacks are seen.

35. Cicatricial pemphigoid Scars become severe after every attack and lead to function disturbances. Eye involvement may lead to blindness.

36. Cicatricial pemphigoid Local or systemic steroids, cytostatics or dapsone may be tried, but responses are unpredictable.

37. Dermatitis herpetiformis Granular IgA is seen at the top of dermal papillae. So little detachments firstly appear on these areas and are filled by serous fluid. (Subepidermal blister)

38. Dermatitis herpetiformis As a result of this phenomenon erythematous and edematous papules appear. Larger detachments lead to vesicle or blister formation in the later phases. Patients have severe itching. Two dermatoses with the most severe itching are dermatitis herpetiformis and scabies in dermatology.

39. Dermatitis herpetiformis The disease begins in young adolescents. Firstly erythematous and edematous papules (mimicking urticaria), secondly grouped vesicles (mimicking herpes simplex) appear. And then vesicles either transform pustules or blisters.

40. Dermatitis herpetiformis Blisters are rarely seen in dermatitis herpetiformis. Bleeding, crusting, excoriation and secondary infection create a polymorphism because of severe scratching. In this phase scabies can be thought in differential diagnosis. But there are not family history and specific features of scabies in dermatitis herpetiformis.

41. Dermatitis herpetiformis Eosinophilia and iodine sensitivitysupport diagnosis but one can made diagnosis without these features. All of the patients have celiac disease, 75% of the patients show clinical symptoms, and in the 25% of the patients course of the disease is subclinical.

42. Dermatitis herpetiformis Prognosis is good. Specific therapy with dapsone is successful. Therapy begins with 200 mg/day dapsone and gluten free diet in adults and then dapsone is tapered according to clinical cure. Gluten free diet lasts lifelong.

43. Chronic bullous dermatosis of childhood There are linear IgA deposits between dermis and epidermis. A subepidermal blister is formed as a result of dermo-epidermal detachment. (Subepidermal blister)

44. Chronic bullous dermatosis of childhood Clinical features are the same with bullous pemphigoid, but the patients are children. Ninety percent of the patients are under the 6 years old and the disease lasts in 2-3 years. Pruritus is not a unique symptom.

45. Chronic bullous dermatosis of childhood Dapsone (sulfone) and corticosteroids are useful in small doses.

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