Skin Disorders

Here is an article I wrote about pemphigus antibodues in CLL.

Oppenheim [1910] probably reported the first patient with CLL and a pemphigoid-like skin disease, although the 2 patients reported by Sachs [1921] had a more certain diagnosis of CLL. A clear diagnosis of antibody-proven bullous pemphigoid in association with CLL was not achieved until 1974 when [Cuni et al] described a single case. In their review of the literature they discovered 16 other cases of CLL with either bullous or vesicular skin lesions. Goodnough and Muir [1980] reported the next case 6 years later, but in the same year Laskaris et al [1980] reported two cases of CLL associated with oral pemphigus. The question as to whether pemphigus or pemphigoid is associated with CLL was resolved when Anhalt et al [1990] described paraneoplastic pemphigus. The clinical features were of painful erosions of the oropharynx, and vermilion borders of the lips that were resistant to conventional treatment. There was a severe pseudomembranous conjunctivitis. Pruritic, polymorphous cutaneous lesions included confluent erythema with skin denudation, and papules on the trunk and extremities forming target lesions with central blistering. Cases had often been previously diagnosed as pemphigus vulgaris or erythema multiforme. Histologically, three elements were observed: suprabasilar intraepithelial acantholysis, necrosis of individual keritinocytes and vacuolar interface change. Immunofluorescence studies revealed the presence in the serum of antibodies that reacted with the intracellular spaces, such as is seen in pemphigus vulgaris or pemphigus foliaceous. However, direct immunofluorescence studies of the skin also demonstrated complement deposition along the basement membrane typical of bullous pemphigoid. The serum from all the patients immunoprecipitated an identical complex of polypeptides from keratinocyte extracts with MWs ranging from 130kD to 250kD. These include the antigens that are implicated in both pemphigus and pemphigoid as well as several others. Although it is rare, paraneoplastic pemphigus is a discrete autoimmune blistering skin disease with characteristic clinical features, a pathognomonic pattern of antibody specificity and an association with lymphoid tumours. It may occur in an array of lymphoid tumours, and especially in Castleman's disease, but about 30% of cases occur in CLL [Anhalt & Nousari 1998]. Paraneoplastic pemphigus following treatment with fludarabine has been reported in 5 cases [Bazarbachi et al 1995, Braess et al 1997, and Littlewod et al 1998]. Treatment This syndrome is sometimes very severe and may be fatal; four of the original five patients died [Anhalt et al 1990] and two patients who developed it following fludarabine also succumbed [Bazarbachi et al 1995, Pott-Hoeck et al 1995]. One patient has survived post-fludarabine paraneoplastic pemphigus after having been treated with prednisolone 500mg/d, cyclophosphamide 100 mg/d for several weeks together with IvIg 120 mg over the first 3 days [Braess et al 1997]. Other patients with a similar syndrome, unrelated to malignancy, have responded to IvIg [Meir et al 1993, Mohr et al 1995]. Four patients have responded to the combination of high dose steroids and cyclosporine or cyclophosphamide, although one later died from sepsis [Littlewood et al 1998, Gergely et al 2003]. Rituximab has also been successful in treating such cases [Heizmann et al 2001]. As the syndrome has become more familiar, less severe cases have been recognized and these seem to be steroid sensitive.