Azathioprine and cyclosporin have been used as immunosuppressants for many years, but long-term use has also been associated with neoplasia. We report three cases of rapidly fatal Merkel cell carcinoma in patients who had been treated with azathioprine for many years either for rheumatoid arthritis or following organ transplantation. Two of these patients had also received cyclosporin. We suggest that Merkel cell carcinoma may be seen more commonly in immunosuppressed patients than in the normal population and that the oncogenic potential of azathioprine and cyclosporin should be borne in mind when prescribing these drugs.
We report the case of a 15-year-old girl who presented at 11 years of age with an interesting, acquired and, to our knowledge, unique blistering disease. It involved both skin and mucous membranes with extensive oral and periungual lesions, clinically resembling paraneoplastic pemphigus. Skin biopsy showed an inflammatory cell infiltrate in the upper dermis with numerous leucocytoclastic nuclear fragments, neutrophilic papillary microabscesses and a small subepidermal bulla. Direct and indirect immunofluorescence studies showed marked intercellular staining with IgA and less prominent staining with IgG. Granular deposition of IgA and, to a lesser extent IgG and C3, was also seen along the basement membrane zone. Immunoblotting and enzyme-linked immunosorbent assay studies showed both IgG and IgA antibodies to desmocollin, desmoglein 3 and desmoplakin. However, despite extensive investigation, no underlying neoplasm was found. Treatment with dapsone and sulphapyridine proved ineffective but methylprednisolone and azathioprine have reduced the blistering. We believe that this patient is unique for her combination of IgA and IgG antibodies to desmoplakin, desmocollin and desmoglein 3, although further studies may provide further clarification.
The immunomodulatory actions of cimetidine, an H2-receptor antagonist, and its use in the treatment of viral warts has been described previously but its effectiveness is still debated. We report the results in 47 patients with multiple, nongenital viral warts who were treated with oral cimetidine in a 3-month open-label study. The drug was generally well tolerated and 87% of children and 68% of adults improved with treatment. Follow-up data in 65% of the patients showed that there had been no recurrence in the majority of those whose warts had cleared completely during treatment, whereas warts tended to persist or recur in those who had stopped treatment before all the warts had resolved. Our data suggests that cimetidine may be helpful in the treatment of viral warts in both adults and children and supports the need for a randomized controlled trial.
Paraneoplastic pemphigus is a relatively recently described immunobullous disease with characteristic features. We report three cases of paraneoplastic pemphigus in adult men with chronic lymphocytic leukaemia arising within a week of completion of treatment with fludarabine. In all cases, withdrawal of fludarabine and treatment of the blistering was associated with marked cutaneous improvement. Fludarabine, a synthetic nucleoside analogue, which has only been available in Britain since 1994, is known to be associated with autoimmune phenomena and may have been involved in the development of paraneoplastic pemphigus in these cases.
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