MUCOCUTANEOUS AUTOIMMUNE SYNDROME FOLLOWING FLUDARABINE THERAPY FOR LOW-GRADE NON-HODGKINS-LYMPHOMA OF B-CELL TYPE (B-NHL)

A 40-year-old patient with low-grade B-NHL developed a generalized mac ular-papular rash following the first cycle of fludarabine treatment w hich progressed to a complete epidermal necrolysis following the secon d cycle. Clinical symptoms and the results of the direct and indirect immunofluorescence were consistent with a mucocutaneous autoimmune syn drome (pemphigus). Immunohistochemical analysis demonstrated a dense e pidermal infiltration of CD8+ lymphocytes associated with the histolog ical features of single-cell necrosis of keratinocytes. Early and aggr essive immunosuppressive treatment with steroids, cyclophosphamide, an d high-dose immunoglobulins resulted in regression of symptoms and com plete reconstitution of epidermal integrity. The malignant lymphoma ha s completely regressed. The findings suggest a fludarabine-induced def ect in immunosurveillance - resulting in the uncontrolled activation o f autoaggressive T-cell clones - as a pathogenetic mechanism of this l ife-threatening dermatological complication.