DRUG-INDUCED IMMUNE DYSREGULATION AS A CAUSE AT ATYPICAL CUTANEOUS LYMPHOID INFILTRATES - A HYPOTHESIS

The authors encountered 22 patients in whom a skin biopsy showed atypi cal lymphoid hyperplasia and in whom a subsequent drug history showed ingestion of one or more agents before lesional onset. In 13 patients, the biopsy had been performed to rule out a diagnosis of malignant ly mphoma, whereas in the other nine the clinical impression was that of a dug eruption. Among the more frequently prescribed agents were calci um-channel blockers, angiotensin-converting enzyme (ACE) inhibitors, a ntidepressants, antihistamines, beta-blockers, benzodiazepines and lip id-lowering agents, all of which are either known to perturb lymphocyt e function or have been implicated as a cause of pseudolymphomata. Twe lve of the patients were on two or more of these drugs. The effect of drug modulation on the clinical course was assessed. The clinical pres entations were as one or more erythematous plaques or multiple infiltr ative papules, or as solitary nodules. The patients had been on one or more of the aforementioned drugs from 2 weeks to 5 years before devel oping the lesions, Resolution of the eruptions occurred in 17 patients within 1 to 32 weeks: (mean, 7 weeks) of discontinuing the medication . Five additional patients had complete excision of solitary lesions w ithout recurrence. A history of atopy, autoimmune disease, or previous carcinoma was elicited in five patients. All biopsy specimens showed atypical lymphoid infiltrates, which assumed one or more of the follow ing patterns: mycosis fungoides (MF)-like, a lymphomatoid vascular rea ction, lymphocytoma cutis, and follicular mucinosis. Based on the hist opathology of the biopsied lesions and the clinical course being one o f lesional resolution after cessation of drug therapy or excision of a solitary lesion without subsequent recurrence, a diagnosis of drug-as sociated lymphomatoid hypersensitivity was established in all specimen s. A diagnosis of dug-associated pseudolymphoma should be excluded bef ore a diagnosis of cutaneous lymphoma is rendered, and should be consi dered if the patient is on a drug known to alter lymphocyte function, particularly in the setting of systemic immune dysregulation or multid rug therapy where agents may act synergistically or cumulatively to al ter lymphoid function. The authors postulate that the drug may promote an aberrant immune response to an antigen that may be the drug itself or some other stimulus. A skin biopsy may be particularly helpful, as the lesions of drug-associated pseudolymphoma have a morphology disti nctive from malignant lymphoma. Copyright (C) 1996 by W.B. Saunders Co mpany.