The histopathology of drug rashes

Iatrogenic rashes present a difficult problem for the histopathologist, who tends to be called in only when the dermatologist is in doubt about the diagnosis. By definition, therefore, the cases submitted for histological examination are in some way atypical clinically, and will therefore be atypical histologically. Most iatrogenic rashes mimic idiopathic skin diseases such as lichen planus, psoriasis, etc. and the histopathologist's problem is to determine whether the lesion is most likely to be idiopathic or the drug-induced equivalent. There are no simple indicators which can be applied across the board; the single most useful indicator (eosinophils in the inflammatory infiltrate) is not foolproof because many idiopathic skin lesions contain eosinophils as a natural component. In this short review, a few clues are given which may indicate an iatrogenic cause for a rash. Even so, it is rare that a histopathologist can be certain that a particular rash is drug-induced rather than idiopathic without full discussion with the clinician, and a full and detailed drug history which should include enquiry into the ingestion of ‘over the counter' and ‘health' preparations. It is also now important to ask about ‘recreational' drugs since the effects on skin of substances such as ‘Ecstasy' and glue are currently unknown. In very few conditions, mainly toxic epidermal necrolysis (Lyell's syndrome), Stevens-Johnson syndrome and fixed drug eruption, can the cause be almost certainly ascribed to drugs. However, these conditions are so clinically characteristic that the histopathologist is rarely called upon to provide a histological diagnosis, except in the most severe cases where histological confirmation is required because of the serious implications of the disease.