Skin manifestations of drug allergy

Abstract

Cutaneous adverse drug reactions range from mild to severe and from those localized only to skin to those associated with systemic disease. It is important to distinguish features of cutaneous drug reactions which help classify the underlying mechanism and likely prognosis as both of these influence management decisions, some of which necessarily have to be taken rapidly. Severe cutaneous reactions are generally T cell-mediated, yet this immunological process is frequently poorly understood and principles for identification of the culprit drug are different to those of IgE mediated allergic reactions. Furthermore, intervention in severe skin manifestations of drug allergy is frequently necessary. However, a substantial literature reports on success or otherwise of glucocorticoids, cyclophsphamide, ciclosporin, intravenous immunoglobulin and anti-tumour necrosis factor therapy for the treatment of toxic epidermal necrolysis without clear consensus. As well as reviewing the recommended supportive measures and evidence base for interventions, this review aims to provide a mechanistic overview relating to a proposed clinical classification to assist the assessment and management of these complex patients.

Figure 2

Clinical photographs depicting classic examples of four similar cutaneous drug eruption patterns. Of note, the plaques of urticarial eruptions (A) have pale centres in contrast to the uniform colour in drug-induced exanthemata (B) and drug reaction with eosinophilia and systemic symptoms (DRESS) (C) and the dark centre (target) in erythema multiforme (D)

Figure 3

A clinical image of toxic epidermal necrolyisis (TEN) demonstrating widespread patchy eryhthema with confluence and darkening at sites of epidermal detachment (blistering)

Figure 1

Careful documentation, with detailed dating of when drugs were started and stopped reveals the timelines which, in conjunction with knowledge of individual reported frequencies of allergy, helps to rank the drugs in order of suspicion. In a severe drug reaction such as toxic epidermal necrolysis, although this format is still very useful to identify a causative drug, it is preferable to recommend cessation of all medications. Time spent accurately drawing out this information at the first clinical encounter is considerably more effective than attempting to do this retrospectively when the condition has resolved. Horizontal arrows represent period of ingestion of listed drug. Arrow tip represents last day of ingestion. Vertical arrow represents a medication switch. Vertical dotted line represents the onset of the rash. It is important to include annotation of the day the chart is documented (Today)