Coexisting linear and disseminated drug eruption: a clinical clue to the understanding of the genetic basis of drug eruptions

ARTICLE

In this issue, Remedios Alfonso and Belinchón Romero from Alicante describe an unusual drug eruption induced by ibuprofen [1]. Initially the patient showed unilateral linear lesions and 5 days later she developed a bilateral disseminated rash. The disseminated form of this reaction is very common, and there are several reports on linear drug eruption [2, 3]. An important feature of this case, however, is the combined occurrence of the two types of adverse reaction.

This case report may provide a clue to the understanding of the genetic basis of drug eruptions. Most likely the proneness to develop such side effects has a polygenic basis. To explain the occurrence of an excessively pronounced linear drug eruption superimposed on less severe, disseminated similar lesions, one may assume that during early embryogenesis loss of heterozygosity occurred in a somatic cell, giving rise to a clonal population of cells being either homozygous or hemizygous for a gene predisposing to the disease [4]. The disseminated rash would reflect a heterozygous state, whereas the more pronounced linear lesions would herald loss of heterozygosity.

In many other inflammatory skin diseases, possible examples of a similar mechanism have been described. So far, the cases of pronounced linear inflammatory skin lesions superimposing a disseminated symmetrical involvement of the same disorder include psoriasis [5], pustular psoriasis [6, 7], atopic eczema [8], systemic lupus erythematosus [9], and pemphigus vulgaris [10]. Inflammatory skin disorders particularly prone to develop coexisting linear and disseminated lesions are lichen planus [11-15] and graft-versus-host reaction [16-19]. In all of these reports, the linear lesions were more pronounced than the disseminated skin changes.

The reported unusual drug eruption [1] can be added to this list. The patient would be heterozygous for a gene predisposing to drug eruptions, and this would explain the disseminated rash. At an early developmental stage, the corresponding wildtype allele may have been lost, resulting in either homozygosity or hemizygosity for the predisposing gene. This would explain the superimposed, excessively pronounced linear eruption. Alternatively, one may assume that during early embryogenesis another mutational event occurred and gave rise to a cell clone more prone to respond in the form of a drug eruption.

Such co-occurrence may provide the opportunity to search for the genes predisposing to drug eruptions. In allergic type IV reactions to various drugs such research is already underway [20, 21]. Publishing cases of coexisting linear and disseminated drug eruption, as observed by Remedios Alfonso and Belinchón Romero [1], may represent a first step to elucidate the genetic basis of this side effect of drug therapy.

References

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