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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