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A transient epidermolysis bullosa simplex‐like phenotype associated with bexarotene treatment in a G138E KRT5 heterozygote
Author(s) -
Trufant Joshua W.,
Kreizenbeck Gretchen M.,
Carlson Kacie R.,
Muthusamy Viswanathan,
Girardi Michael,
Bosenberg Marcus W.
Publication year - 2010
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/j.1600-0560.2010.01557.x
Subject(s) - epidermolysis bullosa simplex , keratin 5 , palmoplantar keratoderma , keratin 14 , dermatology , epidermolysis bullosa , pathology , bexarotene , phenotype , population , compound heterozygosity , biology , keratin , hyperkeratosis , medicine , genetics , gene , transgene , genetically modified mouse , environmental health , nuclear receptor , transcription factor
Basal keratinocyte lysis is the hallmark histopathological finding of epidermolysis bullosa simplex (EBS), a group of rare heritable mechanobullous disorders characterized by intraepidermal blister formation and skin fragility. Over 100 mutations, found predominantly in the genes encoding keratins 5 and 14 ( KRT5, KRT14 ), have been described to account for a variety of clinical subtypes. EBS with mottled pigmentation (EBS‐MP) is a rare variant featuring childhood‐onset reticulate hyperpigmentation and focal palmoplantar keratoderma, typically associated with a P25L KRT5 mutation. In this report, we present the case of a 77‐year‐old woman with a history of palmoplantar keratoderma who developed a transient EBS‐MP‐like phenotype associated with bexarotene treatment for cutaneous T‐cell lymphoma. Genetic sequencing revealed a heterozygous G138E KRT5 variant, present in approximately 10% of the European population and only rarely associated with pathology. Bexarotene, which has been reported to alter keratin synthesis, caused vesiculobullous reactions with similar frequency in clinical trials. We propose that the cumulative effect of drug treatment and underlying G138E polymorphism resulted in transient basal keratinocyte lysis in our patient and provides a plausible explanation for this unusual bexarotene side effect. Trufant JW, Kreizenbeck GM, Carlson KR, Muthusamy V, Girardi M, Bosenberg MW. A transient epidermolysis bullosa simplex‐like phenotype associated with bexarotene treatment in a G138E KRT5 heterozygote.