A transient epidermolysis bullosa simplex-like phenotype associated with bexarotene treatment in a G138E KRT5 heterozygote
- PMID: 20849457
- DOI: 10.1111/j.1600-0560.2010.01557.x
A transient epidermolysis bullosa simplex-like phenotype associated with bexarotene treatment in a G138E KRT5 heterozygote
Abstract
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.
Copyright © 2010 John Wiley & Sons A/S.
Similar articles
-
Keratin mutations in patients with epidermolysis bullosa simplex: correlations between phenotype severity and disturbance of intermediate filament molecular structure.Br J Dermatol. 2010 May;162(5):1004-13. doi: 10.1111/j.1365-2133.2009.09626.x. Epub 2010 Feb 25. Br J Dermatol. 2010. PMID: 20030639
-
Mutations in KRT5 and KRT14 cause epidermolysis bullosa simplex in 75% of the patients.Br J Dermatol. 2011 Mar;164(3):637-44. doi: 10.1111/j.1365-2133.2010.10146.x. Epub 2011 Feb 17. Br J Dermatol. 2011. PMID: 21375516
-
Epidermolysis bullosa simplex due to KRT5 mutations: mutation-related differences in cellular fragility and the protective effects of trimethylamine N-oxide in cultured primary keratinocytes.Br J Dermatol. 2010 May;162(5):980-9. doi: 10.1111/j.1365-2133.2009.09615.x. Epub 2010 Feb 1. Br J Dermatol. 2010. PMID: 20128788
-
Mutation analysis of the entire keratin 5 and 14 genes in patients with epidermolysis bullosa simplex and identification of novel mutations.Hum Mutat. 2003 Apr;21(4):447. doi: 10.1002/humu.9124. Hum Mutat. 2003. PMID: 12655565 Review.
-
Epidermolysis bullosa simplex.Dermatol Clin. 2010 Jan;28(1):23-32. doi: 10.1016/j.det.2009.10.003. Dermatol Clin. 2010. PMID: 19945613 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous