33190 Acral hemorrhagic Darier disease: A case report of a rare variant and literature review

Abstract

Introduction: Acral hemorrhagic Darier disease (DD) is an unusual variant of DD. It presents with acral irregular, jagged shaped hemorrhagic vesicles. A mutation in exon 15 of the ATP2A2 gene that encodes a sarco/endoplasmic reticulum calcium-ATPase pump (SERCA2) is found in 71% in patients with this variant, some with conflicting genetic results. We present 2 patients with this condition. Case: A 41-year-old man presented with several years of evolution of multiple black hemorrhagic vesicles with jagged borders on the dorsum and palms of hands and feet. A punch biopsy showed hemorrhage in the cornified layer with suprabasilar acantholysis and he was diagnosed with acral hemorrhagic DD. His mother had a similar rash affecting acral skin. Genetic testing revealed a p.N676S mutation in the ATP2A2 gene. He was started on acitretin 25 mg/day, increased later to 50 mg/day due to mild improvement. However, he developed facial and truncal lesions resembling classic DD and discontinued treatment. Discussion: 20 cases of this variant have been reported in the literature. In most cases, individuals first developed classic DD and were affected by the hemorrhagic presentation later in life or paradoxically after treatment with a systemic retinoid. It is thought that certain mutations in the ATP2A2 gene may disrupt SERCA2 function of the keratinocytes and vascular endothelium or may produce a mutant SERCA2 protein with a secondary effect in blood vessels. To the best of our knowledge this is the first case of acral hemorrhagic DD that has a p.N676S mutation in the ATP2A2 gene.