Epidermolysis Bullosa Pruriginosa: Further Clarification of the Phenotype

Abstract

A defect in type VII collagen causes dystrophic epidermolysis bullosa (DEB). The pruriginosa variant (DEB-Pr) is unique because its initial presentation may be delayed until adolescence or adulthood, and its predominant feature is scarring and pruritus without the characteristic skin fragility of DEB. We describe three families with multiple affected members in which DEB-Pr shows an autosomal-dominant inheritance pattern. All affected individuals were examined, and three previously unreported COL7A1 mutations were identified.Dystrophic epidermolysis bullosa pruriginosa (DEBPr) is a rare and distinct subset of DEB first described in 1994 characterized by extreme pruritus and lichenoid or prurigo-like nodules that heal with violaceous scars and milia (1). At least 32 specific mutations within the collagen VII (COL7A1) gene have been identified in DEB-Pr (2-6), some overlapping with known mutations causing classic DEB (7). Patients have considerable phenotypic variation, even among those with the same genetic defect (4). We describe three families with DEB-Pr of varying clinical phenotypes resulting from three previously unreported mutations of COL7A1. CASE FAMILY 1The proband is a 30-year-old woman who presented with skin-colored to violaceous papules on her arms and legs, beginning at 11 years of age. New pruritic lesions continued to develop and spread to the trunk, sparing the face, leading to excoriations that healed with extensive scars. She denied skin fragility or intolerance to adhesive tape. Multiple topical corticosteroids, topical tacrolimus, moisturizers, and antihistamines all had minimal benefit. Her medical history was significant for mild anemia thought to be due to menorrhagia and mitral valve replacement for a history of rheumatic fever.On examination were Koebnerized, linear, hypertrophic, violaceous scars and plaques on the torso (Fig. 1A) and anterior tibiae (Fig. 1B). Small, discrete papules were scattered on the arms and abdomen. Mucous membranes, hair, nails, and teeth were normal. The pruritus partially responded to wet dressings with triamcinolone but markedly improved with low-dose broadband ultraviolet B phototherapy.This patient was one of four children born to nonconsanguineous Indian parents. Her monozygotic twin

Identical COL71A1 heterozygous mutations resulting in different dystrophic epidermolysis bullosa phenotypes

“…6 No clear pattern has emerged from attempts to correlate COL7A1 gene mutations with disease phenotype, and our three cases support this. 7,8 As previously reported, identical mutations, dominant or recessive, have been found in patients with different subtypes of DEB, ranging from nails-only disease to DEB-Pr. 9,10 Type VII collagen is composed of three identical alpha chains with a central collagenous domain flanked by an amino terminus and a carboxyl terminus.…”

Coinheritance of 2 New Potentially Damaging Heterozygous COL7A1 Variants in a Family With Autosomal Dominant Epidermolysis Bullosa Pruriginosa

“…Pretibial EB and EBP may be difficult to distinguish clinically, and there is considerable overlap between both conditions. 5 Patients with pretibial EB develop blisters, milia, and atrophic scarring localized to the pretibial skin. This is associated with absent or dystrophic toenails.…”