Case report: bullous pemphigoid development underlies dystrophic epidermolysis bullosa disease worsening.

Autoimmune response to cutaneous basement membrane components superimposed on a genetic skin fragility disease, hereditary epidermolysis bullosa (EB), has been described, but its effects on disease course remain unclear. We report a 69-year-old individual with congenital skin fragility and acral trauma-induced blistering that had suddenly worsened with the onset of severe itch and diffuse spontaneous inflammatory blisters. Next-generation sequencing identified compound heterozygous null and missense COL7A1 mutations, allowing the diagnosis of recessive dystrophic EB. However, the patient's clinical history prompted us to investigate whether he might have developed a pathological autoimmune response against basement membrane components. Tissue-bound and circulating IgG antibodies to the major bullous pemphigoid (BP) antigen, BP180, were detected in the patient's skin and serum, respectively, consistent with a diagnosis of BP. Corticosteroid therapy was initiated resulting in remission of BP manifestations. EB patients presenting rapid disease worsening should be investigated for the development of a concomitant autoimmune blistering disease.

COL7A1 Recessive mutations in two siblings with distinct subtypes of dystrophic epidermolysis bullosa: pruriginosa versus nails only.

Dystrophic epidermolysis bullosa (DEB) is a rare, clinically heterogeneous, blistering genodermatosis inherited as either autosomal dominant or recessive trait. All DEB forms are caused by mutations in the COL7A1 gene, which encodes for type VII collagen, the major component of the anchoring fibrils ensuring epithelial-mesenchymal adhesion. Major determinants of clinical heterogeneity in DEB are COL7A1 mutation types and their consequences at mRNA and protein levels; nevertheless, siblings with the same genetic alterations can manifest highly variable clinical signs. Here, we report novel compound heterozygous recessive COL7A1 missense mutations in 2 siblings presenting different DEB clinical subtypes. Our findings document the rare occurrence of recessive inheritance for the nails only DEB variant and emphasize the role of acquired phenotype-modifying factors in DEB pruriginosa pathogenesis.

Dystrophic epidermolysis bullosa phenotypes in a large consanguineous Tunisian family.

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a clinically heterogeneous blistering disorder of the skin and mucous membranes. DEB is caused by mutations in the COL7A1 gene encoding type VII collagen, the major component of anchoring fibrils. On the basis of the mode of inheritance and the clinical manifestations, DEB is classified into two major subtypes: one dominant (DDEB) and one recessive (RDEB). OBJECTIVE: We report, here, clinical, histological and genetic investigation of a large Tunisian family presenting with a wide range of clinical manifestations of DEB and a pedigree suggestive for a pseudodominant pattern of inheritance of a recessive mutation. METHODS: Indirect immunofluorescence (IF) with the antibody LH7:2 against collagen VII and electron microscopy (EM) analyses were performed. The members of the family were genotyped with five markers flanking COL7A1, and screening for the deleterious mutation by DHPLC and direct sequencing. RESULTS: The family presented four pretibial DEB patients and one generalized RDEB. Molecular investigation showed that all family members, unaffected and affected by the pretibial form, were heterozygous for the c.7178delT mutation, except for the member with the generalized form who was homozygous. IF showed that heterozygous individuals, independently of their clinical status, have a slightly reduced staining, and the homozygous individual with generalized DEB has markedly reduced staining at the dermal-epidermal junction. CONCLUSION: These results are suggestive for an autosomal semidominant model of inheritance with incomplete penetrance and variable expression for the identified mutation. No genotype phenotype correlation was observed suggesting the existence of other genetic determinants influencing dermo-epidermal junction cohesion.