Eosinophil infiltration in three patients with generalized atrophic benign epidermolysis bullosa from a Japanese family: molecular genetic and immunohistochemical studies

Abstract

Generalized atrophic benign epidermolysis bullosa (GABEB), a subtype of epidermolysis bullosa (EB), is an autosomal recessive skin disease characterized by derm-epidermal separation leading to skin fragility and atrophy and other associated abnormalities. Although a few reports demonstrated that eosinophils are infiltrating beneath bullas in infants with some types of EB, no such condition in adult GABEB patients has been known. Here we report on three adult patients with GABEB from a Japanese family, whose bullous skin lesions showed massive eosinophil infiltration. One of the three patients showed amyloid deposition at the intestine, kidney, and skin. Linkage analysis revealed that GABEB in the family was linked to COL17A1 with a maximum LOD score of 3.08. Mutation analysis identified in the three patients a homozygous insertional mutation, 209-210insCA, in exon 5 of COL17A1. The expression of mutated COL17A1 was confirmed by semiquantitative RT-PCR, but no signals for truncated COL17A1 protein were detected by the immunohistochemical studies using antibodies against BP180. Furthermore, no autoantibody against the mutant protein was detected by western blot analysis. It is thus less likely that autoantibody and/or a local immune reaction in their skin has a primary role in eosinophil infiltration in these patients.

Burden of itch in epidermolysis bullosa

“…[8][9][10] Although it is tempting to postulate that the inflammatory infiltrates are responsible for the pruritus, pruritus was a prominent feature in some cases of DDEB pruriginosa in which inflammatory infiltrates were histologically absent. [8][9][10][11][12] Wally et al 13 found that the keratinocytes of patients with the Dowling-Meara subtype of EBS have constitutively activated IL-1b signalling. 13 Glial IL-1b and tumour necrosis factor-a can cause a central sensation of pain, but it is not yet known whether these cytokines activate pruriceptive neurons.…”

Oral steroid improves bullous pemphigoid-like clinical manifestations in non-Herlitz junctional epidermolysis bullosa with COL17A1 mutation

“…A 41‐year‐old Japanese man presented with his entire body covered with blisters, which had started following a minor neonatal trauma. He was the child of a consanguineous couple and had two aunts with JEB‐nH 2 . The diagnosis of JEB was made at Kobe University Hospital when he was 2 years old.…”

“…In 2004, he and his two aunts were diagnosed with JEB‐nH based on the results of genetic linkage and mutation analysis performed at Nagasaki University Hospital. A homozygous insertion mutation, 209–210insCA in exon 5 of COL17A1 encoding type XVII collagen, was detected 2 . Since 2005, he had been suffering from aggressive new blister formations after scratching caused by severe itching, accompanied by general fatigue, fever and appetite loss.…”

Dermal eosinophilic infiltrate in junctional epidermolysis bullosa

“…Mechanobullous disorders and immunobullous disorders have been reported to coexist together. This finding was observed in a 56-year-old male with a clinicopathological diagnosis of junctional EB, generalized 27 3 Junctional EB Eosinophils Drury and Prieto 28 2 Dystrophic EB Eosinophils, leukocytes Ning et al 29 1 Dystrophic EB Eosinophils, neutrophils Grunwald et al 1 1 Dystrophic EB Eosinophils Vivehanantha et al 16 1 Dystrophic EB (EB pruriginosa) Eosinophils, lymphocytes Roth et al 2 24 However, an earlier case reported a 41-year-old male with junctional EB, generalized intermediate, who presented with clinical features of severe itching and eosinophilia, yet DIF was negative for bullous pemphigoid. This patient subsequently improved after treatment with oral steroids.…”