Case Report: Diagnostic and Therapeutic Challenges in Severe Mechanobullous Epidermolysis Bullosa Acquisita

Abstract

Collagen VII is the main constituent of the anchoring fibrils, important adhesive structures that attach the epidermis to the dermal extracellular matrix. Two disorders are caused by dysfunction of collagen VII, both characterized by skin and mucosa fragility, epidermolysis bullosa acquisita (EBA) and dystrophic epidermolysis bullosa (DEB). EBA and DEB share high clinical similarities with significant difference in patients' age of onset and pathogenesis. Our patients presented with severe and recalcitrant mechanobullous EBA with characteristic DIF, IIF and ELISA diagnostics. But in both women recessive COL7A1 variants were also found, in a monoallelic state. Collagen VII from EBA keratinocytes of our cases was significantly more vulnerable to proteolytic degradation than control keratinocytes, hinting that the heterozygous pathogenic variants were sufficient to destabilize the molecule in vitro. Thus, even if the amount and functionality of mutant and normal type VII collagen polypeptides is sufficient to assure dermal-epidermal adhesion in healthy individuals, the functionally-impaired proteins are probably more prone to development of autoantibodies against them. Our work suggests that testing for COL7A1 genetic variants should be considered in patients with EBA, which either have a patient history hinting towards underlying dystrophic epidermolysis bullosa or pose therapeutic challenges.

Keywords: COL7A1; collagen VII; immunoglobulin; rituximab; skin blistering; skin fragility.

Figure 1

Clinical manifestations in both cases. (A) Clinical presentation of case 1 with blisters, erosions and scaring of her back, tongue, scarring alopecia, chest and nail dystrophy/loss presented at her left foot. (B) Case 2 shows similar lesions on her skin, mucous membranes (mouth and esophagus), as well as progressive scarring and milia on the backs of the hands. The finger nails are intact.

Figure 2

Results of the diagnostic assessment. (A) Direct immunofluorescence with linear IgG along the DEJZ and (B) immunofluorescence mapping of patient 1 and 2 showing regular staining of collagen VII compared to healthy control. Collagen VII of patient 1 stains at dermal and epidermal side within the blister, reminiscent of an older blister. Collagen VII of patient 2 shows wider depositions at DEJZ and interruptions due to microblistering. (C) Immunoblot of the trypsine-digested collagen VII shows degradation at lower temperatures in the patients’ keratinocyte lysates, as graphically depicted in (D). * equals p: 0,0118 as tested with 2-WAY ANOVA.