PMC9021387_01
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.
fimmu-13-883967-g001.jpg
PMC9021387_02_fimmu-13-883967-g001.jpg
f1
At admission, a 67-year old female reported that her first symptoms had occurred six months prior with blistering on the skin and mucous membranes, and dysphagia ( Figure 1B ).
PMC9021387_02
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.
fimmu-13-883967-g001.jpg
PMC9021387_02_fimmu-13-883967-g001.jpg
f1
At admission, a 67-year old female reported that her first symptoms had occurred six months prior with blistering on the skin and mucous membranes, and dysphagia ( Figure 1B ).
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.
fimmu-13-883967-g002.jpg
PMC9021387_02_fimmu-13-883967-g002.jpg
f2
In case 1, diagnostics revealed linear IgG deposits in DIF ( Figure 2A ), positive dermal stained ss-IIF, while ELISA diagnostics against the NC1 domain remained negative over years, hindering correct diagnosis (Euroimmun  < 1 ratio; ratio > 1 considered positive). It revealed a dermal blister with no obvious reduction in collagen VII (as shown by staining with an NC1 domain-directed antibody in  Figure 2B ). In patient 2, diagnosis of EBA was confirmed by histopathology, linear IgG deposits along the BMZ in the DIF ( Figure 2A ) and ss-IIF with dermal side staining of IgG. Due to the therapy-refractory course, immunofluorescence mapping was performed in parallel and showed expression of collagen VII comparable to control skin ( Figure 2B ). Interestingly, the collagen VII from EBAK was significantly more prone to proteolytic degradation than NHK in both cases, hinting that the heterozygous pathogenic variants were sufficient to destabilize the molecule in vitro ( Figures 2C, D ).