case_images: PMC10601694_01
case_images: Clinical, histopathological, and immunological characteristics of the patient. a Clinical features of the trunk at the first visit. b Histopathological findings of the biopsy specimen of a vesicle on the back (hematoxylin and eosin staining, original magnification x200). c, d Direct immunofluorescence staining for IgA (c) and C3 (d). e Indirect immunofluorescence using normal human skin. f Indirect immunofluorescence using 1m NaCl-split-normal human skin. g Immunoblotting (IB) using concentrated culture supernatant of HaCaT cells as a substrate revealed strong IgA reactivity with the 120-kDa LAD-1 in the patient serum (lane 6); the supernatant, also reacted with IgG and IgA positive control sera (lanes 3 and 4). Lane 7 indicates the molecular weight markers. h, i Colonoscopy revealed multiple colorectal polyps (h) and adenocarcinoma (i). j Results of the panel sequencing. The identified rare variant, ATM:c.107A>G/p.Asp36Gly is shown by Integrative Genomics Viewer (IGV; Broad Institute), indicated with a red arrow. k Clinical features 1 month after the first visit without significant improvement. l Clinical features after 3 months of treatment. m Clinical features after 2 years of follow-up.
case_images: cde-2023-0015-0001-532104_F01.jpg
case_images: PMC10601694_01_cde-2023-0015-0001-532104_F01.jpg
case_images: F1
case_images: Physical examination revealed multiple erythemas with tense blisters and erosions on their periphery, as well as pigmentation of the trunk and extremities (Fig. 1a). HLA-DQA1 and HLA-DQB1 allelic variations and IgA anti-epidermal transglutaminase antibodies, disease markers for celiac disease, yielded negative results. Histopathological examination of a skin biopsy specimen from a bullous erythematous lesion on the back revealed subepidermal blisters and infiltration of neutrophils, eosinophils, and lymphocytes into the blisters and superficial dermis (Fig. 1b). Direct immunofluorescence revealed a linear deposition of IgA and punctate deposition of C3 in the BMZ (Fig. 1c, d), while indirect immunofluorescence using normal human skin tissue revealed IgA anti-BMZ antibodies at a 10x dilution (Fig. 1e). Additionally, indirect immunofluorescence performed using 1M NaCl-split-skin showed IgA reactivity on the epidermal side (Fig. 1f). Finally, immunoblotting using a concentrated culture supernatant of HaCaT cells as substrate revealed strong IgA reactivity with the 120-kDa LAD-1 in the patient serum (Fig. 1g), which was consistent with the diagnosis of LL-type LAD. Colonoscopy revealed >100 pedunculated polyps, <20 mm in size, in the colorectum (Fig. 1h, i). Although no pathogenic genetic alterations in the germline were found that could explain the development of multiple colorectal polyps, we identified a missense variation, ATM (NM_000051.3): c.107A>G/p.Asp36Gly (dbSNP:rs1488019755), Chr11:108,098,537 (on Assembly GRCh37), which corresponded to an ATM variant of uncertain significance (Fig. 1j). For approximately 1 month, the patient did not respond to initial treatment with oral antihistamines and topical corticosteroids (as shown in Fig. 1k). Within 3 months, the bullous erythematous skin lesions rapidly resolved (Fig. 1l), and no recurrence was observed during the 2 years of follow-up (Fig. 1m).