Supplementary Material for: Nephropathy in a Child with Severe Recessive Dystrophic Epidermolysis Bullosa Treated with Cyclophosphamide: A Case Report

Long-term inflammation and recurrent skin infections in recessive dystrophic epidermolysis bullosa (RDEB) are associated with the presence of immunoglobulin A (IgA)-containing immune complexes in the glomerulus. Only eight pediatric RDEB cases with IgA nephropathy (IgAN) have been documented in English-language literature. Most RDEB patients with IgAN progress to kidney failure within five years of diagnosis, indicating that these patients may require more intensive early treatment compared to those with primary IgAN. However, diagnosing IgAN in RDEB cases with severe cutaneous manifestations can be challenging. Herein, we report a rare case of nephropathy in an 11-year-old boy with severe RDEB and a frameshift mutation on the COL7A1 gene, which may manifest as kidney disorders. He presented with persistent hematuria and progressing proteinuria. A presumptive IgAN diagnosis was based on clinical features and increased IgA serum levels, as kidney biopsy was refused by his parents. Nephrotic-range proteinuria persisted despite initial steroid and lisinopril treatment. Monthly intravenous cyclophosphamide (IV CPA; 500 mg/m2) led to proteinuria remission and preservation of kidney function for two years post-treatment. We conclude that COL7A1 mutations may result in extracutaneous manifestations, including kidney disorders. The association between IgA-containing immune complex deposits in the glomerulus and recurrent skin infections in RDEB may indicate IgAN, particularly when kidney biopsy is infeasible due to severe skin manifestations. In our case, positive results with IV CPA suggest further investigation is needed to explore its potential role in non-rapidly progressing IgAN in children with RDEB.

隐性遗传性营养不良性大疱性表皮松解症（recessive dystrophic epidermolysis bullosa, RDEB）患者的长期炎症与复发性皮肤感染，与肾小球内含有免疫球蛋白A（immunoglobulin A, IgA）的免疫复合物沉积存在关联。目前英文文献中仅报道过8例合并IgA肾病（IgA nephropathy, IgAN）的儿科RDEB病例。多数合并IgAN的RDEB患者在确诊后5年内进展为肾衰竭，这提示相较于原发性IgAN患者，此类患者可能需要更强化的早期治疗。然而，对于皮肤表现严重的RDEB患者，诊断IgAN颇具挑战。本文报告1例罕见病例：患者为11岁男性，患有重度RDEB且携带COL7A1基因移码突变，此类情况可表现为肾脏病变。该患者表现为持续性血尿与进行性蛋白尿。由于患儿父母拒绝行肾活检，临床医师结合其临床表现与血清IgA水平升高，作出了疑似IgAN的初步诊断。尽管初始予糖皮质激素与赖诺普利治疗，肾病范围蛋白尿仍持续存在。每月予静脉注射环磷酰胺（intravenous cyclophosphamide, IV CPA；500 mg/m²）治疗后，患者蛋白尿得以缓解，且治疗后2年内肾功能得以维持。我们据此得出结论：COL7A1基因突变可能导致包括肾脏病变在内的皮肤外表现。RDEB患者肾小球内IgA型免疫复合物沉积与复发性皮肤感染的关联，提示可能存在IgAN，尤其当因严重皮肤表现无法行肾活检时。在本病例中，静脉注射环磷酰胺治疗取得阳性效果，这提示需进一步研究以探索其在RDEB合并儿童非快速进展型IgAN患者中的潜在应用价值。