Department of Dermatology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Pediatric Skin Center, Division of Dermatology, University Children's Hospital Zurich, Zurich, Switzerland.
JAMA Dermatol. 2022 Sep 1;158(9):1057-1062. doi: 10.1001/jamadermatol.2022.2885.
Kidney-urinary tract (KUT) manifestations cause substantial morbidity in patients with junctional epidermolysis bullosa (JEB), but the spectrum of disease severity and the clinical course have been poorly characterized.
To examine in a large cohort of patients with intermediate JEB the KUT manifestations, diagnostic and therapeutic procedures, genotype-phenotype correlations, and outcomes as a basis for recommendations, prognosis, and management.
DESIGN, SETTING, AND PARTICIPANTS: In this retrospective, longitudinal case series study, 99 patients with a diagnosis of JEB based on clinical and genetic findings who were treated in a single dermatology department in Freiburg, Germany, were assessed during an 18-year period (January 1, 2003, to December 31, 2021). Clinical, laboratory, and molecular genetic parameters were extracted from patients' medical records.
Clinical characteristics, natural history, management of KUT manifestations, and genotype-phenotype correlations of intermediate JEB.
Of the 183 patients with JEB, 99 (54%) had intermediate JEB and were included in this cohort. The cohort included 49 female patients and 50 male patients. None of 49 female patients and 15 of 50 male patients had KUT involvement affecting different levels of the urinary tract, resulting in a prevalence of 30% for males; thus, the overall prevalence was 15%. The mean age at onset of KUT manifestations was 6.9 years (range, first weeks of life to 20 years; age was not available for 1 patient). Median follow-up after diagnosis of KUT involvement was 13 years (range, 3 months to 54 years). Patients with laminin 332 or integrin β4 deficiency had at least 1 missense or splice site genetic variant, leading to residual expression of laminin 332 or integrin α6β4, respectively. Severity of KUT complications did not correlate with the extent of skin involvement but with the affected protein.
Physicians and patients with JEB should be aware of the risk for KUT involvement in intermediate JEB, and physicians should apply interdisciplinary and individualized diagnostic and therapeutic procedures for management of these complications. Because this disorder is so rare, multicenter studies are required to make general recommendations.
肾脏-泌尿道 (KUT) 表现会给交界性大疱性表皮松解症 (JEB) 患者带来严重的发病率，但疾病严重程度的范围和临床过程尚未得到很好的描述。
在一个大型中间 JEB 患者队列中检查 KUT 表现、诊断和治疗程序、基因型-表型相关性以及结局，为推荐意见、预后和管理提供依据。
设计、地点和参与者：在这项回顾性、纵向病例系列研究中，评估了德国弗莱堡的一家皮肤科在 18 年期间（2003 年 1 月 1 日至 2021 年 12 月 31 日）治疗的基于临床和遗传发现诊断为 JEB 的 99 名患者。从患者的病历中提取临床、实验室和分子遗传参数。
中间 JEB 的临床特征、自然病史、KUT 表现的管理以及基因型-表型相关性。
在 183 名 JEB 患者中，有 99 名（54%）患有中间 JEB，纳入本队列。该队列包括 49 名女性患者和 50 名男性患者。49 名女性患者中无一例有影响泌尿道不同水平的 KUT 受累，而 50 名男性患者中有 15 例有此受累，因此男性患病率为 30%；因此，总体患病率为 15%。KUT 表现发病的平均年龄为 6.9 岁（范围：出生后数周至 20 岁；1 名患者的年龄不详）。KUT 受累诊断后的中位随访时间为 13 年（范围：3 个月至 54 年）。层粘连蛋白 332 或整合素 β4 缺乏的患者至少有 1 个错义或剪接位点基因突变，分别导致层粘连蛋白 332 或整合素 α6β4 的残留表达。KUT 并发症的严重程度与皮肤受累的程度无关，但与受影响的蛋白有关。
JEB 患者和医生应该意识到中间 JEB 存在 KUT 受累的风险，医生应该应用跨学科和个体化的诊断和治疗程序来管理这些并发症。由于这种疾病非常罕见，因此需要进行多中心研究以提出一般性建议。
