{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T11:45:28Z","timestamp":1782215128644,"version":"3.54.5"},"reference-count":15,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Dermatol"],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:sec id=\"ab-dbr220014-4\"><jats:title>Importance<\/jats:title><jats:p>Kidney\u2013urinary 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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr220014-5\"><jats:title>Objective<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr220014-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>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\u2019 medical records.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr220014-7\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Clinical characteristics, natural history, management of KUT manifestations, and genotype-phenotype correlations of intermediate JEB.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr220014-8\"><jats:title>Results<\/jats:title><jats:p>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 \u03b2<jats:sub>4<\/jats:sub> deficiency had at least 1 missense or splice site  genetic variant, leading to residual expression of laminin 332 or integrin \u03b1<jats:sub>6<\/jats:sub>\u03b2<jats:sub>4<\/jats:sub>, respectively. Severity of KUT complications did not correlate with the extent of skin involvement but with the affected protein.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr220014-9\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamadermatol.2022.2885","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T15:02:18Z","timestamp":1659538938000},"page":"1057","source":"Crossref","is-referenced-by-count":9,"title":["Kidney\u2013Urinary Tract Involvement in Intermediate Junctional Epidermolysis Bullosa"],"prefix":"10.1001","volume":"158","author":[{"given":"Laura","family":"Trefzer","sequence":"first","affiliation":[{"name":"Department of Dermatology, Medical Center\u2013University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Schwieger-Briel","sequence":"additional","affiliation":[{"name":"Pediatric Skin Center, Division of Dermatology, University Children\u2019s Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Nystr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical Center\u2013University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"},{"name":"Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Conradt","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical Center\u2013University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"},{"name":"Faculty of Biology, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Pohl","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, Medical Center\u2013University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arkadiusz","family":"Miernik","sequence":"additional","affiliation":[{"name":"Department of Urology, Medical Center\u2013University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Has","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical Center\u2013University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"5, pt 1","key":"dbr220014r1","doi-asserted-by":"publisher","first-page":"2040","DOI":"10.1097\/01.ju.0000143200.86683.2c","article-title":"Genitourinary complications of inherited epidermolysis bullosa: experience of the national epidermylosis bullosa registry and review of the literature.","volume":"172","author":"Fine","year":"2004","journal-title":"J Urol"},{"issue":"1","key":"dbr220014r2","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1111\/bjd.2007.156.issue-1","article-title":"Nephro-urological complications of epidermolysis bullosa in paediatric patients.","volume":"156","author":"Chan","year":"2007","journal-title":"Br J Dermatol"},{"issue":"6","key":"dbr220014r3","doi-asserted-by":"publisher","first-page":"2122","DOI":"10.1016\/S0022-5347(01)63291-9","article-title":"Epidermolysis bullosa: a review of the associated urological complications.","volume":"159","author":"Glazier","year":"1998","journal-title":"J Urol"},{"issue":"1","key":"dbr220014r4","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1111\/bjd.2013.169.issue-1","article-title":"Phenotypic spectrum of epidermolysis bullosa associated with a6\u00df4 integrin mutations.","volume":"169","author":"Schumann","year":"2013","journal-title":"Br J Dermatol"},{"key":"dbr220014r5","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.matbio.2016.12.003","article-title":"Integrin alpha6 maintains the structural integrity of the kidney collecting system.","volume":"57-58","author":"Viquez","year":"2017","journal-title":"Matrix Biol"},{"issue":"6","key":"dbr220014r6","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.jpurol.2006.01.007","article-title":"Single-centre experience of genitourinary complications of epidermolysis bullosa.","volume":"2","author":"Burgu","year":"2006","journal-title":"J Pediatr Urol"},{"issue":"2","key":"dbr220014r7","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1006\/dbio.2001.0391","article-title":"Involvement of laminin binding integrins and laminin-5 in branching morphogenesis of the ureteric bud during kidney development.","volume":"238","author":"Zent","year":"2001","journal-title":"Dev Biol"},{"issue":"3","key":"dbr220014r8","doi-asserted-by":"publisher","first-page":"218","DOI":"10.4103\/1658-631X.188249","article-title":"Genitourinary tract involvement in a child with epidermolysis bullosa.","volume":"4","author":"Al Moaigel","year":"2016","journal-title":"Saudi J Med Sci"},{"issue":"2","key":"dbr220014r9","doi-asserted-by":"publisher","first-page":"F233","DOI":"10.1152\/ajprenal.2000.279.2.F233","article-title":"Integrins in kidney development, function, and disease.","volume":"279","author":"Kreidberg","year":"2000","journal-title":"Am J Physiol Renal Physiol"},{"issue":"12","key":"dbr220014r10","doi-asserted-by":"publisher","first-page":"2826","DOI":"10.1172\/JCI119474","article-title":"A homozygous mutation in the integrin alpha6 gene in junctional epidermolysis bullosa with pyloric atresia.","volume":"99","author":"Ruzzi","year":"1997","journal-title":"J Clin Invest"},{"issue":"1","key":"dbr220014r11","article-title":"Uniparental disomy of chromosome 2 unmasks new ITGA6 recessive mutation and results in a lethal junctional epidermolysis bullosa in a newborn.","volume":"100","author":"Higgins","year":"2020","journal-title":"Acta Derm Venereol"},{"issue":"1","key":"dbr220014r12","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1159\/000499486","article-title":"Consequences of glomerular hyperfiltration: the role of physical forces in the pathogenesis of chronic kidney disease in diabetes and obesity.","volume":"143","author":"Chagnac","year":"2019","journal-title":"Nephron"},{"issue":"1","key":"dbr220014r13","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1002\/nau.v39.1","article-title":"Vorticity in lower urinary tract can be assessed and associates with urinary tract morphology in men.","volume":"39","author":"Minagawa","year":"2020","journal-title":"Neurourol Urodyn"},{"issue":"4","key":"dbr220014r14","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1590\/S1677-5538.IBJU.2015.0347","article-title":"Metaplastic conditions in the bladder in patient with epidermolysis bullosa.","volume":"42","author":"Yilmaz","year":"2016","journal-title":"Int Braz J Urol"},{"issue":"1","key":"dbr220014r15","doi-asserted-by":"publisher","first-page":"179.e5","DOI":"10.1016\/j.urology.2007.03.073","article-title":"Genitourinary complications of epidermolysis bullosa.","volume":"70","author":"Srinivasin","year":"2007","journal-title":"Urology"}],"container-title":["JAMA Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamadermatology\/articlepdf\/2794592\/jamadermatology_trefzer_2022_br_220014_1662573770.15514.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T15:08:10Z","timestamp":1663772890000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamadermatology\/fullarticle\/2794592"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,1]]},"references-count":15,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamadermatol.2022.2885","relation":{},"ISSN":["2168-6068"],"issn-type":[{"value":"2168-6068","type":"print"}],"subject":[],"published":{"date-parts":[[2022,9,1]]}}}