Kidney-Urinary Tract Involvement with Intermediate Junctional Epidermolysis Bullosa

Laura Trefzer, MD

Individuals with junctional epidermolysis bullosa (JEB) live with fragile, blistering skin and mucosal membranes which can result in skin loss. This autosomal recessive disorder is rare, affecting approximately 3 per million people in the US each year.

When these individuals develop kidney-urinary tract (KUT) involvement, disease morbidity becomes substantial. The spectrum of disease severity and clinical course, however, has been poorly characterized, according to investigators.

A recently published study aimed to amend the gap by examining a large cohort of patients with intermediate JEB, a milder form. By determining the prevalence of kidney-urinary tract manifestations, investigators sought to expand the understanding of specific events associated with these manifestations. Additionally, they hoped to evolve screening and theapeutic recommendations by evaluating outcomes.

Phenotyping Kidney-Urinary Tract Involvement

Laura Trefzer, MD, Department of Dermatology, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, led a team in conducting a retrospective, longitudinal case series study of 99 patients. The patients received treatment in a dermatology department in Freiburg, Germany at some point during January 2003-December 2021.

The research included data on clinical, laboratory, and molecular genetic parameters that were gathered from patient medical records. Main outcomes and measures were clinical characteristics, natural history, management of KUT manifestations, and genotype-phenotype correlations of intermediate JEB.

Of the total 183 patients diagnosed with JEB, 99 (54%) of them had intermediate JEB and were included in the cohort study with 49 women and 50 men. Kidney-urinary tract manifestation was not detected in any of the women, but it was identified in 15 men, yielding a prevalence of 30% for men and 15% overall.

"This study’s findings suggest that KUT involvement is a frequent complication in males with intermediate JEB associated with variations in any JEB-associated gene; interdisciplinary and individualized diagnostic and therapeutic procedures are required for management of these complications," investigators wrote.

Identifying the Affected Proteins

Results indicated a mean age onset of 6.9 years for kidney-urinary tract involvement. The median follow up time post diagnosis of KUT involvement was 13 years, ranging from 3 months to 54 years.

No association was observed between the severity of KUT complications and the expansiveness of skin involvement, though, investigators reported a correlation between severity of complications and the affected protein.

"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," they wrote.

With a rare disorder like Junctional Epidermolysis Bullosa, physician and patient education and awareness around possible complications is imperative for proper management. Investigators emphasized the need for further research.

"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," they concluded. "Because this disorder is so rare, multicenter studies are required to make general recommendations."

The study, "Kidney–Urinary Tract Involvement in Intermediate Junctional Epidermolysis Bullosa" was published in JAMA Dermatology.