IL-6 Cytokine Useful for Monitoring of Severe Epidermolysis Bullosa

Interleukin (IL)-6 is the most consistent cytokine to correlate with wound body surface area (BSA) among patients with junctional and dystrophic epidermolysis bullosa (JEB and RDEB, respectively), recent findings suggest.1

These findings point to the use of IL-6 as beneficial for monitoring purposes in those with severe EB. Additionally, the study suggests that wound area would be a meaningful criterion for subclassification of EB.

These findings were the result of a new study authored by A. Reimer-Taschenbrecker, MD, from the department of dermatology at the University of Freiburg in Germany, and a team of investigators.

“This study evaluates whether specific serum cytokines are significantly elevated in patients with JEB and RDEB and if they correlate with disease severity and age,” Reimer-Taschenbrecker and colleagues wrote. “Understanding which patients are at risk of systemic inflammatory responses will likely help in therapeutic management, risk prevention, and might identify therapeutic targets.”1

Analysis of Cytokines in Junctional and Dystrophic Epidermolysis Bullosa

At the EB Center in Freiburg, Germany, the trial investigators carried out their prospective cohort study in the period between June 2018 - April 2020. At this center, the research team involved children and young adults who had been given diagnoses of JEB and RDEB.

In the study’s initial group, there were a total of 29 participants and 5 individuals with JEB, with a median age of 12 years. The group also included 9 with intermediate RDEB, all of whom had a median age of 7 years. 15 of the cohort reported severe cases of RDEB, with a median age of 11 years.

The research team also utilized a follow-up analysis for the purposes of validating their findings, analyzing C-reactive protein (CRP) and IL-6 during the subjects’ annual assessments between July 2021 - August 2023. This follow-up involved a total of 42 individuals.

Among the members of the validation study cohort, there were 11 who had been in the original group and 31 who were newly-recruited (24 males and 18 females). These subjects had a median age of 20 years, spanning from 0.3 - 59 years.

Fourteen of those in this analysis were diagnosed with JEB (median age 20 years) and 13 with intermediate RDEB (median age 30 years). The research team also highlighted that 15 had been shown to have severe RDEB (median age 17 years).

The investigators clinically evaluated the severity of patients’ epidermolysis bullosa using the standard classification system, although they assessed the extent of subjects’ wounded BSA through the use of a Lund-Browder diagram.

The researchers quantified intensity of pruritus using either a numeric rating scale (0–10) or the Itch Man Scale. The severity of the study subjects’ disease was determined through the use of the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI).

IL-6 in Pediatric Patients with JEB and RDEB

The research team determined that among the cytokines they assessed, IL-6 was shown to be the most significant marker of systemic inflammation. Among those included in both the initial and validation cohorts, it was reported that IL-6 levels correlated heavily with wound BSA.

IL-6 levels were shown to be within the normal range for subjects demonstrating less than 3% wound BSA, but the team concluded that those with wound involvement that went over 5% and 10% had significant elevations (P < .05). Contrasting with this finding, the investigators found that TGF-β levels were only mildly elevated in those who had severe RDEB.

At the same time, IFN-γ, TNF-α, and IL-1β were shown to have inconsistent variations. The research team further expressed that subjects who reported itch experiences were shown to have increased markers of type 2 immune response, including TSLP, IgE, IL-31, and IL-4.

“Our data suggests that IL-6 can be useful to monitor in patients with severe disease, and that wound area is a meaningful criterion for EB subclassification,” they wrote. “Targeted anti-inflammatory therapy may be reasonable, and consequent antibacterial/antiseptic wound care and gene therapy to close wound surfaces would probably address the cause and prevent systemic inflammation in severe JEB and RDEB.”1,2

References

1. Reimer-Taschenbrecker A, Hess M, Davidovic M, Hwang A, Hübner S, Hofsaess M, et al. IL-6 levels dominate the serum cytokine signature of severe epidermolysis bullosa: A prospective cohort study. J Eur Acad Dermatol Venereol. 2025; 39: 202–209. https://doi.org/10.1111/jdv.19898.
2. Eyerich K, Eyerich S. Immune response patterns in non-communicable inflammatory skin diseases. J Eur Acad Dermatol Venereol. 2018; 32: 692–703.