Systemic inflammation in recessive dystrophic epidermolysis bullosa: a five-year longitudinal study.

Abstract

Recessive dystrophic epidermolysis bullosa (RDEB) is characterized by skin fragility, extensive wounding, and systemic complications. While inflammation contributes to disease severity, its pattern, longitudinal dynamics and clinical correlates remain poorly defined. To characterize the course of systemic inflammatory markers over time in patients with RDEB and explore their associations with clinical, microbiological, and laboratory parameters. This retrospective longitudinal study analyzed clinical and laboratory data of 120 visits within 5 years from 44 patients with intermediate (N=22) and severe (N=22) RDEB. Acute-phase proteins (CRP, IL-6, SAA), neutrophil to lymphocyte ratio (NLR), leukocytes, thrombocytes and ferritin were examined in relation to wound body surface area, mucosal involvement, collagen VII (C7) protein expression levels, squamous cell carcinoma (SCC) presence, nutritional status, anemia markers, wound microbiology and immunoglobulins. Severe RDEB showed an early and sustained systemic inflammatory profile, with CRP, IL-6, and SAA elevated >3.5-fold from early childhood, plateauing in mid-adulthood. Intermediate RDEB maintained low inflammatory activity throughout life. Acute phase proteins and NLR were significantly elevated in the presence of SCC (CRP: p<0.001; IL-6: p=0.002; SAA: p=0.011; NLR: p=0.004), collagen VII absence (CRP: p=0.002), and colonization by Pseudomonas (CRP, IL-6: p<0.001) or fungi (CRP: p=0.006). CRP and age were the most robust independent predictors of SCC risk. Streptococcus, Pseudomonas, fungi, or polymicrobial colonization were associated with a broader systemic inflammatory response, when compared to infections with Staphylococcus. Hypoalbuminemia and elevated immunoglobulins correlated with inflammatory markers and anemia of chronic disease was reflected by declining iron and increased ferritin levels. In multivariable models, reduced C7 expression, wound burden and SCC were the strongest independent predictors of acute phase inflammation. This study reveals that severe RDEB involves early-onset, progressive systemic inflammation that peaks in mid-adulthood and then plateaus, suggesting a critical window for therapeutic intervention. In contrast, intermediate RDEB shows minimal systemic inflammation. The findings support a three-tiered treatment approach-wound burden reduction through curative/corrective interventions, antimicrobial strategies and anti-inflammatory therapy -aligned with standard of care and nutritional supplementation.