{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:55:02Z","timestamp":1782233702123,"version":"3.54.5"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To characterize the course of systemic inflammatory markers over time in patients with RDEB and explore their associations with clinical, microbiological and laboratory parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective longitudinal study analysed the clinical and laboratory data of 120 visits within 5\u2005years from 44 patients with intermediate (n = 22) and severe (n = 22) RDEB. Acute-phase proteins [C-reactive protein (CRP), interleukin (IL)-6, serum amyloid A (SAA)], neutrophil-to-lymphocyte ratio (NLR), leucocytes, 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, anaemia markers, wound microbiology and immunoglobulins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Individuals with severe RDEB showed an early and sustained systemic inflammatory profile, with CRP, IL-6 and SAA elevated &amp;gt; 3.5-fold from early childhood, plateauing in mid-adulthood. People with intermediate RDEB maintained low inflammatory activity throughout their lives. Acute-phase proteins and NLR were significantly elevated in the presence of SCC (CRP: P &amp;lt; 0.001; IL-6: P = 0.002; SAA: P = 0.01; NLR: P = 0.004), C7 absence (CRP: P = 0.002), and colonization by Pseudomonas (CRP and IL-6: P &amp;lt; 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 with Staphylococcus infections. Hypoalbuminaemia and elevated immunoglobulins correlated with inflammatory markers and anaemia 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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 \u2013 wound burden reduction through curative or corrective interventions, antimicrobial strategies and anti-inflammatory therapy \u2013 aligned with standard of care and nutritional supplementation.<\/jats:p>\n                    <jats:p>An author video to accompany this article is available online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bjd\/ljag082","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T12:46:28Z","timestamp":1772628388000},"page":"146-157","source":"Crossref","is-referenced-by-count":2,"title":["Systemic inflammation in recessive dystrophic epidermolysis bullosa: a 5-year longitudinal study"],"prefix":"10.1093","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1067-8582","authenticated-orcid":false,"given":"Meropi","family":"Karakioulaki","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereology, Faculty of Medicine 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Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0094-2674","authenticated-orcid":false,"given":"Kilian","family":"Eyerich","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Faculty of Medicine and Medical Center, University Hospital Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6066-507X","authenticated-orcid":false,"given":"Cristina","family":"Has","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Faculty of Medicine and Medical Center, University Hospital Freiburg 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