{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T23:57:28Z","timestamp":1783036648696,"version":"3.54.6"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:00:00Z","timestamp":1674691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 2167, SFB 1526, GRK 2633"],"award-info":[{"award-number":["EXC 2167, SFB 1526, GRK 2633"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Identification of risk factors and sequelae of any given disease is of key importance. For common diseases, primary prevention and disease management are based on this knowledge. For orphan diseases, identification of risk factors and sequelae has been challenging. With the advent of large databases, e.g., TriNetX, this can now be addressed. We used TriNetX to identify risk factors and sequelae of epidermolysis bullosa acquisita (EBA), a severe and orphan autoimmune disease. To date, there is only enigmatic information on EBA comorbidity. We recruited 1,344 EBA patients in the Global Collaborative Network of TriNetX. Using the \u201cexplore outcomes\u201d function we identified 55 diagnoses with a different prevalence between EBA and no-EBA patients. We next performed propensity-matched, retrospective cohort studies in which we determined the risk of EBA development following any of the identified 55 diseases. Here, 31\/55 diseases were identified as risk factors for subsequent EBA. Importantly, the highest risk for EBA were other chronic inflammatory diseases (CID), especially lupus erythematosus and lichen planus. Lastly, we determined the risk to develop any of the identified diseases after EBA diagnosis. Here, 38\/55 diseases were identified as sequelae. Notably, EBA patients showed an increased risk for metabolic and cardiovascular disease, and thrombosis. Furthermore, the risk for CIDs, especially lupus erythematosus and lichen planus, was elevated. These insights into risk factors and sequelae of EBA are not only of clinical relevance, e.g., optimizing cardiovascular disease risk, but in addition, point to shared pathogenetic pathways between EBA and other inflammatory diseases.<\/jats:p>","DOI":"10.3389\/fimmu.2022.1103533","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T16:18:40Z","timestamp":1674749920000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Risk factors and sequelae of epidermolysis bullosa acquisita: A propensity-matched global study in 1,344 patients"],"prefix":"10.3389","volume":"13","author":[{"given":"Khalaf","family":"Kridin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artem","family":"Vorobyev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Papara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"De Luca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Bieber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf J.","family":"Ludwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21386","article-title":"Induction of dermal-epidermal separation in mice by passive transfer of antibodies specific to type VII collagen","volume":"115","author":"Sitaru","year":"2005","journal-title":"J Clin Invest"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2005.23702.x","article-title":"Evidence that anti-type VII collagen antibodies are pathogenic and responsible for the clinical, histological, and immunological features of epidermolysis bullosa acquisita","volume":"124","author":"Woodley","year":"2005","journal-title":"J Invest Dermatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1610-0387.2008.06976.x","article-title":"Prospective analysis of the incidence of autoimmune bullous disorders in lower franconia, Germany","volume":"7","author":"Bertram","year":"2009","journal-title":"J Dtsch Dermatol Ges"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.07.013","article-title":"Prevalence and age distribution of pemphigus and pemphigoid diseases in Germany","volume":"136","author":"H\u00fcbner","year":"2016","journal-title":"J Invest Dermatol"},{"key":"B5","doi-asserted-by":"crossref","DOI":"10.2340\/0001555558241244","article-title":"Epidermolysis bullosa acquisita and crohn\u2019s disease","volume":"58","author":"Livden","year":"1978","journal-title":"Acta Derm Venereol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1177\/014107688808100821","article-title":"Epidermolysis bullosa acquisita and total ulcerative colitis","volume":"81","author":"Hughes","year":"1988","journal-title":"J R Soc Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.231","article-title":"Black patients of African descent and HLA-DRB1*15:03 frequency overrepresented in epidermolysis bullosa acquisita","volume":"131","author":"Zumelzu","year":"2011","journal-title":"J Invest Dermatol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.1985.tb00546.x","article-title":"Epidermolysis bullosa acquisita associated with chronic lymphatic leukaemia","volume":"10","author":"Shaw","year":"1985","journal-title":"Clin Exp Dermatol"},{"key":"B9","article-title":"[Epidermolysis bullosa acquisita and metastatic cancer of the uterine cervix]","volume":"125","author":"Etienne","year":"1998","journal-title":"Ann Dermatol Venereol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1997.tb01119.x","article-title":"Psoriasis vulgaris coexistent with epidermolysis bullosa acquisita","volume":"137","author":"Endo","year":"1997","journal-title":"Br J Dermatol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-199907000-00003","article-title":"Subepidermal autoimmune bullous skin diseases associated with b-cell lymphoproliferative disorders","volume":"78","author":"Aractingi","year":"1999","journal-title":"Med (Baltimore)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/s13023-018-0896-1","article-title":"Meta-analysis of the clinical and immunopathological characteristics and treatment outcomes in epidermolysis bullosa acquisita patients","volume":"13","author":"Iwata","year":"2018","journal-title":"Orphanet J Rare Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2018.11.058","article-title":"Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities","volume":"80","author":"Elmets","year":"2019","journal-title":"J Am Acad Dermatol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000678","article-title":"2019 ACC\/AHA guideline on the primary prevention of cardiovascular disease: A report of the American college of Cardiology\/American heart association task force on clinical practice guidelines","volume":"140","author":"Arnett","year":"2019","journal-title":"Circulation"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31357-5","article-title":"Interpretation of the evidence for the efficacy and safety of statin therapy","volume":"388","author":"Collins","year":"2016","journal-title":"Lancet"},{"key":"B16","volume-title":"EULAR recommendations regarding lifestyle behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases","author":"Gwinnutt","year":"2023"},{"key":"B17","first-page":"234","article-title":"Epidermolysis bullosa acquisita and crohn\u2019s disease","volume":"66","author":"Pegum","year":"1973","journal-title":"Proc R Soc Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1983.03340130064034","article-title":"Epidermolysis bullosa acquisita and inflammatory bowel disease","volume":"250","author":"Raab","year":"1983","journal-title":"JAMA"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/ced.12114","article-title":"Epidermolysis bullosa acquisita and inflammatory bowel disease: a review of the literature","volume":"38","author":"Reddy","year":"2013","journal-title":"Clin Exp Dermatol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2018.00362","article-title":"Epidermolysis bullosa acquisita: The 2019 update","volume":"5","author":"Koga","year":"2019","journal-title":"Front Med (Lausanne)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-1065","article-title":"Epidermolysis bullosa acquisita: A retrospective clinical analysis of 30 cases","volume":"91","author":"Kim","year":"2011","journal-title":"Acta Derm Venereol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2011.549127","article-title":"Current concepts in the treatment of epidermolysis bullosa acquisita","volume":"12","author":"G\u00fcrcan","year":"2011","journal-title":"Expert Opin Pharmacother"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18245","article-title":"Management of psoriasis as a systemic disease: what is the evidence","volume":"182","author":"Korman","year":"2020","journal-title":"Br J Dermatol"},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.2340\/00015555-3387","volume-title":"Psoriasis and Co-morbidity","author":"Amin","year":""},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102925","article-title":"Systematic review and meta-analysis of cardiovascular risk in rheumatological disease: Symptomatic and non-symptomatic events in rheumatoid arthritis and systemic lupus erythematosus","volume":"21","author":"Restivo","year":"2022","journal-title":"Autoimmun Rev"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/ddg.14819","article-title":"DNA Chip-based diagnosis of onychomycosis and tinea pedis","volume":"20","author":"Bieber","year":"2022","journal-title":"J Dtsch Dermatol Ges"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2018.00296","article-title":"Diagnosis of autoimmune blistering diseases","volume":"5","author":"Witte","year":"2018","journal-title":"Front Med (Lausanne)"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.02.009","article-title":"Cardiovascular risk in patients with psoriasis: JACC review topic of the week","volume":"77","author":"Garshick","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1136\/annrheumdis-2020-218272","article-title":"Update on the diagnosis and management of systemic lupus erythematosus","volume":"80","author":"Fanouriakis","year":"2021","journal-title":"Ann Rheum Dis"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102776","article-title":"Rheumatoid arthritis: Extra-articular manifestations and comorbidities","volume":"20","author":"Figus","year":"2021","journal-title":"Autoimmun Rev"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-9-1","article-title":"Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage study","volume":"9","author":"Ramagopalan","year":"2011","journal-title":"BMC Med"},{"key":"B32","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1111\/j.1365-2249.2012.04674.x","article-title":"Prothrombotic state and impaired fibrinolysis in bullous pemphigoid, the most frequent autoimmune blistering disease","volume":"171","author":"Marzano","year":"2013","journal-title":"Clin Exp Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/0190-9622(90)70077-U","article-title":"Epidermolysis bullosa acquisita preceding the development of systemic lupus erythematosus","volume":"22","author":"Boh","year":"1990","journal-title":"2319019"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.1993.tb02224.x","article-title":"Epidermolysis bullosa acquisita occurring in association with systemic lupus erythematosus","volume":"18","author":"McHenry","year":"1993","journal-title":"Clin Exp Dermatol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-014-0098-0","article-title":"Bullous systemic lupus erythematosus: a review and update to diagnosis and treatment","volume":"15","author":"Contestable","year":"2014","journal-title":"Am J Clin Dermatol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2011.10346.x","article-title":"The many faces of epidermolysis bullosa acquisita after serration pattern analysis by direct immunofluorescence microscopy","volume":"165","author":"Buijsrogge","year":"2011","journal-title":"Br J Dermatol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-13-16","article-title":"Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases","volume":"13","author":"Licarete","year":"2012","journal-title":"BMC Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.135.8.954","article-title":"Mucosal morbidity in patients with epidermolysis bullosa acquisita","volume":"135","author":"Luke","year":"1999","journal-title":"Arch Dermatol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"4509","DOI":"10.1038\/s41598-020-60233-w","article-title":"Visualization of autoantibodies and neutrophils in vivo identifies novel checkpoints in autoantibody-induced tissue injury","volume":"10","author":"Hundt","year":"2020","journal-title":"Sci Rep"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/path.2857","article-title":"Autoantibody-induced intestinal inflammation and weight loss in experimental epidermolysis bullosa acquisita","volume":"224","author":"Ishii","year":"2011","journal-title":"J Pathol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1103533\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T17:46:28Z","timestamp":1701798388000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1103533\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,26]]},"references-count":40,"alternative-id":["10.3389\/fimmu.2022.1103533"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.1103533","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,26]]},"article-number":"1103533"}}