Risk factors and sequelae of epidermolysis bullosa acquisita: A propensity-matched global study in 1,344 patients

Abstract

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 “explore outcomes” 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.

Rheumatic diseases associated with autoimmune bullous dermatoses

“…EBA is a relatively rare AIBD resulting from the immunoglobulin G antibody against the type VII collagen within the anchoring fibril. The association between EBA and SLE was well recognized 40 . EBA was also found to share a similar autoantibody with bullous LE 53 .…”

“…The association between EBA and SLE was well recognized. 40 EBA was also found to share a similar autoantibody with bullous LE. 53 Bullous LE is an uncommon variant of SLE, with cutaneous blisters appearing more in sun-exposed areas, such as face, and some on mucosal surfaces.…”

“…and Y.H.H.) to verify their relevance and classify the level of evidence (Table S1 1–3,5–48 ). The rheumatic diseases associated with AIBDs were summarized in Table 1.…”

Case Report: Biological treatment of epidermolysis bullosa acquisita: report on four cases and literature review

“…Recently, it has been found that 55 different diseases had significantly different prevalences among EBA patients compared to the general population. Of these, 23 diseases were identified as risk factors for EBA ( 8 ). In these cases, alternative therapy may be required, as exemplified by our patients.…”

“…Although IBD has long been recognized as a risk factor for EBA ( 2 , 14 – 17 ), recent research on medical records of 1344 EBA cases has challenged this association. The authors did not identify inflammatory bowel diseases as risk factors or sequelae of EBA ( 8 ).…”