Meta-analysis of the clinical and immunopathological characteristics and treatment outcomes in epidermolysis bullosa acquisita patients

Abstract

Background: Epidermolysis bullosa acquisita (EBA) is an orphan autoimmune disease. Several clinical phenotypes have been described, but subepidermal blistering is characteristic of all variants. Limited data on clinical and immunopathological characteristics and treatment outcomes in EBA are available. To fill this gap, we collected this information from EBA cases, meeting current diagnostic criteria, published between 1971 and 2016.

Results: We identified 1159 EBA cases. This number must be, however, interpreted with caution, as it is not possible to check for multiple reporting. The analysis of all cases indicated that EBA affects all age groups (median: 50 years, range: 1 to 94 years) at an equal gender distribution. Non-mechanobullous (non-MB) forms of EBA were observed in 55% of patients, whereas the mechanobullous variant (MB-EBA) or a combination of both variants was described in 38 or 7% of patients, respectively. Type VII collagen (COL7)-specific autoantibodies were primarily of the IgG isotype, but anti-COL7 IgA, IgM and IgE were also documented. Comparison of the 2 clinical EBA types showed a higher frequency of IgA deposits in non-MB EBA as opposed to MB EBA. Mucous membrane involvement was observed in 23% of patients, and 4.4% of cases were associated with other chronic inflammatory diseases. Of note, IgA deposits were more frequently observed in cases with mucous membrane involvement. Our analysis indicated that EBA is difficult to treat and that the choice of treatment varies widely. Chi square was applied to identify medications associated with complete remission (CR). Considering all EBA cases, intravenous immunoglobulin (IVIG, p = 0.0047) and rituximab (p = 0.0114) were associated with CR. Subgroup analysis demonstrated that no treatment was associated with CR for non-MB EBA, while IVIG (p = 0.003) was associated with CR in MB EBA.

Conclusions: Within the limitations of the study, we here document the clinical and immunopathological characteristics and treatment outcomes in a large cohort of EBA patients. The observed associations of single drugs with treatment outcome may serve as a guide to develop clinical trials.

Keywords: Diagnosis; Epidermolysis bullosa acquisita; IVIG; Meta-analysis; Rituximab; Treatment.

Fig. 1

Reported EBA cases and number of publications reporting EBA patients from 1971 to 2016. PubMed was searched using the term “(epidermolysis bullosa acquisita) AND (“1971”[Date - Publication]: “2016”[Date - Publication])”. EBA patients fulfilling the current diagnostic criteria were selected from the retrieved records. A total of 1159 EBA cases (data sets) were identified. Over the years, the number of reported cases ranged from 2 to 5 per year with the exception of 1996–99 and 2011–12, when 11–62 patients were reported per year. The graph displays the cumulative number of EBA patients reported between 1971 and 2016. The number of publications on EBA patients remained relatively constant during the time frame assessed; during this time, 2–6 manuscripts per year were typically published. If publications with a focus on immunological studies, i.e. ELISA development or HLA-associations, are excluded from this analysis, a total of 519 data sets in 194 publications remain. The green arrow indicates the time point when IG deposits were first noticed in EBA patients [3], while the red arrow corresponds to the description of the first [47] and the first commercialized [72] ELISA system detecting autoantibodies directed against COL7