Treatment with intravenous immunoglobulin (IVIG) and off-label rituximab can lead to complete remission of epidermolysis bullosa acquisita (EBA), according to a study that also illustrates the variable clinical and immunological presentations of EBA.
The study, “Meta-analysis of the clinical and immunopathological characteristics and treatment outcomes in epidermolysis bullosa acquisita patients,” was published in the Orphanet Journal of Rare Diseases.
In EBA, immune deposits of immunoglobulin G (IgG), the most abundant antibody class in humans, and complement protein C3 are well-known at the dermal-epidermal skin layer junction. The complement system is a set of more than 20 proteins that form part of the body’s immune defenses.
Autoantibodies against the protein collagen VII (COL7), the main component of so-called anchoring fibrils that hold skin layers together, led to the classification of EBA as an autoimmune disease. The detection of these COL7 autoantibodies is a way to diagnose EBA.
Clinical manifestations in EBA are diverse and may be similar to other EB subtypes, as well as to other autoimmune skin conditions including bullous pemphigoid. A patient’s clinical presentations may change over the course of the disease, but data on the prevalence of different EBA symptoms are not available. Additionally, eye and genital involvement, among other mucosal sites, may be more common than generally recognized.
Aiming to better understand the epidemiological, clinical, and immunological characteristics of EBA patients, a team from Germany, France, and Japan conducted a meta-analysis — a type of statistical study that combines the results of various studies — of all EBA cases published from 1971 to 2016.
The online search identified 1,159 EBA cases, affecting all age groups (median age 50 years, with a range between 1 and 94 years) and men and women equally. Of these, 54 cases occurred in children (17 years or younger), and 132 in adults 65 or older. The mechanobullous variant (MB, non-inflammatory, classical) of EBA was described in 38% of patients, while the non-MB forms were observed in 55% of patients. A combination of both was reported in 7%.
Autoantibodies against COL7 were primarily of the IgG type, but other types — IgA, IgM and IgE — were also found. IgG was the only deposited autoantibody in 62.1% of patients. Overall, deposits of IgG, IgA, IgM, and C3 were more common in non-MB than in MB EBA patients.
Mucosal involvement was found in 23% of patients (mainly the oral mucosa), with IgA deposits more common in cases with mucosal involvement. In addition, 4.4% of patients had other chronic inflammatory diseases – Crohn’s disease was the most common (0.9%). According to the team, the prevalence of Crohn’s disease in EBA was lower than in previous studies, which may be due to different diagnostic criteria.
EBA was found difficult to treat, and with a wide range of treatment choices, the researchers noted. Most patients had been treated with multiple medications due to overall lack of efficacy.
When looking at EBA subtypes, no single treatment correlated with remission in non-MB, while IVIG was associated with complete remission in MB EBA patients.
“Based on the results from our meta-analysis … IVIG and rituximab seem likely candidates to be used in combination therapies as a treatment for EBA patients,” the researchers concluded.
According to the team, this result “has to be interpreted with caution, but may be useful to guide the planning of clinical trials in EBA patients.”