Rituximab in the Management of Autoimmune Bullous Diseases: A Treatment-Resistant Case Series from a Single Central European Referral Center

Abstract

Background and Objectives: Rituximab (RTX) has been the predominant treatment for autoimmune bullous diseases (AIBDs). The objective of this research was to assess the advantages and safety characteristics of RTX treatment in individuals with AIBD. This assessment focused on clinical remission and a reduction in glucocorticosteroid usage, its effect on the titers of autoantibodies targeting desmoglein-1 (DSG-1) and desmoglein-3 (DSG-3), and adverse occurrences during a 12-month follow-up period in a dermatology department within a Central European university context. Materials and Methods: Our case series involved eleven patients, including eight patients with pemphigus vulgaris, two with pemphigus foliaceus, and one with epidermolysis bullosa acquisita. They received a 1 g dose of rituximab, repeated over a two-week interval. Results: The reduction in a prednisone-equivalent dosage after 2, 6, and 12 months following the second RTX infusion was 65.05%, 73.99%, and 76.93%, in that order. The titers of antibodies against DSG-1 exhibited reductions of 43.29%, 75.86%, and 54.02% at 2, 6, and 12 months, respectively. By contrast, the antibody concentrations targeting DSG-3 displayed a decrease of 27.88%, 14.48%, and 5.09% at the corresponding time points. Over the course of the 12-month monitoring period, 18.18% of patients experienced disease relapse, while the remaining individuals achieved either complete or partial remission with minimal or no therapy. Adverse effects were noted in 36.36% of the patient population; they were mild, and no serious adverse effects were reported. Conclusions: RTX represents an efficacious and well-tolerated therapeutic option for the management of AIBD and merits consideration in cases of refractory AIBD. However, further research is imperative to delineate the most optimal dosage, dosing frequency, and total quantity of maintenance infusions required. Additionally, there is a compelling need for studies that explore the impact of RTX on individuals with AIBD who do not exhibit a significant reduction in anti-desmoglein autoantibody levels.

Keywords: autoimmune bullous diseases; desmoglein; glucocorticosteroids; rituximab.

Figure 1

Decrease in mean prednisone equivalent dosage during rituximab (RTX) therapy in AIBD.

Figure 2

Desmoglein concentrations post one-year of RTX treatment.

Figure 3

Percentage distribution of treatment effects during RTX therapy in AIBD.

Figure 4

A noteworthy 62-year-old patient with recalcitrant mechanobullous EBA (#11) in whom the value of IgG antibodies to type VII collagen with multiplex ELISA 3 months post two RTX infusions was highly elevated 4.51 (cut-off value = 1). Despite the RTX treatment regimen, the patient exhibited no clinical improvement. Erosions on an erythematous background are shown, some of which, covered with crusts, were seen on the trunk (A) and thigh (B). A flaccid blister with air bubbles and exfoliation in its vicinity on the dorsal surface of the hand was visible (C). IgG4 antibodies (D), but not IgG antibodies, reacting with the dermal side of salt–split primate skin at a titer above 1:160 were detected with IIF mosaic (Euroimmun, Germany with our own modification) performed simultaneously with multiplex ELISA and visualized with a blue light-emitting diode technology-operated microscopy with an original objective magnification of ×40.