Is there a role for B-cell depletion as therapy for scleroderma? A case report and review of the literature

Rituximab (RTX) has been successfully used in the treatment of several rheumatic diseases with an acceptable safety profile. We present herein a patient with systemic sclerosis (SSc) who exhibited significant improvement of his lung function and skin fibrosis following RTX administration, and review the literature regarding the role of B-cells in SSc and the potential efficacy of RTX in its treatment.

We performed an internet search using the keywords systemic sclerosis, scleroderma, rituximab, B-cells, fibrosis, interstitial lung disease (ILD), and therapy.

Our patient, a 40-year old man with severe SSc-associated ILD, received 4 courses of RTX. The patient's lung function improved; forced vital capacity and diffusing capacity of carbon monoxide reached values of 35% and 33%, respectively, compared with 30% and 14% of pretreatment values. Skin thickening assessed clinically and histologically improved as well. Several lines of evidence suggest that B-cells may have a pathogenic role in SSc. B-cells from tight skin mice--an animal model of SSc--exhibit chronic hyperactivity; likewise, B-cells from patients with SSc overexpress CD19 and are chronically activated. Furthermore, studies have revealed that B-cell genes were specifically transcribed in SSc skin and that B-cell infiltration was a prominent feature of SSc-associated ILD. The potential clinical efficacy of RTX in SSc has been explored in a limited number of patients with encouraging results. Preliminary data suggest that RTX may favorably affect skin as well as lung disease in SSc.

Several basic research data underscore the potential pathogenic role of B-cells in SSc and clinical evidence suggests that RTX might be a therapeutic option in SSc. Large-scale multicenter studies are needed to evaluate the potential clinical efficacy of RTX in SSc.