Rituximab-Associated Flare of Cryoglobulinemic Vasculitis

Background Patients with cryoglobulinemic vasculitis (CV) can develop disease flare after rituximab administration. The objective of our study was to describe the prevalence, clinical characteristics, predisposing factors, and outcomes of patients with rituximab-associated flare of CV. Methods We conducted a retrospective study in a tertiary referral center until March 25, 2020. Results Among 64 patients with CV who received rituximab therapy in our center, 14 (22%) developed disease flare. Median age was 67.5 years. Seven patients (50%) had type II CV and the other half had either type I (n = 6) or type III (n = 1). Twelve patients (86%) had an underlying B-cell lymphoproliferative disorder as the cause of their CV. CV flare occurred after a median time of 5.5 days (range: 2–8 days). The organ systems most involved were the skin (n = 10), kidneys (n = 5), and peripheral nerves (n = 3). Five patients (36%) developed acute kidney injury (AKI), 3 of whom presented with nephritic syndrome secondary to biopsy-proven membranoproliferative glomerulonephritis. Treatment was directed against the underlying disease in addition to supportive care. Patients who developed flare were more likely to have B-cell lymphoproliferative disorder as the underlying etiology of their CV (P = 0.03). Eight patients (57%) died after a median time of 27 months. Conclusions Rituximab-associated flare can occur in all types of CV, tends to arise approximately 2 days and less than 1 week after rituximab administration, and is more likely to happen in patients with an underlying B-cell lymphoproliferative disorder. It does not indicate treatment failure, and rituximab should not be abandoned altogether. AKI is a common manifestation, and mortality rate at 2 years is high.
Graphical abstract