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Semin Arthritis Rheum. 2015 Dec;45(3):334-40. doi: 10.1016/j.semarthrit.2015.06.014. Epub 2015 Jun 26.

Rituximab-induced serum sickness: A systematic review.

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Department of Internal Medicine, Reading Health System, 6th Ave and Spruce St, West Reading, PA 19612. Electronic address:
Department of Internal Medicine, Reading Health System, 6th Ave and Spruce St, West Reading, PA 19612.
Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN.
Department of Medicine, Johns Hopkins University, Baltimore, MD.



To report a case of rituximab-induced serum sickness (RISS) and perform a systematic review and characterize RISS in autoimmune diseases and hematological malignancies.


A comprehensive search of MEDLINE, EMBASE, ACR, and EULAR databases was performed for relevant articles of patients with RISS from inception to September 2014. Statistical analysis of demographic and clinical features was performed using Microsoft EXCEL 2007 and SPSS version 20.0.


In the 33 patients with RISS, the mean age of presentation was 39.1 ± 17.5yr with a female preponderance (n = 23, 76.67%). The majority of cases were associated with an underlying rheumatologic condition (n = 17, 51.5%), most commonly Sjögren's syndrome (n = 8, 44.4%). The classic triad of serum sickness (fever, rash, and arthralgia) was reported in 16 (48.5%) cases. Time from drug exposure to symptom onset was significantly greater with the first doses of rituximab compared to the second dose (mean time 10.00 vs. 4.05d, P = 0.002), and time to resolution was significantly greater for rheumatologic vs. hematological indications (mean time 2.50 vs. 1.00d, P = 0.035). Corticosteroids were the most commonly used treatment (n = 21), with all cases reporting a complete resolution of symptoms in 2.15 ± 1.34d.


It is important to recognize RISS clinically, as it may mimic exacerbation of various rheumatologic conditions. Although RISS is typically self-limited, further infusions of rituximab should be avoided, as it may provoke more severe symptoms.


Infusion reaction; Rheumatoid arthritis; Rituximab; Serum sickness

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