Risks Associated with Arboviral Infections in Rituximab-Treated Patients
Patients undergoing rituximab therapy, a monoclonal antibody known for depleting B-cells, face elevated risks of neuroinvasive diseases and mortality when infected with arboviral pathogens. The true incidence of infections and related fatalities may be underestimated due to the challenging and costly molecular testing often necessary for identifying the cause of illness in immunosuppressed individuals.
Rituximab is employed in the treatment of various immunocompromising conditions such as non-Hodgkin lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis. A study identified 21 individuals undergoing rituximab therapy who were diagnosed with arboviral diseases; all exhibited neuroinvasive disease, with over 70% succumbing to the infection.
Lead study author Carolyn V. Gould, MD, from the CDC’s Division of Vector-Borne Diseases in Fort Collins, Colo., highlighted the severity, atypical nature, prolonged manifestations, and high mortality rate observed in these cases. She emphasized the lack of an antibody response, necessitating molecular testing for viral RNA detection, which deviates from standard testing practices for domestic arboviral diseases.
Surprisingly, initial serological testing for arboviruses yielded negative results in 19 out of 20 patients, compelling the need for molecular testing in 95% of participants for accurate disease diagnosis.
The study cohort, identified through a literature review and CDC requests for arboviral diagnostic testing as of July 1, 2021, consisted of individuals with a median age of 58 years, nearly half being female. Rituximab therapy was primarily indicated for lymphoma or leukemia (71%) and rheumatoid arthritis (14%), with other uses including systemic lupus erythematosus and post-transplant rejection.
West Nile virus emerged as the most prevalent infection among participants, with additional cases of tick-borne encephalitis, eastern equine encephalitis, and viruses like Cache Valley, Jamestown Canyon, and Powassan. Notably, more than half of the patients became ill between June and September.
Symptoms typically appeared about one month after the last rituximab dose, ranging from febrile illness to neurological impairments. Supportive care constituted the primary treatment, but the study reported a 71% mortality rate among the 19 patients with reported outcomes. Survivors faced substantial long-term disabilities.
Recognizing the lack of proven effective treatments for arboviral diseases, the researchers emphasized the importance of outreach to enhance awareness, diagnostic testing, and prevention, particularly in patients at risk due to B-cell–depleting therapies.
Medical professionals need to be aware that patients with rituximab-induced B-cell deficiency are susceptible to severe arboviral infections. When evaluating patients with acute-onset encephalopathy, clinicians should consider this complication and conduct a thorough diagnostic workup, as typical clinical and diagnostic indicators may be absent.
Amanda L. Piquet, MD, associate director of the autoimmune neurology program at the University of Colorado School of Medicine Anschutz Medical Campus, cautioned about the retrospective nature of the study and acknowledged limitations in available information, such as rituximab dosing. She also noted the absence of data on patients using newer anti-CD20 or anti-CD19 agents.
The CDC warns of an increasing threat of arboviral diseases, exacerbated by the growing use of B-cell–depleting therapies, including rituximab biosimilar agents. The approval of these agents, along with their off-label use in treating autoimmune conditions, contributes to the rising risk of arboviral infections.”