Borrelia Infections Under B Cell-Depleting Therapies: A Systematic Review of Diagnostic Challenges and Outcomes With...

B-cell-depleting therapies such as rituximab and newer anti-CD20 agents may impair humoral immune responses and reduce the reliability of serological testing. This systematic review aims to summarize reported cases of Lyme borreliosis and relapsing fever (RF) Borrelia infections in patients receiving B-cell-depleting therapies, focusing on clinical manifestations, diagnostic challenges, and treatment outcomes.

A systematic literature search was conducted using PubMed and the Web of Science Core Collection employing search terms linking B-cell-depleting therapies to Lyme borreliosis and to RF Borrelia infections.

The most reported cases in the literature were neurological infections due to Borrelia; there were 11 cases of Lyme neuroborreliosis and 8 cases of neurological infections due to B. miyamotoi reported. Lyme neuroborreliosis cases all exhibited negative serology. Pleocytosis of cerebrospinal fluid (CSF) was, however, always present, and PCR could confirm the diagnosis in 8 cases. Diagnosis in all B. miyamotoi cases relied exclusively on direct detection methods. All patients responded to standard antibiotic regimens, although persistent symptoms were reported in some cases. The other infections were 7 erythema migrans (EM), 4 disseminated Lyme borreliosis, and 3 cases of relapsing fever.

Neurological Borrelia infections may be underrecognized in patients on B cell-depleting therapies due to atypical presentations and negative serologies. Early consideration of direct diagnostic methods such as PCR or indirect methods such as CSF CXCL13 levels is critical. Neurologists should maintain a high index of suspicion for Borrelia infections in immunocompromised patients presenting with CSF pleocytosis and neurological symptoms.