Borrelia afzelii-associated seronegative Lyme neuroborreliosis in an immunocompromised patient

This case highlights the diagnostic complexity of Lyme neuroborreliosis (LNB) in immunosuppressed patients. A 62-year-old man with a history of follicular lymphoma, previously treated with R-Bendamustine and currently rituximab, presented with generalized symptoms and systemic inflammation. Lymphoma relapse was excluded and diagnostic evaluations for infectious, metabolic, and autoimmune etiologies yielded unremarkable results. Several antibiotic treatments were without effect. An amplicon-based microbiome blood analysis using next-generation sequencing identified Borrelia afzelii, confirmed by specific PCR. Cerebrospinal fluid analysis revealed pleocytosis and elevated CXCL13. Blood serology and intrathecal Borrelia burgdorferi antibodies were negative. Treatment with doxycycline led to clinical and laboratory improvement corroborating LNB diagnosis. The case underscores that B-cell-depleting therapy can impair antibody responses, resulting in false-negative serology and LNB may present atypically. In cases like this advanced diagnostics like PCR and CXCL13 measurement can be valuable tools. Clinicians must consider the impact of immunosuppression on both disease presentation and diagnostic reliability.