Unveiling the Uncommon: Infective Endocarditis Following Ocrelizumab Therapy in Relapsing-Remitting Multiple Sclerosis

Abstract

Ocrelizumab is an anti-CD20 monoclonal antibody approved for relapsing-remitting multiple sclerosis (RRMS) that induces B-cell depletion and may increase susceptibility to infection via hypogammaglobulinemia; however, serious bloodstream infections are uncommon, and infective endocarditis (IE) is rare. We describe a 20-year-old man with RRMS, hypertension, class II obesity, and type 2 diabetes who developed persistent fever 7 days after receiving a 300-mg ocrelizumab infusion, with blood cultures growing Staphylococcus aureus. Transesophageal echocardiography demonstrated a 4-mm mobile vegetation on the atrial aspect of the P2 scallop of the posterior mitral leaflet; chest computed tomography revealed bilateral peripheral nodules consistent with hematogenous infection, and cardiac magnetic resonance imaging suggested concomitant myocarditis. The patient completed 6 weeks of intravenous cefazolin with full clinical recovery, clearance of bacteremia, and echocardiographic resolution of the vegetation. To our knowledge, this represents the second published case report of S. aureus IE temporally associated with ocrelizumab therapy. Although causality cannot be established, anti-CD20-mediated B-cell depletion may be associated with increased infection risk in susceptible hosts, particularly those with cardiometabolic comorbidities and recent corticosteroid exposure. These findings underscore the importance of early evaluation for serious infection, including IE, in patients initiating ocrelizumab who present with persistent fever or bacteremia.

Keywords

multiple sclerosis - relapsing-remitting - ocrelizumab - infective endocarditis - Staphylococcus aureus - echocardiography - transesophageal - immunosuppression

Introduction

The introduction of biologic therapies has transformed the treatment of autoimmune diseases, including relapsing-remitting multiple sclerosis (RRMS), by improving relapse control, reducing disease activity, and delaying disability progression.[1] Ocrelizumab, a humanized monoclonal antibody targeting CD20-positive B cells, has demonstrated superior efficacy compared with interferon β-1a in reducing relapse rates and MRI lesion burden in RRMS and in slowing disability progression.[2] [3] By depleting B cells, ocrelizumab modulates aberrant immune responses; however, this mechanism may also impair host defenses, increasing susceptibility to bacterial, viral, and opportunistic infections.[1] [4] [5] The safety profile of ocrelizumab is generally favorable, with infections commonly reported and reactivation of latent pathogens, including hepatitis B virus and John Cunningham virus, described.[4] Serious bloodstream infections and infective endocarditis (IE) appear to be very uncommon, and a single published case report has previously described Staphylococcus aureus IE in an RRMS patient receiving ocrelizumab.[6] Faissner et al reported this first known instance, which developed insidiously over several months.[6]

We report a second case of IE occurring within 1 week of the first ocrelizumab infusion in a patient with cardiometabolic comorbidities. Hypertension, obesity, and type 2 diabetes may have contributed to the accelerated course.[7] [8] [9] This case highlights the potential interaction between B-cell depletion related immunosuppression and host risk factors in predisposing to IE, and it underscores the importance of early post-infusion vigilance for persistent fever or bacteremia.

Case Description

A 20-year-old man with hypertension, class II obesity, and type 2 diabetes mellitus presented with acute right-sided weakness. Brain MRI revealed multiple supra- and infratentorial hyperintensities, several of which were enhancing, consistent with dissemination in time per the McDonald criteria, while spine MRI was normal. He received intravenous corticosteroids for 5 days with clinical improvement. Baseline immunology obtained within 30 days before initiation of ocrelizumab showed IgG 11.2 g/L, CD19⁺ 230 cells/µL comprising 11% of lymphocytes, and CD20⁺ 225 cells/µL comprising 10.7%. He then received his first 300 mg ocrelizumab infusion.

Within 48 hours of the infusion, he developed a single episode of fever and headache that improved transiently and prompted an emergency department visit. He received supportive care, and the initial laboratory evaluation was unremarkable.

One week after the infusion, he re-presented to the emergency department with persistent fever, headache, and chest discomfort. He was hemodynamically stable, alert, and conversational, with no clinical signs of meningitis. The white blood cell count was approximately 6.0 × 10⁹/L with neutrophilia and relative lymphopenia, and C-reactive protein was 154 mg/L. High-sensitivity troponin T was 1,484 ng/L, with serial troponin T values of 1,350, 1,100, and 1,590 ng/L. NT-proBNP was 482 ng/L, procalcitonin was 0.44 ng/mL, and D-dimer was 0.70 µg/mL FEU. The echocardiography showed sinus rhythm with tall T waves in the anterolateral leads. Urinalysis was negative, and chest radiography was unremarkable. Three sets of peripheral blood cultures were obtained from separate venipuncture sites before initiation of empiric antibiotics; susceptibility testing was performed. Empiric broad-spectrum antibiotic therapy with piperacillin-tazobactam was initiated. All blood culture sets subsequently grew S. aureus, confirming bacteremia. Transesophageal echocardiography demonstrated a 4-mm mobile echodensity on the atrial aspect of the P2 scallop of the posterior mitral leaflet, consistent with a vegetation and confirming IE ([Fig. 1]). Cardiac MRI displayed features suggestive of myocarditis. Autoimmune serologic testing was negative. Infectious testing, including cytomegalovirus testing, Epstein–Barr virus testing, and a respiratory viral panel, was also negative. Repeat brain MRI demonstrated new enhancing lesions in the right temporal lobe and left frontal operculum, while spine MRI showed no evidence of discitis or osteomyelitis.

Fig. 1 Transesophageal echocardiography demonstrating native mitral-valve infective endocarditis. (A) Mid-esophageal view at approximately 59 degrees showing a 4-mm mobile echodensity on the atrial aspect of the P2 scallop of the posterior mitral leaflet (arrow). (B) Mid-esophageal view at 0° degree again demonstrating the same vegetation (arrow).

A multidisciplinary team (hospital medicine, cardiology, neurology, infectious diseases, and radiology) recommended 6 weeks of intravenous cefazolin for native mitral-valve IE. Given the temporal relationship to anti-CD20 initiation and the absence of prosthetic valves, congenital heart disease, injection-drug use, or prolonged central venous access, the infection was considered temporally associated with recent ocrelizumab exposure. The patient's metabolic comorbidities and recent corticosteroid course were thought as additional risk factors.

After therapy, the patient was afebrile with normalization of inflammatory markers. C-reactive protein decreased to 9.2 mg/L; procalcitonin to 0.29 ng/mL; and conventional troponin T to 0.15 µg/L. Follow-up blood cultures were negative. Repeat transthoracic echocardiography demonstrated preserved chamber sizes and function with a left ventricular ejection fraction of 59% and no residual valvular abnormality; no vegetation was seen ([Fig. 2]).

Fig. 2 Follow-up transthoracic echocardiogram after completion of intravenous cefazolin. Parasternal long-axis view shows preserved chamber sizes and systolic function with no residual mitral-valve vegetation. Left ventricular ejection fraction is 59% and no significant residual valvular abnormality is seen.

Discussion

IE is not described as a common adverse event in pivotal RRMS trials and is not specifically emphasized in the manufacturer's safety information; serious infections reported include respiratory and urinary sources.[2] [3] [4]

One prior case report of S. aureus IE during ocrelizumab has been published, with a gradual course over months.[6] Our patient developed native mitral valve IE within 1 week of the first infusion, emphasizing the need for early vigilance when fever persists soon after therapy initiation. Plausible mechanisms exist but remain inferential in this case. Anti-CD20 therapy depletes circulating B cells and may lead to hypogammaglobulinemia, which has been associated with increased infection risk in anti-CD20-treated MS cohorts.[1] [5] Neutrophil perturbations have been described with B-cell depleting agents such as rituximab and could contribute to bacterial susceptibility in selected patients, although we did not document this here.[10] In parallel, translational data show that inflamed or damaged valvular endothelium facilitates S. aureus adhesion and vegetation formation.[11] [12] Together, these pathways provide biological plausibility without proving causality.

Host factors likely amplified risk. Population-based data link hypertension with higher incident IE.[7] Obesity has been reported as a risk factor among hospitalized patients with IE.[8] Type 2 diabetes is associated with impaired neutrophil function, which may increase susceptibility to infection.[9] In our patient, recent corticosteroids and cardiometabolic comorbidities probably acted as risk multipliers in the setting of new B-cell depletion, rather than as solitary causes.

This case also underscores practical steps. In patients who develop persistent fever soon after the first ocrelizumab dose, early blood cultures and a low threshold for echocardiography may help avoid diagnostic delay. In this case, cultures were obtained before antibiotics and transesophageal echocardiography identified a 4-mm P2 vegetation. Cardiac biomarkers were markedly elevated and cardiac magnetic resonance imaging suggested myocarditis; we interpreted this as possible concomitant myocardial injury related to systemic infection (sepsis-related myocardial dysfunction) or demand ischemia, although definitive attribution was not possible. Brain and spine MRI excluded alternative infectious foci and complications. Multidisciplinary input facilitated timely antimicrobial therapy and source evaluation.

Limitations include the single-patient design, which precludes causal inference, and the absence of post-infusion immunoglobulin and B-cell data to quantify the depth and duration of depletion. Larger real-world studies are needed to estimate the incidence of IE among anti-CD20 treated patients and to identify which host factors confer the greatest incremental risk.[1] [5]

Conclusion

This single case cannot establish causality. Recent corticosteroid exposure and cardiometabolic comorbidities are plausible confounders, and post-infusion immunoglobulin and B-cell data were unavailable. Nevertheless, this case highlights a rare but clinically meaningful potential risk signal for IE in patients treated with ocrelizumab, in which B-cell depletion may act as a risk amplifier rather than a sole cause. Clinicians should maintain vigilance for persistent fever or unexplained bacteremia after initiating anti-CD20 therapy and consider early echocardiographic evaluation to facilitate timely diagnosis and management.

Conflict of Interest

None declared.

Authors' Contributions

H.A. and S.F. contributed toward conceptualization. H.A., M.K.M., H.O., and M.A. investigated and curated the data. H.A. and S.F. contributed toward methodology. H.A. wrote the original draft. S.F. did the supervision. All authors wrote, reviewed, and edited the manuscript. They approved the final manuscript and agreed to be accountable for all aspects of the work.

Patient's Consent

The authors confirm that consent was obtained. All potentially identifying details were removed; CARE guidelines were followed.

Compliance with Ethical Principles

IRB approval was not required for a single-patient case report.

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Publication History

Article published online:
10 February 2026