Aseptic Meningitis Following Rozanolixizumab in a Patient With Refractory Anti-MuSK Positive Myasthenia Gravis: A Case Report

Abstract

Rozanolixizumab is a neonatal Fc receptor (FcRn) blocker recently approved for treating generalized myasthenia gravis (gMG), particularly in patients who are anti-AChR or anti-MuSK antibody positive. Although clinical trials have demonstrated a favorable safety profile, rare adverse neurological effects remain underreported. A 36-year-old woman with refractory anti-MuSK-positive generalized myasthenia gravis received an infusion of rozanolixizumab after failing to respond to corticosteroids and azathioprine. 5 days post-infusion, she presented with an acute-onset headache, nausea, vomiting, photophobia, phonophobia, and neck stiffness. Cerebrospinal fluid (CSF) analysis revealed a white blood cell count of 150 cells/μL with 90% neutrophils, normal protein, and glucose levels. The infectious meningitis and encephalitis panel was negative. She was managed supportively, and her symptoms resolved over the following week without antimicrobial therapy. This case suggests a possible link between Rozanolixizumab and aseptic meningitis. Clinicians should be aware of this potential adverse effect and consider drug-induced etiologies in similar clinical scenarios. Early recognition may prevent unnecessary treatment and hospitalizations.

Introduction

Myasthenia gravis (MG) is an autoimmune disorder caused by antibodies directed against components of the neuromuscular junction, most commonly acetylcholine receptors (AChR) or muscle-specific kinase (MuSK). Patients with MuSK antibody-positive MG often have more severe symptoms and respond poorly to conventional therapies, necessitating the use of targeted biologic agents. ¹

Rozanolixizumab is a humanized IgG4 monoclonal antibody that inhibits FcRn, reducing pathogenic IgG antibody levels. Rozanolixizumab (Rystiggo) was approved by the FDA in 2023 for the treatment of adults with generalized myasthenia gravis who are seropositive for AChR or MuSK antibodies. ² Aseptic meningitis is not merely theoretical but is explicitly recognized as a serious adverse event associated with rozanolixizumab in the FDA prescribing information. ³ However, as a relatively new agent, its safety profile outside of clinical trials is still being characterized. Aseptic meningitis is a known complication of several monoclonal antibodies and immune therapies, often presenting within days of administration.^4-6

We describe a case of suspected rozanolixizumab-induced aseptic meningitis in a woman with anti-MuSK-positive MG, emphasizing the importance of vigilance for immune-mediated neurological adverse effects.

Case Description

A 36-year-old Caucasian woman with a 3-year history of anti-MuSK-positive generalized myasthenia gravis (gMG) presented to the emergency department with a 24-h history of severe, throbbing headache, nausea, vomiting, neck stiffness, photophobia, and phonophobia. Her baseline myasthenic symptoms included fluctuating ptosis, dysarthria, and mild dysphagia, and had proven refractory to conventional treatment with pyridostigmine, oral prednisone (up to 60 mg/day), and azathioprine (150 mg/day) over the prior year. She had no history of IVIG or plasmapheresis in the past 6 months and had not previously received any monoclonal antibody therapies.

Given her persistently symptomatic course and prominent bulbar involvement, she was initiated on rozanolixizumab at a dose of 7 mg/kg via subcutaneous infusion as part of a disease escalation strategy. Premedication with acetaminophen and diphenhydramine was given to minimize infusion-related reactions. The infusion was well tolerated, and she was discharged home the same day without immediate adverse events.

Five days post-infusion, she developed acute symptoms prompting emergency evaluation. On presentation, she was afebrile (temperature: 37.9°C), with stable vital signs and a normal mental status. Neurological examination revealed marked nuchal rigidity, photophobia, and phonophobia but no focal deficits. Her myasthenic symptoms remained stable compared to baseline, with no signs of myasthenic crisis.

Initial laboratory testing revealed a normal peripheral white blood cell count, C-reactive protein, and serum electrolytes. A non-contrast head CT was unremarkable, ruling out acute intracranial pathology.

Lumbar puncture demonstrated a cerebrospinal fluid (CSF) white blood cell count of 150 cells/µL with a predominance of neutrophils at 90% (normal reference range: 0-5 cells/microliter). CSF protein was within normal limits at 38 mg/dL (normal reference range: 15-45 mg/dL), and glucose was 68 mg/dL (normal reference range: 40-70 mg/dL) in the context of a normal serum glucose of 92 mg/dL. The opening pressure was measured at 20 cm H₂O, also within normal limits (normal reference range: 20-25 cm H₂O). Microbiological studies, including CSF Gram stain and bacterial cultures, were negative. In addition, a comprehensive meningitis/encephalitis PCR panel was performed and was negative for HSV-1/2, varicella-zoster virus, enterovirus, cytomegalovirus, Epstein–Barr virus, Listeria monocytogenes, Escherichia coli K1, Streptococcus pneumoniae, Neisseria meningitidis, and Cryptococcus neoformans.

Given the CSF findings suggestive of neutrophilic meningitis but a negative infectious work-up, a presumptive diagnosis of drug-induced aseptic meningitis was made. The patient was admitted for observation and managed conservatively with intravenous fluids, antiemetics, and analgesics. No empiric antibiotics or antivirals were initiated, in agreement with infectious disease consultation, based on the clinical stability, lack of fever, and reassuring CSF parameters.

The patient showed gradual clinical improvement within 72 h and was asymptomatic by hospital day 6. She was discharged home on day 7 in stable condition, with follow-up arranged for neurology and immunology. At 1-month follow-up, she remained neurologically stable without recurrence of meningeal symptoms or worsening. Rozanolixizumab infusion was completely stopped as a part of her outpatient MG treatment regimen, and she was transitioned to a complement inhibition-based regimen, specifically eculizumab which she tolerated well.

Discussion

Drug-induced aseptic meningitis (DIAM) is an uncommon but important differential diagnosis in patients receiving biologic therapies. It typically presents with meningeal signs such as headache, photophobia, and neck stiffness, within days of drug exposure. CSF often shows neutrophilic pleocytosis with normal glucose and mildly elevated or normal protein^4-6. Aseptic meningitis has also been described, albeit infrequently, with other biologics used in MG, including rituximab, eculizumab, and, more recently, efgartigimod, underscoring that this adverse effect is not unique to FcRn blockade.^7,8 Emerging real-world pharmacovigilance data suggest that both rozanolixizumab and efgartigimod carry a low but tangible risk of meningitis, though direct comparative evidence remains limited. Importantly, FcRn inhibitors and complement inhibitors differ mechanistically: while both classes can be associated with meningitic presentations, complement blockade is more often linked to meningitis due to infectious etiology, with underlying impaired host defense, whereas FcRn inhibition appears more prone to aseptic or immune-mediated presentations.^8,9

Rozanolixizumab’s safety profile is largely informed by clinical trials, where serious neurological events were rare. ² However, post-marketing pharmacovigilance is essential, especially as real-world populations often differ from trial cohorts. This case mirrors a recent report by Shah et al, ¹⁰ who documented aseptic meningitis following rozanolixizumab administration in a similarly affected patient with MG. Together, these cases underscore the plausibility of a class effect involving FcRn blockade and neuroinflammation. Our case is unique in the perspective that it is one of the earliest documented cases of rozanolixizumab-associated aseptic meningitis in an anti-MuSK–positive MG patient, expanding the spectrum of populations in which this adverse event may occur.

While the precise immunopathogenic mechanism remains speculative, the FcRn pathway plays a role not only in IgG recycling but also in modulating immune homeostasis. Disruption of this pathway may inadvertently trigger pro-inflammatory cascades, including meningeal cytokine activation or transient immune complex deposition.^4,5 In our case, the extensive negative infectious workup, normal systemic inflammatory markers, and the patient’s rapid clinical improvement without immunotherapy argue against autoimmune encephalitis or a systemic autoimmune flare.

Recognizing DIAM is vital because its clinical presentation often mimics meningitis caused by bacteria, viruses, or fungi, leading to empiric antimicrobial therapy, extended hospitalizations, and unnecessary investigations. Unlike bacterial or viral meningitis, DIAM typically follows a self-limited course and resolves with discontinuation of the offending agent and conservative measures. However, misdiagnosis can have substantial implications for patient safety, healthcare resource utilization, and drug tolerability perceptions.

Given the increasing utilization of targeted immunotherapies such as rozanolixizumab in neurology and immunology, clinicians must remain vigilant for atypical and delayed adverse neurological events. High clinical suspicion, timely lumbar puncture, and careful exclusion of infectious etiologies are paramount in establishing the diagnosis of DIAM. Furthermore, this case reinforces the need for ongoing pharmacovigilance and systematic documentation of adverse drug reactions, particularly for newly approved agents with expanding indications.

Conclusions

This report adds to emerging literature on FcRn inhibitors and highlights aseptic meningitis as a potential adverse effect of rozanolixizumab. Clinicians should maintain a high index of suspicion in patients presenting with meningeal symptoms shortly after biologic therapy. Prompt recognition and supportive management can lead to full recovery and avoid overtreatment.

Appendix.

Abbreviations

MG

Myasthenia gravis

gMG

Generalized myasthenia gravis

MuSK

Muscle-specific kinase

FcRn

Neonatal Fc receptor

CSF

Cerebrospinal fluid

DIAM

Drug-induced aseptic meningitis

ORCID iD

Hamza Maqsood https://orcid.org/0000-0001-5721-9511

Consent for Publication

Written informed consent was obtained from the patient for publication of this case report.