Severe enterovirus infections in patients with immune-mediated inflammatory diseases receiving anti-CD20 monoclonal antibodies

RMD Open. 2024 May 20;10(2):e004036. doi: 10.1136/rmdopen-2023-004036.

Abstract

Objective: Patients with X linked agammaglobulinemia are susceptible to enterovirus (EV) infections. Similarly, severe EV infections have been described in patients with impaired B-cell response following treatment with anti-CD20 monoclonal antibodies (mAbs), mostly in those treated for haematological malignancies. We aimed to describe severe EV infections in patients receiving anti-CD20 mAbs for immune-mediated inflammatory diseases (IMIDs).

Methods: Patients were included following a screening of data collected through the routine surveillance of EV infections coordinated by the National Reference Center and a review of the literature. Additionally, neutralising antibodies were assessed in a patient with chronic EV-A71 meningoencephalitis.

Results: Nine original and 17 previously published cases were retrieved. Meningoencephalitis (n=21/26, 81%) associated with EV-positive cerebrospinal fluid (n=20/22, 91%) was the most common manifestation. The mortality rate was high (27%). EV was the only causal agents in all reported cases. Patients received multiple anti-CD20 mAbs infusions (median 8 (5-10)), resulting in complete B-cell depletion and moderate hypogammaglobulinemia (median 4.9 g/L (4.3-6.7)), and had limited concomitant immunosuppressive treatments. Finally, in a patient with EV-A71 meningoencephalitis, a lack of B-cell response to EV was shown.

Conclusion: EV infection should be evoked in patients with IMIDs presenting with atypical organ involvement, especially meningoencephalitis. Anti-CD20 mAbs may lead to impaired B-cell response against EV, although an underlying primary immunodeficiency should systematically be discussed.

Keywords: B-lymphocytes; antirheumatic agents; autoimmune diseases; rituximab.

MeSH terms

  • Adult
  • Agammaglobulinemia / complications
  • Agammaglobulinemia / immunology
  • Aged
  • Antibodies, Monoclonal* / therapeutic use
  • Antigens, CD20* / immunology
  • B-Lymphocytes / immunology
  • Enterovirus Infections* / diagnosis
  • Enterovirus Infections* / immunology
  • Female
  • Humans
  • Inflammation / immunology
  • Male
  • Meningoencephalitis / diagnosis
  • Meningoencephalitis / drug therapy
  • Meningoencephalitis / etiology
  • Meningoencephalitis / immunology
  • Meningoencephalitis / virology
  • Middle Aged
  • Rituximab / therapeutic use