Antiviral treatment with fluoxetine for rituximab‐associated chronic echovirus 13 meningoencephalitis and myofasciitis

Abstract

Background and purpose Enterovirus infections pose a serious threat for patients with humoral deficiencies and may be lethal, whilst the efficacy of proposed treatment options such as corticosteroids, intravenous immunoglobulins and fluoxetine remains debated. Methods Viral clearance was investigated in a patient with rituximab‐induced B‐cell depletion and chronic echovirus 13 (E13) meningoencephalitis/myofasciitis in response to intravenous immunoglobulins and fluoxetine using sequential semi‐quantitative E13 viral load measurements by real‐time reverse transcription polymerase chain reaction. Fluoxetine concentrations in plasma and cerebrospinal fluid were determined by liquid chromatography mass spectrometry. Results Intravenous immunoglobulins appeared ineffective in this case of E13 infection, whereas virus clearance in cerebrospinal fluid was obtained after 167 days of oral fluoxetine. Since treatment with corticosteroids resulted in a flare of symptoms, rechallenge with viral load measurements was not attempted. Conclusion In this report of a patient with rituximab‐associated chronic echovirus 13 meningoencephalitis, viral clearance in response to single treatment options is assessed for the first time. Our observations further support the in vivo efficacy of fluoxetine against enteroviral infections. More research is needed to establish its efficacy in different enterovirus strains.

2C protein of Enterovirus: key protein of viral replication and antiviral target

“…Similarly, Fluoxetine, long used to treat major depression and anxiety disorders, has more recently been used as an antiviral treatment for immunocompromised children with chronic EV encephalitis [81] demonstrating its potential for clinical use as an inhibitor of protein 2C functions. However, its pharmacokinetics and side effects restrict its use to the treatment of chronic EV infections [82]. It is therefore important to continue to optimize molecules based on (S)-Fluoxetine, to clarify the molecular mechanisms determining inhibitor efficacy, and to evaluate the spectrum of efficacy on a wide panel of EVs, especially in relevant in vivo models.…”

“…It has been tested in clinical trials for the treatment of patients with proven or presumed EV-D68-associated AFM (acute flaccid myelitis), but has been shown to be ineffective [79][80]. However, Fluoxetine has been used successfully to treat an immunocompromised child with chronic enteroviral encephalitis [81] and a patient with meningoencephalitis due to chronic E-13 infection [82]. These examples highlight the need for further development of Fluoxetine-derived inhibitors with higher efficacy and specificity for protein 2C, especially in the treatment of EV-D68 infection.…”

Rubella virus chronic inflammatory disease and other unusual viral phenotypes in inborn errors of immunity

“…There is currently an evolving recognition of susceptibility to enterovirus among people treated with rituximab, a B cell depleting agent widely used for lymphoma, multiple sclerosis, and systemic lupus erythematosus 41–54 . The population treated with rituximab has generally had a more acute presentation of disseminated disease or meningoencephalitis compared to the slow onset seen in XLA; however, late relapses and late relapses in different organs have been observed suggesting incomplete clearance even in the setting of clinical improvement.…”

“…There is currently an evolving recognition of susceptibility to enterovirus among people treated with rituximab, a B cell depleting agent widely used for lymphoma, multiple sclerosis, and systemic lupus erythematosus. [41][42][43][44][45][46][47][48][49][50][51][52][53][54] The population treated with rituximab has generally had a more acute presentation of disseminated disease or meningoencephalitis compared to the slow onset seen in XLA;…”

2C protein of Enterovirus: key protein of viral replication and antiviral target

“…Elle a fait l'objet d'essais cliniques dans le traitement de patients présentant une AFM (Myélite flasque aiguë) prouvée ou présumée associée au virus EV-D68, mais s'est avérée inefficace [79], [80]. Toutefois, la Fluoxétine a été utilisée avec succès pour traiter un enfant immunodéprimé atteint d'une encéphalite entérovirale chronique [81], et une patiente atteinte d'une méningoencéphalite par infection chronique à E13 [82]. Ces exemples soulignent la nécessité de poursuivre le développement d'inhibiteurs dérivés de la Fluoxétine de plus forte efficacité et spécificité pour la protéine 2C, notamment dans le traitement de l'infection par EV-D68.…”