Varicella zoster meningitis complicating combined anti-tumor necrosis factor and corticosteroid therapy in Crohn’s disease.

World J Gastroenterol. 2013 Jun 7;19(21):3347-51.

Ma C, Walters B, Fedorak RN.

Division of Gastroenterology, University of Alberta, Edmonton, AL T6G 2X8, Canada.



Opportunistic viral infections are a well-recognized complication of anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD). Cases of severe or atypical varicella zoster virus infection, both primary and latent reactivation, have been described in association with immunosuppression of Crohn’s disease (CD) patients. However, central nervous system varicella zoster virus infections have been rarely described, and there are no previous reports of varicella zoster virus meningitis associated with anti-TNF therapy among the CD population. Here, we present the case of a 40-year-old male with severe ileocecal-CD who developed a reactivation of dermatomal herpes zoster after treatment with prednisone and adalimumab. The reactivation presented as debilitating varicella zoster virus meningitis, which was not completely resolved despite aggressive antiviral therapy with prolonged intravenous acyclovir and subsequent oral valacyclovir. This is the first reported case of opportunistic central nervous system varicella zoster infection complicating anti-TNF therapy in the CD population. This paper also reviews the literature on varicella zoster virus infections of immunosuppressed IBD patients and the importance of vaccination prior to initiation of anti-TNF therapy.

KEYWORDS: Adalimumab, Anti-tumor necrosis factor, Crohn’s disease, Infliximab, Meningitis, Varicella zoster virus, corticosteroids

PMID: 23745038



Biologic therapies targeting tumor necrosis factor (TNF) alpha, including infliximab and adalimumab, have revolutionized the management of Crohn’s disease (CD).  However, their use is associated with opportunistic infections, especially when patients are on combination treatment with other immunosuppressants such as corticosteroids, methotrexate, or azathioprine.  Varicella zoster virus (VZV) infection risk is high among CD patients.  While cutaneous VZV infections are common, neurological VZV is rare.  VZV meningitis in association with adalimumab therapy for CD has not been previously reported.  We presented the case of a 40-year-old male with CD, who developed reactivation dermatomal herpes zoster and VZV meningitis after treatment with adalimumab and prednisone.

The patient presented with a four-day history of insidious onset, bifrontal, progressively worsening headaches with photophobia and generalized malaise.  There were no initial focal neurological deficits.  He also had a two-day history of left upper quadrant abdominal pain, where he subsequently developed a vesicular maculopapular rash in the left T7 dermatome distribution.  Though he had a history of childhood chickenpox, he had not received a herpes zoster vaccination prior to anti-TNF induction.  Diagnostic investigations revealed an elevated CSF protein level (0.76 g/L) and marked CSF lymphocytic pleocytosis (391 x 106 WBC, 98% lymphocytes).  CSF PCR was positive for VZV.  Despite treatment with one month of intravenous acyclovir (10mg/kg q8h) and suppressive valacyclovir 1000mg oral daily for three months, the patient experienced debilitating residual post-meningitis syndrome, continued headaches, and cognitive slowing.

This case highlights the risk of atypical and severe VZV infection among immunosuppressed CD patients.  Additionally, it identified several issues pertinent to the management of VZV infections in this population that remain unanswered.  For instance, there is minimal evidence to base decisions for restarting anti-TNF therapy after VZV infection.  Discontinuation of anti-TNF agents has been recommended for severe, disseminated VZV infections, but this poses a therapeutic dilemma for CD patients who have severe steroid-dependent disease that has failed other treatment options.  Additionally, this case highlights the importance of preventative vaccination before anti-TNF therapy.  The 2009 European Crohn’s and Colitis Organization guidelines recommend VZV vaccination at least three weeks prior to the onset of anti-TNF immunomodulation.  However, timing of vaccination is particularly challenging in the CD population, as many patients are started on rescue anti-TNF therapy for fulminant disease without the opportunity for assessment of immunity or have contraindications to immunization due to concomitant immunosuppressants.

In summary, this case adds to the literature describing opportunistic infections in the CD population.  It is the first case of VZV meningitis in a CD patient on adalimumab, and emphasizes the need for clinicians to be attentive to the high risk of severe and atypical presentations in immunosuppressed patients and to consider vaccination prior to anti-TNF induction.

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