Article, Neurology

Infliximab-induced aseptic meningitis

Unlabelled imageaseptic meningitis“>Case Report

Infliximab-induced aseptic meningitis?

Contents lists available at ScienceDirect

American Journal of Emergency Medicine

journal homepage: locate/ ajem

Abstract

Infliximab is a commonly used biologic agent in the treatment of various autoimmune diseases. Although it is generally well tolerated in most patients, infliximab has been associated with some rare but serious adverse events. Aseptic meningitis is one such distinctly uncommon side effect. We present the case of middle-aged white patient, who presented with fever and headache within a few days of starting the infliximab therapy and was diagnosed with infliximab-induced aseptic meningitis after a complete workup. To our knowledge, this is the fifth case of infliximab-induced aseptic meningitis reported in literature. Because of atypical presentation, the diagnosis can be easily missed. It is vital to increase awareness of this potentially severe side effect among internists and community physicians.

Infliximab (IFX) is commonly used medication for various autoimmune diseases. Aseptic meningitis, although rare, has been associated with use of IFX. The underlying mechanism is not entirely clear, but hypersensitivity is believed to be the possible hypothesis. Because of atypical presentation, diagnosis of aseptic meningitis could be easily missed if clinician is not aware of this potentially serious adverse event. Increased awareness among community physicians and internists is therefore vital.

A 43-year-old white man with known history of ileocolonic Crohn disease (CD) presented to emergency department with acute-onset headache, neck pain, and fever of 2-day duration. A week prior, he had received first induction dose of IFX infusion (dosed at 5 mg/kg) for a flare up of CD. Review of systems was also positive for severe myalgias and polyarthralgias. Patient’s medical history included cavernous malformation of right cerebellum, anxiety, and rectal fistulas. His home medication other than IFX included budesonide, ciprofloxacin, metronidazole, and calcium citrate. He lived with his wife, denied use of alcohol, and smoked cigarettes 1 pack per day and marijuana daily. On presentation, his temperature was 38.8?C, heart rate was 106 beats per minute, and blood pressure was 139/93 mm Hg with normal saturation on room air. He was in distress due to Severe headache, was alert, and oriented to time, place and person. He had significant neck stiffness with positive Kerning and Brudzinski signs. He did not have any focal neurologic deficit. Rest of the physical examination was unremarkable. blood work showed leukocytosis of 13 000/uL without left shift; rest of the laboratories including erythrocyte sedimentation rate and C-reactive protein as well as computed tomography of head was unremarkable. Lumbar puncture showed elevated opening pressures, and Cerebrospinal fluid analysis showed white blood cell of 23/uL with predominant lymphocytes, glucose of 72 mg/dl, and

? Conflict of interest: None.

protein of 109 mg/dl. A diagnosis of aseptic meningitis was thus confirmed. Cerebrospinal fluid viral and encephalitis panel came back negative, and no oligoclonal bands were detected. At this point, IFX- induced meningitis was suspected. Naranjo Adverse drug reaction probability scale confirmed IFX as a “probable” cause. Patient was symptomatically treated with intravenous fluids, antiemetic, and analgesic. His condition improved over the course of hospitalization and was discharged home on day 5 with outpatient follow-up. He was followed up in office after discharge where complete resolution of his symptoms was confirmed.

Infliximab is Food and Drug Administration-approved treatment for CD since 1998 and, due to favorable response, is being widely used in recent times [1]. Infliximab is associated with many common side effects such as headache, fever, infection, arthralgia, and rash [2]. Aseptic meningitis has been reported very rarely with use of IFX. To the best of our knowledge, there are only 4 reported cases of IFX- induced aseptic meningitis in the literature. Two cases were reported in patients with CD [3,4]: 1 with ulcerativE colitis [5] and 1 in patient with rheumatoid arthritis [6].

In our patient, after a full workup, infectious cause for meningitis was ruled out. The timing of first exposure to IFX to development of the symptoms gave us a clue about IFX being a potential suspect. Review of literature strengthened our clinical suspicion of IFX-induced aseptic meningitis. Naranjo adverse drug reaction probability scale was 7, confirming IFX being the most probable cause of aseptic meningitis. When comparing with all previously reported cases, in 2 of 4 reported cases, the symptoms started within few hours of IFX infusion, whereas rest 2 cases had delayed onset by a few days [3]. Patients with underlying autoimmune disease are at high risk for drug-induced meningitis. The exact mechanism of IFX-induced meningitis is un- known, but it is hypothesized to be hypersensitivity reaction. An alternative explanation of IFX-induced meningitis is related to inhibition of peripheral tumor necrosis factor ? that can lead to enhanced action of brain-derived tumor necrosis factor ?, which could lead to central nervous system side effects. Regardless of underlying mechanism, it is imperative that clinicians should be aware of these side effects. Infliximab-induced headache is very common and observed in 29% of cases. In such cases, milder or atypical cases of aseptic meningitis can go unrecognized if clinician is not aware of this possibility.

Rushikesh Shah, MBBS

SUNY Upstate Medical University, 50 Presidential Plaza

Syracuse, NY 13202

Corresponding author. Tel.: +1 972 375 3932

E-mail address: [email protected]

0735-6757/

Mili Shah, MBBS 50 Presidential Plaza, Syracuse, NY 13202 E-mail address: [email protected]

Nidhi Bansal, MBBS Divey Manocha, MBBS

SUNY Upstate Medical University 750 E Adams St, Syaracuse, NY 13210

E-mail addresses: [email protected] (N. Bansal) [email protected] (D. Manocha)

http://dx.doi.org/10.1016/j.ajem.2014.05.045

References

  1. Magro F, Portela F. Management of inflammatory bowel disease with infliximab and other anti-tumor necrosis factor alpha therapies. BioDrugs 2010;24(Suppl 1):3-14. http://dx.doi.org/10.2165/11586290-000000000-00000.
  2. Remicade. Physician’s Desk Reference. Montvale, NJ: Thomson PDR; 2004 1145-8.
  3. Manthey C, Lohse AW, Pace A. Case report of aseptic meningitis in a patient with Crohn’s disease under infliximab therapy. Inflamm Bowel Dis 2011;17(2):E10. http://dx.doi.org/10.1002/ibd.21324.
  4. Hegde N, Gayomali C, Rich MW. Infliximab-induced headache and infliximab-induced meningitis: two ends of the same spectrum? South Med J 2005;98(5):564-6.
  5. Tissot B, Visee S, Pilette C, Prophette B, Puechal X. Lymphocytic meningitis with infliximab for Ulcerative colitis. Gastroenterol Clin Biol 2006;30(12):1420-2.
  6. Marotte H, Charrin JE, Miossec P. Infliximab-induced aseptic meningitis. Lancet 2001;358(9295):1784.