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CASE REPORT
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Listeria Monocytogenes Disease in a Patient Treated with Adalimumab

Marco Distefano, MD*

Infectious Disease Department, ASP 8, Siracusa, Italy

*Corresponding author: Marco Distefano, MD, Infectious Disease Department, ASP 8 Siracusa, via Testaferrata, 1, 96100 Siracusa, Italy, Tel: 00390931724213, E-mail: erdis@tin.it

Distefano. CasesMed Res J 202, Volume 2 Issue 1

Citation: Distefano M (2020) Listeria Monocytogenes Disease in a Patient Treated with Adalimumab. CasesMed Res J 2(1): 13-16.

Copyright: © 2020 Distefano M, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: June 17, 2020 | Accepted: July 21, 2020 | Published: July 23, 2020

Abstract

Background: Listeria monocytogenes is an uncommon Gram-positive pathogen that causes self-limited febrile gastroenteritis in healthy hosts. Listeria is also a cause of invasive disease, including bacteremia and central nervous system infection in individuals at the extremes of age (neonates and older adults), immunosuppressed patients, and pregnant women. The mortality of invasive disease caused by Listeria monocytogenes is 20-40%. TNF? blockers are a new class of immunosuppressant drugs considered the most significant therapeutic advance in the care of IBD and rheumatologic disorders. Few cases of invasive listeriosis are reported after adalimumab (a monoclonal antibody anti-TNF?) therapy.

Case presentation: A patient with ulcerative colitis developed pyrexia, headache, and neck stiffness a few days after his first adalimumab subcutaneous administration. The patient had eaten packaged saladgreens and raw anchovies three days before treatment, and L. monocytogenes meningitis was diagnosed based on positive CSF cultures. Intravenous amoxicillin clavulanate improved the symptoms, and the patient was discharged without neurological sequelae.

Conclusion: Listeriosis associated with adalimumab is a potentially fatal condition. Listeria should be considered when a patient is taking immunosuppressive therapy and develops gastroenteritis, sepsis, or meningitic symptoms. As usually reported, symptoms started rapidly after adalimumab, suggesting that the patient already carried the bacteria before anti-TNFa therapy. The summary of product characteristics should include a recommendation to patients to avoid foods associated with Listeria at least one month after treatment but also the last weeks before treatment.

Keywords: Meningitis, Treatment, Adalimumab, Adverse events, Listeria monocytogenes

Abbreviations

CIOMS: Council for International Organizations of Medical Sciences; SPC: Summary of Product Characteristics; WHO: World Health Organization

The Gram-positive bacteria Listeria monocytogenescause listeriosis usually contracted from unpasteurized dairy products, or products contaminated with L. monocytogenes after pasteurization, like soft cheeses or raw fish and meat. People with defective cellular immunity may develop septicemia, meningitis, or encephalitis, with a mortality rate ranging from 20 to 40% [1,2]. Immunocompetent persons rarely develop severe symptoms. Unless recognized and treated promptly, many patients who develop Listeria meningitis are left with significant neurological sequelae.

The importance of listeriosis associated with TNF? inhibitors has recently been reported to VigiBase©, the World Health Organization international database of adverse drug reactions (adverse events reported in 2.4% of patients) [3]. Listeriosis must be suspected in patients who develop pyrexia during treatment with adalimumab, even in the absence of meningism. A Summary of Product Characteristics (SPC) revision should be done to inform about the risk of this potentially fatal complication

Case Presentation

A 49-years-old man was diagnosed with ulcerative colitis in 2012. He was treated with steroids without good results. Treatment was changed to adalimumab, a fully human monoclonal antibody inhibiting the action of TNF?, one week before his presentation to the emergency room. There was no other significant personal history. Some days after the injection of adalimumab, he became sick with sudden onset of abdominal pain, nausea, and fever up to 40 °C. At admission to the hospital, he was awake and hadphotophobia, neck stiffness, and other meningeal irritation signs were positive (Brudzinsky, Kernig). He was febrile (39.5 °C) and clinically dehydrated but normotensive. Physical examination revealed the absence of skin rash; flaccid paralysis was not present. His blood tests at admission revealed markedly elevated levels of C-reactive protein (CRP) and procalcitonin and are resumed in Table 1. As he did have neurological symptoms, brain imaging and lumbar puncture were performed. The cerebrospinal fluid (CFS) sample contained 1364 leucocytes/?l (lymphocytes + monocytes) and 100 red blood cells/?l, 42 mg/dl of protein, and 32 mg/dl of glucose (blood glucose, 98 mg/dl). The fluid pressure was 140 mmH2O. Gram staining of the cerebrospinal fluid revealed the Gram-positive rods (Figure 1). Empirical treatment was started with acyclovir, ceftriaxone (2 gr q12hr), vancomycin (15 mg/kg q12 hr), and amoxicillin-clavulanic acid (2 gr q4hr). Empiric dexamethasone (10 mg QID) was also administered for the first four days of therapy. The level of consciousness improved. A CT scan ruled out space-occupying lesions. Magnetic resonance imaging (MRI) of he brain was done after four days of therapy, not detecting hyperintensity or areas of restricted diffusion in the cerebral cortex or periventricular or deep white matter (Figure 2). Antibodies (anti-Jo-1, anti-Sm, anti-SS-A, anti-SS-B, anti-nRNP, anti-Scl-70, anti-c-ANCA, anti-pANCA, anti-dsDNA, anti-amphiphysin, anti-CV2, antiPNMA2, anti-Yo (PCCA-1), anti-Hu (ANNA-1), anti-RI (ANNA-2), and anti-ganglioside) were negative. Electromyography (EMG) performed on the fifth evolution day was normal. Cerebrospinal fluid (CFS), serum, and whole-blood samples were analyzed for the identification of possible etiologies. Gram staining of CSF shows the presence of Gram rod, which was identified as L. Monocytogenes. After starting treatment, symptoms disappeared. Cefalea lasted one week, and the performance status rapidly improved. Vancomycin, ceftriaxone, dexamethasone were stopped soon, but amoxicillin-clavulanate was continued for 20 days and stopped after his general condition had remained stable for several days. The patient was subsequently discharged without any neurological sequelae.



Four months later, the patient had a complete recovery. The results of the microbiological assessment were as follows. Firstline investigation: gram stain and bacterial culture, alpha-herpesvirus (herpes simplex virus 1, herpes simplex virus 2, and varicella-zoster virus), and enterovirus were negative. Treponema pallidum and Cryptococcal neoformans (serum and CFS), Mycoplasma pneumoniae, Epstein-Barr virus, and Cytomegalovirus were negative. Screening for HIV (serology and RNA), hepatitis A, B, and C, and Mycobacterium tuberculosis (CSF) was also negative.

Discussion

Adalimumab is a human monoclonal antibody of the class of TNF? antagonists, a class of biologic agents that include infliximab, etanercept, certolizumab, and golimumab. TNF? blockers inhibit the inflammatory cascade by inactivation of TNF?. They are used to treat Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and juvenile idiopathic arthritis. Since TNF? blockers are immunosuppressants, patients treated are at increased risk of serious infections, including fatal. Bacterial, mycobacterial, fungal, viral, and other opportunistic pathogens can cause serious illness when a person's immune system has weakened. Various organ systems and sites can be involved. All these infections are considered contraindications to starting TNF inhibitors. In 2010 the British Society of Rheumatology published data from his registry that showed that cumulative incidence of tuberculosis was higher in patients treated with adalimumab than those treated with infliximab, etanercept of DMARD. Adalimumab is probably the most potent TNF blocker, determining the most significant breakdown of granuloma and the release of virulent organisms determining the highest risk of TB reactivation [4]. Recently, FDA reviewed cases of infection due to Listeria monocytogenes in patients treated with TNF? blockers. A search of the English-language database identified 26 published cases of Listeria infection in TNF? blocker-treated patients, including meningitis, bacteremia, endophthalmitis, and sepsis [5-10]. Seven fatalities were reported in patients receiving concomitant immunosuppressive drugs. Furthermore, FDA identified fatal Listeria infections in a review of data regarding pre-marketing phase 2, phase 3 clinical trials and post-marketing surveillance. In September 2011 the U.S. Food and Drug Administration (FDA) updated the Boxed Warning for the entire class of TNF? blockers. Legionellaand Listeria were included for all of the TNF? blockers and consistent information about the risk of severe infections were added.

We herein report a case of Listeria colitis in a patient receiving adalimumab that progresses to septicemia and meningitis. To our knowledge, this was the 2nd case of Listeriosis associated with adalimumab reported [3], and the 16th occurred in patients treated with TNF? inhibitors. This case suggested a critical clinical issue. Listeriamonocytogenes can exacerbate the inflammation in patients with ulcerative colitis, invade the bloodstream, and cause septicemia and meningitis in patients with an immunosuppressed status. The prevalence of patients with ulcerative colitis has increased in recent years, and TNF? blockers are increasingly used to cure this patient. Adalimumab impairs the action of TNF? secreted by inflammatory monocyte and activated macrophage. We must alert for Listeria infections in patients taking these drugs, especially adalimumab.

In these patients, we performed a lumbar puncture and initiated active antibiotic therapy on the day of the onset of meningitis symptoms. He recovered without any permanent central nervous system damage. We suggest that the rapid onset of therapy might prevent neurological sequelae. Patients should avoid ingestion of uncooked or undercooked meats, soft cheeses, and unpasteurized dairy products the last weeks before therapy and for at least one month after treatment [11,12]. The incubation period of L. monocytogenes varies (1 to 70 days) [1]. Corticosteroids can prolong the persistence of L. monocytogenes after food exposure, routinely administered to patients with ulcerative colitis [13]. Our patient had eaten soft cheese and raw fish, both known sources of L. monocytogenes, three days before the first infusion and six days before the debut of the symptoms. He did not consume any suspicious foods during the treatment cycle, and therefore most likely contracted the infection before the treatment. Patients should avoid eating such food items, not only after treatment. Outbreaks of listeria infections have been described to several food products, including deli meats, hot dogs, soft cheeses (including pasteurized cheeses contaminated after production), celery, sprouts and ice cream [14]. Exposure to L. monocytogenes might, therefore, be difficult to avoid [15].

Conclusion

L. monocytogenes can exacerbate inflammation in ulcerative colitis, invade the bloodstream and cause septicemia and infection in patients treated with TNF? inhibitors. Physicians and patients should consider the potentially lethal side effects of adalimumab. The SPC should be revised and advised patients to avoid foods associated with Listeria during and before treatment with adalimumab. The occurrence of listeriosis associated with adalimumab should be followed closely, and antibiotic prophylaxis could be considered if prophylactic measures are insufficient. An accurate diagnosis and the appropriate treatment of Listeria meningitis may preserve the function of the central nervous system (Table 2).

Acknowledgements

We express gratitude to the patient described in the study, and to all the equip of the Infectious Disease Unit of ASP 8, Siracusa.

Funding

No funding was obtained for the preparation of this case report.
Availability of data and materials: All data are contained within the manuscript.
Authors' contributions: MD planned the study and wrote the manuscript.
Competing interests: The authors declare that they have no Conflict of Interest (COI).
Consent for publication: Written informed consent was obtained for publication of this Case Report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Ethics approval and consent to participate: According to European regulations, no ethics approval was required for this case report.

References

1.Hernandez-Milian A, Payeras-Cifre A (2014) What is new in listeriosis? Biomed Res Int 2014: 358051.
2.Maertens De NC, DevleesschauveerB, AnguloFG, VerbekeG, Haagsma J, et al. (2014) The global burden of listeriosis: a systematic review and meta-analysis. Lancet Infect Dis 14: 1073-1082.
3.Uppsala Monitoring Centre (2017) VigiBase, the World Health Organization (WHO) international database of suspected adverse drug reactions.
4.Dixon WG, Hyrich KL, Watson KD, Lunt M, Galloway J, et al. (2010) Drug-specific risk of tubercolosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society of Rheumatology Biologics Register (BSRBR). Ann Rheum Dis 69: 522-528.
5.Kesteman T, Yombi JC, Gigi J, Durez P (2007) Listeria infections associated with infliximab: case reports. Clin Rheumatol. 26: 2173- 2175.
6.Slifman NR, Gershon SK, Lee JH, Edwards ET, Braun MM (2003) Listeria monocytogenes infection as a complication of treatment with tumor necrosis factor alpha-neutralizing agents. Arthritis Rheum 48: 319-324.
7.Jessel P, Safdar N, McCune WJ, Saint S, Kaul DR (2010) Clinical problem-solving. Thinking inside the box. N Engl J Med 363: 574- 579.
8.Pena-Sagredo JL, Hernandez MV, Fernandez-Llanio N, GimenezUbeda E, Munoz-Fernandez S, et al. (2008) Listeria monocytogenes infection in patients with rheumatic diseases on TNF-alpha antagonist therapy: the Spanish Study Group experience. Clin Exp Rheumatol 26: 854-859.
9.Murphy G, Schmidt-Martin D, Hynes BG, Harney S (2009) Systemic listeriosis with adalimumab therapy. J Clin Rheumatol 15: 369- 370.
10.Ramos JM, Garcia-Sepulcre MF, Masia M, Brotons A, Grau MC, et al. (2010) Listeria monocytogenes infection in patients with inflammatory bowel diseases receiving anti-tumor necrosis factor therapy. Rev Esp Enferm Dig 102: 614-616.
11.Calame DG, Mueller-Ortiz SL, Wetsel RA (2016) Innate and adaptive immunologic functions of complement in the host response to Listeria monocytogenes infection. Immunobiology 221: 1407-1417.
12.(2019) Amgevita (adalimumab) Summary of Products Characteristics. Amgen.
13.Prats N, Lopez S, Domingo M, Briones V, Garcia JA, et al. (1997) Prolonged persistence of Listeria monocytogenes after intragastric infection in corticosteroid-treated mice. Vet Microbiol 58: 79-85.
14.Listeria (2017) Center of Disease Control.
15.Wadamori Y, Gooneratne R, Hussain MA (2016) Outbreaks and factors influencing microbiological contamination of fresh produce. J Sci Food Agric.