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Substantial Epstein–Barr virus reactivation in a case of severe refractory ulcerative colitis: a possible role in exacerbation

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Abstract

Ulcerative colitis (UC) is an inflammatory bowel disease that causes chronic inflammation in the colon. 5-aminosalicylic acid and immunosuppressive medications such as corticosteroids, immunomodulators, and biologic agents are used to treat these patients. However, patients with UC who receive immunosuppressive medications may be at risk for certain opportunistic infections. Epstein–Barr virus (EBV) is one of those opportunistic infections, and its pathogenic role has been implicated in refractory UC, but its pathogenicity should be further investigated. Here, we report a surgical case of refractory UC that demonstrated a serologically post-infected pattern of EBV at admission but that later had a high load of EBV in both the peripheral blood and colonic mucosa. These findings suggest that EBV may have been reactivated in the colon, after which it damaged the colonic mucosa and aggravated inflammation in this patient with UC. Thus, EBV might lead to severity and a refractory response against corticosteroids and anti-TNFα agents, necessitating emergency surgery. Viral surveillance for EBV in patients with refractory UC may facilitate understanding of the patient’s pathophysiology and predicting response to medications, and the development of antiviral intervention for those patients may improve their prognosis.

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Fig. 1
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Fig. 4

taken from the edge of ulcers obtained through colonoscopy on the day of admission

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Abbreviations

Anti-TNF-α:

Antitumor necrosis factor alpha

CMV:

Cytomegalovirus

EBV:

Epstein–Barr virus

EBER-1:

EBV-encoded small RNA-1

anti-EBNA antibody:

Anti-EBV nuclear antigen antibody

5-ASA:

5-Aminosalicylic acid

IBD:

Inflammatory bowel disease

IFX:

Infliximab

PSL:

Prednisolone

PCR:

Polymerase chain reaction

UC:

Ulcerative colitis

anti-VCA antibody:

Antiviral capsid antibody

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Acknowledgements

Enago (www.enago.jp) provided English writing assistance for this manuscript.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Shu Kato, Hiromichi Shimizu, Hitoshi Uchida, Ami Kawamoto, Shuji Hibiya, Toshimitsu Fujii, Eiko Saito & Masakazu Nagahori

  2. Department of Endoscopy, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Maiko Motobayashi, Kento Takenaka & Kazuo Ohtsuka

  3. Division of Surgical Pathology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Shohei Tomii, Mariko Negi & Takumi Akashi

  4. Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Takatoshi Matsuyama & Yusuke Kinugasa

  5. Institute of Advanced Study, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Mamoru Watanabe

Authors
  1. Shu Kato
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  2. Hiromichi Shimizu
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  3. Shohei Tomii
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  4. Hitoshi Uchida
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  5. Ami Kawamoto
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  6. Shuji Hibiya
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  8. Kento Takenaka
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  9. Toshimitsu Fujii
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  11. Masakazu Nagahori
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  16. Yusuke Kinugasa
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  17. Mamoru Watanabe
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Contributions

All authors contributed to the study conception and design. Material preparation, collection, and analysis were performed by SK, HU, ST, and MN. The first draft of the manuscript was written by SK and HS, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hiromichi Shimizu.

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Conflict of interest

The authors disclose the following associations: Toshimitsu Fujii received a research grants/clinical trial funding from AbbVie, Boehringer Ingelheim, Celgene, EA Pharma, Eisai, Gilead Sciences, and Eli Lilly. TF serves as speaker’s bureau for AbbVie, Ajinomoto Pharma, Boehringer Ingelheim, Daiichi Sankyo, EA Pharma, Kyorin Pharma, Kyowa Hakko Kirin, BMS, Nichiiko, Kyorin, Nippon Kayaku, Kissei Pharma, Zeria Pharma, and Janssen Pharma. Mamoru Watanabe received research grants/clinical trial funding from AbbVie, Boehringer Ingelheim, Celgene, EA Pharma, Eisai, Gilead Sciences, Eli Lilly, and Mitsubishi Tanabe Pharma. MW serves as speaker’s bureau for Ajinomoto Pharma, Kyorin Pharma, Mitsubishi Tanabe Pharma, Kyorin, Mochida Pharma, Nippon Kayaku, and Janssen Pharma. Masakazu Nagahori serves as a consultant to Kissei Pharma and Takeda. MN serves as speaker’s bureau for AbbVie, Mitsubishi Tanabe Pharma, Kyorin, Nippon Kayaku, Kissei Pharma, Asashi Kasei, Zeria Pharma, Astellas Pharma, and Janssen Pharma. Kazuo Ohtsuka serves as speaker’s bureau for AbbVie, Mitsubishi Tanabe Pharma, Kyorin, Mochida Pharma, and Zeria Pharma. Kento Takenaka serves as speaker’s bureau for Mitsubishi Tanabe Pharma, Kyorin, Mochida Pharma, and Zeria Pharma. The remaining authors have no conflicts to disclose.

Human Rights

All procedures followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed Consent

Informed consent was obtained from the patient for being included in the study.

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Kato, S., Shimizu, H., Tomii, S. et al. Substantial Epstein–Barr virus reactivation in a case of severe refractory ulcerative colitis: a possible role in exacerbation. Clin J Gastroenterol 14, 584–588 (2021). https://doi.org/10.1007/s12328-020-01319-w

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  • DOI: https://doi.org/10.1007/s12328-020-01319-w

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