aAIDS Clinical Center, National Center for Global Health and Medicine, Tokyo
bDepartment of Gastroenterology and Hepatology
cDepartment of Pathology, Division of Clinical Laboratory, National Center for Global Health and Medicine, Tokyo, Japan.
Correspondence to Naoyoshi Nagata, MD, Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. Tel: +81 3 3202 7181; fax: +81 3 3208 4244; e-mail: firstname.lastname@example.org
Received 14 November, 2011
Accepted 15 November, 2011
Epstein–Barr virus (EBV)-associated lymphoma of the gastrointestinal tract is common in HIV-infected patients . However, EBV involvement of the gastrointestinal tract without frank lymphoma is rare . Although a few cases of EBV-associated colitis in both immunocompetent and immunocompromised patients have been reported [2,3], to our knowledge, EBV-associated colitis in HIV-infected patients has never been reported. We report a case of EBV-associated colitis with HIV infection successfully treated by combination antiretroviral therapy (cART).
A 40-year-old homosexual man who had had diarrhea for a few years developed bloody diarrhea. After persistence of the symptom for 2 months, he sought medical advice at a local hospital. He was diagnosed with HIV infection and referred to our hospital for further examination. On admission, the patient was alert with body temperature of 37.6°C. Physical examination showed oral candidiasis but no peripheral lymphadenopathy or abdominal tenderness. Laboratory tests at admission showed low CD4+ cell count (84 cells/μl), anemia (hemoglobin 10.6 g/dl), low serum albumin (2.1 g/dl), and elevated C-reactive protein (3.45 mg/dl). Colonoscopy showed diffuse edematous mucosa with deep ulcers in the rectum, sigmoid colon, and descending colon (Fig. 1a), suggestive of either cytomegalovirus (CMV) colitis or amebic colitis. Based on the clinical suspicion, we initiated empirical treatment of gancicrovir and metronidazole. However, the results for amebic colitis such as stool microscopy, serum antiamebic antibody, and trophozoites in colonic biopsy specimens were all negative. Furthermore, histopathology revealed no inclusion bodies and negative immunological staining for CMV. Then, we suspected inflammatory bowel disease (IBD), and mesalazine 4 g/day was initiated on day 7. Since there was no sign of other opportunistic infections, cART of raltegravir and emtricitabine/tenofovir was initiated on day 13. However, the bloody diarrhea persisted and a repeat colonoscopy was performed on day 19 to investigate the cause. The edematous mucosa and deep ulcers were still observed on colonoscopy. To identify infectious agents, a polymerase chain reaction (PCR) assay for EBV in the biopsy sample was performed, which showed 9000 copies/ml. Histopathological examination showed dense lymphoplasmacytic infiltration and mild neutrophil infiltration (Fig. 1c). In-situ hybridization (ISH) for EBV-encoded small RNA-1 (EBER-1) showed some positive cells (Fig. 1d). Based on these tests, the final diagnosis was established as EBV-associated colitis. The treatment plan included continuation of cART and withdrawal of mesalazine since IBD was considered unlikely. The symptom of bloody diarrhea gradually improved and disappeared by cART alone. At 3 months, the CD4 cell count had increased to 190/μl and the third colonoscopy showed significant improvement (Fig. 1b). PCR for EBV DNA in the biopsy sample showed a decrease to 80 copies/ml, and ISH showed no EBER-1-positive cells.
Although EBV-associated lymphoma of the gastrointestinal tract is common, EBV-associated colitis is very rare. To our knowledge, this is the first study demonstrating EBV-associated colitis in an HIV-infected patient. In addition, the significant improvement was achieved by cART alone. Several cases of EBV-associated colitis have been reported previously in immunocompromised patients, such as post-transplant patients and patients with IBD treated with immunosuppressants [2,3]. For this reason, EBV reactivation due to impaired immunity is considered to be a major causative factor of EBV-associated colitis.
In this case, EBV-associated colitis was diagnosed by the presence of EBV DNA and EBER-1-positive cells in the biopsy sample, and the improvement of colonoscopic findings associated with a decrease in EBV DNA. Because colonic appearance is grossly indistinguishable from that of CMV colitis, other forms of infectious colitis and IBD, positive EBV DNA and EBER-1 in the colonic specimens are important findings for establishing the correct diagnosis. In the case of delayed recognition of EBV colitis, treatment for IBD with corticosteroids can lead to unfavorable outcome . Thus, EBV-associated colitis should be considered in HIV-infected patients, especially those with low CD4+ cell counts, who present with colitis of unclear cause.
Because there is no established treatment for EBV infection, we treated this case with cART alone without specific treatment for EBV . The loss of CMV viremia by cART in the absence of specific anti-CMV therapy has been reported previously ; therefore, it is likely that the suppression of EBV was also achieved by cART alone. Because most reported cases of EBV colitis occurred from EBV reactivation due to impaired immunity, it is rational that restoration of the immune system by cART allowed the suppression of EBV activation and resulted in the resolution of colitis.
In conclusion, cART was effective against EBV-associated colitis. Clinicians should consider EBV infection in HIV-infected patients who present with colitis of unclear cause.
The authors thank all the clinical staff at the AIDS Clinical Center and also all the staff of the endoscopy unit.
All of the authors contributed to the concept, design, and writing of this submission. No financial support was received for this article.
Conflicts of interest
There are no conflicts of interest.
1. Carbone A, Cesarman E, Spina M, Gloghini A, Schulz TF. HIV-associated lymphomas and gamma-herpesviruses
2. Karlitz JJ, Li ST, Holman RP, Rice MC. EBV-associated colitis mimicking IBD in an immunocompetent individual
. Nat Rev Gastroenterol Hepatol
3. Tashiro Y, Goto M, Takemoto Y, Sato E, Shirahama H, Utsunomiya A, et al. Epstein-Barr virus-associated enteritis with multiple ulcers after stem cell transplantation: first histologically confirmed case
. Pathol Int
4. Kobayashi CI, Yamamoto G, Hayashi A, Ota S, Imai Y, Fukayama M, et al. Fatal amebic colitis after high-dose dexamethasone therapy for newly diagnosed multiple myeloma
. Ann Hematol
5. Torre D, Tambini R. Acyclovir for treatment of infectious mononucleosis: a meta-analysis
. Scand J Infect Dis
6. Deayton J, Mocroft A, Wilson P, Emery VC, Johnson MA, Griffiths PD. Loss of cytomegalovirus (CMV) viraemia following highly active antiretroviral therapy in the absence of specific anti-CMV therapy