Case Report

Cytomegalovirus Infection-Associated Toxic Megacolon in a Malnourished Patient with Chronic Alcohol Abuse

Toshiyuki Kobayashi1*, Takenori Hibino2, Kanami Waki2, Masami Inase3, Atsushi Kusaba4, Hiroshi Tadokoro1

1Department of General Medicine, Zama General Hospital, Zama, Kanagawa, 252-0011, Japan
2Department of General Medicine, Ebina General Hospital, Ebina, Kanagawa, 243-0433, Japan
3Department of Gastroenterology, Ebina General Hospital, Ebina, Kanagawa, 243-0433, Japan
4Department of Rheumatology General Medicine, Zama General Hospital, Zama, Kanagawa, 252-0011, Japan

*Corresponding author: Dr. Toshiyuki Kobayashi, Department of General Medicine, Zama General Hospital, 1-50-1,
Sobudai, Zama Kanagawa 252-0011, Japan, Tel: +81-46-2511311; Fax: +81-46-2515050; Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

 Submitted: 05-06-2017 Accepted: 05-26-2017 Published: 05-27-2017

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Abstract

Cytomegalovirus (CMV) infection usually occurs in immunocompromised patients, such as solid organ or hematopoietic cell transplant recipients, HIV-infected patients, and those treated with immunomodulating drugs. Toxic megacolon is a rare but potentially life-threatening complication of CMV colitis. We report a CMV colitis occurred in a 58-year-old male with chronic alcohol abuse and malnutrition. He had no findings suggestive of immunodeficiency. Despite anti-viral treatment, toxic megacolon associated with CMV infection developed; he was treated by colostomy with double orifices. Thus, CMV infection can develop in patients without immunodeficiency but with chronic alcohol abuse and malnutrition. Furthermore, in such patients, toxic megacolon can develop, which may require surgical treatment. If a patient with chronic alcohol abuse and malnutrition develops fever, abdominal pain, and/or diarrhea, the possibility of infectious enteritis due to opportunistic infection should be considered. Toxic megacolon caused by viral infection is rare, but a life-threatening complication, so its possibility should be considered even during proper treatment for CMV colitis.

 

Introduction
Cytomegalovirus (CMV) infection of the gastrointestinal tract usually occurs in immunocompromised patients, such as solid organ transplant recipients, hematopoietic cell transplant recipients, those infected with HIV, or those treated with immunomodulating drugs [1,2]. The toxic megacolon is a rare but potentially life-threatening complication of CMV colitis [3,4]. We experienced a rare CMV toxic megacolon lacked of immunodeficiency. The possibility of CMV colitis and toxic megacolon must be excluded even in patients without immunodeficiency but with chronic alcohol abuse and malnutrition.

 

Case Reports

A 58-year-old man was brought to our emergency department via ambulance with a 1-month history of anorexia and malaise. He had been dependent on alcohol (approximately 245 g of alcohol per day) and did not consume adequate meals. He had reported neither regular medication use nor signs of immuno deficiency in the past. Upon admission, he presented with anorexia and malaise. The vital signs were as follows; body temperature: 36.9°C; blood pressure; 96/70 mmHg: pulse rate: 94 beats/min: SpO2, 99% on room air. He presented remarkable macies; 170.5 cm of height, 42.2 kg of body-weight, and 14.5 of BMI. His abdominal wall was soft and flat and had no tenderness, no organomegaly, and no palpable mass. The laboratory data showed a moderate inflammatory reaction; 15,400/mL of white blood cell, 12.6 g/dL of hemoglobin, 43.5 × 103/μL of Platelet, 28.7 mg/dL of blood urea nitrogen, 0.47 mg/dL of Creatinine, 15 IU/L of aspartate transaminase, 9 IU/L of alanine transaminase, 137 mg/dL of Glu, 12.31 mg/dL of CRP. Abdominal CT on day 1 revealed mild bowel edema in the ileocecal and ascending colon (Figure 1).

 

Case fig 1.1

Figure 1. Abdominal CT on day 1 revealed mild bowel edema in the ileocecal and ascending colon.

On day 8, his stool culture was positive for Escherichia coli and Pseudomonas aeruginosa but revealed no Clostridium difficile. Since day 15, he had watery stool three to four times or more. We feared C. difficile infection though the culture was negative and thus metronidazole was administrated orally from day 21 for 10 days. His condition gradually worsened. On day 22, the colonoscopy revealed severe colitis with diffuse patchy erosion and longitudinal ulceration from the distal rectum to the cecum (Figure 2).

Case fig 1.2

Figure 2. Colonoscopic image revealed diffuse patchy erosion and longitudinal ulceration from the distal rectum to the cecum.

 

Also, stool tests, including stool culture and tests for C. difficile toxin and parasites or parasite eggs, showed no significant changes as the previous one. The biopsy-specimen of the intestinal mucosa revealed the presence of hematoxylin - eosin stained CMV inclusion bodies and an additional immunohistochemistry test showed positive staining for CMV (Figure 3).

Case fig 1.3 

Figure 3. Hematoxylin and eosin (a) and immunohistochemical staining with anti-cytomegalovirus (CMV) monoclonal antibody (b) confirmed the presence of CMV inclusion bodies.

 

Despite the administration of antiviral treatment, the patient’s symptoms were still worsening, including high fever, impaired consciousness, low blood pressure, tachycardia, and leukocytosis. On day 31, the CT scan study showed dilatation of the colon without mechanical obstruction (Figure 4). Serologic test for CMV was positive in IgG and negative in IgM on day 31 and suggested persistent latent infection. Both CMV C10/C11 antigenemia in peripheral blood leukocytes in day 43 and CMV polymerase chain reaction viral load in peripheral blood in day 44 were negative. No markers showed effectiveness of the antiviral treatment. The patient’s clinical manifestation was compatible with toxic megacolon associated with CMV infection. Large-volume infusion, electrolyte correction, and blood transfusion had been performed. Based on discussions at our hospital’s surgery conference, we believed that an appropriate surgery for the toxic megacolon was essential though moving to another hospital was necessary for the surgery. However, the patient and his family refused the surgery. Thus, we chose conservative treatments to relieve the symptoms with antiviral treatment and decompressing the colon using a nasogastric tube and a retrograde bowel drainage tube.

Case fig 1.4

Figure 4. On day 31, abdominal CT showed dilatation of the colon without mechanical obstruction.

After 1 month of intravenous ganciclovir administration, his fever decreased and diarrhea gradually improved. On day 74, colonoscopy showed that the mucosal lesions and longitudinal ulcer remained only in the sigmoid colon and colitis in other parts of colon was improved (Figure 5).

Case fig 1.5

Figure 5. On day 74, colonoscopy showed that mucosal lesions and longitudinal ulcer remained only in the sigmoid colon and colitis in other parts of the colon was improved.

 

Biopsy in the sigmoid lesion showed mild inflammation and no CMV inclusion bodies. However, the dilatation of the entire colon did not improve. On day 72 abdominal radiographs revealed marked dilatation in the transverse colon; on day 79 in the transverse colon and descending colon; and on day 91, from the ascending to the descending colon (Figure 6).

Case fig 1.6 

Figure 6. (a) On day 72, abdominal radiograph showed marked dilatation in the transverse colon. (b) On day 79, there was marked dilatation in the transverse colon and descending colon. (c) On day 91, there was further marked dilatation from the ascending colon to the descending colon.

 

The retrograde decompression of the colon was ineffective. We again persuaded the patient and his family that he should undergo surgery in another hospital. They finally accepted our proposal and the patient moved to another hospital. On day 102, surgeons performed transverse colostomy with double orifices. Subsequently, the patient was successfully managed with decompression of the colon by colostomy, and his general condition and functional ability improved. After 7 weeks of the intravenous ganciclovir administration, the patient left the hospital and moved to an extend care hospital.

 

Discussion

CMV infection in immunocompromised patients causes substantial morbidity and mortality, especially in transplant recipients and those infected with HIV. CMV infection in an immunocompetent host is generally asymptomatic or may present symptoms similar to that of mononucleosis. Even among patients with symptomatic CMV infection, the illness is generally self-limited with complete recovery over a period of several days to weeks. Antiviral therapy is not usually necessary for such cases. Based on his medical history and the findings, he had no immunodeficiency disorder such as cellular immunity, humoral immune deficiency, or complement deficiency. On the other hand, he had been consuming large amounts of alcohol for a long period. CMV infection is mainly associated with CD4+ and CD8+ T cell. Individuals with human immunodeficiency virus (HIV) infection and CD4+ cell counts <100 cells/mm3 are at significant risk for CMV reactivation leading to invasive disease [5,6] while our patient had a well-preserved CD4 cell count (781/μL). Previous study showed that chronic alcohol exposure interferes with the normal functioning of all aspects of the adaptive immune response, including both cell-mediated and humoral responses [7,8]. In those infected with CMV, the CMV has been reactivated locally, but the antibody and CMV-specific T cells prevent the spread of infection. Antiviral immunity utilizes natural killer cells and antibody-directed cellular cytotoxicity, both of which are adversely affected by alcohol [9,10].


Toxic megacolon is a potentially lethal complication of inflammatory bowel disease or infectious colitis, which is characterized by total or segmental nonobstructive dilatation of the colon greater than 6 cm with concomitant onset of systemic toxicity [4,11]. CMV colitis can induce toxic megacolon when the patient affected with HIV infection or AIDS. Our patients well met the Jalan’s criteria [12] for toxic megacolon. At present, we could not find any reports of toxic megacolon induced by CMV colitis without immunodeficiency in literatures.


Generally, a toxic megacolon should be treated by means of a nasogastric tube or long intestinal tube and/or retrograde bowel drainage tube for gastrointestinal decompression. However, a surgical consultation should be obtained upon admission, and the patient should be evaluated daily by both the medical and surgical team. Subtotal colectomy with end-ileostomy of the toxic megacolon should be selected for urgent or emergent surgery. The absolute indication for colectomy is perforation, uncontrollable bleeding, and progressive dilation [3]. We respected his and his family’s decision not to perform surgery initially, but if early surgical intervention had been performed, we were likely to have managed the patient more safely and discharged him earlier. Our treatment may be controversial because a delay of the surgical treatment generally leads to fatal progress [3,13].


Malnutrition and specific nutrient deficiencies are the primary underlying causes of immune deficiency, leading to infections and other diseases [14,15]. Malnutrition also has been associated with impaired T-cell function, thereby potentially predisposing patients to CMV reactivation [16]. Indeed, there are several case reports of CMV pneumonia in malnourished individuals who were otherwise immunocompetent [17,18]. In our case, the patient’s malnutrition likely made him more susceptible to infection, and the infection also likely contributed to his malnutrition. Anyhow he fortunately survived probably because he did not have complete immunodeficiency.


Conclusion

Not only immunodeficiency but also alcohol abuse and malnutrition have possibility to cause CMV infection and secondary toxic megacolon. In addition, we physicians should consider viral opportunistic enteritis when a chronic alcoholist shows acute abdominal complaint even the patient has no immunodeficiency.

 

Acknowledgments

The authors would like to thank Honyaku Center Inc. (https://www.honyakucenter.jp/) for the English language review.

 

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Cite this article: Dr. Toshiyuki Kobayashi. Cytomegalovirus Infection-Associated Toxic Megacolon in a Malnourished Patient with Chronic Alcohol Abuse. OAJ Case Reports. 2017, 1(1): 001.