CASE REPORT

대한소화기학회지 2004;44:224~228

INTRODUCTION

¹⁾

Cytomegalovirus (CMV) is one of the most common opportunistic infections complicating the acquired immuno- deficiency syndrome (AIDS).^1,2However, CMV colitis can be developed in a healthy person and in most of these cases, CMV infections are due to reactivation of latent virus.^3-5In Korea, the prevalence of AIDS is not as high as that of other countries. Thus, it is difficult to suspect opportunistic infection in healthy-looking young people. We, herein, report a problematic case in diagnosing CMV ulcer in a young Korean man who initially denied homosexual habit.

접수: 2004년 월6 23 ,일 승인: 2004년 월8 30일 연락처 한동수: , 471-701, 경기도 구리시 교문동 249-1

한양대학교 구리병원 소화기내과

Tel: (031) 560-2226, Fax: (031) 555-2998 E-mail: [email protected]

CASE REPORT

A 32-year-old man was hospitalized with 3-weeks history of abdominal pain, fever, and watery diarrhea in September 2002. During one week just before presenting to the hospital, his diarrhea had worsened. He described his diarrhea as loose, watery stools that occurred three to four times per day, with no associated or relieving factors. There was no previous history of irritable bowel syndrome. He denied melena or bright red blood per rectum. The patient had no medical history and was not taking any medication. On physical examination, the patient looked acutely ill, dehydrated, and was in moderate²⁾distress. Vital signs

Correspondence to: Dong Soo Han, M.D., PhD

Department of Internal Medicine, Hanyang University Kuri Hospital 249-1 Gyomun-dong, Guri-si, Gyeonggi-do 471-701, Korea Tel: +82-31-560-2226, Fax: +82-31-555-2998 E mail: [email protected]

후천성 면역결핍증 환자에서의 회맹부 궤양으로 발현한 거대세포바이러스 대장염 예 1

한양대학교 의과대학 내과학교실 한림대학교 의과대학 내과학교실, *

김진배* 한동수현일식이항락김종표손주현함준수

Cytomegalovirus Colitis Manifested with a Ring like Ileocecal Valve Ulcer Cytomegalovirus Colitis Manifested with a Ring like Ileocecal Valve Ulcer Cytomegalovirus Colitis Manifested with a Ring like Ileocecal Valve Ulcer Cytomegalovirus Colitis Manifested with a Ring like Ileocecal Valve Ulcer

in a Korean AIDS Patient in a Korean AIDS Patient in a Korean AIDS Patient in a Korean AIDS Patient

Jin Bae Kim,

Jin Bae Kim, Jin Bae Kim,

Jin Bae Kim, M.D.*, Dong Soo Han,Dong Soo Han,Dong Soo Han,Dong Soo Han, M.D., Il Sik Hyun,Il Sik Hyun,Il Sik Hyun, M.D., Hang Lak Lee,Il Sik Hyun, Hang Lak Lee,Hang Lak Lee, M.D., Jong Pyo Kim,Hang Lak Lee, Jong Pyo Kim,Jong Pyo Kim,Jong Pyo Kim, M.D., Joo Hyun Sohn,

Joo Hyun Sohn,Joo Hyun Sohn,

Joo Hyun Sohn, M.D., and Joon Soo Hahm,Joon Soo Hahm,Joon Soo Hahm, M.D.Joon Soo Hahm,

Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea Department of Internal Medicine, Hallym University College of Medicine *, Seoul, Korea

A 32-year-old man, who had no previous medical history, was hospitalized with 3-week duration of abdominal pain, fever, and watery diarrhea. Initial colonoscopy showed subepithelial hemorrhagic spots throughout the entire colon together with well-circumscribed ulcer around the ileocecal valve. Serologic test disclosed HIV-positive and repeated biopsies at ulcer base finally revealed that the patient had cytomegalovirus ulcer in ileocecal area.

(Korean J Gastro (Korean J Gastro (Korean J Gastro

(Korean J Gastroenterol 2004;44:224-228) enterol 2004;44:224-228) enterol 2004;44:224-228) enterol 2004;44:224-228) Key Key

Key Key Words: Words: Words: CMV; HIV; AIDS; Ileocecal valve; Colonoscopy Words:

김진배 외 인 후천성 면역결핍증 환자에서의 회맹부 궤양으로 발현한 거대세포바이러스 대장염 예6 . 1

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revealed a blood pressure of 120/70 mmHg, pulse 88 beats/minute, and during hospitalization his temperature ranged from 38 to 39 . Pharyngeal examination was unremarkable and abdominal examination showed mild tenderness in right lower quadrant area. The white cell count was 3,700/mm³, hemoglobin level was 12.0 g/dL, and platelet count was 180,000/mm³. Electrolyte, BUN, creati- nine, and glucose values were normal. The total protein count was 6.5 g/dL, and albumin was 3.6 g/dL. Alkaline phosphatase, lactate dehydrogenase, transaminase, and biliru- bin were in normal. range or values were normal Chest x-ray and urinalysis also showed negative findings. Cultures of blood for bacteria were negative. Stool examinations for ova and parasites, bacterial pathogens,

Clostridium difficle

toxin, and Mycobacteria were also negative. Colonoscopy showed diffuse subepithelial hemorrhage with patchy erosions throughout the entire colon. Well-circumscribed ulcer around the ileocecal valve was associated with pancolitis (Fig. 1).

Biopsy specimens from the ileocecal area revealed acute and chronic inflammation with ulcer. Empiric therapy for common bacterial infection was begun with intravenous ciprofloxacin and metronidazole. Three days later, he discharged with a slight clinical improvement.

Three weeks later, he presented again with unremitting fever and intermittent right lower abdominal pain, but he denied diarrhea. Another series of laboratory studies revealed unremarkable. Endoscopic examination showed an

unchanged circumscribed ulcer around the ileocecal valve without evidence of colitis elsewhere (Fig. 2). Serology for CMV at the time of the second colonoscopy revealed an increased IgG titer for CMV, but the serum was negative for IgM CMV antibody. Histopathologic examination and repeated stool specimens for CMV did not show specific finding. Anti-tuberculosis medication started without proven

Fig.

Fig.Fig.

Fig. 1.1.1.1. Initial colonoscopic finding. (A) Wide spread subepithelial hemorrhagic spots are noted throughout the entire colon. (B) Circumscribed superficial ulcer is noted around the ileocecal vave.

Fig. 2.

Fig. 2.

Fig. 2.

Fig. 2. Second colonoscopy performed 3 weeks after the initial examination. Unchanged circumscribed ulcer around the ileocecal valve is noted without evidence of colitis elsewhere.

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Fig. 3.

Fig. 3.Fig. 3.

Fig. 3. Fourth colonoscopy performed two months after the initial examination. Unchanged circumscribed ulcer around the ileocecal valve is still noted.

pathologic result of granuloma on the basis of the high prevalence of tuberculosis in Korea.

In November 2002, he was readmitted with fever and newly developed hematochezia. Examination revealed oral ulcer and whole body skin rash. The white cell count was 1800/mm³, hemoglobin level was 9.8 g/dL, and platelet count was 86,000/mm³. Electrolytes, BUN, creatinine, and glucose

Fig. 5.

Fig. 5.

Fig. 5.

Fig. 5. Sixth colonoscopy performed three and half months after the initial examination. Nearly healed ulcer around the ileocecal area is noted 15 days after ganciclovir treatment.

values were normal. Anti-tuberculosis medication was discontinued and upper and lower gastrointestinal endoscopy was performed. There was no significant interval change of ileocecal ulcer on colonoscopic exam (Fig. 3), and multiple round erosions suggesting viral infection and candida mucosal patches were noted on mid-esophagus. Serum ELISA test for HIV was positive, and he confessed the

Fig.

Fig.Fig.

Fig. 4.4.4.4. Histologic findings obtained 3 months after the initial examination. (A) Photomicrograph of biopsy specimen obtained from margin of the ulcer showing lymphocytic infiltration and a large cell containing an intranuclear inclusion body (black arrow) (H&E, orig. mag. × 100). (B) Photomicrograph of immunohistochemically stained biopsy showing that the cell is positive for cytomegalovirus (CMV antibody,

×100).

Kim JB, et al. CMV colitis in a Korean AIDS patient

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homosexual episode 10 years prior to admission. Subsequent Western blot for HIV was also positive, and the CD4 was 76/mm³. Given the HIV status of the patient, opportunistic infection was suspected and he began to receive zidovudine, indinavir, and 3TC as well as intravenous acyclovir and fluconazole.

In December 2002, colonoscopy showed the decreased size of circumscribed ulcer around the ileocecal valve, which is considered as healing process. Biopsy specimen of ulcer base demonstrated diffuse infilatration of acute and chronic inflammatory cells and some stromal cells were enlarged with CMV inclusions that were confirmed on immunohistochemical staining (Fig. 4). Intravenous gan- ciclovir was added to the anti-HIV medication, and follow- up colonoscopy was performed 2 weeks later. Follow-up colonoscopy disclosed a completely healed ulcer on ileocecal valve (Fig. 5).

DISCUSSION

Since the discovery of AIDS in 1981, HIV infection has spread quickly and has become the most serious health problem for mankind. The number of those infected with HIV has now reached nearly 40 million world-wide.⁶After the first case of HIV infection was reported in Korea in 1985,⁷the number of those infected with HIV increased annually and reached 1,280 as of December 2000.⁶Oppor- tunistic diseases are related to microorganisms invading from the outside in addition to endogenous microorganisms within the infected person. Thus, the type and frequencies of opportunistic diseases differ according to the region, country, race, and environment.⁸In terms of the frequency of opportunistic diseases in Korean AIDS patients, candidiasis,

pneumocystis carinii

, tuberculosis, and CMV infection have been reported most frequently.^6,9In Korea, seroprevalence of IgG against CMV is over 95%. Therefore, CMV diseases are expected to be a prevalent opportunistic infection in AIDS patients of Korea.¹⁰

In general, the best diagnostic test for establishing CMV infection or mononucleosis is serology for CMV IgM antibody. The result should be positive in the majority of patients during the symptomatic phase of the illness.¹¹ However, demonstrating viral cytopathic effect in tissue specimens is the best way.²In the diagnosis of organ involvement, in the presented case, repeated serologic tests

for anti-CMV IgM antibody and PCR for CMV DNA could not demonstrate any evidence for CMV infection, nor did histopathological findings. From the retrospective view, negative test for anti-CMV IgM in the presented case well agree with the fact that only 20% of the known CMV infection in AIDS patients shows anti-CMV IgM antibody and there is no correlation between serological and histopathological diagnosis.¹²This might be due to the decreased effector/ memory function of T cell to viral infections in AIDS patients. From this point of view, more vigorous effort to obtain adequate biopsy specimens should be tried for earlier diagnosis in patients with AIDS.

The endoscopic patterns of CMV colitis in AIDS are heterogenous, although subepithelial hemorrhage, colitis, and/or ulcers are typical.¹³In the presented case, initial manifestation of colonoscopy was a peri-ileocecal ulcer along with pancolonic subepithelial hemorrhages. Although subepithelial hemorrhages totally disappeared after antibiotic treatment, an ileocecal ulcer was not imporved or more consolidated thereafter. It suggested that other viral or vasculitis were implicated in disease process, and clinical findings such as oral ulcer and skin lesion supported this assumption. However, it was not easy to differentiate them from drug reaction at that time. A case of a ring like CMV ulcer around the ileocecal valve has been reported in a patient with AIDS, which is just like in our case.¹³We strongly suspected CMV infection on the basis of both immune-compromised status and peculiar ulcer appearance.

In summary, this report describes a HIV positive man with a ileocecal CMV ulcer who initially thought to have infectious diarrhea. When there are subepithelial hemor- rhages and/or a ring like ileocecal ulcer, it is recommended that serologic test for HIV and vigorous tissue sampling for CMV inclusion should be done for earlier diagnosis.

요 약

후천성 면역결핍증에서의 거대세포 바이러스 대장염의 양상은 다양하지만 주로 미만성 상피하 출혈반과 궤양의

형태로 나타난다 본 증례는 고열과 설사를 주소로 내원한.

평소 건강하던32세 남자 환자에서 대장내시경에서 미만성

상피하 출혈반과 반지 모양의 회맹판 주위 궤양을 보였던 경우로 반복된 병력 청취와 대장내시경조직검사로 후천성 면역결핍증에 동반된 거대세포 바이러스 대장염으로 진단 하였던 예이다.

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