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Cytomegalovirus Colitis Mimics Amebic Colitis in a Man With AIDS
Cytomegalovirus Colitis Mimics Amebic Colitis in a Man With AIDS YUNG-CHIH WANG, MD; HERNG-SHENG LEE, MD; TE-YU LIN, MD; NING-CHI WANG, MD
ABSTRACT: Opportunistic gastrointestinal infections are common in patients with HIV infection; both amebic colitis and cytomegalovirus (CMV) colitis are common causes of chronic diarrhea. It is difficult to distinguish these 2 diseases by nonspecific clinical symptoms such as diarrhea, abdominal pain, and weight loss. Here we report a case of CMV colitis mimicking amebic colitis with elevated indirect hemagglutination assay antibody titer against Entamoeba histolytica and negative IgM antibody titer against CMV. The diagnosis of CMV colitis was confirmed by eosinophilic nucleoli and inclusion bodies in colon biopsies. The patient recovered after
C
hronic diarrhea is frequent in patients infected with HIV. A wide range of pathogens have been reported to cause diarrhea in HIV-infected patients including cytomegalovirus (CMV), cryptosporidia, microsporidia, Mycobacterium spp, and Entamoeba histolytica etc.1 Both amebic colitis and CMV colitis are common causes of diarrhea, but their treatments are quite different. Metronidazole is the standard treatment for amebic colitis whereas CMV colitis is treated with ganciclovir. We present a case of an HIV-infected patient who had an elevated indirect hemagglutination assay (IHA) antibody titer against E. histolytica and negative IgM antibody titer against CMV, but was without response to metronidazole. CMV colitis was proved by colonoscopy with colon biopsies and positive serum polymerase chain reaction (PCR) for CMV. The patient had a good response to ganciclovir. Highly active antiretroviral therapy (HAART) was also prescribed and his AIDS status remained under control.
From the Division of Infectious Disease and Tropical Medicine (YCW, TYL, NCW), Department of Medicine; and Department of Pathology (HSL), Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Submitted September 3, 2007; accepted in revised form October 3, 2007. Correspondence: Ning-Chi Wang, MD, Division of Infectious Disease and Tropical Medicine, Department of Medicine, TriService General Hospital, National Defense Medical Center, 7F, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan (E-mail: [email protected]).
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ganciclovir and highly active antiretroviral therapy. Exact diagnoses are important for treating opportunistic infections. Other pathogens should be considered in patients with chronic diarrhea who are refractory to initial treatments. Our case highlights the importance of histopathological diagnosis for chronic diarrhea in patients with HIV infection and the possibility of falsepositive results for indirect hemagglutination assay antibody against Entamoeba histolytica despite high titers. KEY INDEXING TERMS: Cytomegalovirus; Amebic colitis; Indirect hemagglutination assay; Human immunodeficiency virus. [Am J Med Sci 2008;336(4):362–364.]
Case Report A 47-year-old man was first diagnosed with HIV infection in April 2005, but received no treatment. Three months before admission, he had poor appetite and watery diarrhea. The symptoms became gradually aggravated. In October 2005, he visited our hospital for poor intake and watery diarrhea with stools up to 15 times per day. Body weight loss of ⬎10 kg within 3 months was noted. On admission, the CD4 lymphocyte count was 22 cells/mm3 and the HIV viral load was 201,000 RNA copies/mL. We initiated HAART with lamivudin, zidovudine, and lopinavir/ritonavir on the seventh day of admission. Stool culture was negative for bacteria and no parasite or ovum was detected by stool microscopic examinations. The IgM antibody titer against CMV was negative. An axial spiral CT scan of the abdomen and pelvis disclosed generalized dilation of the whole course of the colon (Figure 1). However, the exact etiology was still undetermined. The IHA antibody titer against E. histolytica showed 1:2048 and amoebic colitis was our impression. The patient was treated with metronidazole (500 mg intravenously, every 8 hours), but symptoms persisted. Colonoscopy was performed and revealed a diffuse, ulcerated-like colitis from the descending colon to the rectum (Figure 2). Histopathologic findings of biopsy specimens showed a picture of an ulcer in a colon tissue with inflammatory infiltration, inclusion bodies, and prominent eosinophilic nucleoli without evidence of either amebiasis or malignancy (Figure 3). CMV viremia was also disclosed by serum PCR for CMV. CMV colitis was confirmed and ganciclovir 300 mg iv q12 hours was prescribed for 4 weeks. The diarrhea subsided. We repeated the serum and stool PCR tests for CMV, 2 weeks after completion of therapy. All results were negative. The patient showed complete resolution of his diarrhea and was discharged. He continued to receive HAART from the outpatient department and no relapse of his CMV colitis was observed. The CD4 lymphocyte count increased to 335 cells/mm3 and the HIV viral load decreased to less than 500 RNA copies/mL, 3 months after the initiation of HAART. Eight months after discharge, the IHA antibody titer October 2008 Volume 336 Number 4
Wang et al
Figure 1. Abdominal CT scan showing the generalized dilation of the colon with mild wall thickening (arrow) and air-fluid levels.
against E. histolytica decreased to 1:512 without therapy for amebiasis.
Discussion CMV infection is a common viral opportunistic infection in patients with HIV infection and results in significant morbidity and mortality. Most cases occur in HIV-infected patients with CD4 counts ⬍100 cells/mm3.2 The clinical presentations of CMV colitis are nonspecific, including diarrhea, abdominal pain, weight loss, fever, bleeding, and anorectal pain, etc.3 Diagnostic tests for CMV infections include viral culture, antigen detection, PCR, serology, and histo-
Figure 2. Colonoscopic view of the disseminated ulcers with yellowish mucus.
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Figure 3. Hematoxylin and eosin stain of colon tissue (1000⫻): Mixed inflammatory infiltration including active epithelioid histiocytes, prominent vessels and characteristic eosinophilic intranuclear inclusion bodies (arrow).
pathology. Of all the laboratory tests, CMV-PCR is the most sensitive method.4 The most specific method for diagnosis of CMV infection is the cytomegalic intranuclear inclusion in tissue.5 Positive blood and urine viral cultures are helpful but not necessary for the diagnosis of CMV colitis.6 Bini et al reported that colonoscopy was the most cost-effective endoscope procedure for patients with a CD4 count ⬍100 cells/mm3 and unexplained diarrhea.7 Colonoscopy with biopsies should be performed early in the diagnosis of CMV colitis.6,8 Ganciclovir and foscavir are the drugs of choice in CMV disease. In 2000, Bini et al2 reported that a complete response was seen in 87% of patients treated with ganciclovir, foscavir, or both. The introduction of HAART also significantly decreases the relative hazard of AIDS-associated opportunistic infection.7 IHA is a serologic test for detecting bacterial, viral, and parasitical infections. It has been shown a good diagnostic tool in patients with amebiasis since the 1960s.9 The results of the IHA were considered positive if the titer is ⱖ1:128. The IHA test has good specificity and negative predictive value in the diagnosis of invasive amebiasis.10 In the diagnosis of invasive amebiasis, the sensitivity is ⬎70%11 and specificity is 99.1%.10 In Hung et al’s study,10 the positive predictive value is 92.9% and the negative predictive value is 95.5%. In endemic areas, the level of antiamebic antibodies remains elevated in serum for many years after resolution of the disease.12 This may lead to inability to distinguish positive results from previous to current infection.13 The patient we presented had a positive IHA antibody titer against E. histolytica and the symptoms of amebic colitis. The positive result of IHA antibody titer and nonspecific symptoms make it difficult to 363
Cytomegalovirus Colitis Mimics Amebic Colitis
achieve early diagnosis. He was initially treated under suspicion of amebic colitis but had a poor response. CMV colitis was confirmed by the histopathological characteristics of the specimens. Administration of ganciclovir led to a complete remission of the disease. HAART was prescribed for his HIV infection. The CD4 cell count increased and the HIV viral load dropped after therapy. Both CMV colitis and the HIV infection showed good responses to our treatments. This case emphasizes the importance of histology for the correct diagnosis of chronic diarrhea in HIV-infected patients who do not respond to empiric treatment. References 1. Sharpstone D, Gazzard B. Gastrointestinal manifestations of HIV infection. Lancet 1996;348:379 – 83. 2. Bini EJ, Gorelick SM, Weinshel EH. Outcome of AIDSassociated cytomegalovirus colitis in the era of potent antiretroviral therapy. J Clin Gastroenterol 2000;30:414 –19. 3. Wilcox CM, Chalasani N, Lazenby A, et al. Cytomegalovirus colitis in acquired immunodeficiency syndrome: a clinical and endoscopic study. Gastrointest Endosc 1998; 48:39 – 43. 4. Dodt KK, Jacobsen PH, Hofmann B, et al. Development
364
5.
6.
7.
8.
9. 10.
11. 12.
13.
of cytomegalovirus (CMV) disease may be predicted in HIVinfected patients by CMV polymerase chain reaction and the antigenemia test. AIDS 1997;11:F21–F28. De La Hoz RE, Stephens G, Sherlock C. Diagnosis and treatment approaches of CMV infections in adult patients. J Clin Virol 2002;25 (suppl 3):S1–S12. Dieterich DT, Rahmin M. Cytomegalovirus colitis in AIDS: presentation in 44 patients and a review of the literature. J Acquir Immune Defic Syndr1991;4 (suppl 1):S29 –S35. Bini EJ, Cohen J. Diagnostic yield and cost-effectiveness of endoscopy in chronic human immunodeficiency virus-related diarrhea. Gastrointest Endosc 1998;48:354 – 61. Mentec H, Leport C, Leport J, et al. Cytomegalovirus colitis in HIV-1-infected patients: a prospective research in 55 patients. AIDS 1994;8:461– 67. Healy GR. Laboratory diagnosis of amebiasis. Bull NY Acad Med 1971;47:478 –93. Hung CC, Chen PJ, Hsieh SM, et al. Invasive amoebiasis: an emerging parasitic disease in patients infected with HIV in an area endemic for amoebic infection. AIDS 1999;13: 2421–28. Haque R, Huston CD, Hughes M, et al. Amebiasis. N Engl J Med 2003;348:1565–73. Fotedar R, Stark D, Beebe N, et al. Laboratory diagnostic techniques for Entamoeba species. Clin Microbial Rev 2007; 20:511–32. Li E, Stanley SL Jr. Protozoa. Amebiasis. Gastroenterol Clin North Am 1996;25:471–92.
October 2008 Volume 336 Number 4
ABSTRACT: Opportunistic gastrointestinal infections are common in patients with HIV infection; both amebic colitis and cytomegalovirus (CMV) colitis are common causes of chronic diarrhea. It is difficult to distinguish these 2 diseases by nonspecific clinical symptoms such as diarrhea, abdominal pain, and weight loss. Here we report a case of CMV colitis mimicking amebic colitis with elevated indirect hemagglutination assay antibody titer against Entamoeba histolytica and negative IgM antibody titer against CMV. The diagnosis of CMV colitis was confirmed by eosinophilic nucleoli and inclusion bodies in colon biopsies. The patient recovered after
C
hronic diarrhea is frequent in patients infected with HIV. A wide range of pathogens have been reported to cause diarrhea in HIV-infected patients including cytomegalovirus (CMV), cryptosporidia, microsporidia, Mycobacterium spp, and Entamoeba histolytica etc.1 Both amebic colitis and CMV colitis are common causes of diarrhea, but their treatments are quite different. Metronidazole is the standard treatment for amebic colitis whereas CMV colitis is treated with ganciclovir. We present a case of an HIV-infected patient who had an elevated indirect hemagglutination assay (IHA) antibody titer against E. histolytica and negative IgM antibody titer against CMV, but was without response to metronidazole. CMV colitis was proved by colonoscopy with colon biopsies and positive serum polymerase chain reaction (PCR) for CMV. The patient had a good response to ganciclovir. Highly active antiretroviral therapy (HAART) was also prescribed and his AIDS status remained under control.
From the Division of Infectious Disease and Tropical Medicine (YCW, TYL, NCW), Department of Medicine; and Department of Pathology (HSL), Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Submitted September 3, 2007; accepted in revised form October 3, 2007. Correspondence: Ning-Chi Wang, MD, Division of Infectious Disease and Tropical Medicine, Department of Medicine, TriService General Hospital, National Defense Medical Center, 7F, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan (E-mail: [email protected]).
362
ganciclovir and highly active antiretroviral therapy. Exact diagnoses are important for treating opportunistic infections. Other pathogens should be considered in patients with chronic diarrhea who are refractory to initial treatments. Our case highlights the importance of histopathological diagnosis for chronic diarrhea in patients with HIV infection and the possibility of falsepositive results for indirect hemagglutination assay antibody against Entamoeba histolytica despite high titers. KEY INDEXING TERMS: Cytomegalovirus; Amebic colitis; Indirect hemagglutination assay; Human immunodeficiency virus. [Am J Med Sci 2008;336(4):362–364.]
Case Report A 47-year-old man was first diagnosed with HIV infection in April 2005, but received no treatment. Three months before admission, he had poor appetite and watery diarrhea. The symptoms became gradually aggravated. In October 2005, he visited our hospital for poor intake and watery diarrhea with stools up to 15 times per day. Body weight loss of ⬎10 kg within 3 months was noted. On admission, the CD4 lymphocyte count was 22 cells/mm3 and the HIV viral load was 201,000 RNA copies/mL. We initiated HAART with lamivudin, zidovudine, and lopinavir/ritonavir on the seventh day of admission. Stool culture was negative for bacteria and no parasite or ovum was detected by stool microscopic examinations. The IgM antibody titer against CMV was negative. An axial spiral CT scan of the abdomen and pelvis disclosed generalized dilation of the whole course of the colon (Figure 1). However, the exact etiology was still undetermined. The IHA antibody titer against E. histolytica showed 1:2048 and amoebic colitis was our impression. The patient was treated with metronidazole (500 mg intravenously, every 8 hours), but symptoms persisted. Colonoscopy was performed and revealed a diffuse, ulcerated-like colitis from the descending colon to the rectum (Figure 2). Histopathologic findings of biopsy specimens showed a picture of an ulcer in a colon tissue with inflammatory infiltration, inclusion bodies, and prominent eosinophilic nucleoli without evidence of either amebiasis or malignancy (Figure 3). CMV viremia was also disclosed by serum PCR for CMV. CMV colitis was confirmed and ganciclovir 300 mg iv q12 hours was prescribed for 4 weeks. The diarrhea subsided. We repeated the serum and stool PCR tests for CMV, 2 weeks after completion of therapy. All results were negative. The patient showed complete resolution of his diarrhea and was discharged. He continued to receive HAART from the outpatient department and no relapse of his CMV colitis was observed. The CD4 lymphocyte count increased to 335 cells/mm3 and the HIV viral load decreased to less than 500 RNA copies/mL, 3 months after the initiation of HAART. Eight months after discharge, the IHA antibody titer October 2008 Volume 336 Number 4
Wang et al
Figure 1. Abdominal CT scan showing the generalized dilation of the colon with mild wall thickening (arrow) and air-fluid levels.
against E. histolytica decreased to 1:512 without therapy for amebiasis.
Discussion CMV infection is a common viral opportunistic infection in patients with HIV infection and results in significant morbidity and mortality. Most cases occur in HIV-infected patients with CD4 counts ⬍100 cells/mm3.2 The clinical presentations of CMV colitis are nonspecific, including diarrhea, abdominal pain, weight loss, fever, bleeding, and anorectal pain, etc.3 Diagnostic tests for CMV infections include viral culture, antigen detection, PCR, serology, and histo-
Figure 2. Colonoscopic view of the disseminated ulcers with yellowish mucus.
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Figure 3. Hematoxylin and eosin stain of colon tissue (1000⫻): Mixed inflammatory infiltration including active epithelioid histiocytes, prominent vessels and characteristic eosinophilic intranuclear inclusion bodies (arrow).
pathology. Of all the laboratory tests, CMV-PCR is the most sensitive method.4 The most specific method for diagnosis of CMV infection is the cytomegalic intranuclear inclusion in tissue.5 Positive blood and urine viral cultures are helpful but not necessary for the diagnosis of CMV colitis.6 Bini et al reported that colonoscopy was the most cost-effective endoscope procedure for patients with a CD4 count ⬍100 cells/mm3 and unexplained diarrhea.7 Colonoscopy with biopsies should be performed early in the diagnosis of CMV colitis.6,8 Ganciclovir and foscavir are the drugs of choice in CMV disease. In 2000, Bini et al2 reported that a complete response was seen in 87% of patients treated with ganciclovir, foscavir, or both. The introduction of HAART also significantly decreases the relative hazard of AIDS-associated opportunistic infection.7 IHA is a serologic test for detecting bacterial, viral, and parasitical infections. It has been shown a good diagnostic tool in patients with amebiasis since the 1960s.9 The results of the IHA were considered positive if the titer is ⱖ1:128. The IHA test has good specificity and negative predictive value in the diagnosis of invasive amebiasis.10 In the diagnosis of invasive amebiasis, the sensitivity is ⬎70%11 and specificity is 99.1%.10 In Hung et al’s study,10 the positive predictive value is 92.9% and the negative predictive value is 95.5%. In endemic areas, the level of antiamebic antibodies remains elevated in serum for many years after resolution of the disease.12 This may lead to inability to distinguish positive results from previous to current infection.13 The patient we presented had a positive IHA antibody titer against E. histolytica and the symptoms of amebic colitis. The positive result of IHA antibody titer and nonspecific symptoms make it difficult to 363
Cytomegalovirus Colitis Mimics Amebic Colitis
achieve early diagnosis. He was initially treated under suspicion of amebic colitis but had a poor response. CMV colitis was confirmed by the histopathological characteristics of the specimens. Administration of ganciclovir led to a complete remission of the disease. HAART was prescribed for his HIV infection. The CD4 cell count increased and the HIV viral load dropped after therapy. Both CMV colitis and the HIV infection showed good responses to our treatments. This case emphasizes the importance of histology for the correct diagnosis of chronic diarrhea in HIV-infected patients who do not respond to empiric treatment. References 1. Sharpstone D, Gazzard B. Gastrointestinal manifestations of HIV infection. Lancet 1996;348:379 – 83. 2. Bini EJ, Gorelick SM, Weinshel EH. Outcome of AIDSassociated cytomegalovirus colitis in the era of potent antiretroviral therapy. J Clin Gastroenterol 2000;30:414 –19. 3. Wilcox CM, Chalasani N, Lazenby A, et al. Cytomegalovirus colitis in acquired immunodeficiency syndrome: a clinical and endoscopic study. Gastrointest Endosc 1998; 48:39 – 43. 4. Dodt KK, Jacobsen PH, Hofmann B, et al. Development
364
5.
6.
7.
8.
9. 10.
11. 12.
13.
of cytomegalovirus (CMV) disease may be predicted in HIVinfected patients by CMV polymerase chain reaction and the antigenemia test. AIDS 1997;11:F21–F28. De La Hoz RE, Stephens G, Sherlock C. Diagnosis and treatment approaches of CMV infections in adult patients. J Clin Virol 2002;25 (suppl 3):S1–S12. Dieterich DT, Rahmin M. Cytomegalovirus colitis in AIDS: presentation in 44 patients and a review of the literature. J Acquir Immune Defic Syndr1991;4 (suppl 1):S29 –S35. Bini EJ, Cohen J. Diagnostic yield and cost-effectiveness of endoscopy in chronic human immunodeficiency virus-related diarrhea. Gastrointest Endosc 1998;48:354 – 61. Mentec H, Leport C, Leport J, et al. Cytomegalovirus colitis in HIV-1-infected patients: a prospective research in 55 patients. AIDS 1994;8:461– 67. Healy GR. Laboratory diagnosis of amebiasis. Bull NY Acad Med 1971;47:478 –93. Hung CC, Chen PJ, Hsieh SM, et al. Invasive amoebiasis: an emerging parasitic disease in patients infected with HIV in an area endemic for amoebic infection. AIDS 1999;13: 2421–28. Haque R, Huston CD, Hughes M, et al. Amebiasis. N Engl J Med 2003;348:1565–73. Fotedar R, Stark D, Beebe N, et al. Laboratory diagnostic techniques for Entamoeba species. Clin Microbial Rev 2007; 20:511–32. Li E, Stanley SL Jr. Protozoa. Amebiasis. Gastroenterol Clin North Am 1996;25:471–92.
October 2008 Volume 336 Number 4