Journnl of Internal Medicine 1992: 232: 357-359
Case report
Self-limited primary cytomegalovirus colitis in an immunocompetent individual M. MAIGNAN, D. WAHL, D. THIAUCOURT, D. BACH, J.-D. DE KORWIN, G. VAILLANT, F. PAILLE & J. SCHMITT From the Service de MMecine H . CHUN, NANCY Cidex. France
Abstract. Maignan M, Wahl D, Thiaucourt D, Bach D, de Korwin J-D, Vaillant G, Paille F. Schmitt J (Service de MCdecine H, CHUN, Nancy CCdex, France). Self-limited primary cytomegalovirus colitis in an immunocompetent individual. journal of Internal Medicine 1992; 232: 357-359. Cytomegalovirus colitis in immunocompetent patients has rarely been reported without another severe illness. The prognosis is usually bad, leading to toxic megacolon or death due to multi-organ system failure. We report a case of a self-limited cytomegalovirus colitis in a young patient with no risk factor for CMV infection or associated disease. This suggests that self-limiting CMV colitis may be more frequent than is usually believed, and its prognosis may be better in young patients with normal immune functions. Therefore it should be sought systematically even in immunocompetent young patients. Keywords: colitis, cytomegalovirus.
Introduction Cytomegalovirus (CMV) colitis in transplant and immunosuppressed patients is well known [l].Primary CMV infection in immunocompetent individuals usually results in a mononucleosis syndrome and/or acute hepatitis [l]. We report the case of a 36-year-old heterosexual male who developed, in January 1991, fever up to 39 O C , myalgia and asthenia. The patient had no risk factor for human immunodeficiency virus (HIV) infection. After 1 week he developed severe rectal pain, diarrhoea and haematochezia. Flexible sigmoidoscopy (31 January) showed oedematous and inflamed mucosa in the rectum and sigmoid area. Lesions were predominant in the lower rectum and anus, where linear ulcers were also present. Rectal biopsy specimens showed an ulcer base with lamina propria inflammation and a submucosal inflammatory infiltrate. Typical CMV cells were found (Fig. I), and CMV inclusions were confirmed by immunofluoresence. The patient was referred to our unit 11 d later; his state had improved and fever
then resolved within 2 d. There was no indication of pulmonary involvement. The patient had one normal daily bowel movement. There was no adenopathy or hepatosplenomegaly . Laboratory studies revealed a leucocyte count of 6.3 x 1091-1 with a differential fraction of 36 polymorphonuclear cells, 53 lymphocytes and 11 monocytes. The platelet count was 2.5 x 10" I-' and the haemoglobin concentration was 1 4 g d1-l. The erythrocyte sedimentation rate was 24 mm h-I. CRP was 2.5 mg 1-', and fibrinogen was 2.59 g I-'. Aspartate and alanine aminotransferases were moderately increased (34 IU I-' and 147 IU I-', respectively). Stool culture was negative for parasites and bacteria. Blood cultures were negative. Cytomegalovirus antibodies titres were obtained during the third week after the onset of symptoms. ELISA titres were moderately positive for IgG antibodies and strongly positive for IgM antibodies. Viral cultures of the stool were negative. Blood and urine cultures were also negative for CMV. IgM titres for hepatitis A, EpsteinBarr, varicella-zoster and herpes simplex virus were negative. Hepatitis B markers showed evidence of a 357
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M. MAIGNAN et al.
Fig. I . Rectal biopsy from the patient showing submucosal inflammatory infiltration and a cytomegalic cell with a typical intranuclear inclusion, conlirmed by immunofluorescence (magnification x 500).
former infection which was healed. Hepatitis C and Delta markers were negative. HIVl and HIV2 titres were negative, and HIVl antigens were absent. No other systemic or organ involvement was found in our patient. Broncho-alveolar lavage, upper gastrointestinal tract endoscopy and biopsies, and ophthalmological examination were negative. On a second sigmoidoscopy 1 2 d after the first one, inflammation and ulcers were significantly improved. Studies of immune function including tuberculin test, serum protein fractions, IgG, IgA and IgM levels, total haemolytic serum complement CH50, C3 and C4 were normal, as well as cell counts of bone marrow. Circulating lymphocyte subpopulations count showed 567 CD4 mm-3 (normal range, 400-1400 mm-')), 2037 CD8 mm-' (normal range, 200-850 mm-')). The CD4/CD8 ratio was 0.28 (normal range, 0.80-2.60); the low CD4/CD8 ratio is often a reflection of a viral infection [2]. The outcome was a spontaneous improvement of the infection before any anti-CMV therapy had been given. Two months later the patient was free of any symptoms ; blood cell counts were normal and aminotransferase levels were decreased. HIVl and HIV2 antibodies and HIVl antigens were negative. CMV antibodies titres were weakly positive for IgM and strongly positive for IgG. This case is quite remarkable with respect to published cases because of both its clinical presentation and the outcome. CMV colitis usually affects immunosuppressed patients after renal or bone
marrow transplant [ 11, haematological malignancies, HIV infection and acquired immunodeficiency syndrome [11, and idiopathic inflammatory bowel disease (IBD). In these situations CMV is believed to be an opportunistic infection [ 3 ] .When patients with IBD ware excluded, 1 6 case records [4-131 of proven CMV colitis in immunocompetent patients have been published: 8 females and 8 males. Their ages ranged from 2 5 to 80 years (10 were elderly, over 65 years). Eight patients died ( 7 were over 45 years of age and three had pulmonary involvement). Emergency colectomy was performed in 4 patients who did not survive. It has been suggested [9] that CMV enterocolitis may affect patients debilitated by a severe illness. Among the published cases patients were either debilitated (malnourished, treated with corticosteroids, alcoholic) or had a specific physiological status (old age, pregnancy). When associated conditions were absent, transmission of CMV was identified (anal intercourse, blood transfusions). Our patient had no associated illness before this infection, and transmission was not caused by anal intercourse or transfusion. This supports the hypothesis [9] that a number of CMV colitis cases may be caused by direct patient-to-patient spread. CMV enterocolitis is probably more common than is currently suspected. Our case record shows that selflimited colitis may occur in immunocompetent patients even without sexual or blood transmission. These patients may not require anti-CMV therapy.
S EL F-LI MITED PRIMARY C Y TO MEG ALO V IRU S COLITIS
Undiagnosed cases may facilitate the spread of the disease even nosocomially. particularly if the virus is shed in the stool, urine or respiratory tract.
8
9
References Ho M. Epidemiology of cytomegalovirus infections. Kev InJect Dis 1990: 12: 5701-10. Dc WaeIe M. Thielemans C. Van Camp B. Imrnunoregulatory 1' cells in mononucleosis and toxoplasmosis. N Engl ] Med 1981 : 305: 228. Surawicx CM. Myerson D.Self-limited cytornegalovirus colitis in immunocompetcnt individuals. Gastroenterologg 1988 : 94: 194-9. Nakonecxna I. Kay S. Fatal disseminated cytomegalic inclusion disease in an adult presenting with a lesion of the gastrointestinal tract. Arri I Clin h t h o l 1967: 47: 124-8. Taniura H. Acute ulcerative colitis associated with cytomegalic inclusion virus. Arch Pathol 1973: 96: 164-7. Druart F. Matuchansky C. Blavon-Duchesne N. Babin P. Barbier J , Beauchant J. Colite ulcereuse aigue avec inclusions cytomtgaliques chex un suiet non immunodeprimk. Sem Hbp f+wis 1979; 5 5 : 85-7. Spiegel JS, Schwabe AD. Disseminated cytomegalovirus in-
10
11 12
13
3 59
fection with gastrointestinal involvement. Am ] Gaslroenterol 1980: 73: 3 7 4 4 . Beaugrand L, Poynard T, Callard P et a/. Infections a cytornegalovirus au cours des colites pseudo-membraneuses. Nouv Presse Med 1981 ; 10: 1199-204. Bennett MR. Fine AP. Hanlon JT, Cytomegalovirus hemorrhagic colitis in a nontransplant patient. Postgrad Med 1985 : 77: 227-32. Arsene D.Callet E, Freyrnuth F, Caillez D. Valla A, Verwaerde JC. Colite aigue ulcereuse et infection a cytomegalovirus chex un patient non immunodeprime: apparition retardee des anticorps specifiques. Ann Med Interne (Paris) 1987: 138: 375-6. Orloff JJ, Saito R. Lasky S. Dave H. Toxic megacolon in cytomegalovirus colitis. Am Gnstroenterol 1989: 84: 794-7. Banerjee AK. Cytomegalovirus (CMV) enterocolitis. ] K Soc Med 1989: 82: 446. Diepersloot RIA. Kroes ACM, Visser W. Jiwa NM. Rothbarth PH. Acute ulcerative proctocolitis associated with primary cytomegalovirus infection. Arch Intern Med 1990; 1 5 0 : 1749-5 1.
Received 12 December 1991, accepted 8 January 1992. Correspondence: Dr Denis G. Wahl. Service de Medecine H,CHUN. 29 avenue MarCchal de Lattre de Tassigny. CO N". 34, F-54035 Nancy Cedex, France.
Case report
Self-limited primary cytomegalovirus colitis in an immunocompetent individual M. MAIGNAN, D. WAHL, D. THIAUCOURT, D. BACH, J.-D. DE KORWIN, G. VAILLANT, F. PAILLE & J. SCHMITT From the Service de MMecine H . CHUN, NANCY Cidex. France
Abstract. Maignan M, Wahl D, Thiaucourt D, Bach D, de Korwin J-D, Vaillant G, Paille F. Schmitt J (Service de MCdecine H, CHUN, Nancy CCdex, France). Self-limited primary cytomegalovirus colitis in an immunocompetent individual. journal of Internal Medicine 1992; 232: 357-359. Cytomegalovirus colitis in immunocompetent patients has rarely been reported without another severe illness. The prognosis is usually bad, leading to toxic megacolon or death due to multi-organ system failure. We report a case of a self-limited cytomegalovirus colitis in a young patient with no risk factor for CMV infection or associated disease. This suggests that self-limiting CMV colitis may be more frequent than is usually believed, and its prognosis may be better in young patients with normal immune functions. Therefore it should be sought systematically even in immunocompetent young patients. Keywords: colitis, cytomegalovirus.
Introduction Cytomegalovirus (CMV) colitis in transplant and immunosuppressed patients is well known [l].Primary CMV infection in immunocompetent individuals usually results in a mononucleosis syndrome and/or acute hepatitis [l]. We report the case of a 36-year-old heterosexual male who developed, in January 1991, fever up to 39 O C , myalgia and asthenia. The patient had no risk factor for human immunodeficiency virus (HIV) infection. After 1 week he developed severe rectal pain, diarrhoea and haematochezia. Flexible sigmoidoscopy (31 January) showed oedematous and inflamed mucosa in the rectum and sigmoid area. Lesions were predominant in the lower rectum and anus, where linear ulcers were also present. Rectal biopsy specimens showed an ulcer base with lamina propria inflammation and a submucosal inflammatory infiltrate. Typical CMV cells were found (Fig. I), and CMV inclusions were confirmed by immunofluoresence. The patient was referred to our unit 11 d later; his state had improved and fever
then resolved within 2 d. There was no indication of pulmonary involvement. The patient had one normal daily bowel movement. There was no adenopathy or hepatosplenomegaly . Laboratory studies revealed a leucocyte count of 6.3 x 1091-1 with a differential fraction of 36 polymorphonuclear cells, 53 lymphocytes and 11 monocytes. The platelet count was 2.5 x 10" I-' and the haemoglobin concentration was 1 4 g d1-l. The erythrocyte sedimentation rate was 24 mm h-I. CRP was 2.5 mg 1-', and fibrinogen was 2.59 g I-'. Aspartate and alanine aminotransferases were moderately increased (34 IU I-' and 147 IU I-', respectively). Stool culture was negative for parasites and bacteria. Blood cultures were negative. Cytomegalovirus antibodies titres were obtained during the third week after the onset of symptoms. ELISA titres were moderately positive for IgG antibodies and strongly positive for IgM antibodies. Viral cultures of the stool were negative. Blood and urine cultures were also negative for CMV. IgM titres for hepatitis A, EpsteinBarr, varicella-zoster and herpes simplex virus were negative. Hepatitis B markers showed evidence of a 357
358
M. MAIGNAN et al.
Fig. I . Rectal biopsy from the patient showing submucosal inflammatory infiltration and a cytomegalic cell with a typical intranuclear inclusion, conlirmed by immunofluorescence (magnification x 500).
former infection which was healed. Hepatitis C and Delta markers were negative. HIVl and HIV2 titres were negative, and HIVl antigens were absent. No other systemic or organ involvement was found in our patient. Broncho-alveolar lavage, upper gastrointestinal tract endoscopy and biopsies, and ophthalmological examination were negative. On a second sigmoidoscopy 1 2 d after the first one, inflammation and ulcers were significantly improved. Studies of immune function including tuberculin test, serum protein fractions, IgG, IgA and IgM levels, total haemolytic serum complement CH50, C3 and C4 were normal, as well as cell counts of bone marrow. Circulating lymphocyte subpopulations count showed 567 CD4 mm-3 (normal range, 400-1400 mm-')), 2037 CD8 mm-' (normal range, 200-850 mm-')). The CD4/CD8 ratio was 0.28 (normal range, 0.80-2.60); the low CD4/CD8 ratio is often a reflection of a viral infection [2]. The outcome was a spontaneous improvement of the infection before any anti-CMV therapy had been given. Two months later the patient was free of any symptoms ; blood cell counts were normal and aminotransferase levels were decreased. HIVl and HIV2 antibodies and HIVl antigens were negative. CMV antibodies titres were weakly positive for IgM and strongly positive for IgG. This case is quite remarkable with respect to published cases because of both its clinical presentation and the outcome. CMV colitis usually affects immunosuppressed patients after renal or bone
marrow transplant [ 11, haematological malignancies, HIV infection and acquired immunodeficiency syndrome [11, and idiopathic inflammatory bowel disease (IBD). In these situations CMV is believed to be an opportunistic infection [ 3 ] .When patients with IBD ware excluded, 1 6 case records [4-131 of proven CMV colitis in immunocompetent patients have been published: 8 females and 8 males. Their ages ranged from 2 5 to 80 years (10 were elderly, over 65 years). Eight patients died ( 7 were over 45 years of age and three had pulmonary involvement). Emergency colectomy was performed in 4 patients who did not survive. It has been suggested [9] that CMV enterocolitis may affect patients debilitated by a severe illness. Among the published cases patients were either debilitated (malnourished, treated with corticosteroids, alcoholic) or had a specific physiological status (old age, pregnancy). When associated conditions were absent, transmission of CMV was identified (anal intercourse, blood transfusions). Our patient had no associated illness before this infection, and transmission was not caused by anal intercourse or transfusion. This supports the hypothesis [9] that a number of CMV colitis cases may be caused by direct patient-to-patient spread. CMV enterocolitis is probably more common than is currently suspected. Our case record shows that selflimited colitis may occur in immunocompetent patients even without sexual or blood transmission. These patients may not require anti-CMV therapy.
S EL F-LI MITED PRIMARY C Y TO MEG ALO V IRU S COLITIS
Undiagnosed cases may facilitate the spread of the disease even nosocomially. particularly if the virus is shed in the stool, urine or respiratory tract.
8
9
References Ho M. Epidemiology of cytomegalovirus infections. Kev InJect Dis 1990: 12: 5701-10. Dc WaeIe M. Thielemans C. Van Camp B. Imrnunoregulatory 1' cells in mononucleosis and toxoplasmosis. N Engl ] Med 1981 : 305: 228. Surawicx CM. Myerson D.Self-limited cytornegalovirus colitis in immunocompetcnt individuals. Gastroenterologg 1988 : 94: 194-9. Nakonecxna I. Kay S. Fatal disseminated cytomegalic inclusion disease in an adult presenting with a lesion of the gastrointestinal tract. Arri I Clin h t h o l 1967: 47: 124-8. Taniura H. Acute ulcerative colitis associated with cytomegalic inclusion virus. Arch Pathol 1973: 96: 164-7. Druart F. Matuchansky C. Blavon-Duchesne N. Babin P. Barbier J , Beauchant J. Colite ulcereuse aigue avec inclusions cytomtgaliques chex un suiet non immunodeprimk. Sem Hbp f+wis 1979; 5 5 : 85-7. Spiegel JS, Schwabe AD. Disseminated cytomegalovirus in-
10
11 12
13
3 59
fection with gastrointestinal involvement. Am ] Gaslroenterol 1980: 73: 3 7 4 4 . Beaugrand L, Poynard T, Callard P et a/. Infections a cytornegalovirus au cours des colites pseudo-membraneuses. Nouv Presse Med 1981 ; 10: 1199-204. Bennett MR. Fine AP. Hanlon JT, Cytomegalovirus hemorrhagic colitis in a nontransplant patient. Postgrad Med 1985 : 77: 227-32. Arsene D.Callet E, Freyrnuth F, Caillez D. Valla A, Verwaerde JC. Colite aigue ulcereuse et infection a cytomegalovirus chex un patient non immunodeprime: apparition retardee des anticorps specifiques. Ann Med Interne (Paris) 1987: 138: 375-6. Orloff JJ, Saito R. Lasky S. Dave H. Toxic megacolon in cytomegalovirus colitis. Am Gnstroenterol 1989: 84: 794-7. Banerjee AK. Cytomegalovirus (CMV) enterocolitis. ] K Soc Med 1989: 82: 446. Diepersloot RIA. Kroes ACM, Visser W. Jiwa NM. Rothbarth PH. Acute ulcerative proctocolitis associated with primary cytomegalovirus infection. Arch Intern Med 1990; 1 5 0 : 1749-5 1.
Received 12 December 1991, accepted 8 January 1992. Correspondence: Dr Denis G. Wahl. Service de Medecine H,CHUN. 29 avenue MarCchal de Lattre de Tassigny. CO N". 34, F-54035 Nancy Cedex, France.
