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Home , Cytomegalovirus colitis, Proctocolitis

Postgrad MedJ 1998;74:486-491 © The Fellowship of Postgraduate Medicine, 1998 Short reports

Cytomegalovirus associated with Postgrad Med J: first published as 10.1136/pgmj.74.874.486 on 1 August 1998. Downloaded from ulcerative in immunocompetent individuals

Carmit Rachima, Eran Maoz, Sara Apter, Michael Thaler, Ehud Grossman, Talma Rosenthal

Summary vealed an enlarged liver 2 cm below the costal Gastrointestinal infection with cytomega- margin, with a rebound tenderness over the lovirus (CMV) is usually found in immu- right upper quadrant. nocompromised patients and rarely Laboratory investigations revealed leucocy- affects imnmunocompetent subjects. We tosis of 33.1 x 109/l with 59% polymorphonu- describe two immunocompetent patients cleocytes, and 33% lymphocytes with atypical who had primary CMV infection, and in forms. Haemoglobin was 1 1.6 g/dl with normal both the disease was associated with platelet count. Other laboratory studies were . Both patients recovered normal except for an elevated alkaline phos- from the CMV infection spontaneously. phatase (262 IU/1, normal <1 15 IU/1) and lac- tate dehydrogenase (464 IU/1, normal <250 Keywords: cytomegalovirus infection; ulcerative colitis; IU/1). Chest X-ray showed bilateral lung immunocompetent subjects infiltrates. Electrocardiogram was normal ex- cept for sinus tachycardia. Cytomegalovirus (CMV) is recognised as an On the second day of hospitalisation she important pathogen with a worldwide distribu- became dyspnoeic and hypoxemic with a tem- tion. Gastrointestinal with CMV, perature of 39.60C and severe abdominal pain especially colitis, are usually found in immuno- mainly in the right upper quadrant. Physical compromised patients and rarely affect immu- examination noted guarding on the right upper nocompetent subjects."9 CMV infection has quadrant, suggesting peritoneal . also been related to inflammatory bowel HIDA (99mTc-labeled N-substituted immuno- disease (IBD), either as a precipitating factor or diacetic acid) biliary scan findings were con- as a coincidental infection.'" sistent with the diagnosis of , and We report two cases of immunocompetent intravenous antibiotics were started. Blood, patients with primary CMV infections. In the urine and stool cultures remained sterile. first case acute CMV infection was associated Abdominal computed tomography (CT) scan with exacerbation ofIBD, and in the second case showed thickening of the gallbladder wall as CMV infection coincided with the onset, and led well as thickening of the colonic wall without http://pmj.bmj.com/ to the diagnosis of IBD. Both patients recovered evidence of (figure 1). Sero- from the CMV infection spontaneously. logic tests for B and C, human immu- nodeficiency (HIV), and Epstein Barr viruses Case reports were negative. Solid-phase enzyme immuno- assay for IgM antibodies to CMV was highly Case 1 positive (3+) on admission and decreased to

A 38-year-old woman was hospitalised because (1+) over time."6 Immunofluorescence assay on October 2, 2021 by guest. Protected copyright. of spiking , dyspnoea, abdominal pain, for IgG antibodies to CMV showed a titre of and non-bloody diarrhoea. Eight years earlier 1:160 on admission and increased to 1:320 she had been diagnosed as having ulcerative later.'7 Subsequently, CMV was detected in the colitis; she was treated with a short course of urine by polymerase chain reaction and the steroids and had remained symptom-free ever Shell vial assay.'8 since. Thirteen weeks prior to admission she Sigmoidoscopy up to 40 cm revealed oede- The Chaim Sheba had an uneventful childbirth. Seven weeks later matous, inflamed mucosa with Medical Center, fibrinopurulent Tel-Hashomer, 52621 she developed a febrile illness with watery diar- and small haemorrhages. Mucosal Israel rhoea. Stool cultures were positive for Shigella specimens demonstrated acute and Internal Medicine D mansoni, and she was treated successfully with chronic inflammatory process with crypt ab- C Rachima amoxycillin. Two weeks before admission she scess. CMV inclusion bodies were not identi- E Maoz again developed fever up to 39.7°C, chills, fied, and CMV was not detected by immuno- M Thaler abdominal and E Grossman weakness, dyspnoea, pain peroxidase staining. T Rosenthal watery diarrhoea. During the first 3 weeks the patient had a Department of Physical examination revealed an ill-looking temperature of 38-40°C and severe watery diar- Imaging woman with a blood pressure of 90/60 mmHg, rhoea. Blood counts were notable for marked S Apter pulse rate of 104 beats/min, and a temperature leucocytosis (20-30 x 109/1) with 30-40% of 39°C. No lymphadenopathy was noted. lymphocytes and marked thrombocytosis (up to Correspondence to Ehud Grossman, MD Cardiac examination was normal, and de- 1000 x 109/1). In addition, signs of malabsorp- creased breathing sounds were heard over the tion developed with hypoalbuminaemia of 2 g/dl Accepted 10 March 1998 right lung base. Abdominal examination re- and hypocholesterolaemia of 58 mg/dl. CMV infection and colitis 487

Figure 1 Abdominal tomy and cholecystectomy at the age 12 years CT scan showing (A) because of congenital spherocytosis, was hospi- thickening of the gall- bladder wall (arrow), (B) talised with a febrile illness. His medications thickening of the colonic included amoxycillin, which he had been taking Postgrad Med J: first published as 10.1136/pgmj.74.874.486 on 1 August 1998. Downloaded from wall (arrow) prophylactically since the splenectomy, and inhaled steroids during exacerbation of his asthma. Four days before admission, he devel- oped a fever of 39.5°C with diffuse abdominal pain and a nonproductive cough. On admission, he had a temperature of 38.2°C, pulse rate of 88 a, beats/min, and blood pressure of 1 10/60 mmHg. The physical examination was otherwise unre- markable. Laboratory investigations were nor- mal except for a leucocytosis of 12.7 x 10iI, an elevated bilirubin level of 34.2 jmol/H and an elevated lactate dehydrogenase up to 300 IU/l. Because of his history of splenectomy he was given amoxycillin clavulonate. During the first 2 weeks of hospitalisation, abdominal pain was localised in the right lower quadrant and was associated with fever of 38-40'C, chills and abdominal guarding sug- gesting peritoneal signs. Laboratory evaluation showed a marked leucocytosis of up to 33 x ' f X to' 1i0/l with 58% lymphocytes and abnormal liver function tests (bilirubin 15.4-56.4 ptmol/l, lac- tate dehydrogenase 359-642 IU/1, aspartate transaminase 335-397 IU/l, alanine transami- nase 332-360 IUll). Repeated blood, urine and stool cultures were negative. Chest and ab- The colonic findings were compatible with dominal CT scans showed marked colonic wall exacerbation of ulcerative colitis and she was thickening with a small amount of peritoneal treated with 5-aminosalicylic acid (2 g/day). Her fluid (figure 2). Gallium scan showed increased symptoms resolved completely after 2 months of isotope concentration in the right lower treatment with no antiviral therapy or steroids. abdomen and over the lungs. After 2 weeks of observation, spontaneous clinical and laboratory improvement was ob- Case 2 served. Serological tests for , B and A 20-year-old man, who had a history of C viruses, and HIV were negative. Solid-phase bronchial asthma and had undergone splenec- enzyme immunoassay for IgM antibodies to

CMV was highly positive (3+) on admission http://pmj.bmj.com/ and decreased to (1 +) over time. Immunofluo- rescence assay for IgG antibodies to CMV Figure 2 CT scans showing (A) thickened showed a titre of 1:160 on admission and had wall of the colon (arrow), increased to 1:320 2 months later. (B) thickened wall of the Three weeks later he again developed fever caecum (long arrow), and peritoneal fluid (short X associated with mucoid and bloody diarrhoea.

Blood, urine and stool cultures were negative. on October 2, 2021 by guest. Protected copyright. His blood count was normal except for a leucocytosis of 17.8 x 109/l with 43% lym- phocytes. Sigmoidoscopy showed evidence of an inflammatory process, and mucosal biopsy demonstrated an inflammatory process with crypt abscess; CMV inclusion bodies were not identified and CMV was not detected by immunoperoxidase staining. A diagnosis of ulcerative colitis was made and treatment with arr) t metronidazole and 5-aminosalicylic acid was initiated. A month later his clinical condition had improved, and during a follow-up period of 3 years he fully recovered from the CMV infection but had repeated bouts of colitis. Discussion niz3~~~~~WCMV can affect many organs including the lungs, retina, liver, and .'9 Gastrointestinal tract disease may involve the mouth, oesophagus, stomach, and colon.'9 CMV colitis is a major cause of 488 Rachima, Maoz, Apter, et al

morbidity and mortality in immunocompro- mised patients but less so in immunocompe- Summary points tent individuals.20 CMV colitis produces mu- cosal ulceration that can result in abdominal * CMV infection may be associated with ulcerative

colitis Postgrad Med J: first published as 10.1136/pgmj.74.874.486 on 1 August 1998. Downloaded from pain, bloody diarrhoea and even perforation, a * CMV infection associated with ulcerative colitis clinical picture that resembles IBD."-" Suraw- may occur in immunocompetent patients itz and Myerson" described three cases of iso- * ulcerative colitis may recover when CMV lated CMV colitis with a presentation of infection improves haematochezia. In all three patients the initial * steroid therapy is not recommended in patients differential diagnosis of the colitis was idi- with ulcerative colitis associated with CMV opathic IBD but colonic showed typi- infection cal CMV inclusion bodies without any other histological features of IBD. The radiographic findings are not specific and the differential diagnosis includes granulomatous ileocolitis had relapses ofthe ulcerative colitis. Orvar et all' and ulcerative colitis.24 described two patients in whom the primary The link between IBD and CMV infection is CMV infections coincided with the onset and unclear. Our immunocompetent individuals diagnosis of ulcerative colitis. It has been had CMV infection associated with ulcerative suggested that primary CMV infection precipi- colitis. Although, the second patient had a pre- tated IBD by enhancing surface antigen marker vious splenectomy this is not known to predis- expression in a host predisposed to IBD.2 It pose to viral infection. The first patient had a remains uncertain whether CMV merely has a history of inactive ulcerative colitis when she predilection for inflamed mucosa or actually presented with CMV infection. In her case the plays a role in the pathogenic process. CMV infection was associated with exacerba- The association of CMV infection and tion of silent ulcerative colitis. Several case ulcerative colitis raises the problem of whether reports have described CMV colitis in patients or not steroids should be used. It has been with IBD.10 11 23 25-30 In all these cases CMV shown in patients with severe ulcerative colitis, inclusion bodies were detected in the colonic who were resistant to steroid therapy, and had mucosa. Indeed, the possibility that acute CMV inclusion bodies in the mucosa, that CMV colitis mimics IBD cannot be excluded, steroid withdrawal led to a clinical and however the absence of CMV inclusion bodies histological improvement."'9 It seems that in mucosal biopsies make this unlikely. It has cessation of enables the patient been shown that patients with ulcerative colitis to overcome the CMV infection. A similar are more likely to show elevated titres to CMV mechanism was described for chronic hepatitis than normal subjects.'"15 Moreover, it has been B virus, in which immunosuppressive drugs suggested that resistant ulcerative colitis that were shown to enhance viral replication, while requires may be related to CMV cessation of these drugs decrease its infection. Indeed, Cooper et all' described replication." 32 The controversy remains as to CMV inclusion bodies in a subgroup of whether steroids or immunosuppressive drugs patients with ulcerative colitis who underwent can cause CMV superinfection with IBD exac- partial colectomy. erbation. It is noteworthy that our patients http://pmj.bmj.com/ Our second patient had no history of recovered from the ulcerative colitis without ulcerative colitis. In his case CMV infection steroid therapy when the CMV infection coincided with the onset, and led to the diagno- improved. Thus, steroid therapy should be sis, of acute ulcerative colitis. Although he used with caution in patients with ulcerative recovered from the acute CMV infection he has colitis associated with CMV infections. on October 2, 2021 by guest. Protected copyright. 1 Drew WL, Mintz L, Miner RC, Sands M, Ketterer B. 11 Cooper HS, Raffensper EC, Jonas L, Fitts WT. Cytomega- Prevalence of cytomegalovirus infection in homosexual lovirus inclusions in patients with ulcerative colitis and toxic men. J Infect Dis 1981;143:188-92. dilatation requiring colonic resection. 1977; 2 Gertler SL, Pressman J, Price P, Brozinsky S, Miyai K. Gas- 72:1253-6. trointestinal cytomegalovirus infection in homosexual men 12 Orvar K, Murray J, Carmen G, Conklin J. Cytomegalovirus with severe acquired immunodeficiency syndrome. Gastro- infection associated with onset of inflammatory bowel enterology 1983;85:1403-6. disease. Dig Dis Sci. 1993;38:2307-10. 3 Quinnan GV Jr, Masur H, Rook AH, et al. Herpesvirus 13 Diepersloot RJA, Kroes ACM, Visser W, Jiwa NM, infections in the acquired immune deficiency syndrome. Rothbarth PH. Acute ulcerative proctocolitis associated JAMA 1984;252:72-7. with primary cytomegalovirus infection. Arch Intern Med 4 Schooley RT. Cytomegalovirus in the setting of infection 1990;150:1749-51. with human immunodeficiency virus. Rev Infect Dis 14 Farmer GW, Vincent MM, Fuccillo DA, et al. Viral investi- 1990;12:S811-9. gations in ulcerative colitis and regional . Gastroen- 5 Spencer GD, Hackman RC, McDonald GB, et al. terology 1973;65:8-18. A prospective study of unexplained nausea and vomiting 15 Bernades P. Antibodies to cytomegalovirus in ulcerative coli- after marrow transplantation. Transplantation 1986;42:602- tis and Crohn's disease. Gastroenterol Clin Biol 1980;4:128-33. 7. 16 Schmitz H, Doerr HW, Kampa D, Vogt A. Solid-phase 6 Rubin RH. Impact of cytomegalovirus infection on organ enzyme immunoassay for immunoglobulin M antibodies to transplantation recipients. Rev Infect Dis 1990;12:s754-66. cytomegalovirus. Jf Clin Microbiol 1977;5:629-34. 7 Orioff JJ, Saito R, Lasky S, Dave H. Toxic 17 Phipps PH, Gregoire L, Rossier E, Perry E. Comparison of in cytomegalovirus colitis. Am j Gastroenterol 1989;84: five methods of cytomegalovirus antibody screening of 794-7. blood donors. J Clin Microbiol 1983;18: 1296-300. 8 Henson D. Cytomegalovirus inclusion bodies in the 18 Miller MJ, Bovey S, Pado K, Bruckner DA, Wagar EA. gastrointestinal tract. Arch Pathol 1972;93:477-82. Application of PCR to multiple specimen types for diagno- 9 Ayulo M, Aisner SC, Margolis K, Moravec C. Cytomegalo- sis of cytomegalovirus infection: Comparison with cell virus associated in a compromised host. JtAMA culture and shell vial assay. J7 Clin Microbiol 1994;32:5-10. 1980;243: 1364-7. 19 Goodgame RW. Gastrointestinal cytomegalovirus disease. 10 Berk T, Gordon SJ, Choi HY, Cooper HS. Cytomegalovirus Ann Intern Med. 1993;1 19:924-35. infection of the colon: a possible role in exacerbation of 20 Buckner FS, Pomeroy C. Cytomegalovirus disease of the inflammatory bowel disease. Am J Gastroenterol 1985;80: gastrointestinal tract in patients without AIDS. Clin Infect 355-60. Dis 1993;17:644-56. CMV infection and colitis 489

21 Surawitz CM, Myerson D. Self-limited cytomegalovirus 27 Levine RS, Warner NE, Johnson CF. Cytomegalic inclusion colitis in immunocompetent individuals. Gastroenterology disease in the gastrointestinal tract of adults.Ann Surg 1964; 1988;94: 194-9. 159:37-48. 22 Cunningham M, Cantoni L, Humair L. Cytomegalovirus 28 Keren DF, Milligan FD, Strandberg JD, Yardley JH. primoinfection in a patient with idiopathic . Am J Intercurrent cytomegalovirus colitis in a patient with ulcera-

Gastroenterol 1986;81:586-8. tive colitis. _ohns Hopkins MedJ3 1975;136:178-82. Postgrad Med J: first published as 10.1136/pgmj.74.874.486 on 1 August 1998. Downloaded from 23 Guttman D, Raymond A, Gelb A, Ehya H, Mather V, Mild- 29 Dent DM, Duys PJ, Bird AR, et al. Cytomegalovirus van D, et al. Virus-associated colitis in homosexual men: two infection of the bowel in adults. S Afr Med J 1975;49:669- case reports. Am J7 Gastroenterol 1983;78: 167-9. 72. 24 Balthazar EJ, Megibow AJ, Fazzini E, Opulencia J, Engel I. 30 Sidi S, Graham JH, Razvi SA, et al. Cytomegalovirus infec- Cytomegalovirus colitis in AIDS: Radiographic findings in tion of the colon associated with ulcerative colitis. Arch Surg 11 patients. Radiology 1985;155:585-9. 1979;114:857-9. 25 Powell RD, Warner NE, Levine RS, et al. Cytomegalic 31 Swarbrick ET, Kingham JGC, Price HL, et al. Chlamydia, inclusion disease and ulcerative colitis. Report of a case in a cytomegalovirus and Yersinia in inflammatory bowel young adult. AmJ Med 1961;30:334-40. disease. Lancet 1979;2:11-2. 26 Wong TW, Warner NE. Cytomegalic inclusion disease in 32 Scullard GH, Smith CI, Merigan TC, et al. Effects of adults. Report of 14 cases with review of the literature. Arch immunosuppressive therapy on viral markers in chronic Pathol. 1962;74:403-22. active . Gastroenterology 1981;81:987-91.

Familial cavernous angiomas masquerading as multiple sclerosis

C F Dougan, A Coulthard, N E F Cartlidge, D J Burn

Summary sequently developed horizontal diplopia, We report here two cases of cavernous worse on right lateral gaze, and incoordina- angioma, in the proband and her father, tion, with a tendency to fall to the left. On the with quite different clinical presentations. day prior to admission she had developed The proband presented with a brainstem patchy sensory disturbance in her left arm and syndrome, mimicking multiple sclerosis, leg. Her medical history was unremarkable. while the father had a history ofmild epi- She was taking the oral contraceptive pill. She lepsy. Both patients were managed con- was one of four siblings and her father had servatively. The cases also demonstrate epilepsy. the utility of magnetic resonance imaging On general medical examination the only in the diagnosis of cavernous angioma. findings ofnote were haemangiomatous lesions on the dorsum of her left hand, left calf and Keywords: cavernous angiomas; multiple sclerosis; right thigh. Neurologically, her gait was ataxic. magnetic resonance imaging Fundoscopy was normal, but there were bilat- eral partial sixth nerve palsies, and upbeat nys- tagmus on upgaze. There was a left sensory

Cavernous http://pmj.bmj.com/ angiomas (also known as caverno- trigeminal and mas and cavernous haemangiomas) are a form neuropathy mild subjective of intracranial blunting ofhearing on the left side. In the limbs vascular malformation that are there was a mild reported to affect 0.5% of the In left-sided pyramidal weakness, population.' with subjective reduction of light touch and up to 75% of patients the lesions are multiple. pin-prick They are characterised by collections of large, distally in the left arm and leg. A abnormal vascular spaces without diagnosis of demyelination was suspected. intervening Visual evoked potentials were normal. A com-

brain parenchyma.' Up to 50% of patients on October 2, 2021 by guest. Protected copyright. with cavernous puted tomography (CT) scan of the cranium angiomas have a familial form two of the disorder which is inherited in an revealed small high-density lesions in the autosomal dominant mode, with incomplete right side of the brainstem and left putamen, clinical penetrance.' The familial form may be thought to represent areas of haemorrhage. more frequent in the Hispanic population.' Cerebrospinal fluid (CSF) examination was Recent genetic studies have entirely normal, with absent oligoclonal bands. identified linkage The patient's Royal Victoria of this trait to chromosome 7ql 1.2-q21 in condition spontaneously im- Infirmary, Queen some families.' 2 Although cavernous angio- proved, and follow-up CT brain scan 2 weeks Victoria Road, mas are rarely life-threatening, they may cause later showed considerable resolution of the Newcastle upon Tyne significant morbidity related to their size and high density lesions. NE1 4LP, UK location. Eight months later she was re-admitted with Department of a relapse comprising similar brainstem symp- Neurology C F Dougan Case reports toms and signs, following a minor acute neck N E F Cartlidge sprain. Cranial magnetic resonance imaging D J Burn (MRI) scan revealed three separate lesions Department of Case 1 typical of cavernous angiomas, including a Radiology A 19-year-old, right-handed woman was large lesion in the tegmentum of the midbrain, A Coulthard admitted in 1988 with a 5-day history of pro- eccentrically located to the right (figure). gressive neurological dysfunction. At the onset Correspondence to The patient has been managed conserva- Dr DJ Burn she had awoken with numbness of the left side tively to date. She has suffered a number of of her tongue, which spread over 24 hours to relapses referable to the brainstem cavernous Accepted 10 March 1998 affect the whole left side of her face. She sub- angioma but has recovered to normal