To the Editor:

In the natural course of Crohn's disease (CD), postoperative recurrence and opportunistic infections such as human cytomegalovirus (HCMV) infection are two conditions that may lead to a more disabling behavior, despite intensive first-line treatments.1 Early recognition of these conditions may help to manage severe CD by choosing adequate treatments to avoid more severe disease complications. We describe an early postoperative recurrence of severe CD, with colonic involvement and superimposed HCMV infection, treated with oral valganciclovir and adalimumab subcutaneously.

A 52-year-old female patient, affected by a recently diagnosed ileocolonic steroid-dependent CD, was admitted to our department with a history of nonbloody diarrhea and severe weight loss, without abdominal pain or other symptoms of possible intestinal obstruction.

Six months previously she underwent a bowel resection with ileocolonic anastomosis for an intestinal subocclusion due to a stenosis of the ileocecal valve, complicated by pelvic abscess.

On physical examination the patient presented signs of severe malnutrition (body mass index [BMI] 12), without any abdominal tenderness or fever, with a blood pressure of 100/50 mmHg and pulse rate of 80 beats/min. Her Crohn's Disease Activity Index (CDAI) score on admission was 297. Laboratory tests showed neutrophilic leukocytosis, erythrocite sedimentation rate (ESR) of 45 mm/hr, C-reactive protein (CRP) of 7 mg/L (n.v. 0.5 mg/L), and severe hypoalbuminemia (1.7 g/dL).

X-ray of the abdomen showed no signs of megacolon. Therapy with systemic corticosteroid was started. An elementary diet to correct malnutrition was also tried; however, it was not tolerated by the patient (worsening of the diarrhea), so a total parenteral nutrition was started. Stool cultures, parasitologic tests, pp65-antigenemia on peripheral leukocytes to check HCMV in serum were performed. Abdominal ultrasound showed thickening of the preanastomotic ileum and diffuse edema of descending colon walls. X-ray enteroclysis showed an irregular and marked mucosal relief into duodenum and proximal jejunum, which appeared with a nodular aspect and a “jejunalization” of the remaining ileal loops. Colonoscopy, with multiple biopsies, was also performed, showing a severe CD with multiple ulcerations around the ileocolonic anastomosis and in the whole colon. Histology showed typical features of active CD, while hematoxylin and eosin staining and immunohistochemistry were markedly positive for CMV detection. Stool cultures and parasitologic tests were negative, while the pp65-antigenemia showed a positivity of 72 fluorescent nuclei/2 × 105 leukocytes. Antiviral therapy with oral valganciclovir (450 mg twice daily) was started for systemic infection due to HCMV and prolonged for 21 days, concomitant to steroid tapering and resumption of oral alimentation, with a good clinical response and viral undetectability 15 days after the first pp65-antigenemia. The presence of marked disease activity with severe colonic involvement led us to an aggressive therapeutic approach, starting biologic therapy with adalimumab, at the induction dosage of 160 mg followed by 80 mg 2 weeks later,6 after performing the recommended screening. After the second injection the patient was in clinical remission (CDAI score <150) and with improved nutritional status (BMI 14), so adalimumab was maintained at a dose of 40 mg every other week. Six months later remission was maintained and nutrition status further improved. Laboratory tests, including ESR and CRP, were normal.

Since 2007, adalimumab has been endorsed for the treatment of moderate-to-severe luminal CD.2 However, starting a biologic therapy means paying attention to serious adverse events such as opportunistic infections, such as HCMV, whose role in inflammatory bowel disease is still unclear.3–5 Its pharmacological treatment is mandatory when it causes a systemic infection or a symptomatic end-organ disease. It is not clear which is the correct approach when HCMV is detected only in the colon, such as detection of colitis, thus antiviral therapy should be initiated.1, 6

Our patient was affected with severe colonic CD, needing an early and aggressive therapeutic approach, but adalimumab was only started after treating the HCMV with oral valganciclovir.7

In the scientific literature a case of Crohn's colitis complicated by HCMV infection, in which oral valganciclovir was used as switching therapy after intravenous ganciclovir has been described.8

We report a case of severe Crohn's colitis complicated by HCMV infection, in which oral valganciclovir therapy allowed us to start biologic therapy with quick, long, and safe efficacy.


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    Rahier JF, Ben-Horin S, Chowers Y, et al. European evidence-based Consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2009; 3: 4791.
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    Van Assche G, Vermeire S, Rutgeerts P. Adalimumab in Crohn's disease. Biologics. 2007; 1: 355365.
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    Kandiel A, Lashner B. Cytomegalovirus colitis complicating inflammatory bowel disease. Am J Gastroenterol. 2006; 101: 28572865.
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    Kim J, Simpson N, Klipfel N, et al. Cytomegalovirus infection in patients with active inflammatory bowel disease. Dig Dis Sci. 2010; 55: 10591065.
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    Lawlor G, Moss A. Cytomegalovirus in inflammatory bowel disease: pathogen or innocent bystander? Inflamm Bowel Dis. 2010; 16: 16201627.
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    Orlando A, Armuzzi A, Papi C, et al. Clinical practice guidelines: the use of tumor necrosis factor-alpha antagonist therapy in inflammatory bowel disease. Dig Liver Dis. 2011; 43: 120.
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    Cvetković RS, Wellington K. Valganciclovir: a review of its use in the management of CMV infection and disease in immunocompromised patients. Drugs. 2005; 65: 859878.
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    Levesque BG, Pai R, Cartwright CA. Crohn's colitis complicated by cytomegalovirus infection. Dig Dis Sci. 2009; 54: 18641867.

Emanuele Sinagra M.D.*, Sara Renna M.D., Ph.D.*, Filippo Mocciaro M.D., Ph.D.*, Mirko Olivo M.D., Ph.D.*, Mario Cottone Prof.*, Ambrogio Orlando M.D.*, * Department of Medicine Pneumology and Physiology of Nutrition, Division of Internal Medicine, “Villa Sofia-V. Cervello” Hospital, Palermo University Palermo, Italy.