Is it really necessary to check for Cytomegalovirus in Children with Inflammatory Bowel Disease?

A recent retrospective study (W El-Matary et al. JPGN 2018; 67: 221-24) examined the practice of looking for Cytomegalovirus (CMV) in children with a flareup of their inflammatory bowel disease (IBD) which is currently recommended by expert consensus (JPGN 2018; 67: 292-310 –recommendation #3).

Key findings:

  • “Four of 61 patients encounters (6.6%) with UC/IBD-U, two with corticosteroid refractory disease, had positive biopsies for CMV by PCR but negative H&E and IHC.  They responded to escalated medical therapy, without needing anti-viral therapy.”
  • All children who had colectomy during the study did not have CMV detected in colonic mucosa.

The authors note that the rationale for looking for CMV is derived mainly from adult populations.  Since age is a known risk factor for CMV reactivation, the risk of CMV causing refractory IBD in children is less.

My take (borrowed in part from authors): “The low frequency of CMV in our study challenges current guidelines that recommend assessment for CMV in all pediatric patients with acute severe UC refractory to corticosteroids.”  This issue would be another that would benefit by collecting the experience of a large cohort (eg. ICN).

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

CMV in IBD: Tissue Matters

A recent study (P Tandon et al. Inflamm Bowel Dis 2017; 23: 551-60) was a systemic review regarding the accuracy of blood-based testing for predicting colonic CMV reactivation in patients with inflammatory bowel disease.  The review identified 9 studies.  The overall sensitivity of blood-based testing (either pp65 antigenemia or blood PCR) for CMV was 50.8% and the specificity was 99.9%. Blood PCR was better at 60% sensitivity.

My take: Blood-based tests are not sensitive enough to exclude colonic CMV reactivation. The authors recommend the use of immunohistochemistry or tissue PCR for detecting CMV reactivation in inflammatory bowel disease.

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Compared with Zika, CMV is a Greater Threat and Less Discussed

A recent article in NY Times provides another example of how a common infectious problem has been overshadowed by a more recent epidemic.  CMV is A Greater Threat to Infants Than Zika

Two years ago, it was well-recognized that the flu virus is vastly more dangerous for U.S. than Ebola (Related post:Scarier than Ebola -the Flu | gutsandgrowth). This year, CMV should get more attention.

Here’s an excerpt:

Every year, 20,000 to 40,000 infants are born with CMV. At least 20 percent — up to 8,000 — have or develop permanent disabilities, such as hearing lossmicrocephaly, intellectual deficits and vision abnormalities. There is no vaccine or standard treatment…

CMV is the most common congenital viral infection and the leading nongenetic cause of deafness in children. Roughly 400 children die from it annually. By contrast, roughly 900 pregnant women in the continental United States have contracted the Zika virus

CMV is the most common congenital viral infection and the leading nongenetic cause of deafness in children. Roughly 400 children die from it annually. By contrast, roughly 900 pregnant women in the continental United States have contracted the Zika virus.

The American College of Obstetricians and Gynecologists used to encourage counseling for pregnant women on how to avoid CMV. But last year, the college reversed course, saying, “Patient instruction remains unproven as a method to reduce the risk of congenital CMV infection.”

My take: Perinatal CMV infection merits more discussion.

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Will Infliximab Worsen Flare-ups Associated with Cytomegalovirus Infection?

Another look (Pillet S, et al. Inflamm Bowel Dis 2015; 21: 1580-86) at Cytomegalovirus (CMV) infection in patients with ulcerative colitis (UC) examines 109 flareups in 73 patients who were receiving maintenance therapy with anti-TNF therapy.

This was a single-center prospective observational study.  CMV load was determined with PCR based on a pair of biopsies. DNA load was either undetectable, mild (10-250 copies/mg of tissue) or high (>250 copies/mg of tissue). 69 patients with anti-TNF therapy were compared with 40 patients receiving azathioprine. Key findings:

  • CMV reactivation was noted in 35% of anti-TNF therapy patients and 38% in azathioprine patients.
  • Among 45 patients requiring infliximab optimization, clinical remission was not significantly impacted by the presence of CMV reactivation.
  • 17 of 20 who had repeat biopsies 8 weeks later had stable or decreased CMV load.

Bottomline: This prospective, small study shows that “in patients with moderate-to-severe UC, treatment with anti-TNF mab does not increase the risk of colonic CMV infection.”  In addition, “no adverse influence of CMV colonic infection was observed in patients with flare-up treated by anti-TNF mabs.”

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

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Utility of Antiviral Therapy for Cytomegalovirus in the Setting of Inflammatory Bowel Disease

According to a recent study (Jones A et al. Clin Gastroenterol Hepatol 2015; 13: 949-55), the tissue density of cytomegalovirus (CMV) is an important determinant of antiviral response in patients with inflammatory bowel disease (IBD).

In this case-control study, the authors identified 68 samples from 1111 patients with IBD that were found to contain CMV.  Adequate data was available for 50, including 16 with high-grade CMV (all treated) and 34 with low-grade CMV (20 treated).  High-grade CMV was defined as biopsies with 5 or more inclusions.  Treatment included ganciclovir, valganciclovir or both; 33 of 36 treated patients received at least 21 days of therapy.

Key findings:

  • Patients with high-grade CMV showed significant benefit from treatment: they had the best outcomes with “only 33% undergoing surgery by 1 year after biopsy.”
  • All patients with low-grade CMV, treated or not, were more likely to undergo surgery than those with high-grade CMV, with HR of 2.13.  However, the treated low-grade CMV had a lower risk of surgery (HR 0.39) compared with the untreated group.  73% of the untreated low-grade CMV group had undergone resection by 1 year after biopsy.

The authors note the many limitations of the study.  Requests to rule out CMV were not done uniformly but “usually reflected refractoriness of steroids or failure to respond to escalation of therapy.”

Bottomline: In those with high-grade CMV, the likelihood of responding to antiviral therapy was much higher than in patients with low-grade CMV; however, treatment in all patients with CMV inclusions was associated with improved outcomes.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

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