Cytomegalovirus and Inflammatory Bowel Disease
Cytomegalovirus and Inflammatory Bowel Disease
Colitis remission rates after anti-viral treatment in IBD patients with CMV infection range from 67% to 100% (Table 2). When the full course of anti-viral therapy is completed, immunosuppressant therapies including thiopurines may be safely re-commenced.
Ganciclovir is a nucleoside analogue that acts by inhibiting viral DNA polymerase. It is the first line treatment for CMV infection which is given intravenously, at a dose of 5 mg/kg, twice per day, initially. If there is a clinical response then it may be switched to oral therapy; however, some authors advocate a full 14 day course of intravenous treatment. Valganciclovir, the pro-drug of ganciclovir, has superior oral absorption and may be preferred for out-patient management, although most patients requiring therapy will be in-patients. The most frequent side effects of ganciclovir are neutropenia, thrombocytopenia, rash, hypotension, nausea, vomiting and headache.
Ganciclovir resistance is an evolving issue and should be considered if patients fail to respond to treatment. After 3 months of therapy, the emergence of ganciclovir resistant strains approaches 10% and after 12 months 30%. Ganciclovir resistance usually arises as a result of a mutation in the UL97 CMV phosphotransferase gene.
For those patients who are intolerant, or lack clinical response, to ganciclovir, foscarnet is the second choice. Foscarnet is an inhibitor of DNA polymerase of all herpes viruses. Foscarnet does not require phosphorylation by UL97 and so is most often active against ganciclovir resistant strains. Foscarnet is given at 90 mg/kg, intravenously, twice per day for 2–3 weeks. Foscarnet toxicity includes renal impairment, central nervous system side effects, hypomagnesaemia, hypocalcaemia, hypophosphataemia and anaemia.
An alternative strategy for dealing with concerns about CMV colitis is to treat all patients with severe UC with ganciclovir. Kim et al. reported a series of 72 patients with moderate to severe UC treated with glucocorticoids. In patients with steroid resistance (defined as absence of clinical improvement 7–14 days after intravenous steroid treatment) ganciclovir was administered for 2 weeks: remission was achieved in 11 of 14 patients treated, the remainder undergoing colectomy. This strategy might be appropriate when there is reasonable clinical suspicion of CMV, without risking the inherent delays of a laboratory assessment of CMV in colonic tissue samples, however, the two studies by Delvincourt et al. mentioned earlier suggest this is actually unnecessary.
Treatment of CMV Colitis
Colitis remission rates after anti-viral treatment in IBD patients with CMV infection range from 67% to 100% (Table 2). When the full course of anti-viral therapy is completed, immunosuppressant therapies including thiopurines may be safely re-commenced.
Ganciclovir is a nucleoside analogue that acts by inhibiting viral DNA polymerase. It is the first line treatment for CMV infection which is given intravenously, at a dose of 5 mg/kg, twice per day, initially. If there is a clinical response then it may be switched to oral therapy; however, some authors advocate a full 14 day course of intravenous treatment. Valganciclovir, the pro-drug of ganciclovir, has superior oral absorption and may be preferred for out-patient management, although most patients requiring therapy will be in-patients. The most frequent side effects of ganciclovir are neutropenia, thrombocytopenia, rash, hypotension, nausea, vomiting and headache.
Ganciclovir resistance is an evolving issue and should be considered if patients fail to respond to treatment. After 3 months of therapy, the emergence of ganciclovir resistant strains approaches 10% and after 12 months 30%. Ganciclovir resistance usually arises as a result of a mutation in the UL97 CMV phosphotransferase gene.
For those patients who are intolerant, or lack clinical response, to ganciclovir, foscarnet is the second choice. Foscarnet is an inhibitor of DNA polymerase of all herpes viruses. Foscarnet does not require phosphorylation by UL97 and so is most often active against ganciclovir resistant strains. Foscarnet is given at 90 mg/kg, intravenously, twice per day for 2–3 weeks. Foscarnet toxicity includes renal impairment, central nervous system side effects, hypomagnesaemia, hypocalcaemia, hypophosphataemia and anaemia.
An alternative strategy for dealing with concerns about CMV colitis is to treat all patients with severe UC with ganciclovir. Kim et al. reported a series of 72 patients with moderate to severe UC treated with glucocorticoids. In patients with steroid resistance (defined as absence of clinical improvement 7–14 days after intravenous steroid treatment) ganciclovir was administered for 2 weeks: remission was achieved in 11 of 14 patients treated, the remainder undergoing colectomy. This strategy might be appropriate when there is reasonable clinical suspicion of CMV, without risking the inherent delays of a laboratory assessment of CMV in colonic tissue samples, however, the two studies by Delvincourt et al. mentioned earlier suggest this is actually unnecessary.
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