CLINICAL REVIEW Varicella Zoster Virus Infection in Inflammatory Bowel Disease Garret Cullen, MD,* ,† Rachel P. Baden, MD, †,‡ and Adam S. Cheifetz, MD* ,† Background: The risk of viral infection is increased in immunosuppressed inflammatory bowel disease (IBD) patients. Varicella zoster virus (VZV) is of particular interest in IBD because of a number of reports of severe, disseminated, and occasionally fatal varicella infection in immu- nosuppressed IBD patients. Methods: We reviewed publications describing VZV infection in IBD patients and combined these data with a review of the current literature relating to both primary and secondary varicella in IBD. Results: Twenty cases of primary varicella infection and 32 cases of herpes zoster infection have been reported in IBD. Additional cases are reported in clinical trials. The risk of VZV infection is increased with all immunosuppressants used in IBD, but corticosteroids and combination immunosuppression appear to be a particular risk. Conclusions: Healthcare providers need to be aware of the various manifestations of primary and secondary VZV infection in immunosup- pressed IBD patients. Patients should be screened for VZV immunity and vaccinated prior to commencing immunosuppression. (Inflamm Bowel Dis 2012;18:2392–2403) Key Words: viral infection, immunosuppressed, inflammatory bowel disease, Varicella zoster virus T he risk of viral infection is increased in immunosup- pressed patients. Data from the rheumatology literature suggest that 30% of all infections and 11% of serious infec- tions related to antitumor necrosis factor (TNF) therapy are vi- ral in nature. 1 Varicella zoster virus (VZV) is of particular in- terest in inflammatory bowel disease (IBD) because of a number of reports of severe, disseminated, and occasionally fatal varicella infection in immunosuppressed IBD patients. Gastroenterologists should be aware of its various presenta- tions and be able to diagnose, treat, and prevent VZV. VZV, herpes simplex virus (HSV), cytomegalovirus, and Epstein–Barr virus are all members of the herpes virus family. Over 90% of adults living in temperate climates have been exposed to VZV, but as varicella is a less common childhood infection in tropical areas, up to 50% of adults in these areas may have no history of primary infection. 2,3 The herpes viruses are the most commonly reported viral infections in the cohort studies of immunosuppression- related complications in IBD. 4,5 Specifically, the risk of vari- cella zoster infection is increased in IBD. Data from the UK General Practice Research Database (GPRD) demonstrate an incidence rate ratio of 1.6 (95% confidence interval [CI] 1.4–1.9) in Crohn’s disease (CD) and 1.2 (95% CI 1.1–1.4) in ulcerative colitis (UC) overall, compared to non-IBD patients. 6 In the United States, the rate ratio is 1.8 (95% CI 1.7–2) for zoster infection in CD compared to the general population. 7 As awareness of this potential infectious com- plication increases, the hope is that more IBD patients will be screened for varicella immunity prior to initiating immu- nosuppression. This review describes the issues surrounding VZV infection in IBD patients, including presentation, diag- nosis, treatment, and prevention. PATHOGENESIS VZV is spread through respiratory secretions and infected cellular material shed from the skin. The virus is associated with two periods of viremia, the first immedi- ately after inoculation and the second at the end of the 10– 21-day incubation period, just prior to the development of the skin rash. 8 Following this primary infection, the virus establishes latency in sensory ganglia and, upon reactiva- tion, causes herpes zoster or shingles. Zoster is thought to be due to retrograde transport of the virus from ganglia to the skin, but isolation of the virus from the blood of Received for publication February 15, 2012; Accepted February 20, 2012. From the *Center for Inflammatory Bowel Disease, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, † Harvard Medical School, Boston, Massachusetts, ‡ Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Financial disclosures: A.S.C.: UCB (advisory board), Abbott (advisory board), Janssen (advisory board); the remaining authors have no relevant financial disclosures. Reprints: Garret Cullen, MD, Center for Inflammatory Bowel Disease, Division of Gastroenterology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215 (e-mail: gcullen@bidmc.harvard.edu). Copyright V C 2012 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.22950 Published online 20 March 2012 in Wiley Online Library (wileyonlinelibrary. com). Inflamm Bowel Dis  Volume 18, Number 12, December 2012 2392