INTRODUCTION:
Patients have a higher risk of HZ with diseases such as rheumatoid arthritis (RA), psoriasis (PsO), and inflammatory bowel-related diseases (IBD) such as ulcerative colitis (UC) and Crohn’s disease (CD). Using immunosuppressive therapy, which treats these diseases, increases the risk of HZ.

DISCUSSION:
The most common risk factor for HZ is increasing age, presumably due to a weakening immune system as we age. In approximately 15% of the general population, varicella-zoster virus (VZV) reactivates after a latency period to cause HZ (shingles). Patients with autoimmune diseases, such as RA, IBD, UC, PsO, and CD diseases, have an increased risk of HZ compared to the general population. The risk of HZ increases by the use of immunosuppressive therapy to treat autoimmune diseases. One such drug for treatment is Janus kinase (JAK) inhibition. Tofacitinib, an oral JAK inhibitor for the treatment of RA and psoriatic arthritis, is under investigation for the treatment of UC and previously for PsO. Although there is a dose-dependent risk for HZ when taking tofacitinib, the majority of HZ cases reported are non-complicated, mild to moderate in severity, and manageable with standard antiviral therapy (acyclovir). Vaccination (Shingrix) should be considered before treating patients to reduce the risk of HZ patients receiving JAK inhibitors1Colombel, J. F. (2018). Herpes zoster in patients receiving JAK inhibitors for ulcerative colitis: mechanism, epidemiology, management, and prevention. Inflammatory Bowel Diseases, 24(10), 2173-2182. https://doi.org/10.1093/ibd/izy150. Cullen, Baden, and Chiefetz2Cullen, G., Baden, R., P., & Cheifetz, A. S. (2012). Varicella zoster infection in inflammatory bowel disease. Inflammatory Bowel Diseases, 18(12), 2392-2403. https://doi.org/10.1002/ibd.22950 presented a review of publications describing VZV infections in inflammatory bowel disease (IBD) patients. They looked at 20 cases of primary VZV infection with IBD and 32 cases of HZ infections in patients with IBD. Fifteen of the 20 VZV cases had CD, which likely reflects the greater use of immunosuppression in this disease than UC. They identified various immunosuppressive drugs used in 20 patients, including anti-TNF (9 patients), corticosteroids (13), and either thiopurine or methotrexate (12). All 32 cases of HZ in IBD patients were on immunosuppression with corticosteroids, thiopurines, and anti-TNF. Combination therapy increased the risk of HZ even further. However, in a more comprehensive nationwide Veteran Administration study with 295 patients, Khan et al.3Khan, N., Trivedi, C., Shay, Y., Patel, D., Lewis, J., & Yang, Y. (2018). The severity of herpes zoster in inflammatory bowel disease patients treated with anti-TNF agents. Inflammatory Bowel Diseases, 24(6), 1274-1279. https://doi.org/10.1093/ibd/izx115 found that the incidence and severity of HZ in patients on anti-TNF medications were found not to be associated with an increased risk of developing severe HZ among these IBD patients. They believed TNF-α to play an important role in viral clearance, so it was logical to think anti-TNF medications could impair host immune function. Still, the data suggest that IBD patients who develop HZ during anti-TNF therapy are not at increased risk of developing complications from the HZ infection.

CONCLUSION:
Despite the risk of a reactivating HZ infection in persons with autoimmune diseases, such as those described, there are several immunosuppressive drugs available to treat these diseases, while not increasing the further risk of HZ infections. Both tofacitinib and anti-TNF therapies, as referenced above, are two such drugs. There is growing support for patients with IBD to receive vaccination against HZ using the newly released vaccine, Shingrix, before immunosuppressive therapy treatment. Shingrix vaccination is recommended even if patients have received the previous live virus vaccine.

By David Kilpatrick, PhD and Abbas Vafai, PhD

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