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Herpes zoster, immunosuppression, and vaccination: Far from a blistering pace

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By Warren R. Heymann, MD
July 5, 2016

Do you recognize the name Chris Gueffroy? He was the last person shot trying to escape from East Berlin, before the wall came down. I had long promised myself that I would get Zostavax when I turned 60. Now 61, I am actively procrastinating — I decided to wait for a new VZV subunit zoster vaccine that consists of recombinant VZV glycoprotein E and a liposome-based ASO1B adjuvant system (1). I am convinced that I will be the last person to get shingles prior to the release of the new vaccine. On the other hand, if I were at high risk, I would have had it already.

Robinson et al note that the incidence of herpes zoster (HZ) is increased in many autoimmune diseases. In their retrospective study of 186 patients with cutaneous lupus erythematosus (CLE), dermatomyositis (DM), pemphigus vulgaris, and bullous pemphigoid, they determined that the risk of zoster was highest in patients with dermatomyositis followed by lupus compared to healthy controls. Within each disease group, there was no significant difference in the proportion of patients with zoster and without zoster on immunosuppressive agents, including steroids. They noted, however, that “Prior studies sound that patients with DM on chloroquine had a 6-fold increased risk of zoster compared with those not on chloroquine, and that the use of hydroxychloroquine in rheumatoid arthritis was associated with a statistically significant increase risk of zoster.” The authors recommended considering utilizing the varicella zoster vaccine in patients with CLE or DM prior to their receiving immunosuppressive agents. They correctly state that the standard age of immunization for zoster is now 50 years (it is my understanding that most insurers will not pay for it until age 60), making it a further challenge (2).

We recently made a similar recommendation after seeing a patient with lupus develop CLE lesions as a Koebner phenomenon following her zoster episode (3).

Aside from the immunologic aberrations of the autoimmune diseases that increase the risk of zoster, additional immunosuppression related to therapy must be addressed. Hu et al compared 1555 patients with SLE and HZ to a control group of 3049 matched patients with SLE without HZ. They concluded that recent immunosuppression is related to HZ in patients with SLE, especially for those on high dose steroids or multiple immunosuppressive agents, based on the following results:

Medications associated with greater HZ risk in patients with SLE included oral corticosteroids, intravenous methylprednisolone, hydroxychloroquine, oral cyclophosphamide, intravenous cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil. Combination immunosuppressive therapy was common in patients with SLE and was associated with greatly increased HZ risk. For oral corticosteroids and hydroxychloroquine, the risk of HZ was strongly dependent on the medication dose.

HZ appears when there is a reduction of cell-mediated immunity, whether due to age-related senescence, an autoimmune disease, treatment for that disease, or any combination of the three. If you look at the package insert for Zostavax immunosuppression is a contraindication for the vaccine. Despite age restrictions and the risk of immune suppression of the disease itself, we need to weigh the risk/benefit ratio of administering the vaccine to those patients who have not yet received their immunosuppressive drugs. In my estimation the benefits clearly exceed the risks. I completely concur with Oxman and Schmader (5) who opine:

In view of the very high degree of attenuation of the Oka vaccine strain of VZV, these observations suggest that it may be time to reconsider the use of zoster vaccine in selected populations of immunocompromised patients who are at increased risk of HZ infection and its debilitating complications. Such considerations should not, however, divert attention from the urgent need to increase the woefully inadequate uptake of zoster vaccine by adults ≥60 years of age, for whom it is already recommended.

1. Gagliardi AM, et al. Vaccines for preventing herpes zoster in older adults. Cochrane Database Syst Rev 2016 Mar 3:3:CD008858.
2. Robinson ES, et al. The incidence of herpes zoster in cutaneous lupus erythematosus (CLE), dermatomyositis (DM), pemphigus vulgaris (PV) and bullous pemphigoid (BP). J Am Acad Dermatol 2016; 75:42-8.
3. Anywanu C, Sommer LL, Heymann WR: Discoid lupus following herpes zoster: potential prophylaxis for the isomorphic response. Cutis (in press)
4. Hu S C-S, et al. Immunosuppressive medication use and risk of herpes zoster (HZ) in patients with systemic lupus erythematosus (SLE): A nationwide case-control study. J Am Acad Dermatol 2016; 75: 49-58.
5. Oxman MN, Schmader KE. Editorial commentary: Zoster vaccine in immunocompromised patients: time to reconsider current recommendations. Clin Infect Dis 2014; 59: 920-2.

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