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Risk of Disseminated Disease in Immunosuppressed Patients Receiving Live Zoster Vaccine

      To the Editor:
      I read with interest the letter by Bubb
      • Bubb M.R.
      Risk of disseminated varicella zoster in immunosuppressed patients receiving zoster vaccination.
      and the reply by Cheetham et al
      • Cheetham T.C.
      • Sy L.S.
      • Jacobsen S.J.
      In reply—Risk of disseminated varicella zoster in immunosuppressed patients receiving zoster vaccination.
      in the November 2015 issue of Mayo Clinic Proceedings regarding the risk of disseminated disease in immunosuppressed patients receiving live zoster vaccine. Although the vaccine has been found to be highly effective and there is a paucity of cases of vaccine-related infections, the following report serves to highlight the need for caution when immunizing highly immunosuppressed patients.
      A 62-year-old man who had granulomatosis with polyangiitis (Wegener granulomatosis) diagnosed 5 years previously was admitted to the Michael E. DeBakey VA Medical Center in February 2015 with a rash that began on his face 2 days before admission and had spread to his trunk, upper arms, and legs. In 2014, he had been admitted to another hospital with pulmonary hemorrhage and was treated with rituximab, methylprednisolone, and azathioprine. The patient had schizophrenia and nonischemic cardiomyopathy with an ejection fraction of 30%. At the time of admission, he was taking prednisone, 40 mg/d orally, plus mycophenolate mofetil, 500 mg orally twice daily. He also was undergoing hemodialysis thrice weekly. He had accidentally received a subcutaneous injection of Zostavax, 0.65 mL (live varicella vaccine), at a VA outpatient clinic 47 days before admission.
      In the emergency department of the DeBakey Medical Center, the patient was short of breath and was noted to have cushingoid features (moon facies, lipodystrophy, and central obesity). There were hemorrhagic monotonous vesicles on an erythematous base covering the trunk, the proximal and distal upper extremities, and the proximal lower extremities. A punch skin biopsy revealed immunohistochemical evidence of human herpesvirus 3. The tissue block was later sent to the Centers for Disease Control and Prevention's Herpesvirus Laboratory, where the virus was confirmed to be the vaccine strain. The patient experienced respiratory distress and required emergent tracheal intubation and mechanical ventilation. Chest radiography revealed bilateral lung infiltrates, and both sputum and blood cultures grew methicillin-resistant Staphylococus aureus. Bronchoscopy revealed purulent secretions but no evidence of pulmonary hemorrhage. Treatment included acyclovir, vancomycin, and cefapime. Although the bacteremia cleared and there was crusting of some of the skin lesions, the patient's condition gradually worsened, and eventually the family requested that treatment be discontinued; the patient died after 2 weeks of hospitalization. The event was investigated, and the guidelines for varicella zoster virus vaccination within the clinics were reviewed with all staff to ensure that such an event does not recur.

      References

        • Bubb M.R.
        Risk of disseminated varicella zoster in immunosuppressed patients receiving zoster vaccination.
        Mayo Clin Proc. 2015; 90: 1585-1586
        • Cheetham T.C.
        • Sy L.S.
        • Jacobsen S.J.
        In reply—Risk of disseminated varicella zoster in immunosuppressed patients receiving zoster vaccination.
        Mayo Clin Proc. 2015; 90: 1586-1587

      Linked Article

      • In reply—Risk of Disseminated Varicella Zoster in Immunosuppressed Patients Receiving Zoster Vaccination
        Mayo Clinic ProceedingsVol. 90Issue 11
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          We thank Dr Bubb for his interest in our study and appreciate the opportunity to respond to his questions and concerns. Specifically, concern was raised about our conclusion that our findings “support the current recommendations for zoster vaccination in that patients should withhold their immunosuppressants for 4 weeks before immunization,”1 even though we found no cases of disseminated varicella zoster among 4826 vaccinated individuals who were taking immunosuppressant medication. Additional concerns centered on our findings related to herpes zoster, specifically that (1) our data revealing a higher risk of herpes zoster in immunosuppressed patients who stopped immunosuppressive therapy argue that it would be prudent to vaccinate immunosuppressed patients as soon as possible, (2) the data do not support withholding immunosuppressant therapy for a minimum of 4 weeks before vaccination compared with any other arbitrarily chosen interval, and (3) vaccination is unlikely to be the cause of the increased risk of zoster during the 42 days postvaccination in the current vs remote immunosuppressant users.
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      • Risk of Disseminated Varicella Zoster in Immunosuppressed Patients Receiving Zoster Vaccination
        Mayo Clinic ProceedingsVol. 90Issue 11
        • Preview
          The report by Cheetham et al1 in the July 2015 issue of Mayo Clinic Proceedings uniquely addresses the risk of disseminated varicella zoster in patients taking immunosuppressant drugs at the time of zoster vaccination. For those of us providing care to immunosuppressed patients, 2 key questions are (1) whether immunosuppression reduces the efficacy of vaccination and (2) whether there are any risks specifically related to the use of a live attenuated vaccine. The first question is not addressed in the study by Cheetham et al, but the fact that there were no cases of disseminated zoster in this study's 4826 immunosuppressed patients who were vaccinated provides reassuring evidence that the risk of dissemination is low in this population.
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      • In Reply I—Risk of Disseminated Disease in Immunosuppressed Patients Receiving Live Zoster Vaccine
        Mayo Clinic ProceedingsVol. 91Issue 7
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          The package insert for Zostavax lists “immunosuppression or immunodeficiency” as contraindications for use, so complications resulting from its use in a very highly immunosuppressed patient may be anticipated.1 However, reports of such complications, such as those described by Dr Young, remain rare. The risks of Zostavax become notable somewhere between moderate and very high levels of immunosuppression, and data, such as results from the ongoing VERVE trial2 of vaccination during treatment with anti–tumor necrosis factor therapy, are needed to define risks in specific populations.
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      • In Reply II—Risk of Disseminated Disease in Immunocompromised Patients Receiving Live Zoster Vaccine
        Mayo Clinic ProceedingsVol. 91Issue 7
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          The case reported by Dr Young illustrates the potential for vaccine-related herpes zoster infections in highly immunosuppressed patients. In our original study published in the July 2015 issue of Mayo Clinic Proceedings,1 there were only 500 individuals who were receiving corticosteroid doses similar to the regimen reported in this case, and therefore, conclusions could not be drawn regarding the safety of the zoster vaccine in the population we described. The case reported by Dr Young highlights the need for caution or possibly withholding zoster vaccination in highly immunosuppressed patients.
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