I have been asked to consult on a 65 year-old patient who needs the shingles vaccination, she has borderline low IgG and is not on replacement therapy, she has a history of stromal tumor of her small intestine which was removed, no radiation and no chemo needed and the consult is to see if she can get the shingles vaccination. She is otherwise healthy and has no other medical history. what are your thoughts?


Any decision in clinical medicine is a balance of the risk and benefit and many times the evidence is not black and white. Treating your patient as you would your family member is a statement our program director, Richard Lockey, often shares with our fellows when discussing such decisions.

In this case, I would feel comfortable in administering the vaccine as the risk is minimal and the benefits are significant in light of the potential morbidity associated with shingles. The borderline IgG concentration and history of stromal tumor would not sufficiently impact cellular immune response, the most important factor for a live virus vaccine, to make me uncomfortable with administering.

I have attached an archived Ask The Expert question which is not focused on your issue but gives some useful background information.

The Advisory Committee for Immunization Practices of the CDC specifies the immunodeficiencies in which caution should be used for zoster vaccine (Zoster Vaccine Recommendations). I have copied these conditions below and you will notice hypogammaglobulinemia is mentioned as not precluding the vaccine and no mention is made of prior cancers being a contraindication.

Immunocompromised Persons
Zoster vaccine should not be administered to persons with primary or acquired immunodeficiency including:
• Persons with leukemia, lymphomas, or other malignant neoplasms affecting the bone marrow or lymphatic system. However, patients whose leukemia is in remission and who have not received chemotherapy (e.g., alkylating drugs or antimetabolites) or radiation for at least 3 months can receive zoster vaccine (209).
• Persons with AIDS or other clinical manifestations of HIV, including persons with CD4+ T-lymphocyte values <200 per mm3 or <15% of total lymphocytes.
• Persons on immunosuppressive therapy, including high-dose corticosteroids (>20 mg/day of prednisone or equivalent) lasting two or more weeks. Zoster vaccination should be deferred for at least 1 month after discontinuation of such therapy (209). Short-term corticosteroid therapy (<14 days); low-to-moderate dose (<20 mg/day of prednisone or equivalent); topical (e.g., nasal, skin, inhaled); intra-articular, bursal, or tendon injections; or long-term alternate-day treatment with low to moderate doses of short-acting systemic corticosteroids are not considered to be sufficiently immunosuppressive to cause concerns for vaccine safety. Persons receiving this dose or schedule can receive zoster vaccine. Therapy with low-doses of methotrexate (<0.4 mg/Kg/week), azathioprine (<3.0 mg/Kg/day), or 6-mercaptopurine (<1.5 mg/Kg/day) for treatment of rheumatoid arthritis, psoriasis, polymyositis, sarcoidosis, inflammatory bowel disease, and other conditions are also not considered sufficiently immunosuppressive to create vaccine safety concerns and are not contraindications for administration of zoster vaccine.
• Persons with clinical or laboratory evidence of other unspecified cellular immunodeficiency. However, persons with impaired humoral immunity (e.g., hypogammaglobulinemia or dysgammaglobulinemia) can receive zoster vaccine.
• Persons undergoing hematopoietic stem cell transplantation (HSCT). The experience of HSCT recipients with VZV-containing vaccines (e.g., zoster vaccine) is limited. Physicians should assess the immune status of the recipient on a case-by-case basis to determine the relevant risks. If a decision is made to vaccinate with zoster vaccine, the vaccine should be administered at least 24 months after transplantation (209).
• Persons receiving recombinant human immune mediators and immune modulators, especially the antitumor necrosis factor agents adalimumab, infliximab, and etanercept. The safety and efficacy of zoster vaccine administered concurrently with these agents is unknown. If it is not possible to administer zoster vaccine to patients before initiation of therapy, physicians should assess the immune status of the recipient on a case-by-case basis to determine the relevant risks and benefits. Otherwise, vaccination with zoster vaccine should be deferred for at least 1 month after discontinuation of such therapy.
In summary, if your patient does not have a significant lymphopenia (less than 750/uL), I would administer the zoster vaccine. I would document a discussion of the issues since this is a live virus vaccine. You may also wish to mention there should be limited contact with others who are immunosuppressed, such as family members receiving aggressive chemotherapy.

Shingles vaccine, varicella zoster
Q: 5/21/2013
I recently evaluated a 45year-old female with recurrent “shingles”. She has had three episodes in 3 ½ years and chicken pox at age 10. Except for pneumonia lasting six weeks in 2011 she is otherwise healthy. Her work-up to date includes the following normal studies: T& B studies, IgG, IgA, IgM, Diphtheria, Tetanus, and Pneumococcal titers, and CBC with differential. Delayed hypersensitivity panel was (+) candida, and (-) trichophytin, and PPD. Does she need more detailed cell-mediated studies before recommending a varicella zoster shot? Thank you.

A: I believe that your workup is sufficient. Copied below, for your interest, is a posting from our “Ask the Expert” website in response to a similar inquiry. This will give you references to pursue in regards to your question.

Recurrent herpes zoster in an apparent immunocompetent patient
38 year old female has had 5 episodes of Zoster. Breaks out in Zoster even on prophylactic Valtrex. HIV testing negative. No evidence of cancer/leukemia/lymphoma. Immune work up normal (immunoglobulins, cbc, cmp, complement levels, CD4/CD8 profile, tsh, ana, esr). She has good titers to vaccines. Has a low vitamin D3 at 18. Has a positive TB skin test (not treated yet -seeing ID). VZV IgG AB 3.48 (> 1.09 positive).

Started her on Vitamin D3.

She remains on Valtrex prophylactically.

Is there any other work up necessary? Am I missing something? Any other ideas? Is there any other immune work up needed.

Thank you for your inquiry.

I think that you have done due diligence in your evaluation. Recurrent herpes zoster, in terms of immunodeficiency, is usually related to a defect in cell-mediated immunity, and in view of the fact that this patient has a positive tuberculin test, such is unlikely.

There are three other salient points, however, which I can mention.

First of all, as you can see from the 2011 Mayo Clinic Proceedings article (abstract copied below), recurrent zoster is probably more common in immunocompetent patients than previously thought.

Secondly, as you can see from the quote taken from the Cleveland Clinic Journal of Medicine, January 2009, and derived from the ACIP recommendations, you might consider zoster vaccination if you have not done so. The recommended age for the initiation of zoster in people who have not had recurrent zoster has been recently lowered to 50. This 38-year-old female is not too far from that age, and has a complication which I think could be considered in many circles justification for the vaccination.

Finally, I am sure that you have the correct diagnosis, but nonetheless I call to your attention to the observation that through the years there have been many cases of recurrent herpes simplex confused with zoster. The article from the Journal of the American Academy of Dermatology by Heskel and Hanifin is a nice review of this issue.

Thank you again for your inquiry and we hope this response is helpful to you.

Mayo Clin Proc. 2011 Feb;86(2):88-93. Epub 2011 Jan 10.
Herpes zoster recurrences more frequent than previously reported.
Yawn BP, Wollan PC, Kurland MJ, St Sauver JL, Saddier P.
Department of Research, Olmsted Medical Center, 210 9th Street SE, Rochester, MN 55904, USA.
Objective: To present population-based estimates of herpes zoster (HZ) recurrence rates among adults.
Patients and Methods: To identify recurrent cases of HZ, we reviewed the medical records (through December 31, 2007) of all Olmsted County, Minnesota, residents aged 22 years or older who had an incident case of HZ between January 1, 1996, and December 31, 2001. Kaplan-Meier curves and Cox regression models were used to describe recurrences by age, immune status, and presence of prolonged pain at the time of the incident HZ episode.
Results: Of the 1669 persons with a medically documented episode of HZ, 95 had 105 recurrences (8 persons with >1 recurrence) by December 31, 2007, an average follow-up of 7.3 years. The Kaplan-Meier estimate of the recurrence rate at 8 years was 6.2%. With a maximum follow-up of 12 years, the time between HZ episodes in the same person varied from 96 days to 10 years. Recurrences were significantly more likely in persons with zoster-associated pain of 30 days or longer at the initial episode (hazard ratio, 2.80; 95% confidence interval, 1.84-4.27; P<.001) and in immunocompromised individuals (hazard ratio, 2.35; 95% confidence interval, 1.35-4.08; P=.006). Women and anyone aged 50 years or older at the index episode also had a greater likelihood of recurrence.
Conclusion: Rates of HZ recurrence appear to be comparable to rates of first HZ occurrence in immunocompetent individuals, suggesting that recurrence is sufficiently common to warrant investigation of vaccine prevention in this group.

Quote from Cleveland Clinic Journal of Medicine:
Vaccinate even if the patient has had shingles The ACIP says that people with a history of zoster can be vaccinated. Recurrent zoster has been confirmed in immunocompetent patients soon after a previous episode. There is no test to confirm prior zoster episodes, and if the patient is immunocompetent, no different safety concerns are anticipated with vaccination in this group.16
16. Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2008; 57:1–30.
SOURCE: doi: 10.3949/ccjm.75a.08046 Cleveland Clinic Journal of Medicine January 2009 vol. 76 1 45-48.

“Recurrent herpes zoster”: An unproved entity
Journal of the American Academy of Dermatology
Volume 10, Issue 3, 1984, Pages 486-490
Neil S. Heskel M.D., Jon M. Hanifin M.D.
Accepted 29 July 1983. Available online 16 June 2008.
Physicians sometimes misdiagnose recurrent zosteriform herpes simplex virus (HSV) skin infections as “zoster” or “recurrent zoster.” Misdiagnosis can lead to inappropriate therapy with potentially harmful consequences, particularly in patients with ophthalmitis or immunosuppression, in which early institution of the correct antiviral therapy may be crucial. We report three patients who were originally misdiagnosed to have recurrent herpes zoster skin infections before we cultured HSV from their vesicles. We suggest: (1) that most recurrent zosteriform eruptions are caused by HSV; (2) that “recurrent zoster” has yet to be documented; and (3) that the diagnosis of “recurrent zoster” be reserved for those patients who have laboratory confirmation of recurrent varicella zoster (VZ). Viral culture or examintion of vesicle contents by indirect immunofluorescent technic can provide definitive diagnosis of the etiology of a zosteriform eruption.

Clin Infect Dis. 2010 Jul 15;51(2):197-213.
Zoster vaccine: current status and future prospects.
Oxman MN.
Infectious Diseases Section, Department of Veterans Affairs San Diego Healthcare System, and Division of Infectious Diseases, University of California, San Diego, USA.
Live, attenuated Oka/Merck varicella-zoster virus (VZV) vaccine (zoster vaccine) protects immunocompetent adults from herpes zoster and its complications. Success of zoster vaccine in preventing the clinical manifestations of latent VZV reactivation contrasts with the failure to achieve similar results with vaccination to prevent recurrent herpes simplex. This reflects major differences in the pathophysiology of latency and reactivation of these 2 alphaherpesviruses. The Shingles Prevention Study and many others have demonstrated that VZV-specific cell-mediated immunity, but not VZV antibody, plays a critical role in limiting reactivation and replication of latent VZV and, thus, in preventing herpes zoster and its complications. Consequently, induction of VZV-specific cell-mediated immunity and not antibody should be used as a proxy for the clinical efficacy of new formulations and uses of zoster vaccine. Prospects for improved zoster vaccines and their use in immunocompromised patients are discussed, and questions related to zoster vaccine use are addressed.

Phil Lieberman, M.D.

I hope this information is of help to you and your patient.

All my best.
Dennis K. Ledford, MD, FAAAAI

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