Varicella & Shingles Vaccines, DMARDs & Biologics

Varcella vaccine and Zoster (Shingles) vaccine are both comprised of the same strain- Oka- but are not the same vaccine. While the varicella vaccine (Varivax®, Varilix®) contains 1350 Plaque forming units (PFU), the zoster vaccine (Zostavax®) contains 18,700-60,000 PFU, i.e. at least 14 times more virus. The varicella vaccine needs to be given in two doses 4-8 weeks apart, while only one dose of the Zoster vaccine need be given.


In Rheumatology, the varicella vaccine is indicated in subjects who are about to start immunosuppression and are non-immune. Although, a history of chicken-pox is a reliable indicator that the subject will have protective antibodies, it is customary to check the varicella serology before starting immune-suppressive treatment. It is estimated that 90% of adults in the UK will have had either clinical or sub-clinical exposure to varicella growing up and will be immune- i.e. have protective levels of antibodies to varicella in the serum.


In the minority of patients with auto-immune disease that do not have protective antibodies, 2 doses of the varicella vaccine are administered 4-8 weeks apart. This should ideally be done 4 weeks before starting DMARDs.


For subjects who are already on DMARDs, it may not be too late to give the varicella vaccine. If the subject is on <0.4 mg methotrexate per kg body weight per week (equivalent to 25 mg weekly in a 60 kg subject), or receiving <3 mg azathioprine daily, or <1.5 mg 6-mercaptopurine daily, the varicella vaccine may still be administered. Similarly, those on low dose steroids (<20 mg daily for less than 2 weeks) are considered eligible. These are expert (level 3, not based on RCTs or case control studies) recommendations made by the Advisory Committee on immunization Practices (ACIP) based in the USA, an organisation that celebrates its 50th year in 2014. This is a body that has shaped immunisation guidelines worldwide. The Zoster or Shingles vaccine is recommended for subjects between 70 and 80 years in the UK. This year, the vaccine is being rolled out to subjects who are 70, 78 or 79 years old as of 1 September 2014, but not to other subjects. This is because it is quite expensive- each dose costs ~£100. A prior history of chickenpox or immunity to varicella is not considered necessary by the ACIP for giving the shingles vaccine. However the UK guidelines by the Joint Committee on Vaccination and Immunisation advice that such history be established before giving the shingles vaccine for fear of causing varicella in virus-naïve subjects late in life. The zoster vaccine provides only 50% protection to subjects from shingles, compared with no immunisation. While vaccinated subjects may still develop shingles, the disease is often attenuated. Live virus vaccines should never be given to subjects on biologics or pregnant women. Further, if the subject is about to receive, or has received rituximab, the vaccine must be given either 4 weeks before giving rituximab or 6 months after giving rituximab. With other biologics, varicella or zoster vaccines can be given 4 weeks before starting the biologic or approximately 5 half-lives after completing the biologic. What if a subject on immunosuppression is non-immune and has had a “significant” exposure to varicella or shingles? Significant exposure is defined as “face to face” contact or being in the same room or in the same 4-6 bedded bay. Exposure in more open wards or subjects living in a different part of the house or those exposed in a larger area such as a classroom are treated on a case to case basis. For such purposes, exposure to anybody with chickenpox is considered significant. Exposure to immunocompetent subjects with localised shingles in a covered area such as the thoracolumbar area is not considered significant. However exposure to shingles in an exposed area such as ophthalmic shingles is considered significant. Further, any exposure to shingles developing in an immunosuppressed subject, whether covered or not, is considered significant, as such subjects shed the virus at a much faster rate than immunocompetent subjects. Vulnerable subjects with such significant exposure are treated with varicella zoster immunoglobulin (VZIG). Currently, VZIG is prepared from pooled plasma accumulated from donors outside the UK. Donors from UK are not accepted for this purpose because of concerns about vCJD. Donors are screened for hepatitis B, hepatitis C and HIV, and the collected plasma is also screened for RNA and DNA from these viruses. Subjects who are considered eligible for VZIG are non-immune subjects with “significant exposure” as follows: 1. Immunosuppressed subjects- on biologics, high dose steroid therapy (>20 mg prednisolone for 4 weeks or longer), subjects with leukaemia, lymphoma, myeloma or generalised solid cancers, subjects who have had chemotherapy or have inherited disorders of immune deficiency. (Hopefully, most of these subjects would have been screened for varicella early in their illness trajectory).
2. Pregnant women in the first 20 weeks of pregnancy. Exposure in this period carries a risk of “congenital varicella syndrome” in the foetus, comprising microcephaly, maldeveloped limbs, skin lesions and other features.
3. In women who have been exposed to varicella during the last 7 days of their pregnancy or during the first 7 days after giving birth, the neonate must receive VZIG. During this period, the neonate is at risk of disseminated varicella. The risk lessens considerably after the first 7 days of life.



However, if the mother develops shingles rather than varicella during this period, VZIG need not be given to the neonate as it would have received pre-formed antibodies from the mother.



Prophylaxis still required if the neonate is exposed to chickenpox or shingles from another source apart from the mother in the first 7 days of life.



The dose of VZIG is as follows:
0-5 years- 500 mg
6-10 years- 1000 mg
11-15 years- 1500 mg
>15 years- 2000 mg


VZIG is given intramuscularly. If the subject has a bleeding diathesis and cannot receive IM injection, IVIG can be given in a dose of 0.2 mg/kg.


A subject receiving VZIG will not respond to the varicella vaccine if given concurrently. If VZIG has to be given within 4 weeks of giving the varicella vaccine, it is advisable to re-administer the vaccine after 3 months. VZIG also interferes with immunity to other viral vaccines with the exception of yellow fever, something that should be kept in mind for travellers.


There is no need to give VZIG in any subject who has protective levels of varicella antibodies in blood. The titre of such antibodies is not increased significantly by giving VZIG.


It is worth mentioning that many subjects will develop varicella despite receiving the VZIG. Only 50% of subjects are fully protected from chickenpox by VZIG. However, it is thought to attenuate the severity of chickenpox if it does develop.


VZIG must be given ideally within 7 days, and certainly within 10 days of exposure to provide protection. If the subject’s immune status is not known, it is possible to send off the serology and receive a report within a week under current arrangements. Therefore, in such cases, VZIG can still be given.


It is occasionally possible for immunosuppressed subjects to develop varicella despite having protective antibodies in blood. In such subjects, it is thought that a deficit in cellular immunity contributes to development of chickenpox.


Treatment with acyclovir should be promptly administered to immunosuppressed subjects who develop chickenpox or disseminated zoster despite immunisation or in non-immune immunosuppressed subjects who develop varicella despite receiving VZIG.