Immunizations in Immunocomprised Patients

SAN FRANCISCO—Rheumatologists face several questions when choosing appropriate vaccinations for their patients with rheumatoid arthritis (RA) and other diseases such as lupus that may be treated with immunosuppressive agents. Some, in fact, may wonder whether vaccinations should be given at all because their patients are likely to have a reduced immunologic response. Camille N. Kotton, MD, adopts a glass-half-full approach to influenza and pneumonia vaccinations in this vulnerable population. “As someone who deals with very ill immunocompromised patients, I feel strongly that some immunologic protection is better than none,” she asserted in the session, “Immunization in the Immunosuppressed Host,” held at the 2008 ACR/ARHP Annual Scientific Meeting.

Dr. Kotton is clinical director of the Transplant and Immunocompromised Host Infectious Diseases Group at Massachusetts General Hospital, Boston; assistant professor at Harvard Medical School, Boston; and president of the Transplantation Infectious Diseases Section at the Transplantation Society. She explained that her stance on influenza and pneumococcus vaccination has been informed by her experience at Massachusetts General, where vaccination of immunocompromised transplant recipients on the transplant service has become routine. “You may not always be able to prevent disease,” she noted, “but the disease we do see may be significantly attenuated.”

More Vulnerable

Patients with rheumatic diseases have twice the risk of acquiring infection than those in the general population.¹ However, the question often arises as to whether vaccines might precipitate or worsen rheumatologic disease. Dr. Kotton pointed out that the jury is still out on this question: Most of the arguments against the use of vaccines are based on case reports, which are inadequate to establish a link between immunizations and worsening of preexisting rheumatologic disease. In addition, possible mechanisms of viral-induced autoimmunity (e.g., change in the host antigen and expression of HLA antigen) have yet to establish how vaccinations could trigger autoimmunity.

In the meantime, some guidance is available from several studies that show that influenza and pneumococcus vaccines are basically safe in patients with rheumatic disease. Dr. Kotton summarized several investigations that have demonstrated differing seroconversion rates in response to influenza, pneumococcus, and tetanus vaccines in RA and systemic lupus erythematosus patient populations. Again, Dr. Kotton repeated her assertion that some protection is better than none. She also suggested that clinicians might consider giving the flu vaccine later in the fall (closer to November) so that patients would have greater immunity coverage for the duration of the flu season, which tends to hit in December.

The ACR states in its recently released “2008 Recommendations for the Use of Nonbiologic and Biologic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis” that all RA patients should be given the influenza vaccine, whether or not they are on biologic or nonbiologic disease-modifying antirheumatic drugs (DMARDS).² Pneumococcus vaccine is also recommended by the ACR for patients with RA starting leflunomide, methotrexate, or sulfsalazine. The hepatitis B vaccine is recommended for some patients with RA, including those on leflunomide, methotrexate, and biologic agents, and those who fall into risk factor categories (e.g., healthcare personnel or those with intravenous drug use or multiple sexual partners).

ACR recommendations clearly state that all live vaccinations should be avoided in those who are receiving biologic DMARDs. Zoster vaccine; varicella; and measles, mumps, and rubella vaccines are generally contraindicated in immunosuppressed hosts, said Dr. Kotton. Another precaution: “Family members and others living intimately with immunosuppressed hosts should not be given the live influenza nasal vaccine,” she said, because the live attenuated virus can replicate in the nose for a week or longer and could be easily transmitted and potentially cause disease in the immunosuppressed patient who has secondary exposure to the vaccine given to the family member. Although the oral polio vaccine is no longer given in the United States, patients traveling to countries where the live attenuated vaccine is still used should be counseled on risks.

Special Issues with Zoster

Prevention of herpes zoster is a special concern due to the elevated rates of the infection in patients with rheumatic disease (13 to 14 cases per 1,000 person-years compared with 1.5 to 4 cases per 1,000 in the normal population). As shown by the three-year-long Shingles Prevention Study Group led by Oxman and Levin, giving the zoster vaccine (Zostavax) to adults aged 60 years or older who were not immunosurpressed lowered the incidence of zoster by 51%; the risk for post-herpetic neuralgia was 67% lower.³ Dr. Kotton presented the following key points extracted from a June 2008 Morbidity and Mortality Weekly Report study on the prevention of herpes zoster that applied the vaccine to those on immunosuppressant therapy.⁴ As shown in some of the points below, timing issues are critical.

• Defer the zoster vaccine for at least one month after discontinuation of immunosuppressant therapy (high-dose corticosteroids, >20 mg/day of prednisone or the equivalent for two or more weeks);
• Do not give the zoster vaccine to those receiving immune modulators, such as tumor necrosis factor–a blockers, and defer the vaccine for a least a month after discontinuation of such therapy;
• Consider the zoster vaccine for those on short-term corticosteroids (fewer than 20 mg/day of prednisone or equivalent for less than 14 days), those given topical steroids, or those on long-term, alternate-day, low-dose treatment; and
• Consider the zoster vaccine for those on low doses of methotrexate (<0.4 mg/kg/week) or azathioprine (<3 mg/kg/day) and those with impaired humoral (as opposed to cellular) immunity.

Counsel Patients About Travel Concerns

Dr. Kotton said that her solid-organ transplant patients wait a year after transplant and achieving stability before they attempt travel to foreign countries. Some of the important issues for immunosuppressed RA patients include:

• Location of travel and risk of infection: ideally, patients should avoid travel to countries in the yellow fever zones, but at the very least they should avoid times of peak yellow fever activity (see “Additional Resources for Clinicians,” below right);
• Availability of good healthcare in the regions of travel;
• Length of travel: Dr. Kotton recommends shorter stays to reduce the risk of acquiring infections; and
• Type of travel: Visiting friends and relatives entails a higher risk for acquiring infections, while risk of infection is lower with luxury travel compared with backpacking or other more rustic modes.

Precautions regarding food- and water-borne illness, mosquito-borne illness, blood- and sex-borne infection, sun and altitude damage, and traveler’s diarrhea, including obtaining a course of antibiotics, should be part of every traveler’s preparations. Additionally, required vaccinations should be started early, said Dr. Kotton, and patients with immunosuppression must carry a yellow fever waiver letter, because the vaccine is contraindicated for them. Medical evacuation insurance can be a good precaution in case patients become sick in a foreign country, she added.

In her closing remarks, Dr. Kotton also touched on issues of infectious disease prevention in children with juvenile idiopathic arthritis and urged her colleagues to make use of the Centers for Disease Control and Prevention/Food and Drug Administration Vaccine Adverse Event Reporting System to help add to the knowledge base about zoster vaccines in immunosuppressed patients.⁵

References

1. Gluck T, Muller-Ladner U. Vaccination in patients with chronic rheumatic or autoimmune disease. Clin Infect Dis. 2008;46:1459-1465.
2. Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59:762-784.
3. Oxman MN, Levin MJ. Shingles Prevention Study Group. Vaccination against herpes zoster and postherpetic neuralgia. J Infect Dis. 2008;197 Suppl 2:S228-S238.
4. Harpaz R, Ortega-Sanchez IR, Seward JF. Advisory Committee on Immunization Practices; Centers for Disease Control and Prevention. Prevention of herpes zoster: Recommendations from the Advisory Committee on Immunization Practices. MMWR Recomm Rep. June 6, 2008;57:1-30.
5. Centers for Disease Control and Prevention; Food and Drug Administration. Vaccine Adverse Event Reporting System. Available at: http://vaers.hhs.gov/vaers.htm. Accessed May 17, 2009.