Vaccinations and Rheumatic Disease

Common questions about vaccinations for patients with rheumatic disease fall into four categories:

1. Does vaccination cause rheumatic disease?
2. Does vaccination worsen rheumatic disease?
3. Is vaccination effective in rheumatic disease?
4. Are vaccinations dangerous for someone with rheumatic disease?

Because there are many types of vaccinations (see Table below), many different vaccination schedules, and many differences among patients with rheumatic diseases, definitive answers are few. However, a number of specific studies permit general answers. In general, those answers are:

1. Vaccination does not cause rheumatic disease.
2. Vaccinations do not worsen rheumatic disease.
3. Vaccinations are generally effective in patients who are not taking high doses of prednisone or immunosuppressive drugs.
4. Vaccinations are not dangerous for persons with rheumatic disease, except: live-virus and bacterium vaccinations are dangerous for, and are contraindicated in, patients who take high doses of prednisone or immunosuppressive drugs, or who have very low white blood cell counts or are otherwise immunocompromised.

References to medical articles (below) can provide readers with information on specific rheumatic diseases. references to medical articles are attached. Detailed information about vaccinations, including immunization schedules and doses are available from the National Centers for Disease Control, Advisory Committee On Immunization Practices (CDC, ACID), which provides a comprehensive website. What follows are brief answers to questions patients with rheumatic disease may ask.

What is a vaccination?

Vaccination is deliberate exposure, by injection, ingestion, or inhalation, to a non-toxic product that will cause the patient to make an antibody. The antibody will protect the patient by preventing infection or injury from a toxin. The word vaccination comes from the use of the cowpox virus (vaccinia), which causes a very mild illness in humans, to prevent smallpox, a very severe, often lethal, infection in humans.

Vaccines are of three types.

1. Most are killed bacteria or viruses. Assuming the killing process is done correctly, this type of vaccination is very safe. (In the early days of the polio vaccine, one manufacturer's process was faulty, and some children were unintentionally infected with live poliovirus.) Killed vaccines today are closely monitored to be certain that no live organism remains.
2. A second type of vaccine uses a markedly weakened (attenuated) version of the real virus or bacterium. In this case, the weak virus or bacterium is given live to the patient; that is, they infect patients, inducing antibodies that protect them against the more virulent organism. This type of vaccination is also usually safe. However, because these vaccines do produce a mild infection, they can infect fetuses of pregnant women and can spread in an uncontrolled fashion in people whose immune systems are weakened, such as those taking prednisone or other immunosuppressive drugs, patients on chemotherapy or those with AIDS. Thus live vaccines are contraindicated in pregnant women and immunocompromised people.
3. In some cases a protein or a sugar that induces a protective antibody has been extracted from a virus or bacterium or has been recreated in the laboratory. This protein or sugar is injected into the patient to induce protective antibodies. This type of vaccination is the safest of all, since nothing live of the original organism remains.

Who should be vaccinated?

Common childhood diseases and threatening toxins are the reasons for universal vaccination against diphtheria, hemophilus influenza (a bacterium that causes meningitis, not related to the common 'flu'), measles, mumps, rubella, poliomyelitis, and tetanus, and for the general recommendation for immunization against hepatitis A and chicken pox (varicella). Diminished ability to fight off the infection of common pneumonia (Pneumococcus) is the reason for immunizing older people, people with lung disease, and immunocompromised people. Anticipated high exposure is the reason for immunizing college students against meningococcus and immunizing veterinarians against anthrax. Travel accounts from most requests for cholera and yellow fever vaccination. Unfortunately, threats of terrorism have raised the issue of immunization of at-risk people against anthrax and-in an extremely unlikely scenario-smallpox. The table below lists current types of vaccinations used, the type of product that is used, and the persons for whom vaccination is recommended.

Do vaccines cause rheumatic disease?

Some lurid publications, and occasional medical alarmists, have suggested that vaccinations cause, among other things, multiple sclerosis, attention-deficit/hyperactivity disorder, autism, juvenile diabetes (type I), rheumatoid arthritis, and lupus. Careful studies, done in a number of different ways, have largely shown these statements to be false. Some live virus vaccines, especially rubella (German measles), do cause an arthritis that may last for several weeks, similar to arthritis caused by other viruses, such as parvovirus (Fifth disease). This type of arthritis spontaneously subsides and does not become rheumatoid arthritis or lupus. When viruses have been sought in joint fluid from recently vaccinated patients with arthritis, they have not been found. Influenza vaccination may on rare occasions induce a neurological disease, known as Guillain-Barré syndrome, which is considered to be autoimmune. Overall, however, the evidence says that vaccines do not cause rheumatic disease.

Do vaccines worsen rheumatic disease?

Most relevant studies have been done in lupus patients, whose disease activity is easily measurable. In studies going back to the influenza vaccination program in the United States in the 1970s (and recently updated), and in other studies on vaccination against Pneumococcus, the conclusion is unequivocal: lupus is not worsened. There is less information for patients with rheumatoid arthritis, but the information that does exist is parallel: no worsening of disease. No studies exist regarding the less common autoimmune rheumatic diseases. Osteoarthritis and osteoporosis are common rheumatic illnesses that have no immunological implications; it is assumed-but no one has actually looked-that patients with these two illnesses have normal responses to vaccination. Many vaccines cause a transient fever and aching that may be mistaken for disease worsening, but is harmless. In summary, the evidence is limited, but what does exist says that vaccinations do not worsen any rheumatic disease.

Are vaccinations effective in patients with rheumatic diseases?

The same studies of lupus patients mentioned above also examined efficacy of vaccination. Patients on low-dose or no prednisone have good antibody responses to vaccination, suggesting that they are well protected against the infections to which they have been immunized. Patients on high-dose prednisone or immunosuppressive drugs do not make good antibodies, suggesting that they are not protected. In other words, efficacy is determined by the treatment but not by the disease. Therefore, patients should be vaccinated when they are well and on little or no treatment, and not during flares of disease or when they are on intensive therapy, because the treatment will prevent the vaccine from taking hold.

Are vaccinations dangerous for patients with rheumatic disease?

Live-virus vaccines can spread throughout the body and should not be given to pregnant women or to patients on immunosuppressive drugs or patients whose spleens have been removed (splenectomy), because they may cause uncontrolled infection. One of the live vaccines, BCG (for bacille-Calmette-Guérin), given to protect against tuberculosis in parts of Europe and Asia, persists in the body and can re-emerge when a patient is given immunosuppressive therapy. The other live vaccines persist for only a short while. Live vaccines are safe for patients who are not immunocompromised. Killed vaccines and protein and sugar vaccines are safe for everyone.

Summary

Vaccines are generally safe and effective for patients with autoimmune rheumatic disease. Patients on immunosuppressive therapy may not be adequately protected (they may not make good antibodies); patients on immunosuppressive therapy should not receive live virus vaccines.

Annotated References:

1. Abu-Shakra M, et al. Influenza virus vaccination of patients with systemic lupus erythematosus: effects on disease activity. J Rheumatol. 2000;2:1681-5. Shows no worsening of disease.
   
   
2. Aron-Maor, Shoenfeld Y. Vaccination and systemic lupus erythematosus: the bi-directional dilemmas. Lupus. 2001; 10:237-40. Thoughtful discussion of the issues.
   
   
3. Bach JF. Protective role of infections and vaccinations on autoimmune disease. J Autoimmun. 2001;61:347-53. Argues that autoimmune diseases are more common in developed countries because infections protect populations.
   
   
4. Battafarano DF, et al. Antigen-specific antibody responses in lupus patients following immunization. Arthritis Rheum. 1998;41:1828-34. Pneumococcal, tetanus, and HIB vaccines are safe and effective.
   
   
5. Chen RT, Pless R, Destefano F. Epidemiology of autoimmune reactions induced by vaccination. J Autoimmun. 2001;16:309-18. Examines evidence that multiple sclerosis, type 1 diabetes, Guillain-Barré syndrome, idiopathic thrombocytopenic purpura, and rheumatoid arthritis are caused by vaccinations, and concludes that data are insufficient to decide.
   
   
6. Frenkel LM, et al. A search for persistent rubella virus infection in persons with chronic symptoms after rubella and rubella immunization and in patients with juvenile rheumatoid arthritis. Clin Infect Dis. 1996;22:287-94. Reports virus not found.
   
   
7. Ioannou Y, Isenberg DA. Immunisation of patients with systemic lupus erythematosus: the current state of play. Lupus. 1999;8:497-501. General review, indicating safety and efficacy of contemporary vaccinations.
   
   
8. Older SA, et al. Can immunization precipitate connective tissue disease? Report of five cases of systemic lupus erythematosus and review of the literature. Semin Arthritis Rheum. 1999;29:131-9. Case reports suggesting that vaccination does induce disease.
   
   
9. Pope JE, et al. The development of rheumatoid arthritis after recombinant hepatitis B vaccination. J Rheumatol. 1999;25:1687-93. Case reports suggesting that genetically susceptible persons can develop RA after vaccination.