Article In Brief
Experts in multiple sclerosis and myasthenia gravis discuss the pros and cons of vaccines in people with neuroimmunologic disorders for measles and other infectious diseases.
As of late May, at least 940 cases of measles had been reported to the US Centers for Disease Control and Prevention. That's the most cases the country has seen since 1994, when the total was 958—and the number keeps edging upward. Although many of the cases are clustered around outbreak areas in New York, California, and Washington State, a total of 26 states have now reported at least one case of the vaccine-preventable disease. The resurgence of measles, which was officially declared “eradicated” in the United States in 2000, has been attributed to a decline in vaccination rates.
Many people with neuroimmunologic disorders, such as multiple sclerosis (MS) and myasthenia gravis (MG), have concerns about the safety of vaccines for measles and other conditions. But they also are rightfully concerned about their additional risks of infection. Measles is a highly contagious virus. A child with measles can cough in his grandmother's living room, and that space can still be contaminated and infectious two hours later.
According to the CDC, measles is so contagious that if one person has it, up to 90 percent of the people close to that person who are not immune will also become infected. Since many people with MS and MG are taking immunosuppressive therapies, that puts them at even greater risk of developing the disease.
And if they do, they face not only all the symptoms and risks of measles itself, but also added risks of disease exacerbations that could be caused by a viral infection like measles or shingles.
“A person without a chronic neurologic illness has to contend with the symptoms of measles or shingles alone, but with one of these disorders, the disease itself can be worsened by that infection,” said Nicholas J. Silvestri, MD, FAAN, associate professor of neurology at the University at Buffalo Jacobs School of Medicine and Biomedical Sciences and a member of the medical and scientific advisory board for the Myasthenia Gravis Foundation of America (MGFA). “In MG, for example, a major concern would be the development of myasthenic crisis—respiratory failure related to myasthenia—or a more general significant worsening of the disease.”
Given these competing concerns, how should you advise your patients?
The Measles Debate
“Measles is a serious problem, because immunization involves a live-pathogen vaccine,” said Michelle Fabian, MD, assistant professor of neurology at Mount Sinai Medical Center in New York and an attending physician at the Corinne Goldsmith Dickinson Center for Multiple Sclerosis. “Giving someone with an autoimmune disorder like multiple sclerosis or myasthenia gravis a live vaccine puts them at risk of a new relapse.”
But not all live virus vaccines have the same picture of risks and benefits, and overall, the National Multiple Sclerosis Society (NMSS) has determined that the measles-mumps-rubella (MMR) vaccine is, overall, “probably” safe for people with MS who are not on immunosuppressant medications. The MGFA has made a similar recommendation for people with MG. (By contrast, the NMSS says that the yellow fever vaccine, also a live-attenuated vaccine, “may not be safe.”)
“I have a number of immunosuppressed patients in New York and New Jersey who have had family members with measles, but have not developed the disease, so it appears that their childhood vaccines against the disease continue to be effective.”
—DR. MICHAEL LEVY
Most adult patients with MS or MG were likely immunized against measles in childhood, but questions have recently been raised as to whether or not that immunity persists years later and if adults require a booster. Experts are divided on this question, and the CDC still only recommends boosters for high-risk individuals: international travelers, health care workers, and those living in communities that are in the throes of an outbreak.
Dr. Fabian recommends assessing an individual patient's situation to determine if the risk of an exacerbation triggered by vaccination appears to be higher than the risk of developing measles and its associated complications.
“If someone would need to take active measures to avoid measles risk—for example, if they live in a community with a high rate of measles cases and perhaps family members who have been diagnosed with measles—then you might consider the vaccine much more seriously than if they are in an area with no outbreaks,” she said. “For example, if your patient is a pregnant woman in an area with high rates of measles, that might outweigh the risk, but I would say that most people with MS would be better off not being re-immunized.”
(In a paper published May 9 in the online edition of The Lancet Infectious Diseases, researchers at the University of Texas at Austin and Johns Hopkins University identified the 25 US counties most at risk for measles outbreaks, based on international travel from foreign countries with large measles outbreaks and the prevalence of nonmedical exemptions from childhood vaccinations.)
If a patient is very worried about their risk of contracting the disease, you can order a blood test to check their antibodies against measles—but that's not entirely reliable in patients with any kind of autoimmune disease or taking immune-suppressive therapies.
“These tests only measure the level of measles antibodies in the blood, which is just one measure of immunity and can often be suppressed in patients with MS or MG,” said Michael Levy, MD, PhD, FAAN, associate professor of neurology at Johns Hopkins University in Baltimore. “Blood tests don't assess cellular immunity, which is a major component of the immune response. I have a number of immunosuppressed patients in New York and New Jersey who have had family members with measles, but have not developed the disease, so it appears that their childhood vaccines against the disease continue to be effective.”
“Giving someone with an autoimmune disorder like multiple sclerosis or myasthenia gravis a live vaccine puts them at risk of a new relapse.”
—DR. MICHELLE FABIAN
“A person without a chronic neurologic illness has to contend with the symptoms of measles or shingles alone, but with one of these disorders, the disease itself can be worsened by that infection.”
—DR. NICHOLAS SILVESTRI
In a multicenter retrospective analysis published in the journal, Multiple Sclerosis and Related Disorders, in July 2018, Dr. Levy and colleagues assessed the risk of relapses associated with vaccines in patients with neuromyelitis optica spectrum disorder, a rare neurologic autoimmune disorder that in its early stages is sometimes confused with MS. Ninety patients who met 2015 diagnostic criteria received a total of 211 vaccinations (the study did not break vaccines out by type) and experienced 340 relapses over a median disease course of 6.6 years. Among these patients, they did find that the rate of vaccine-associated relapses within 30, 60, and 90 days was significantly higher than the likelihood of a relapse spontaneously occurring within each of the given time frames (p = 0.034—0.01, 0.016, respectively)—among patients who were not on preventive treatment only.
“In other words, patients who are not on treatment do indeed have a risk of any immunization inducing a relapse,” Dr. Levy said. “Just taking them over the threshold by activating the whole immune system can trigger the disease into attacking. However, for patients who are on medications that suppress attacks, you not only mitigate the risk of the vaccine inducing a relapse, but also you gain a benefit; there are fewer relapses among this group than even among those who are on treatment and who did not vaccinate. We posit that this is because those who do not vaccinate are more likely to get the infection, which will activate the immune system and cause a relapse. These findings could potentially apply in other neurologic autoimmune diseases as well.”
The other vaccine-preventable condition that may be a particular concern for many neurologists' patients is shingles, a painful infection of the nerve and skin surface caused by the dormant varicella zoster virus, the same virus that causes chicken pox. If someone has never developed chicken pox because they were vaccinated for the varicella zoster virus, they will also never get shingles. But for those individuals who either contracted chicken pox before the vaccine became available in 1995, or who did get the vaccine and had chicken pox, the virus lives on, dormant, in their body after recovering from the disease.
For about one in three adults, the virus will become active again, causing burning and shooting pain, tinging and itching, as well as a rash and/or blisters. There are an estimated 1 million cases of shingles each year in this country, with the risk of developing shingles increasing with age and among people with weakened immune systems.
“With our patients, we do worry that the infection may trigger a relapse. Also, there is a concern that clearing the virus may be more difficult for those patients that are immunosuppressed,” Dr. Fabian said. “That said, I've had many patients have shingles outbreaks while on MS treatment, and they've done reasonably well overall.”
Fortunately, there is now an inactivated vaccine available to prevent shingles. Shingrix, a genetically engineered, recombinant vaccine introduced in 2017, has been found to be more than 90 percent effective. While studies are underway to evaluate its safety in patients with reduced immune function, Dr. Silvestri said that there is little concern that this or other inactivated vaccines would cause exacerbations of MG or MS, or other existing autoimmune diseases.
The current vaccine for chicken pox itself, by contrast, is a live-attenuated vaccine.
For adults who came of age before the introduction of the chicken pox vaccine and somehow avoided contracting the disease, it's important to know that certain immunosuppressive medications—including fingolimod (Gilenya), alemtuzumab (Lemtrada), and ocrelizumab (Ocrevus)—can increase the risk of developing chicken pox. The CDC recommends that patients about to initiate one of these therapies who have not been vaccinated or had the disease receive the varicella vaccination, and not start therapy until at least one month afterward.
“In many cases, I would probably just pick another treatment for the patient, because I wouldn't want to wait to initiate therapy,” says Dr. Fabian. (In adults, the chicken pox vaccine is given in two doses at least four weeks apart, which would delay treatment onset by approximately two months.)
Dr. Levy agrees. “In these patients, instead of fingolimod I might select a drug that is just as effective but less immune-suppressing, such as dimethyl fumarate (Tecfidera) or teriflunomide (Aubagio). It's always a balance as we try to suppress the immune system in order to control an autoimmune disease like MS, while not overly suppressing it and leaving them vulnerable to other diseases.”
Both the NMSS and the MGFA have comprehensive, patient-friendly guides on vaccines to share with your patients.