Understanding Immunologic Complications of Measles

With recent outbreaks of measles reported, the future status of measles elimination in the U.S. is uncertain. Many rheumatology patients are asking questions about whether they need revaccination or tests to check for measles immunity. Although most will not need revaccination, rheumatologists should be familiar with the topic to provide reassurance and guidance.

Pathophysiology & Natural Course

Before the advent of an effective vaccine, measles infected almost everyone at some point during childhood, resulting in 2 million to 3 million deaths per year globally.¹ The RNA-based virus is a member of the Morbillivirus genus of the broader Paramyxoviridae family, which also includes the parainfluenza and mumps viruses.

The disease manifests with the classic three Cs: cough, conjunctivitis and coryza (runny nose, sneezing and congestion), as well as maculo­papular rash, fever and malaise. Notably, individuals can spread the incredibly contagious virus through respiratory droplets and aerosols about four days before the rash manifests, delaying diagnosis and limiting the effectiveness of isolation as a method of controlling disease spread.²

Most people with measles fully recover within a week or two. However, the disease can cause complications, especially pneumonia from the virus itself or from a secondary infection. The disease can also lead to rare but serious neurologic complications: the autoimmune condition acute disseminated encephalomyelitis; inclusion body encephalitis; and subacute sclerosing panencephalitis, which can occur several years after measles infection.²

It’s thought that some of these complications may be more common or more severe in immunosuppressed people, such as people receiving immunomodulatory therapies for rheumatic disease. However, the true risks are hard to quantify, and they might vary on the basis of individual factors, such as medications and underlying disease severity.¹

Immunomodulatory Effects

Importantly, although the immune response to measles itself is robust and long-lasting, measles leads to an increased risk of secondary infections for as long as two to three years.

Dr. Moss

William J. Moss, MD, MPH, executive director of the International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, explains that this immune suppressive effect was described early in the 20th century, but it was thought to last only a few months. For example, clinicians noted that children who had previous positive responses to tuberculosis skin tests became negative after measles, indicating impaired cellular immunity.

Other studies noted that atopic dermatitis seemed to temporarily recede in some patients who’d had measles. A few isolated reports of temporary remission of autoimmune conditions, such as juvenile rheumatoid arthritis and idiopathic nephrotic syndrome, also occur in the literature, consistent with this immunosuppressive effect.^3-5 However, in the past several years, researchers further quantified this effect and began to get a better sense of its scope, using the term immune amnesia to refer to the phenomenon.^6,7

“Measles infects lymphocytes widely, particularly memory B cells and T cells,” explains Dr. Moss. “This leads to destruction of the memory immune response and, thus, [to] a loss of immunologic memory.” Among other effects, measles reduces the antibody diversity of, and antibody quantity in responding to, previously encountered pathogens.

At the population level, recent analyses of historical data have shown the impact of measles goes far beyond deaths from initial infection due to increased infectious disease deaths from other causes over the next few years. In the past, measles may have been associated with as many as 50% of all infectious disease deaths during childhood.^6,7

Dr. Moss notes this impact is most profound in children in parts of the world at risk of undernourishment and vitamin A insufficiency, which multiply infectious disease risks. Worldwide, measles still leads to between 100,000 and 200,000 deaths each year, mostly in children in under-resourced areas.²

Vaccination & Recent Outbreaks

Most RNA viruses have high mutation rates, such as the influenza virus. Fortuitously, the epitope region of the measles virus, which is most important for inducing immunity, is found near the virus’ receptor binding site. Because of this, new mutations in this region are non-pathogenic. This antigenic stability has meant that live measles virus vaccines, first developed from a strain in the 1950s, still provide protection against currently circulating strains.²

In 1963, the U.S. Food & Drug Administration approved two different vaccines against measles—a live vaccine produced by Merck and an inac­tivated-type vaccine produced by Pfizer. From 1963 to 1967, less than 5% of children received the latter, which was ultimately found to be less effective than the live virus vaccine. An improved version of the live vaccine was released in 1968; it is still the foundation of modern measles vaccination, usually packaged with vaccinations for mumps and rubella (MMR).⁸

In response to measles outbreaks in school-aged children in 1989, the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics began recommending a second, live MMR vaccine dose for all children, which reduced measles outbreaks even further.⁹

Dr. Calabrese

Cassandra Calabrese, DO, a double-boarded rheumatologist and infectious disease specialist who is an assistant professor of medicine at the Cleveland Clinic Lerner College of Medicine, notes that this second dose is not considered a booster and is not necessary for inducing immunity, but it does increase the overall effectiveness from 93% to 97%.

Thanks to these changes and effective public health efforts, the disease was considered eliminated in the U.S. in 2000—defined as having no locally transmitted virus within a 12-month period, although isolated cases may still occur in people traveling to places where the virus remains endemic.¹

Recent U.S. Outbreaks

Despite these gains, global case numbers rose in the 2010s. In 2019, measles’ elimination status in the U.S. was threatened, with almost 1,300 documented measles cases in a large outbreak in New York and additional cases in another 30 states.¹

In a webinar, Daniel Salmon, PhD, MPH, speculated that the U.S. probably would have lost its elimination status in 2020 had not the COVID-19 pandemic intervened, causing global decreases in case numbers due to measures to decrease the spread of SARS-CoV-2. Dr. Salmon is director of the Institute for Vaccine Safety at the Johns Hopkins Bloomberg School of Public Health, Baltimore.¹⁰

Dr. Salmon

The pandemic disrupted regular measles immunization schedules in many countries.^1,11 And the incidence of measles cases has continued to rise since, with particularly large outbreaks in parts of Africa, Asia and Europe.

As of mid-July, the Centers for Disease Control and Prevention (CDC) reports that more than more than 1,300 cases of measles have occurred in 40 U.S. jurisdictions in 2025, leading to hospitalization in 13% of patients (164 individuals) and three deaths. Notably, 96% of cases occurred in people who were unvaccinated or had an unknown vaccination status.¹²

“Should transmission exceed 12 months, we may lose our measles elimination status,” says Dr. Moss.

“Outbreaks of a vaccine-preventable illness like this are always unfortunate and disappointing,” says Dr. Calabrese, “but I think the current rise in cases is quite disconcerting.”

In the U.S., vaccination rates widely vary by state (below 80% in Idaho to 98% in West Virginia) and county, with even smaller areas of geographic clustering. More than 550 of the current reported cases are from west Texas, centered on a close-knit, unvaccinated Mennonite community.¹³ Dr. Calabrese points out that vaccination rates in these areas are well below the roughly 95% vaccination threshold necessary to prevent spreading.

Although overall MMR vaccination rates in Texas are about 94%, in Gaines County, the location of the Mennonite community, overall rates are 82%. Most public schools nationwide require some sort of mandatory vaccine schedule, including MMR, with some state exceptions for medical conditions or personal beliefs. Vaccination rates for home-schooled or private school students may be much lower.^12,13

Kevin Winthrop, MD, MPH, a pro­fessor of public health and infectious diseases at Oregon Health and Science University, Portland, notes the true numbers of cases are probably much higher than the officially confirmed cases would indicate because many patients may not come to medical attention.

Dr. Winthrop

“If measles gets into a pool of people where there’s little vaccination,” says Dr. Winthrop, “it’ll spread like wildfire.”

In the webinar, Dr. Salmon expressed concern that if we were to reach a point of widespread community transmission it would be very hard to eliminate the disease again. “We could see substantial morbidity and mortality,” he said. “So I’m quite worried.”

Management Considerations

With respect to prevention and management of measles infections, many of the recommendations for the general population also apply to people with rheumatologic diseases. One important caveat is that certain rheumatology patients should not receive live vaccines such as the MMR, out of concern for vaccine-associated illness.

Assess Immunity & Vaccination Status

Dr. Winthrop notes that in light of media coverage of measles, many rheuma­tology patients are concerned about their immunocompromised status. They’re asking whether their vaccinations are up to date and wondering if they may need revaccination.

“If someone hasn’t been vaccinated before, now is a good opportunity to do that,” says Dr. Winthrop. However, he notes, in most circumstances, practitioners can reassure previously vaccinated patients that neither re-vaccination nor retesting immunity via IgG titers is necessary. “If a patient [were at] high risk for exposure, like a healthcare worker in the heart of the outbreak in Texas, I would certainly check titers and make sure they’re adequate, and if not, give them a booster,” he says.

Dr. Calabrese does not routinely recom­mend IgG titers to check for immunity status in patients with documented, appropriate MMR vaccination because the test may underestimate the level of immunity actually present. “The vast majority of our patients are protected against measles, either [they] had measles as a child or [were] appropriately vaccinated. It just comes down to figuring out their vaccine and natural immunity history,” she says. “But I would caution patients not to travel to areas of active outbreaks.”

Our current measles vaccine is effective with durable protection; however, natural measles infection provides even better protection than vaccination, even many decades later, explains Dr. Calabrese. Patients born before 1957, when the measles virus was actively circulating, are generally considered to have lifelong immunity.

The large majority of people who received at least one measles vaccination should be sufficiently protected. However, the ACIP recommends re-vaccination for the small percentage of people who received an inactive version of the vaccine from 1963 to ’67, who never received an additional live vaccine or whose vaccination type during this time frame is uncertain.¹⁴

If a patient’s vaccination status is unclear, practitioners may consider drawing an IgG measles titer to check immunity. If negative, the measles vaccine is recommended. The measles vaccine is also recommended for patients who’ve had a known measles exposure (if born after 1957 and without at least one previous vaccination with live measles virus vaccine). Giving the vaccine within 72 hours can help prevent infection or lessen its severity.¹⁴

The situation can be more complicated for rheumatology patients taking certain therapies. Per recommendations from the Infectious Diseases Society of America (IDSA) and the ACR, live vaccines, such as the measles vaccine, are not recommended for people taking biologic medications. For these patients, live vaccinations should be deferred. Or, if deemed necessary, such medications should be held for several weeks prior to and post vaccination, with careful shared decision making based on specific patient risks of disease flare versus infection.¹⁵

However, patients on less than 20 mg equivalent prednisone or low-dose, non-biologic DMARDs (e.g., less than 0.4 mg/kg methotrexate per week) can safely receive live virus vaccines.^15,16

No antiviral therapies are available for measles, but for patients on these medications, IVIG given within six days of exposure can provide some limited protection, Dr. Calabrese notes. In case of a confirmed measles infection, immunosuppressant medications should be held, she adds.

Current recommendations do not speak to the need to check IgG levels for evidence of immunity before starting a biologic, which would delay treatment and be unnecessary for most patients. However, providers practicing in areas with more active outbreaks may need to be more proactive in assessing immunization (and titers, if immunization status is unknown) before starting a biologic therapy.

Vaccine Hesitancy

High vaccine uptake is needed to provide sufficient community herd immunity to protect immunocompromised people, infants and the low percentage of people who failed to respond to their measles vaccinations. But for complex reasons, vaccine hesitancy may be on the rise, partly in response to vaccine rollout during the COVID-19 pandemic.

“There has been a ton of cultural and political backlash against vaccinations, particularly mRNA vaccinations,” says Dr. Winthrop, “and there’s a lot of skepticism out there.”

Rates of MMR vaccination have decreased across the U.S. compared with six years ago, with some states showing particularly dramatic falls. Although some of this can be attributed to missed regular pediatric appointments due to the pandemic, rates have not fully bounced back in most states.¹⁰

Since the pandemic, some states have made efforts to loosen existing laws, allowing for more non-medical exemptions from vaccination requirements in public school children, Dr. Salmon noted. Historically, states with easy vaccine exemptions have been associated with higher rates of exemptions and higher rates of infections, such as pertussis, compared with states with more restrictive criteria.

“I think a lot of people have lost faith in vaccine recommendations,” says Dr. Calabrese. People may reasonably argue about the true need for seasonal COVID-19 vaccines. “But for measles, we have irrefutable data that infection can cause serious complications, and we have this vaccine that is almost 100% effective in preventing measles and incredibly safe,” she adds.

Learn More

For recommendations on MMR, influenza, pneumo­coccal, zoster and other vaccines for adults and children with rheumatic and musculoskeletal diseases, see the ACR’s 2022 guideline.¹⁵

Ruth Jessen Hickman, MD, a graduate of the Indiana University School of Medicine, is a medical and science writer in Bloomington, Ind.

References

1. Paules CI, Marston HD, Fauci AS. Measles in 2019—Going backward. N Engl J Med. 2019 Jun 6;380(23):2185–2187.
2. Moss WJ, Griffin DE. What’s going on with measles? J Virol. 2024 Aug 20;98(8):e0075824.
3. Boner AL, Valletta EA, Bellanti JA. Improvement of atopic dermatitis following natural measles virus infection. Four case reports. Ann Allergy. 1985 Oct;55(4):605–608.
4. Simpanen E, van Essen R, Isomäki H. Remission of juvenile rheumatoid arthritis (Still’s disease) after measles. Lancet. 1977 Nov 5;2(8045):987–988.
5. Lin CY, Hsu HC. Histopathological and immunological studies in spontaneous remission of nephrotic syndrome after intercurrent measles infection. Nephron. 1986;42(2):110–115.
6. Mina MJ, Metcalf CJE, de Swart RL, et al. Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality. Science. 2015 May 8; 348(6235):694–699.
7. Mina MJ, Kula T, Leng Y, et al. Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens. Science. 2019 Nov 1;366(6465):599–606.
8. Vaccines & Immunizations: Routine measles, mumps, and rubella vaccinations. Centers for Disease Control and Prevention. https://tinyurl.com/339umhyc.
9. Measles (Rubeola): History of measles. Centers for Disease Control and Prevention. 2024 May 9. https://www.cdc.gov/measles/about/history.html.
10. Johns Hopkins Bloomberg School of Health. Measles in America: Causes, risks, and responses—World Immunization Week webinar. 2025 April 30. https://www.youtube.com/watch?v=Tbwfz6iUqe4.
11. Global measles vaccination: Global measles outbreaks. Centers for Disease Control and Prevention. 2025 Jul 9. https://tinyurl.com/yk8tv8cr.
12. Measles (Rubeola): Measles cases and outbreaks. Centers for Disease Control and Prevention. 2025 July 9. https://tinyurl.com/m3xpywzp.
13. Shastri D, Nogueras C. Mennonites, West Texans at center of measles outbreak choose medical freedom over vaccine mandates. PBS News. 2025 March 4. https://tinyurl.com/yau97v3x.
14. McLean HQ, Fiebelkorn AP, Temte JL, et al. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: Summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013 Jun 14;62(RR-04):1–34.
15. Bass AR, Chakravarty E, Akl EA, et al. 2022 American College of Rheumatology Guideline for Vaccinations in Patients with Rheumatic and Musculoskeletal Diseases. Arthritis Care Res (Hoboken). 2023 Mar;75(3):449–464.
16. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host. Clin Infect Dis. 2014 Feb;58(3):309–318.