Shingles is a condition caused by the virus that causes chickenpox that lies dormant in the body and reactivates when the immune system is compromised. It manifests itself as a painful vesicular rash, usually on the chest, abdomen, or face, and can be extremely painful and lead to serious complications, including postherpetic neuralgia. Shingles is especially dangerous for people with weakened immune systems.

Patients who use immunomodulatory drugs, including those with rheumatoid arthritis, are at a significantly higher risk of developing shingles than the general population. For this reason, experts strongly recommend immunocompromised people get the shingles vaccine. The U.S. Advisory Committee on Immunization, the American College of Rheumatology, and the Korean Society of Infectious Diseases recommend vaccination with the recombinant shingles vaccines for adults 19 and older receiving immunosuppressive therapy.

The recombinant shingles vaccine Shingrix introduced in Korea is expected to provide significant protection for immunocompromised individuals, including rheumatoid arthritis patients. Shingrix produces a strong and long-lasting immune response to prevent shingles in adults 50 and older and immunocompromised individuals 18 years and older. In clinical trials, it has demonstrated a prevention effect of more than 90 percent and is expected to play an important role in protecting against shingles and its serious complications.

Korea Biomedical Review spoke with Professor Hong Seung-jae of the Department of Rheumatology at Kyung Hee University Medical Center to learn about the need to prevent shingles in immunocompromised individuals, including rheumatologic patients, and the expected effects of the introduction of the recombinant shingles vaccine in Korea.

Question: What infectious diseases are common among people with rheumatic diseases?

Answer: Immunocompromised individuals, such as those with rheumatic diseases, are vulnerable to most infectious diseases, including shingles, influenza, pneumococcus, hepatitis A and B, and Covid-19, and should be prioritized for vaccination. In particular, people with rheumatoid arthritis are at twice the risk of being hospitalized due to viral, bacterial, or other infections and have higher mortality rates for common infections so they need to be vaccinated sooner rather than later. In the case of shingles, people with rheumatoid arthritis are 2.8 times more likely to develop the disease than the general population, and people with lupus are 3.5 times more likely.

The risk of infection and the need for vaccination in immunocompromised individuals has been discussed during the Covid-19 pandemic. In Korea, older adults were prioritized for vaccination based on their age. The Korean College of Rheumatology also issued health guidelines and vaccination guidelines for people with rheumatic diseases and strongly requested that people with rheumatic diseases be prioritized for vaccination, and they were duly prioritized.

Q: You said that the risk of infection is numerically double in people with rheumatologic conditions. What are the additional effects of infectious diseases on people with rheumatic diseases?

A: People with rheumatic diseases have lung disease, which makes them more prone to pneumonia, and studies have shown that rheumatoid arthritis patients with shingles had 3.4 and 3.7 times more hospitalizations and emergency room visits than those without shingles.

Q: So how aware are people with rheumatic conditions of the need to get vaccinated against infectious diseases?

A: In the past, awareness was similar to that recommended for the general population: influenza vaccine in the fall, pneumococcal vaccine for older adults, etc. The general public and patients have become more aware of the concept and importance of vaccines, especially those with underlying medical conditions. In the case of the shingles vaccine, the recent increase in outbreaks has increased awareness of the need for vaccination.

Q: To what extent is vaccination recommended in healthcare settings for people with rheumatic diseases?

A: Currently, vaccination is strongly recommended for people with rheumatic diseases. In the case of the shingles vaccine, doctors were not very interested in it in the past. Still, the emergence of various rheumatologic drugs, such as TNF inhibitors, biologics, and JAK inhibitors, has changed their perception.

In particular, in 2010, a sharp increase in the number of patients with shingles as a clinical side effect of the JAK inhibitor Xeljanz (tofacitinib) led to the discovery that the incidence of shingles increases when patients with rheumatic diseases use JAK inhibitors and targeted therapies. That confirmed the vulnerability of patients with rheumatic diseases to shingles and recognized the need for shingles prevention. Therefore, shingles vaccination is recommended before taking JAK inhibitors. Vaccination before starting treatment can significantly reduce the risk of developing shingles.

In addition, in the past, only live shingles vaccine was available in Korea, resulting in a low vaccination rate. Immunocompromised patients, especially those with rheumatic diseases, were worried and burdened by the live vaccine because they use immunomodulatory drugs. Fortunately, the introduction of the genetically recombinant vaccine, Shingrix, at the same time that interest in shingles vaccination among people with rheumatic diseases began to increase, opened the door for people with rheumatic diseases and other immunocompromised individuals to receive shingles vaccine. Currently, the inactivated vaccine is also recommended during treatment for rheumatic diseases.

Q: What are the benefits of inactivated vaccines compared to existing attenuated vaccines for people with rheumatologic conditions?

A: People with rheumatic diseases have had two concerns about vaccination. The first is that vaccination while immunocompromised due to an underlying medical condition could make them sicker, and the second is that vaccination in an immunosuppressed state might not be effective due to immunosuppressive medications.

The inactivated (or killed) vaccine contains the shell of the strain, so there is no risk of getting sick. In addition, since the vaccine is administered twice, the effectiveness of immunity is enhanced, so the prevention effect is certain. You might think that two doses are less convenient. However, for immunocompromised people, including rheumatoid patients, the number of doses is not a problem because they constantly visit the doctor. The intervals between doses can be scheduled around their outpatient appointments, with the next dose given two to three months later.

Since attenuated (or live) vaccines cannot be administered to immunocompromised people, they need to be vaccinated with the inactivated vaccine Shingrix to prevent shingles. Therefore, immunocompromised people and medical staff in Korea have been waiting for the release of the inactivated Shingrix. It consists of a formulation containing antigens and immune-boosting agents so that a high immune response is maintained for a long time through two doses. The live vaccine can still cause an outbreak of shingles after vaccination but it has a milder effect on symptoms.

Since the U.S. Food and Drug Administration (FDA) approved Shingrix for immunocompromised individuals in 2021, clinical data on rheumatology patients have been published. At the American College of Rheumatology (ACR) meeting in June, various data on the immunogenicity and effectiveness of Shingrix were presented, and the clinical evidence for the need for Shingrix continues to accumulate.

Q: Are there certain groups of patients with rheumatic diseases, including age groups, for whom shingles vaccination is more recommended?

A: Patients with rheumatic conditions, such as rheumatoid arthritis, lupus, and polymyalgia rheumatica, who visit a rheumatology office are considered immunocompromised and recommended for vaccination, even if they are not older adults. While rheumatoid arthritis is most commonly seen in women in their 40s, 50s, and older, close to the recommended age for the shingles vaccine, ankylosing spondylitis is more common in men in their 20s and 30s, and lupus is more common in women in their teens and 20s. Therefore, immunocompromised individuals should be vaccinated regardless of age.

Q: What is the most common complication of shingles in people with rheumatic diseases?

A: It’s called postherpetic neuralgia. As the name suggests, the pain is severe. It’s a knife-like pain that follows the ganglion, and the later it’s treated, the more likely it is that postherpetic neuralgia will occur. Some patients may only suffer from blisters, while others suffer severe sequelae. Symptoms and complications vary depending on the immune system.

Q: Do you have any memorable cases of rheumatologic patients with herpes zoster that you have encountered in your practice?

A: A patient who developed herpes zoster over her eyes five years ago and still complains of pain and paresthesia during outpatient visits. She regrets not having been vaccinated beforehand. Although shingles does not cause facial paralysis, it can leave serious sequelae, such as eye disease and postherpetic neuralgia if it occurs around the eyes. While it varies from person to person, postherpetic neuralgia can cause pain along the ganglia that can last for more than a year. Based on this patient's story, the value of shingles vaccination for people with rheumatic diseases is very high. In the past, shingles has occurred after vaccination with the live vaccine alone, but no patients have developed shingles after receiving Shingrix.

Q: Are there any precautions for people with rheumatic diseases to take when getting the shingles vaccine?

A: As with any vaccine, it's best to avoid it if you have a cold or are not feeling well. Because the vaccine is perceived as foreign, it's best to get vaccinated when you're feeling well, i.e., when your underlying condition, such as rheumatoid arthritis or lupus, is well controlled and in remission. It is also recommended to reduce activity and rest after vaccination.

There are concerns about pain, but it should be similar to the pain experienced during the COVID-19 vaccine. People with rheumatic diseases often take painkillers or steroid medications for their underlying condition, so they tend to experience fewer pain-related side effects. If you are diagnosed with a rheumatic disease, get vaccinated as soon as possible.

Q: If you take immunomodulators, you may need to adjust the interval between vaccinations.

A: For the quadrivalent vaccine, it doesn't matter; it can be given before or during immunization. During the Covid-19 pandemic, there were some suggestions to take a few days off of immunomodulators to increase vaccine effectiveness but this is no longer recommended.

Q: What percentage of people with rheumatic diseases follow their healthcare provider's recommendation to get the shingles vaccine? Some patients may have problems with the cost.

A: Immunocompromised people believe that the cost-effectiveness of the vaccine is worth it because of the severe sequelae of a shingles outbreak. Since the launch of Shingrix, healthcare providers are actively recommending it, and patients are more likely to get vaccinated if their healthcare provider recommends it.

Many people with rheumatic diseases should get the shingles vaccine, so if the price is too high for them to decide to get it on their own, encouraging them to bring their children with them as chaperones will help them to get it. Buying healthy food for your parents is great but giving them the gift of vaccination is even better. Studies have shown that Shingrix maintains a high level of protection (89 percent) for over 10 years, and simulations show that the effectiveness is predicted to wear off after 50 years.

The most effective way to increase shingles vaccination rates is to include it in the government's National Immunization Program (NIP). However, the government reportedly considers supporting vaccination for people 75 and older and those with rare and incurable diseases, due to financial constraints. These people are in critical need of shingles vaccination and are not in large numbers. Since shingles outbreaks are covered by health insurance for treatment and hospitalization, supporting vaccination could help ease the burden on healthcare finances.

The Covid-19 vaccine was made available for free in response to the pandemic. While the shingles vaccine is not expected to cover the entire population like the Covid-19 vaccine, we believe that people at risk of shingles, such as the elderly, people with rare diseases, and people with special needs, should be supported. Managing the cost of care for seriously ill patients and those with rare diseases is important for health insurance.

Q: The American College of Rheumatology recommends that people with rheumatic diseases (excluding those under 18) taking immunosuppressive drugs be vaccinated with a recombinant vaccine starting in 2022. We wonder if the Korean College of Rheumatology is also preparing for this.

A: The Korean College of Rheumatology also recognizes the need to update its guidelines. It plans to update and include it in the “Guidelines for Vaccination in Korean Autoimmune Rheumatic Diseases” published in 2020 with the Korean Society for Infectious Diseases. It is currently being prepared by the guideline committee.

Q: Any message you want to share with healthcare providers or patients?

A: Prevention is more important than cure. People practice good diet and exercise to prevent illness. While diet and exercise are important, vaccines are the most effective way to prevent infectious diseases. We need to eliminate vague misconceptions about vaccines and be proactive about getting vaccinated. Vaccination is crucial for people with underlying medical conditions or immunocompromised individuals, such as those with rheumatic diseases.

For them, an outbreak of shingles can greatly affect the effectiveness of their treatment and quality of life. Therefore, healthcare providers should not only explain rheumatic diseases and prescribe medications but also explain the vaccine and actively encourage vaccination. In addition, social vaccination campaigns should be sustained, and the media should pay continuous attention to this issue.