Tuberculosis and Arthritis

The possibility of developing tuberculosis (TB) comes up early and often — 37 times in the package insert for etanercept (Enbrel), for example — when you read about the biologic drugs used to treat rheumatoid arthritis and other kinds of inflammatory arthritis. That’s scary, and a concern that deserves the attention of you and your doctors, but the risk of tuberculosis may be smaller and more manageable than you realize.

Here’s what you need to know about tuberculosis when you have inflammatory arthritis.

1. What is tuberculosis, anyway?

TB is a bacterial infection that mainly affects the lungs. The bacteria, Mycobacterium tuberculosis, is passed from person to person through the air. According to the American Lung Association, tuberculosis is not that easy to catch: Usually you have to be in close proximity with someone who has it over an extended period of time. Even if you do become infected, as long as your immune system keeps the bacteria in check you won’t get sick and can’t pass the disease onto anyone else. This is a condition called latent TB.

2. How common is tuberculosis?

According to the World Health Organization, TB ranks in the top 10 causes of death globally.

“Tuberculosis is a very important public health and clinical issue in many parts of the world. In the U.S. it’s less common, but TB can occur in some groups of individuals at risk, including people previously exposed and/or who are on immunosuppressive medications,” says Patricio Escalante, MD, associate professor of medicine in the pulmonology and critical care division of the Mayo Clinic.

In fact, active TB was reported in all 50 states in 2017, and as many as 13 million people in the United States have been exposed and often do not know that they have latent TB infection. Latent TB infection can become activated (growing in the body and causing illness) under the right circumstances, such as when you start taking an immune-suppressing drug to treat inflammatory arthritis.

This is why it’s important to test for the presence of TB before you begin taking immune-suppressing drugs such as biologics.

3. How will my doctor assess whether I have latent TB?

Because of large geographic differences in the likelihood of your having tuberculosis, your doctor will be more concerned you may have picked up the TB germ if you have lived or travelled extensively in a region with rates of TB.

“The World Health Organization website will tell you what the high-risk countries are. Outside of western Europe, Australia, New Zealand and North America, most countries have moderate or high risk,” says Kevin Winthrop, MD, professor of infectious diseases and public health at the Oregon Health & Sciences University in Portland.

In the United States, you’re more likely to have been exposed to TB if you have lived in a large-group setting such as a prison or homeless shelter, or if you have worked in a hospital or in one of those settings.

4. Should I be screened for TB?

It’s standard to test you for a tuberculosis infection before you start a biologic medication that suppresses your immune system. If you’re found to be infected, your doctor will treat you for latent TB before starting the biologic drug in order to prevent a latent infection from becoming active.

“TB is rare, but if you have risk factors that’s important for your doctor to know, and you need to be screened if you are going on drugs that raise your risk of tuberculosis. TB is totally treatable and curable. If you develop active TB, the problem is you can give it to other people, so if it’s treated before it becomes active you prevent a lot of potential problems,” says Dr. Winthrop.

Although biologics get most of the publicity when it comes to increasing TB risk, you may also be tested prior to starting corticosteroids, especially if taken at high doses. Other doctors test even earlier.

“To be honest, whenever you have patients with autoimmune disease who are likely to go on an immune-suppressing drug, go ahead and screen right away,” suggests Dr. Winthrop.

Simply having uncontrolled RA can also raise your TB risk, he says. “If you’ve been exposed to TB in the past, you are definitely at higher risk to activate that TB if you have high RA disease activity. Treating your RA and putting you into low disease activity lowers your risk because your body’s immune system works better,” Dr. Winthrop says.

5. What tests will I get for TB?

You may be most familiar with the tuberculin skin test, in which a health care provider injects a small amount of fluid (called tuberculin) into the skin on the lower part of the arm and then you return 48 to 72 hours later to see if your arm developed a reaction.

But in this case, you’re actually more likely to be given one of two blood tests called interferon gamma release assays.

That’s not just for convenience – a skin test requires a second appointment to check your response – but because skin testing has more false positives. In a 2018 study on almost 400 patients from Spain, Dr. Escalante and Spanish colleagues found that arthritis patients who were taking the disease-modifying drug methotrexate were more likely to have positive tuberculin skin test (usually false positive) readings than patients on other medications.

6. What if my TB screening test is positive?

People at risk for tuberculosis with positive test results should be carefully evaluated with chest X-rays by a medical professional familiar with TB infections, such as an infectious disease specialist or a pulmonologist.

“Anybody with a positive test needs a chest X-ray. There are probably more false positives with skin tests but they can happen with any test. If a patient has zero risk factors, then a positive test is often a false positive. If there are risk factors for prior TB exposure, however, the chance that a positive test is a real or true positive is much, much higher,” says Winthrop.

There can also be false negatives on the tests.

“If someone is already on immune-suppressing drugs, or if their underlying disease is quite active and they are immune suppressed, they’re more likely to have false negative tests on skin or blood tests. The assessment boils down to the risk factors: If someone with a negative test is heavily immune suppressed and from the Philippines, I would consider them much more likely to be infected than someone from Oregon or Idaho, for example [where TB is very rare]. Whenever I don’t trust the result, whether positive or negative, I repeat the test,” Dr. Winthrop says.

If you are found to have latent TB, the CDC suggests using one of three antibiotic drug regimens. The shortest and most convenient, a combination of isoniazid and rifapentine, can be completed in 12 weekly doses.

7. Will I be checked for TB while I’m taking a biologic?

If you test negative for TB prior to starting a biologic, you don’t really need to be tested during treatment unless you have risk factors for a new TB exposure. However, some insurance plans might require you to be re-tested when starting a new biologic medication. During treatment, let your physician know if you develop any symptoms that might turn out to be active TB.

“If you experience night sweats, weight loss, fever, or just feel like you are [unwell] for several weeks, that’s suspicious for some bad infection [which might be TB] or cancer or autoimmune disease. You also need to be evaluated if you have a cough that lasts more than a month,” Winthrop says.

If you develop active TB, it can be treated using several different drug regimens. “You will have to stop your immunosuppressant for a while, until you have been treated and made progress against your TB,” says Dr. Winthrop.

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