What is Cachexia?

People with rheumatoid arthritis (RA) often have to deal with other conditions related to their arthritis. One of the more serious of these is cachexia, which causes a loss of muscle mass and strength and can diminish people’s ability to function in their everyday lives. Cachexia that is brought on by RA is known as rheumatoid cachexia. Below you will find answers to some common questions about rheumatoid cachexia.

What is RA?

RA is a chronic condition in which the immune system attacks the tissue that lines the joints, causing inflammation, swelling, and pain. RA typically affects several joints on both sides of the body, most commonly the wrists, fingers, knees, feet, and ankles. The joint inflammation may cause joint damage, resulting in chronic pain, loss of function, and disability if left unchecked. RA is not always limited to the joints and can affect many other parts of the body, including the heart, lungs, skin, kidneys, nerves, gastrointestinal tract, and muscles. In addition, people with RA often experience fatigue and weakness that significantly affect their quality of life.

What is rheumatoid cachexia?

Cachexia is derived from the Greek word kachexia, which means “bad condition.” People with cachexia have a decrease in muscle mass that reduces their muscle strength. The loss of muscle is often accompanied by an increase in body fat that may result in an overall increase in body weight, a condition known as cachectic obesity.

Cachexia is often seen in people with chronic conditions such as cancer, acquired immunodeficiency syndrome (AIDS), tuberculosis, heart failure, and chronic lung disease. Rheumatoid cachexia was first described more than a century ago. The extent of muscle loss that constitutes cachexia is still debated, and estimates of the percentage of people with RA who have cachexia range from 10% to 67%, depending on the criteria used to make the diagnosis. What seems clear, however, is that most people with RA have some muscle loss as a result of their condition.

Why does cachexia occur in RA?

RA is an autoimmune inflammatory condition. This means that in people with RA, and for reasons still not well understood, the immune system produces substances that attack the body’s own cells, causing inflammation. Some of the substances in the blood responsible for the inflammation are called cytokines, and of these, tumor necrosis factor–alpha (TNF-alpha) seems to play a particularly important role in RA.

In rheumatoid cachexia, the body stops building muscle protein while increasing the breakdown of muscle. This process of muscle breakdown is called catabolism and is thought to be caused by cytokines such as TNF-alpha. In fact, TNF-alpha was initially called “cachectin” because of its suspected role in cachexia. The central role TNF-alpha is believed to play in both RA and cachexia may account for the connection between the conditions.

Another reason people with RA are at high risk for cachexia is that the pain and stiffness of RA can limit physical activity. Inactivity can cause people to lose muscle mass and gain fat, thus perpetuating a cycle in which muscle loss and an inactive lifestyle reinforce each other.

What are the effects of cachexia?

Although cachexia is often overlooked by doctors, it can have a significant impact on people with RA. Muscle weakness can limit people’s ability to go about their daily activities. In addition, rheumatoid cachexia may adversely affect the cells in the immune system, making people more susceptible to infections. Cachexia may also contribute to the loss of bone mass, which can lead to osteoporosis, a condition in which bones are porous and easily broken. Finally, the changes that characterize cachexia — loss of muscle mass and an increase in fat — raise the risk of developing heart disease, high blood pressure, and high cholesterol. If severe, cachexia can decrease life expectancy.

Who is at risk?

People with more severe RA are more likely to develop cachexia. This may be because people with severe RA have more cytokines circulating in their blood, and these cytokines are thought to be the cause of rheumatoid cachexia. As noted earlier, physical inactivity, which can be brought on by RA, also predisposes people to cachexia.

How is cachexia treated?

Because cachexia is more common in people with severe RA, controlling RA is key to preventing or treating rheumatoid cachexia. (We’ll say more about this below.) The only other treatment that has been shown to improve rheumatoid cachexia is exercise. Exercise not only increases muscle mass and strength, improving overall body composition, but it can also help to relieve pain and fatigue in people with RA. It is important for people with RA not to exercise for longer or at a greater intensity than they can safely tolerate. This is especially important during an RA flare, when symptoms are more severe than usual. People with very active symptoms should limit physical activity to gentle exercises and stretching. Once the RA is well controlled with medicine, a combination of aerobic exercise and resistance training can improve cardiovascular health and increase muscle mass. Appropriate exercise that gradually increases in intensity does not damage joints in people with RA. However, people with RA should consult with a doctor, physical therapist, or other health professional before beginning an exercise program.

What is the role of diet?

Dietary therapy or nutritional supplementation has not been shown to be effective in restoring muscle mass in people with rheumatoid cachexia. As discussed earlier, the bodies of people with cachexia are unable to build muscle protein, even when they are getting enough protein in their diets. As a result, eating more calories is not an effective way to increase muscle mass. In fact, people with RA often burn fewer calories than people without RA because they get less physical activity. So if a person with rheumatoid cachexia simply takes in more calories, the result may be an increase in fat — especially if the person is taking corticosteroids, which can cause fat cells to accumulate. A diet high in protein but low in calories and fat may help to preserve muscle mass. If you are considering making dietary changes, it’s best to discuss them with a dietitian to make sure you’re getting the nutrients you need and the right amount of calories to maintain a healthy weight.

Do medicines help?

Absolutely. Rheumatoid cachexia reflects the activity of RA; that is, the people with the most severe cachexia usually have the most active RA. Controlling RA by taking medicines can therefore prevent, control, or reduce cachexia.

Because TNF-alpha is thought to play a major role in rheumatoid cachexia, medicines that block this substance have been studied as treatments for cachexia. These drugs, known as anti-TNF drugs or TNF-blockers, include etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), and golimumab (Simponi). Research has shown that in some people with rheumatoid cachexia, anti-TNF drugs help to improve muscle mass. Bone mass may also be increased in people treated with these medicines. More research is needed to confirm the effect of anti-TNF drugs, and at present, there is no standard therapy for rheumatoid cachexia. But the results of studies done to date suggest that drug treatment, together with exercise, can help people with rheumatoid cachexia increase their muscle strength and maintain their ability to function and their quality of life.

Richard S. Panush is Professor and Chair of the Department of Medicine at Saint Barnabas Medical Center in Livingston, New Jersey. Samir D. Bhangle and Deepali Sen are senior assistant residents, Rosy Rajbhandary is a junior assistant resident, and Azadeh S. Khezri is an intern, all at the St. Barnabus Medical Center in Livingston, New Jersey.

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