What’s the Difference Between Rheumatoid Arthritis and Lupus?

If you’re experiencing joint pain that comes with swelling, fatigue, fevers, and other concerning symptoms, it could be a sign that you are dealing with an autoimmune disease. But which one? Both rheumatoid arthritis (RA) and lupus (systemic lupus erythematosus, or SLE) have overlapping symptoms like these.

“RA and lupus can feel very similar because both cause arthritis,” says Donald Thomas, M.D., a rheumatologist at Arthritis and Pain Associates of Prince Georges County, a clinical associate professor of medicine at Walter Reed National Military Medical Center in Bethesda, MD, and the author of The Lupus Encyclopedia. “People with RA will 100% develop an inflammatory arthritis and 90% of those with lupus will develop inflammatory arthritis.”

But having the right diagnosis is key, since each condition requires a different approach to care, and getting to the root cause can play out like a game of medical Clue. We’re unpacking the warning signs of rheumatoid arthritis and lupus, including why they feel so similar and how to tell the two apart, plus the best treatment options for each.

“RA is a systemic autoimmune disease,” says Dr. Thomas. “Instead of the immune system recognizing foreign entities and protecting the body, it has difficulty telling the difference between the body’s own cells and tissues versus foreign invaders. As a result, the immune system attacks the person’s own body.” More specifically, immune cells mistakenly attack the synovial membrane, which is the layer of tissue that lines your joints.

RA causes a host of issues, but people will first notice joint pain, swelling, and a loss of mobility. These symptoms are usually symmetrical (meaning they occur in the same joints on both sides of the body) and will often start in the hands or feet and then may spread to larger joints like the knees, ankles, elbows, hips, shoulders, or neck.

RA affects about 1% of the population and is more common in women than men, says Katherine Yates, M.D., a rheumatologist at The Ohio State University Wexler Medical Center in Columbus, OH. In fact, about three times as many women as men develop rheumatoid arthritis. “RA has what we call bimodal distribution in terms of age [two age-related peaks]. It commonly pops up in people between their 20s to 30s, as well as those in their 60s,” she adds.

Lupus is also a systemic autoimmune disease—and that where things can get confusing. Lupus has many of the same textbook descriptions as RA, but this time your body’s immune system is attacking a variety of tissues and organs, including your joints, skin, kidneys, blood cells, brain, heart, and lungs.

The Lupus Foundation of America estimates that 1.5 million Americans have lupus—and like RA and other autoimmune diseases, it is more prevalent in women, especially those in their child-bearing years, says Dr. Yates. According to the Lupus Foundation of America, nine out of 10 people with lupus are women.

Lupus also disproportionately affects people of color: It is two to three times more prevalent among African American, Hispanic/Latina, Asian American, Native American, Alaska Native, Native Hawaiian, and other Pacific Islander women than white women, according to the Lupus Foundation of America. For Black and Hispanic women, lupus is one of the top 10 causes of death, per research published in Annals of Internal Medicine.

RA and lupus both cause arthritis, which means their most common similarity is the way they affect the joints.

“Both conditions attack the wrists, knuckles, middle joints of the fingers, elbows, knees, and the front joints of the feet,” says Dr. Thomas. “Since both are inflammatory, they infiltrate the joint lining with white blood cells. This causes a rubbery swelling around the joint.” This swelling can cause stiffness, especially in the morning. In both RA and lupus, these symptoms can occur symmetrically, meaning they can affect the same joints on both sides of the body.

According to Dr. Thomas, other overlapping symptoms include:

• Fatigue

• Fever

• Depression

• Loss of appetite

• Weight loss

Although they are both autoimmune diseases that cause joint pain, RA and lupus do have other symptoms and presentations that set them apart.

How RA Differs From Lupus

One of the biggest ways RA is different from lupus is that the most common symptoms first appear in the joints, especially in the early stages. These include:

• Joints that are red, hot, and swollen

• Pain initially in the small joints

• Stiffness, especially in the morning, that lasts 30 minutes or longer

In addition, with RA there can be irreversible symptoms, adds Dr. Thomas. “For example, with RA a finger can have what we call ‘swan neck deformity.’ This is when the end joint will be flexed and the middle joint will be extended.” While both RA and lupus can cause this condition, with RA it won’t go away, while with lupus it can go away. That’s because with RA the deformity is due to erosions (bone damage), while in lupus it is mostly due to laxity in the joint which can be put back into their original position, according to the Hospital for Special Surgery.

How Lupus Differs From RA

While RA is closely linked to joints, lupus is more systemic, often affecting other parts of the body, says Dr. Yates. It’s this trickle-down impact on other systems and organs in the body that strongly differentiates lupus from RA.

Other symptoms of lupus can include:

• Chest pain

• Headaches

• Joint deformities like Jaccoud’s arthropathy, which can be reversed

• Rashes (especially the malar rash or butterfly rash that appears on the face)

• Sensitivity to light

• Swelling in the hands, feet, or around the eyes

“Lupus can lead to more serious issues with other internal organs,” says Dr. Yates. “Many people with lupus experience pleuritic chest pain, where there’s inflammation that lines the lungs and the heart and taking big deep breaths can be painful.”

About 40% of people with lupus develop lupus nephritis, adds Dr. Thomas. “This is when lupus attacks the kidneys.” It can potentially lead to kidney failure.

RA and lupus can appear to be similar in the beginning stages, especially when inflammatory arthritis is the primary symptom. But your health care team can help make a more definitive diagnosis.

Classification Criteria for RA

Your doctor will consider a few factors when it comes to diagnosing rheumatoid arthritis.

• Physical exam: Your doctor may look for a rubbery-type of swelling around the joints, especially the hands and feet.

• Imaging tests like X-rays: You may see large erosions in the joints, where the inflammation has “eaten away” at the bones, says Dr. Thomas.

• Blood tests: “People with RA are more likely to be positive for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (CCP) antibody,” says Dr. Thomas.

Classification Criteria for Lupus

Lupus can be more complicated to diagnose, as there is no single test for the condition, per the Lupus Foundation of America, and it can take months or even years to confirm the diagnosis.

Some factors that doctors use to make a diagnosis of lupus include:

• Medical history: Because there’s a large genetic component to lupus, your doctor will likely ask if someone else in your family has the condition, along with questions about your symptoms.

• Blood tests: These may include a test that looks for antinuclear antibodies (ANA), which are antibodies that attack healthy cells in the immune system. ANAs that indicate lupus include anti-double stranded DNA (dsDNA), anti-ribonucleoprotein (RNP), or anti-Smith (anti-Sm). “There are also some classic changes in blood work, like lower blood cell counts and lower platelet counts,” says Dr. Yates.

• Physical exam: There some distinct clinical manifestations of lupus that are important to take note of, says Dr. Thomas. These can include discoid lupus (where lupus attacks the skin and causes scarring, round rashes) and malar rash, or butterfly rash (a red rash over the nose and cheeks that looks like a butterfly after exposure to the sun).

The good news is that both RA and lupus can be managed with the right medical approach. “There are a lot of treatments for RA and lupus, making it easy to live in remission or low disease activity because these treatments are very good,” says Dr. Thomas. “The only way to treat these autoimmune diseases is to calm down the immune system to keep it from attacking the joints with immunomodulatory drugs.” Some of the same medications may be used to treat both RA and lupus.

Treating Rheumatoid Arthritis

Most patients who are first diagnosed with RA will take a disease-modifying anti-rheumatic drug (DMARD), such as methotrexate, as a first-line treatment. If that is not effective, you may go on to take an immunosuppressant, or biologic, as part of your treatment plan.

Some of the most common drugs to treat RA include:

Conventional DMARDs:

• Arava (sulfasalazine and leflunomide)

• Otrexup, Rasuvo, Rheumatrex, and Trexall (methotrexate)

• Plaquenil (antimalarials)
  

Biologics:

• Cimzia (certolizumab pegol)

• Enbrel (etanercept)

• Humira (adalimumab)

• Kineret (anakinra)

• Orencia (abatacept)

• Remicade (infliximab)

• Rituxan (rituximab)

• Simponi (golimumab)

In addition, Janus kinase (JAK) inhibitors are a newer class of drug your doctor may prescribe for rheumatoid arthritis. A recent study in Arthritis & Rheumatology found JAK inhibitors to be more effective at pain management than more traditional DMARDs in people living with RA. JAK inhibitors include:

• Olumiant (baricitinib)

• Rinvoq (upadacitinib)

• Xeljanz (tofacitinib)

Treating Lupus

With lupus, the treatment goals are also to control your symptoms and keep your immune system from attacking your body, as well as protect your organs from damage. The initial drug of choice for lupus is the anti-malarial medication hydroxychloroquine.

Other drugs to treat lupus include:

• Arava (leflunomide)

• Azasan, Imuran (azathioprine)

• Benlysta (belimumab)

• Cellcept (mycophenolate)

• Medrol (methylprednisolone)

• Otrexup, Rasuvo, Rheumatrex, and Trexall (methotrexate)

• Plaquenil (hydroxychloroquine)

• Rituxan, Truxima (rituximab)

• Sandimmune, Neoral, Gengraf (cyclosporine)

• Saphnelo (anifrolumab-fnia)

Lifestyle Changes for RA and Lupus

Taking your medications isn’t the only thing that can help minimize flares. Healthy lifestyle habits—like not smoking and moderate exercise—can help to lower inflammation and reduce the severity of symptoms.

“Good dental care and following an anti-inflammatory diet can also help improve the immune system and how you respond to treatment,” says Dr. Thomas. “If you have lupus, UV light can be a triggering factor, so wearing sunscreen and avoiding UV light when possible can help.”

It’s rare but not impossible to have RA and lupus together. There’s even a name for it—rhupus. It’s estimated that the incidence of rhupus in people with arthritis is only 0.1% to 0.2%.

If that does happen to you, your treatment options may not be that dissimilar. “It comes down to what symptoms someone is experiencing and then trying different immunosuppressive medications based off those symptoms,” says Dr. Yates. Your doctor may first prescribe a DMARD like methotrexate to treat both rheumatoid arthritis and/or lupus, she says.

But if one condition seems to have the upper hand, that may change the picture. “As physicians, our job is to determine if lupus is the driving force for arthritis or is it RA?,” says Dr. Thomas. “Based on that we can prescribe a lupus-specific or RA-specific drug. I may have someone on hydroxychloroquine for the lupus part and methotrexate for RA. There are also a couple of biologics that target both of them very well, such as Orencia (abatacept) and Rituxan or Truxima (rituximab).”

Whether you have RA, lupus, or both, regular check-ins with your rheumatologist are key to managing the disease. “Treatment is a balance of having the necessary immunosuppressants to minimize symptoms without having too much of the risks that can come with those medications,” says Dr. Yates. “It’s important to have regular contact with your rheumatologist to change medications as needed as your symptoms flare or improve over the years.”

Perhaps the most important thing to keep in mind is that early treatment matters. Getting the care you need will help to minimize complications and reduce inflammation. Having good lifestyle habits like not smoking, regular exercise, and a healthy diet and staying in touch with your doctor can help you successfully navigate either condition for years to come.