Are you frustrated because your joints are stiff, painful and swollen and you’re tired all the time…yet your doctors can’t tell you what’s wrong? You may have a hard-to-diagnose form of rheumatoid arthritis. The longer it stays undiagnosed—and untreated—the greater your risk for permanent disability. You need to read this now.

Rheumatoid arthritis (RA) is an autoimmune disease. Antibodies produced by the body’s immune system attack joint tissues, causing pain, swelling and stiffness in multiple joints. These antibodies, called rheumatoid factor (RF) and anti-CCP antibodies, are detectable in blood tests and help to diagnose RA.

However, up to 20% of people with RA have a form of the disease that doesn’t show up in blood tests—seronegative rheumatoid arthritis. In the past, doctors thought that seronegative RA was a milder form of regular (seropositive) RA. It may be that patients with seronegative aren’t producing enough antibodies to show up in current blood tests. Recent studies show that seronegative RA is just as serious as the regular kind…and for some patients can be hard to treat.


To diagnose seronegative RA, imaging studies, such as X-ray and ultrasound, may be taken to look for joint changes. However, such changes may take time to develop. Blood tests, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), also may be done to look for evidence of generalized inflammation. But without the confirmation of antibodies, diagnosing seronegative RA is mainly based on a physical exam and symptoms.

Unlike with osteoarthritis, which usually causes symptoms in a single joint, RA causes pain and stiffness in multiple joints all over the body—including hands, knees, elbows, hips, feet and ankles. Joints, especially knuckles but also throughout the body, are evaluated for swelling and stiffness…and then monitored over at least six weeks or longer for any progression of swelling and stiffness. In addition, doctors check for…

  • Morning stiffness that lasts longer than 30 minutes after waking and gets better with movement.
  • Joint swelling or redness throughout the body.
  • Unusual fatigue that can’t be explained by other causes.


In most ways, seronegative RA acts just like regular RA and is treated the same. For mild cases, treatment may start with steroids to reduce inflammation and nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce inflammation and pain. For more severe cases, drugs called disease-modifying antirheumatic drugs (DMARDs) may be used to try to halt or slow disease progression. Recently, new DMARDs called biologics have been found to be very effective for moderate-to-severe disease. To help reduce symptoms, doctors sometimes keep patients on steroids or NSAIDs while waiting for DMARDs or biologics to take effect, and then taper off the NSAIDs and/or steroids. The American College of Rheumatology guidelines support a “treat-to-target” strategy for medication, with the target being remission.

There are also nondrug approaches that can help ease RA symptoms, such as range-of-motion exercises, deep abdominal breathing and capsaicin creams.


Seronegative RA can change over time. Some patients will start to produce enough antibodies to become seropositive. Seronegative RA can also evolve into other seronegative diseases, such as psoriatic arthritis, spondyloarthritis, polymyalgia rheumatica or osteoarthritis. That is one reason why it’s important to check with your doctor regularly if you have seronegative RA. If your diagnosis changes, your treatment may need to change.

And if you think you might have seronegative RA but confirmation is proving elusive, don’t give up! Getting diagnosed and starting treatment as early as possible can prevent long-term disability. If your symptoms have lasted longer than six weeks without a diagnosis, ask your primary care doctor to refer you to a rheumatologist. This kind of specialist is best at diagnosing seronegative RA and at developing a treatment plan.

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