Seronegative rheumatoid arthritis and fibromyalgia

Seronegative rheumatoid arthritis and fibromyalgia may be more closely linked than we think, according to 2016 study published in American College of Rheumatology. Researchers of the study found strong evidence that seronegative rheumatoid arthritis and fibromyalgia are connected.



What is Seronegative Rheumatoid Arthritis?

There are two main subgroups of rheumatoid arthritis (RA), seronegative rheumatoid arthritis and the more common seropositive rheumatoid arthritis.

In usual cases of RA, patients would score positive for rheumatoid factor and/or anti-citrullinated peptides (CPP) antibodies. This means that he/she is seropositive and therefore carries the antibodies which causes inflammation in the joints. Patients that are seropositive suffer more severely in joint symptoms such as pain, damage, deformities and even inflammation in adjacent areas.

On the other hand, RA patients who experience characteristic symptoms of RA but test negative for rheumatoid factor and/or anti-citrullinated peptides (CPP) antibodies are diagnosed with seronegative RA. These patients either do not or do not yet carry sufficient antibodies. However, many of them can develop antibodies years after their early diagnosis, hence changing their condition to seropositive RA.

Many consider Seronegative RA to be the less severe form of RA. However, studies have shown that as the disease progresses, it can be comparable to seropositive RA. Therefore, it can be tricky to categorise RA into sub-types and to derive a clear diagnosis.



How are Seronegative Rheumatoid Arthritis and fibromyalgia linked?

As mentioned, seronegative RA is a less common sub-type of RA and not much study has been done on it. Researchers at the Duke University of North Carolina conducted a study to investigate medical conditions related to this form of RA. They hope that their study would spark more research on this subgroup which constitutes 20-40%, is a significant percentage, of all RA cases.

The researchers carried out the investigation with phenome-wide association study (PheWAS) analysis of electronic health records (EHRs) to identify disease related to both seropositive and seronegative RA patients. The findings suggest a strong connection between seronegative rheumatoid arthritis and fibromyalgia. According to the findings, seronegative RA patients have double the chance of having PheWAS codes for “myalgia and myositis”. These codes “myalgia and myositis” signify fibromyalgia in 80 out of 100 cases. Therefore, researchers believe that this finding indicates a strong association between seronegative rheumatoid arthritis and fibromyalgia. Furthermore, the data collected also showed that seronegative RA patients are more susceptible to back pain, a common fibromyalgia symptom.

Despite limitations of PheWAS, researchers conclude that their study indicates a connection between seronegative rheumatoid arthritis and fibromyalgia. They suggest that physicians should be mindful of the higher occurrence of fibromyalgia in seronegative RA patients.

Symptoms and misdiagnosis of Seronegative Rheumatoid Arthritis and fibromyalgia

To diagnose a patient with Seronegative RA, he/she must exhibit a specific group of symptoms. Some of them include:

  • Pain and stiffness in the joints particularly in the hands, elbows, knees, ankles and feet.
  • Signs of inflammation in the joints such as swelling and redness
  • Soreness in the joints
  • Mirroring symptoms in various joints
  • Persistent inflammation in the joints
  • Morning stiffness which continues for more than half an hour
  • Fatigue
  • Redness in the eye

The absence of anti-bodies makes seronegative RA difficult to diagnose. This is where seronegative rheumatoid arthritis and fibromyalgia are similar and can sometimes be confused. Both conditions are difficult to diagnose. Furthermore, they exhibit overlapping symptoms which may cause them to be mistaken as the other.

One motivating factor of the aforementioned study is the diagnostic difficulty in Seronegative RA patients. In fact, misdiagnosis is quite common in seronegative patients. Seronegative patients may display symptoms which can be mistaken as seropositive RA but are actually due to a different condition. One commonly confused condition is osteoarthritis where inflammation exists and is consistent. Varied levels of inflammation and affected joints can also indicated other conditions. They include conditions such as ankylosing spondylitis, reactive arthritis and psoriatic arthritis.

Researchers of the study believe that the missing antibodies in seronegative RA patients can cause physicians to misdiagnose patients with fibromyalgia, a musculoskeletal pain condition. In their study, researchers observed that fibromyalgia diagnosis occurred shortly before or after RA diagnosis. Hence, they believe there is a likelihood of diagnostic confusion before or after seronegative RA diagnosis.

In conclusion, this study warrants more research on seronegative rheumatoid arthritis and fibromyalgia. It is common knowledge that RA patients are more likely to suffer from fibromyalgia. However, the reason why fibromyalgia co-exists more frequently in seronegative RA patients remains unclear.



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