• Recent genetic evidence suggests fibromyalgia is best defined as a central nervous system disorder.
• Exercise, improved sleep and stress reduction are recommended interventions for fibromyalgia.

Recent genetic evidence from more than 2.5 million individuals suggests that fibromyalgia is a central nervous system disorder, rather than an autoimmune or psychiatric disease, according to data published in Nature Medicine.

In that study, published in July, Daniel J. Clauw, MD, director of the Chronic Pain and Fatigue Research Center, and professor of anesthesiology, medicine and psychiatry at the University of Michigan, and colleagues conducted a multi-ancestry genome-wide association meta-analysis of 54,629 patients with fibromyalgia and 2,509,126 controls.

The researchers identified 26 risk loci for fibromyalgia, according to the findings. They additionally observed that a coding variant in HTT, which is implicated in Huntington’s disease, carried the strongest association with fibromyalgia. The HTT regulator GPR52, along with DCC, DRD2/NCAM1, MDGA2 and CELF4 were also implicated.

Further results demonstrated correlations between fibromyalgia and several associated conditions, ranging from low back pain and chronic pain, to PTSD, IBS and psychiatric and somatic disorders. No gender differences were observed in the genetic architecture of fibromyalgia, according to the researchers.

Another paper, a Clinical Practice article published that same month in the New England Journal of Medicine, noted the challenges in finding biomarkers and blood tests to identify fibromyalgia, and the subsequent diagnostic complications.

In the article, authors David A. Williams, PhD, and Clauw wrote that although fibromyalgia has historically been characterized by some as an autoimmune disorder, a small-fiber neuropathy or a psychiatric disorder, current clinical evidence does not support these claims.

These mischaracterizations can lead to mistreatment, Williams and Clauw added. They additionally stressed that exercise and improved sleep are cornerstones of fibromyalgia management. Cognitive behavioral therapy may also offer benefits, along with yoga, tai chi and efforts to reduce stress. If pharmacotherapeutics are necessary, tricyclic drugs, gabapentinoids and serotonin-norepinephrine reuptake inhibitors are recommended.

Healio sat down with Clauw, who coauthored both papers, to discuss this comprehensive research in the fibromyalgia space, and the role rheumatologists should play in the management of this complex patient population.

Healio: In the NEJM paper, you and Williams write: “Claims that fibromyalgia is an autoimmune disorder, a small-fiber neuropathy, or primarily a psychological problem remain unsubstantiated.” What kind of research needs to be done to substantiate (or not) these perceptions of fibromyalgia? What do we still need to learn?

Clauw: Rheumatologists can decide if fibromyalgia is an autoimmune disease. Given that we see fibromyalgia so commonly with autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus, why does the treatment of these diseases not lead to an improvement in the comorbid fibromyalgia? If this is autoimmune where is the tissue damage?

Small fiber neuropathy has been noted in hundreds of conditions, most of which are not associated with pain. It is an extremely non-specific finding.

As for the psychological explanation, I believe it is overly simplistic. Many studies suggest that there are a multitude of factors that increase risk for fibromyalgia and psychological factors are just one of them — and a weak factor. Many studies in chronic pain now suggest that the anxiety, depression and catastrophizing are due to the pain, and if you make pain better, these resolve rapidly.

Healio: In the NEJM paper, you also suggest that fibromyalgia can be managed by primary care. What are some of the ways to manage fibromyalgia?

Clauw: Explain the condition, get people sleeping and moving using any number of therapies, judiciously use non-opioid analgesics such as cyclobenzaprine or duloxetine. Aggressive use of non-pharmacological therapies can also be beneficial. There are 15 to 20 non-pharmacological integrative therapies with an evidence base that providers can choose from.

Healio: What role can or should rheumatologists play in the management of fibromyalgia?

Clauw: In most settings, they should simply be able to see patients once and confirm the diagnosis, especially to be certain the individual does not have an autoimmune disease.

Healio: Turning to the Nature Medicine study, was there anything surprising or unexpected about the results?

Clauw: Not surprising to me, but reassuring.

Healio: Why?

Clauw: All of the genes identified were in the central nervous system, and there was no evidence for the types of genetic findings typically seen in autoimmune diseases. This study simply confirms that fibromyalgia is a CNS-based disease.

Healio: What would be your take-home message for practicing rheumatologists based on these two papers?

Clauw: I may be wrong, but my sense is that rheumatologists already knew much of this and it was simply confirmation. Rheumatologists are already fairly anti-opioid, and understand how helpful drugs like cyclobenzaprine can be, and understand the importance of non-pharmacological approaches.

However, the lack of availability of and reimbursement for these therapies is a significant barrier in clinical practice.

Daniel Clauw, MD, can be reached at dclauw@med.umich.edu.