Diagnosis, Neurobiology, Pathophysiology and Treatment of Fibromyalgia for Primary Care Physicians

Fibromyalgia is one of the most common pain syndromes in the United States, affecting an estimated 10 million people. fibromyalgia can occur in both genders and all ages, but over 70% of patients diagnosed with this condition are women. The disorder is characterized by chronic widespread body pain, in addition to secondary symptoms such as moderate to severe fatigue, sleep disorders, problems with cognitive functioning, irritable bowel syndrome, headaches and migraines, anxiety and depression, and environmental sensitivity.

The first stop for fibromyalgia patients is often their primary care physician (PCP). But unfortunately, a study in 2009 found that between 16% and 71% of PCPs and specialists (including rheumatologists, neurologists, pain specialists, and psychiatrists) surveyed indicated they were “not very” or “not at all” confident about their ability to identify fibromyalgia symptoms. Most importantly, the survey revealed that a lack of physician education was a major factor in the delay in diagnosing fibromyalgia. Another survey found that a correct diagnosis for fibromyalgia can take as long as five to eight years from the original disease onset.

Despite these challenges, being up to date on the current research and knowing what pieces of the puzzle to look for can greatly assist clinicians in diagnosing fibromyalgia more quickly and accurately. For this article, MD Magazine: Peers & Perspectives convened three fibromyalgia experts for a discussion of the condition’s neurobiology, pathophysiology, and treatment. The discussion was moderated by Peter Salgo, MD.

Philip J. Mease, MD, chief of rheumatology research at the Swedish Medical Center in Seattle, said it has been a “fascinating journey” for him as he has observed how the understanding of this condition has evolved over time. He noted that the term “fibrositis” was coined at the beginning of the last century when many people thought that the condition represented some type of inflammation of connective tissue.

In the last two decades, we’ve come to the realization that patients with other rheumatic diseases, indeed, patients with other chronic diseases that may not be rheumatic, may also have fibromyalgia, and it may either be secondary to the underlying disease or it may be an entity entirely separate and distinct from it.

—Allan Gibofsky, MD

“In fact, there was a fad in the 1920s of taking out internal organs, like the appendix or the ovaries, because some had the idea that there was a deep-seated infection leading to inflammation in connective tissue,” said Mease, who is also a clinical professor of medicine at the University of Washington in Seattle. He added that in the prior century, it was known as neurasthenia, and has gone through an evolution ranging from a perception of it being primarily a psychological illness in women who had some type of weakness of their soul and spirit, to the internal inflammation that was mysterious and not quite well defined.

But that has changed, especially over the last 30 or 40 years. “Fortunately, with current science, we now have a sophisticated methodology to better understand the fact that the problem lies in the central nervous system primarily, having to do with a dysregulation of the way sensory processing occurs in the central nervous system,” Mease said.

Fortunately, with current science, we now have a sophisticated methodology to better understand the fact that the problem lies in the central nervous system primarily, having to do with a dysregulation of the way sensory processing occurs in the central nervous system.

—Philip Mease, MD

Patients experience heightened sensitivity to pain and other stimuli, but clinicians now have sophisticated neuroimaging techniques that show that fibromyalgia patients do experience pain at a lower threshold than other individuals. “We think that some of this has to do not only with the genetics of those individuals but also a variety of factors, both developmental and the current illnesses that they may have which upset the way neurotransmitters are functioning in the central nervous system,” Mease said.

Why It Hurts

Researchers are continually working on determining the pathophysiology of the disease. Mease said that cerebrospinal fluid studies show that patients with fibromyalgia have increased levels of noxious neurochemicals, like substance-P and glutamate, involved in transmitting pain into the central nervous system.

There have also been neuroimaging studies that show abnormalities in glutamate metabolism and function of the brain in fibro emission. Researchers are also learning that at the same time, there is a problem with the modulating influence of neurotransmitters, such as serotonin and norepinephrine. “It’s this perfect storm of having too much noxious neurochemical function and too little inhibitory neurochemical function that leads, we feel, to the increased pain expression,” Mease said.

Tender Points

In the 1980s, there was growing recognition that patients with fibromyalgia had something called both allodynia and hyperlgesia. Allodynia is a painful appreciation of a normal sensory stimulus and a heightening to a painful stimulus. This sensitivity was detected by pressing the patient at various connective tissue areas and seeing if they had a hyper-reaction.

Various maps of the body were generated in the 1980s that suggested that patients with fibromyalgia had widespread pain in multiple connective tissue areas. An exercise was published in 1990 that became the American College of Rheumatology (ACR) criteria for the classification of fibromyalgia. According to these criteria, a patient with at least 11 of 18 tender points present above and below the waist and on both sides of the body, as well as a history of chronic widespread pain, could qualify for the diagnosis, Mease said. When that criteria is used, anywhere from 2% to 5% of the general population, predominantly women, will qualify for the diagnosis of fibromyalgia.

Allan Gibofsky, MD, an attending rheumatologist at the Hospital for Special Surgery in New York, added that when testing the 18 tender points, there is a specific application of four kilograms of digital pressure. “We can make anyone hurt at any point by putting sufficient pressure on them, but we’re talking about a standardized pressure that would be insufficient to cause pain in a normal individual but sufficient to cause unpleasantness and abnormality in individuals with these abnormal sensory processing problems”, said Gibofsky, who is also a professor of medicine and public health at the Weill Medical College of Cornell University.

Revised ACR Criteria

Although the ACR criteria were a step ahead at the time, they were far from perfect. One problem was that many clinicians simply were not familiar with tender point exams and did not know how to do them; they wanted something that took more of the widespread symptoms of the illness into account.

In 2010, revised guidelines from the ACR were published in Arthritis Care & Research. Frederick Wolfe, MD, of the National Data Bank for Rheumatic Diseases and University of Kansas School of Medicine, both in Wichita, was the lead author on the 1990 guidelines and the leader of the new initiative. Mease, who was involved in developing the new guidelines, said the researchers studied approximately 1,000 patients, about half of whom were estimated to have fibromyalgia; the other patients had other painful rheumatic conditions but did not have fibromyalgia.

“At the end of the day, what seemed to define the illness, without using a tender point exam, was a patient describing widespread pain in a number of different areas of their body, but also a gradation of severity of fatigue, sleep disturbance, and cognitive dysfunction, as well as other somatic symptoms,” Mease said. Wolfe used computer algorithms to develop a quantitative symptom severity score and widespread pain index that can diagnose a patient without necessarily going through a tender point exam, but which also requires careful analysis of how much of the body is involved with pain.

Mease said that resulted in a “significant” increase in the diagnosis of fibromyalgia by about 7% to 8%, but Gibofsky said those numbers are “probably on the low side.”

He added that research has shown that 20% of patients with rheumatic diseases, such as lupus, rheumatoid arthritis, and osteoarthritis, may have some current fibromyalgia. Because patients with fibromyalgia are often diagnosed with other pain-related conditions, fibromyalgia may go undetected.

Mease added that the new criteria mean that many patients who are only categorized as having rheumatoid arthritis or osteoarthritis can also be categorized as having fibromyalgia.

Inclusion and Exclusion

Originally, fibromyalgia was thought to be a diagnosis of exclusion, Gibofsky said. If a patient had met the ACR criteria for rheumatoid arthritis or lupus, then, by definition, it was thought that he or she could not have fibromyalgia.

“However, in the last two decades, we’ve come to the realization that patients with other rheumatic diseases, indeed, patients with other chronic diseases that may not be rheumatic, may also have fibromyalgia, and it may either be secondary to the underlying disease or it may be an entity entirely separate and distinct from it,” Gibofsky said. The challenge is that when it exists as a consequence of, or in association with, another disease, it frequently makes it difficult to discern the complaint of the original disease from the complaint of fibromyalgia. “Patients with rheumatic diseases often have fatigue; so do patients with fibromyalgia,” Gibofsky said. “So, how will I know whether the fatigue that my patient’s complaining of is exacerbation of another rheumatic disease or perhaps secondary fibromyalgia?

He added that it is difficult to answer this question. There are some standardized tests used to assess disease activity in rheumatoid arthritis and in lupus, for example, but standardized tests for assessing the activity of fibromyalgia are not as widely used. So, in the absence of positive findings for rheumatoid arthritis or lupus, clinicians will ascribe the complaint to fibromyalgia, but that may not be necessarily correct.

Mease gave an example to illustrate the difficulty of diagnosing fibromyalgia. A patient with rheumatoid arthritis is being optimally treated with several medications that are useful for the condition. Their blood markers for inflammation are now normal, the swelling in their joints has resolved, but they are still in great pain and fatigued and have sleep disturbance. “That’s when the light bulb should go off in the clinician’s mind that they may have accompanying fibromyalgia and that it’s time to begin to focus our treatment paradigm there instead. And, unfortunately, it’s often late in the game when that ah-ha moment occurs,” Mease said.

Want to read more about what these experts had to say about the diagnosis and treatment of fibromyalgia? Go to www.MDMag.com to read the complete version of this article and to check out additional features from the recently launched MD Magazine: Peers & Perspectives, published by Intellisphere, LLC.