Fibromyalgia characterized by controversy

Much research is currently delving into the pain mechanisms of fibromyalgia, a disorder defined by widespread muscle pain that many patients find debilitating and that has such associated symptoms as fatigue, lack of restorative sleep, and memory difficulties. But there remains considerable dissent among the medical community about the condition's cause.

Fibromyalgia is a contested illness. While some physicians characterize it as a purely organic illness based on abnormal pain amplification, others consider it a bio-psycho-cultural disorder with a multifactorial etiology.

These 2 groups do mostly agree on management, however: Opioids don't work, the medications that appear to be effective are limited in their therapeutic ability, and nonpharmacological treatment approaches (particularly exercise) seem to be paramount in decreasing patients' pain and increasing function.

“[Fibromyalgia] is a fairly common and almost ubiquitous problem. It doesn't matter what type of subspecialty someone is in; they're going to see these patients,” said Daniel Clauw, MD, a professor of anesthesiology, rheumatology, and psychiatry at the University of Michigan Medical School in Ann Arbor. “This is a different type of pain that needs a fundamentally different type of treatment.”

The controversy

For Dr. Clauw, author of a fibromyalgia review article published in 2014 by JAMA, “There's very clear, objective evidence that this is a real problem: The volume control or gain is set too high in the central nervous system, so people with these problems feel things as being painful that are not usually experienced as painful,” such as tight clothing or an inflating blood pressure cuff. This pain amplification, he said, extends to other sensory stimuli, such as bright lights or loud noises “because in the brain, regions that interpret any sensory stimuli are all increased in volume or increased in gain.”

But longtime fibromyalgia researcher Frederick Wolfe, MD, founder of the National Data Bank for Rheumatic Diseases, sees these central nervous system observations as being the mechanism by which disease is expressed, not necessarily the cause.

“What I think is bad is trying to say we know what causes this, that this is really a disease of the central nervous system caused by central pain. We really don't know that,” he said. Because studies compare people with fibromyalgia to people with no pain, it's not surprising that there's a difference in brain activity, he said.

In terms of potential causes of fibromyalgia, Dr. Wolfe said many factors play a role, including basic biological, psychological, societal, and individual ones. In general, people with fibromyalgia tend to have less education, be more distressed, and have more life events, he noted. “In fact, in our National Health Interview Survey, we found that people who have [fibromyalgia] were actually more likely to have cancer, heart disease, and kidney disease,” he said. “And it seemed to us that one of the associations with fibromyalgia was the stress that being sick or having a social disadvantage might incur.” Furthermore, Dr. Wolfe said, the illness is “entirely subjective,” as diagnosis is now usually based on reported symptoms. Indeed, he noted, contested illnesses such as fibromyalgia and chronic fatigue syndrome lack a clear-cut medical basis.

“That doesn't mean that these illnesses don't exist and that these people don't have problems,” Dr. Wolfe said. “It means that there's uncertainty among doctors and patients.”

Making the diagnosis

In 1990, the American College of Rheumatology's diagnostic criteria involved a physical examination of the many tender points on the bodies of patients with fibromyalgia. “This [exam] was of striking importance to us all because before this came out, we had no way of being able to diagnose the illness,” Dr. Wolfe said.

However, future studies have pointed out the limitations of the exam, including a 2015 study by Dr. Wolfe and his colleagues published in PLOS ONE finding that 75% of patients who reported a fibromyalgia diagnosis didn't satisfy the 1990 criteria.

“Tender points looked as if they were objective, and all of us who used them in those days believed that they were objective, but it turns out that the reliability of this examination is really not very good,” Dr. Wolfe said.

The American College of Rheumatology's most recent recommendations on fibromyalgia were published in 2010 by Arthritis Care & Research, although they remain preliminary, and the most current guidelines were released by the Canadian Fibromyalgia Guidelines Committee in 2012. The American College of Rheumatology's preliminary criteria no longer recommend using tender points and instead support diagnosis based on symptoms. The criteria employ a “widespread pain index” that evaluates 19 areas of the body for pain and a “symptom severity score” that analyzes the severity of somatic and cognitive symptoms. Both of these measures produce numeric scores that, when combined, may be helpful in diagnosing fibromyalgia. The Canadian guidelines also do not require a tender point exam for diagnosis, instead recommending a clinical evaluation and physical exam to exclude other conditions presenting with body pain, similar to the American College of Rheumatology guidelines.

Robert S. Katz, MD, a professor of medicine at Rush Medical College and a privately practicing rheumatologist in Chicago, coauthored the newer diagnostic criteria with Dr. Wolfe, Dr. Clauw, and others. He said he has patients fill out a handout of the widespread pain index in the office, which takes about a minute. “I think that primary care doctors should use some tool to say, ‘In my judgment, yes or no,’ not ‘I don't believe in it’ or ‘You look OK’ or ‘Your tests are normal.’ I think there needs to be a true evaluation of it, and this little sheet is helpful,” Dr. Katz said.

Although a fibromyalgia diagnosis can be approximated by a combined score of greater than 12 in many instances, some physicians view the condition as occurring on a continuum. It makes sense to start treating even patients with lower scores before symptoms become severe and potentially irreversible, Dr. Clauw said.

“If someone scores a 6 to 9, those might be the ideal people to identify in routine clinical practice and treat with the same drug and nondrug therapies that we use for fibromyalgia because those people haven't gotten so far down the continuum that they're impossible to get better,” he said.

Despite the uncertainties surrounding fibromyalgia, Leslie Crofford, MD, said the diagnostic criteria are pretty straightforward. “I think there's a misconception that fibromyalgia is hard to diagnose because the symptoms are relatively nonspecific. When viewed in aggregate, the symptoms can clearly point to fibromyalgia as the diagnosis of patients with chronic widespread or multifocal pain. … The main concern that most internists have is that they're afraid that they're missing something because the patients can be terribly symptomatic and quite distressed about it,” said Dr. Crofford, a professor of medicine at Vanderbilt University School of Medicine in Nashville who has presented on fibromyalgia at ACP's Internal Medicine Meeting.

Once a diagnosis is suspected, internists should next ask themselves whether another disorder could be mimicking fibromyalgia, Dr. Crofford said. Diseases such as lupus, thyroid disease, seronegative spondyloarthritis, rheumatoid arthritis, and polymyalgia rheumatica can all cause widespread musculoskeletal pain, but they aren't typically common in the primary care setting, she said.

“That's where the partnership between the rheumatologist and internist comes in. Particularly if the internist has done some laboratory testing, then they may be a little bit confused about what the patient has and may not feel comfortable making those exclusions on their own,” Dr. Crofford said.

Performing imaging tests for fibromyalgia can be a “treacherous” endeavor, Dr. Katz said, as an MRI of the back or neck may show something from long ago that may not be clinically relevant and may lead to further unnecessary testing. General laboratory tests such as a complete blood count and blood chemistries can be helpful, “but not to make the diagnosis, just to be sure we're not missing anything,” Dr. Katz said, adding that abnormalities in erythrocyte sedimentation rate and C-reactive protein levels can indicate a different illness.

Erythrocyte sedimentation rate or C-reactive protein tests can rule out polymyalgia rheumatica, particularly if a patient is over 50 years old, said Dr. Crofford. If a patient has joint symptoms, an internist could also check rheumatoid factor and anti-cyclic citrullinated peptide antibody, and if a patient reports weakness (which is not particularly characteristic of fibromyalgia), internists could also check creatine phosphokinase, she said. If any tests come back positive, a rheumatologist could then evaluate the patient for an autoimmune inflammatory musculoskeletal problem and could work together with the internist on management.

For fibromyalgia, however, “My own view is that in most cases, once the diagnosis is confirmed, that it would be acceptable for internists to manage patients … because the drugs are drugs that they use regularly in their practice,” Dr. Crofford said.

Treatment

The types of treatments that work for peripheral or nociceptive pain, such as nonsteroidal anti-inflammatory drugs, opioids, injections, and surgery, won't work for the centralized pain that occurs in fibromyalgia, Dr. Clauw said. “The most recent data from prescription databases suggest 35% to 40% of people with fibromyalgia are on an opioid, which has absolutely never been recommended,” he said.

Instead, experts agreed that the first step is educating patients about what fibromyalgia is and what it isn't. Next should be some kind of encouragement or prescription for light exercise to increase heart rate, or referral to physical therapy, experts said. A 2007 Cochrane review of 34 studies found moderate-quality evidence that aerobic-only exercise training has positive effects on global well-being and physical function in fibromyalgia patients.

“I really think that if these people who hurt get somewhat more active and then get into a light form of exercise like walking, that is the cornerstone of treatment of centralized pain and fibromyalgia,” Dr. Clauw said.

Dr. Crofford noted that “The biggest challenge is making sure they start off at a slow pace and build back up slowly so they don't try to do too much too soon.” Internists who refer patients to physical therapy should ensure that the therapist has experience with fibromyalgia and that the proper diagnosis is communicated, she added.

Evidence suggests that an online form of self-management with cognitive behavioral therapy (CBT) is helpful, Dr. Clauw said. But Dr. Crofford noted that patients with fibromyalgia often use up their will-power to get through the day with chronic pain and may benefit from the guidance of a professional. For patients with psycho-social stressors or those who are having difficulty coping with symptoms, another challenge is finding a therapist who is comfortable with CBT approaches and patients with chronic pain, she added. “I think that's a huge failure of the health care system's ability to address these conditions,” Dr. Crofford said.

If nonpharmacological treatments are not enough, select medications can be used to tackle patients' most prominent symptoms. Although the FDA has approved 3 drugs for fibromyalgia—pregabalin (Lyrica) in 2007, duloxetine hydrochloride (Cymbalta) in 2008, and milnacipran HCl (Savella) in 2009—these medications have a relatively low effect size and carry the risk of adverse effects.

Dr. Clauw said his favorite medications to start with are tricyclic antidepressants such as amitriptyline or cyclobenzaprine at bedtime to help with sleep and pain. Dr. Katz said he'll begin with amitriptyline, doxepin, or trazadone at a low dose at 6 or 7 p.m. (so that the long-acting medicine doesn't make patients too sluggish the next morning) to see if restorative sleep alleviates symptoms. “In my experience, the most helpful treatment is medicine that makes them sleep through the night and light, regular aerobic exercise,” he said.

If patients don't improve on a tricyclic drug, Dr. Clauw said he'll add either a gabapentinoid, such as gabapentin or pregabalin, or a serotonin-norepinephrine reuptake inhibitor (SNRI), such as duloxetine or milnacipran. This second therapy depends on a patient's most bothersome symptoms: Go the gabapentinoid route for sleep problems, pain, and anxiety, or choose an SNRI for depression, fatigue, and memory problems, he recommended.

Dr. Clauw added that in a small randomized controlled trial, published in the July issue of Pain, patients achieved better overall symptom control with a combination of a gabapentinoid and an SNRI than with placebo or either agent alone. “So [clinicians] should feel comfortable, if need be, using a low dose of the tricyclic at bedtime combined with a SNRI like duloxetine during the day and a little bit more gabapentin or pregabalin at night to help the person sleep better and help with some of the other symptoms,” he said. In the trial, dual therapy was associated with side effects such as moderate-to-severe drowsiness, and patients could tolerate only small amounts of each drug.

Dr. Katz said he hasn't had much success with pregabalin, duloxetine, and milnacipran. “One of the reasons I'm a little skeptical of this central sensitization hypothesis is that those therapies may seem to work in controlled studies … and I think what happens with a lot of primary care doctors is that they try those therapies because those are FDA-approved and they don't work—they don't work for me, and I've been doing this for years—and they don't know where to go next,” he said.

Management

One of the biggest challenges in managing fibromyalgia, Dr. Crofford said, is obtaining a complete medical history and understanding the day-to-day lives of these patients in a 10- to 15-minute office visit. She suggested asking open-ended questions about childhood challenges, first onset of chronic pain, and ongoing social stresses.

“I think it's important not only for the doctor to appreciate what's happening, but for the patient to make that link in their brain between the stresses they may be experiencing and their symptom flares,” Dr. Crofford said. If patients have a number of symptoms or concerns that can't be effectively addressed in 1 appointment, serial appointments can allow for deeper discussion, she added.

Dr. Clauw stressed that chronic pain from fibromyalgia is not something that physicians can cure outright, so patients should have reasonable expectations. “We might in some instances dramatically reduce someone's pain level—even, if you will, put them in remission from their chronic pain—but that's because they're using some combination of drug and nondrug treatments that has worked,” he said. “If they stop using the treatments that we're giving them, then that condition will go back to the way it was before it was being treated.”

Dr. Wolfe said internists should focus primarily on how they can make life better for these patients. “Try to encourage people to get better, to find resources in the community, to find friends and strength,” he said. “What patients want to know is that you're there for them and that you believe them and that you listen to their story and that you help them for flare-ups, and I think that's really what we should do.”