Understanding of fibromyalgia syndrome (FMS) has evolved over the past 20 years. Once thought to be related to muscular pain and inflammation, it is now more widely understood to be a largely noninflammatory, soft-tissue pain condition, best separated from the entity of myofascial pain, with which it has traditionally been grouped. FMS also has strong associations with other diseases that are deemed central sensitivity syndromes, suggesting that central sensitization plays an important role in the chronic nature of fibromyalgia.¹ Because of the complexity of the disorder, a multimodal approach has the most success in effectively treating the physical, psychological, and emotional aspects of FMS.

DIAGNOSIS

The hallmarks of FMS are widespread pain, fatigue, sleep disturbances, and cognitive changes, as well as psychological distress. Patients often complain of pain “all over my body.” They often report chronic insomnia, either having trouble falling asleep or waking up frequently in the night, leaving them exhausted and stiff in the daytime. They also complain about difficulty with cognition and concentration; the phenomenon of “fibro fog” is frequently mentioned in patient forums and websites. Additionally, patients experience depression; in one study, as many as 40% of patients with FMS were diagnosed with depression at the same time as their FMS was diagnosed.² Many features of FMS overlap with other diseases, and, indeed, FMS is often seen in conjunction with other diseases that lack structural pathology, including irritable bowel syndrome (IBS), interstitial cystitis, temporomandibular disorder, tension headache and migraine, chronic fatigue syndrome, posttraumatic stress disorder, and vulvodynia. These disease states all share a common feature of central sensitization and have been named central sensitivity syndromes to denote this.¹ Any patient with this broad spectrum of symptoms should be evaluated for FMS.

The diagnosis of FMS is criteria-based rather than a diagnosis of exclusion.² The American College of Rheumatology (ACR) developed criteria for FMS research that have been used clinically to diagnose FMS since their publication in 1990.³ The diagnosis depends on the presence of generalized pain in three or more sites, as well as the physical examination finding of tenderness in at least 11 of 18 defined anatomic locations (Table 59-1 and Fig. 59-1). Patients with FMS have pain with 4 kg of digital pressure; this can be estimated by pressing the examining thumb against the spot in question with enough pressure to blanch the thumbnail about halfway down the nail bed.²

Since publication of the ACR criteria, many clinicians have used them but bemoaned the lack of attention given to the other clinically important features of FMS such as fatigue and depression. Multiple other surveys, scales, and questionnaires have been developed to try to follow objectively these very subjective complaints. None has proved universally satisfactory, but consensus in research circles shows relevant aspects of FMS to be pain, fatigue, problems with sleep, diminished global as well as physical functioning, depression, anxiety, and cognitive dysfunction.⁴ These domains demonstrate areas that clinicians must investigate and follow in patients with FMS in order to better diagnose the disorder and to assess the results of treatment.

Although FMS is not a diagnosis of exclusion, other causes of reported symptoms should be investigated before concluding that a patient has FMS. FMS occurs frequently as a secondary diagnosis with a host of other rheumatologic diseases such as systemic lupus, rheumatoid arthritis, and Sjögren’s syndrome. Conditions such as hypothyroidism, Lyme disease, tuberculosis, and HIV can cause similar findings as well. Conversely, after a patient is diagnosed with FMS, these other disease states can still occur and should not be overlooked.

There is no gold standard of testing for FMS. Rather, the clinician must rely largely on patient history for the diagnosis; there is a relatively minor role for the physical examination. Patients may report hyperalgesia (increased experience of pain to a normally painful stimulus) or allodynia (experience of pain with a nonpainful stimulus). Many clinicians still use the tender point examination, but the importance of this finding in the treatment of FMS is dwindling.

PATHOPHYSIOLOGY

New understanding of central sensitization (discussed elsewhere in this book) has led to useful information in understanding the etiology of FMS. Although the “causes” of FMS have not been discovered, it has proven useful clinically, and with regard to treatment, to view the disorder as one of altered sensory processing. Patients with FMS not only have increased pain with pressure applied to various body parts but also have lower pain thresholds for cold, heat, and electrical stimuli, as well as lower noxious thresholds to auditory stimuli.⁴ These findings imply that individuals with FMS experience a biologic amplification of sensory stimuli, which has been likened to an altered “volume control” with respect to their pain and sensory processing. Functional MRI (fMRI) studies of patients with fibromyalgia seem to support this concept. Patients with FMS consistently show increased activity in the so-called “pain matrix” of the primary and secondary somatosensory cortex, the insula, and the anterior cingulate cortex; these areas light up in healthy control participants undergoing painful stimuli, but they light up more often in people with FMS at baseline and light up more actively in people with FMS undergoing pressure stimuli.⁴

There is also a role for peripheral input or nociception. FMS is a soft-tissue pain disease, and many patients report deep aching pain, as well as increased pain with applied pressure. In attempts to locate structural pathology, multiple muscle biopsy studies of patients with FMS have been done, but none has borne out inherent differences when blinded and matched for inactive normal control participants.¹ Therapeutically, however, trigger point injections into tender muscle spots have had some success in ameliorating FMS pain despite a lack of randomized controlled trials (RCTs).⁵ Studies involving lidocaine and saline injection into muscles did show an interesting effect on decreasing heat hyperalgesia at a remote site in patients with FMS, indicating that perhaps there is a role for peripheral input.⁶ In some reports, there is a temporal relationship between physical trauma, especially of the trunk, and the development of FMS,⁴ implying that potentially some triggering incident provokes the altered processing, a concept widely accepted as the way in which central sensitization occurs.⁷ Other stressors such as infections (e.g., hepatitis C, Lyme disease, Epstein-Barr virus), emotional stress, and concomitant diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus) all predispose patients to develop FMS as well.

The role of neurotransmitters and cytokines is less clear, but there are abnormalities in patients with FMS. Cerebrospinal fluid analysis shows higher than normal levels of pronociceptive substances such as substance P,⁸ glutamate, and nerve growth factor⁹ and low levels of antinociceptive substances such as serotonin, norepinephrine, and dopamine metabolites.¹⁰ The overall effect of these imbalances supports the concept of altered processing of sensory information augmenting pain. Interestingly, the endogenous opioid system in patients with FMS seems increased rather than reduced; some authors suggest that this may explain why opioids often fail to help with the pain of FMS.⁴ Many of these findings have pointed in the direction of explaining responses to certain medications and suggest targets for future treatment.