Many patients with fibromyalgia—a multisystem illness of unknown etiology that is characterized by generalized muscle and joint pain, sleep disturbances, and fatigue—have faced the question of whether the condition is real. Fibromyalgia often has been misdiagnosed as arthritis or even a psychological issue. Increasingly, though, scientific research is leading to a greater understanding of diagnosing and characterizing sleep disturbances in patients with fibromyalgia.

PATHOPHYSIOLOGY

While the precise etiology of fibromyalgia is unknown, a growing body of evidence implicates disturbances in the neuroendocrine axis as a primary cause,1-4 particularly with regard to the sleep disturbances that are characteristic of the syndrome. Sleep electroencephalograms of patients with fibromyalgia typically show disturbance of non-rapid eye movement (REM) sleep by intrusions of alpha waves and infrequent progression to Stage 3 and Stage 4 sleep.5

Additional derangements of the endocrine and neurologic systems in patients with fibromyalgia have been observed. For example, the concentration of substance P (a neurotransmitter associated with enhanced pain perception) in the cerebrospinal fluid has been found to be up to three times greater than normal in patients with fibromyalgia.6 Dysregulation of the hypothalamic-pituitary-adrenal axis has been noted, with reduced production of cortisol by the adrenal glands.7 These observations suggest that some aberration in the endocrine and/or neurologic response to stress may exist in patients with fibromyalgia.

DIAGNOSIS

The diagnosis of fibromyalgia is generally a diagnosis of exclusion, and is based on the presence of widespread pain. Diagnostic criteria developed by the American College of Rheumatology (ACR) include diffuse soft tissue pain for 3 months or longer and pain on palpation in at least 11 of 18 specific muscle-tendon sites.8 Pain syndromes typical of fibromyalgia are shown in Figure 1, and include any combination of headaches, pain in the jaw, shoulder stiffness when waking up, chronic muscle and joint pain, diarrhea or constipation, sensitivity to chemicals or skin contact, numbness and tingling in the extremities, menstrual cramping, and generalized fatigue. Symptoms are often exacerbated by exertion, stress, lack of sleep, and weather changes. Associated symptoms usually include sleep disturbances and fatigue, and also may include irritable bowel syndrome, depression, and anxiety. Less common associated features include abdominal pain, bloating, dry eyes, dry mouth, and palpitations. Precipitating factors for fibromyalgia include flu-like viral illness, rheumatic disorders, human immunodeficiency virus infection, Lyme disease, physical trauma, emotional trauma, and medications (particularly corticosteroid withdrawal).

Initial routine laboratory tests typically include a complete blood count, standard blood chemistries, erythrocyte sedimentation rate, and thyroid function studies. These studies are normal in fibromyalgia, and facilitate a diagnosis by exclusion of fibromyalgia. Other laboratory studies are usually obtained only if there is clear suspicion from the history or physical examination of another disease.

CHARACTERIZATION OF SLEEP DISTURBANCES IN FIBROMYALGIA

Figure 1. Pain syndromes typical of fibromyalgia. ©morefocus 2004, www.mindbodyfocused.com

The pattern of sleep disturbance may facilitate the diagnosis of fibromyalgia. Patients with fibromyalgia often report early-morning awakenings; awakening feeling tired or unrefreshed; insomnia; and mood and cognitive disturbances related to poor quality of sleep.9 They also may experience primary sleep disorders such as sleep apnea.10 Interestingly, a distinct relationship has been noted between poor sleep quality and pain intensity.9-11 Although a history of sleep disorder is often present in patients with fibromyalgia, the use of sleep studies is controversial.

A growing body of evidence suggests that sleep studies are important for determining the underlying reason for the poor sleep in patients with fibromyalgia, and perhaps even for confirming a diagnosis of fibromyalgia.12 Recently, a sleep index has been used to characterize and quantify the sleep complaints of patients with fibromyalgia.13 The Pittsburgh Sleep Quality Index (PSQI) is an instrument used to measure the quality and patterns of sleep in older adults. It differentiates “poor” from “good” sleep by measuring seven sleep domains: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction over the last month. Patients self-rate each of these seven areas. Scoring of answers is based on a 4-point numeric scale (0 = strongly disagree; 3 = strongly agree). A global total score of > 5 indicates a “poor” sleeper. In the study, the PSQI was applied to 30 patients with fibromyalgia based on the ACR classification criteria, and to 30 healthy control subjects: The median global PSQI score in the fibromyalgia patients and healthy controls was 12.0 and 3.0, respectively (P<0.001). All PSQI component scores except sleep medications were significantly greater in fibromyalgia patients than controls. Sleep latency, sleep disturbances, and daytime dysfunction were the most frequent sleep difficulties experienced by patients with fibromyalgia. This study suggests that the PSQI is a useful instrument for characterizing and quantifying sleep disturbances in patients who have fibromyalgia.

In another study, pain and sleep symptoms of 40 female patients with fibromyalgia and 43 healthy control subjects were studied before and after overnight polysomnography in an effort to characterize the patterns of alpha electroencephalographic sleep and their associations with pain and sleep in patients with fibromyalgia.14 In this study, blinded analyses of alpha activity in non-REM sleep were performed using time domain, frequency domain, and visual analysis techniques. Three distinct patterns of alpha sleep activity were detected among the patients with fibromyalgia: phasic alpha (simultaneous with delta activity) in 50% of patients, tonic alpha (continuous throughout non-REM sleep) in 20% of patients, and low alpha activity in the remaining 30% of patients. On the other hand, low alpha activity was exhibited by 84% of control subjects (P<0.01). All fibromyalgia patients who displayed phasic alpha sleep activity reported worsening of pain after sleep, compared with 58% of patients with low alpha activity (P<0.01), and 25% of patients with tonic alpha activity (P<0.01). A post-sleep increase in the number of tender points occurred in 90% of patients with phasic alpha activity, 42% of patients with low alpha activity, and 25% of those with tonic alpha activity (P<0.01). Self-ratings of poor sleep were reported by all patients with phasic alpha activity, 58% of patients with low alpha activity (P<0.01), and 13% of those with tonic alpha activity (P<0.01). Patients with phasic alpha activity reported longer duration of pain than patients in other subgroups (P<0.01). Moreover, patients with phasic alpha sleep activity exhibited less total sleep time than those in other subgroups (P<0.05), as well as lower sleep efficiency (P<0.05) and less slow-wave sleep (P<0.05) than patients with a tonic alpha sleep pattern. This study adds considerably to our understanding of the patterns of sleep disturbances in patients with fibromyalgia, including the relationship of specific sleep-disturbance patterns to pain.

TREATMENT

The treatment of fibromyalgia is largely empiric. There is no Food and Drug Administration-approved treatment specifically indicated for fibromyalgia. Frequently employed therapeutic approaches include antidepressants, nonsteroidal anti-inflammatory agents, and exercise. More extreme approaches include chronic opioid analgesic therapy with or without psychotherapy. Behavioral therapy may help patients with fibromyalgia who experience work or social difficulties because of poor symptom control.,15,16 Recent evidence suggests that acupuncture may significantly reduce pain in patients with fibromyalgia.17 Early study suggests that pulsed electromagnetic fields may have therapeutic value in fibromyalgia.18

SUMMARY

Fibromyalgia has been classically viewed as a subjective diagnosis. All patients with fibromyalgia, by definition, experience pain, and most experience sleep disturbances. Over the past several years, new studies have provided needed insight into the characterizations of sleep disturbances in patients with fibromyalgia and the relationship between these patterns and the occurrence of pain. With further study, we may identify sleep-disturbance parameters, with suitably high selectivity and specificity, that can actually be used in the diagnosis of the syndrome. Clearly, sleep study is becoming increasingly recognized as an important component of the work-up of patients with known or suspected fibromyalgia.

John D. Zoidis, MD, is a contributing writer for Sleep Review. He can be reached at .

Search Sleep Review’s online archives for more information on fibromyalgia. Go to the search box at the top of the page and type in “fibromyalgia.”

REFERENCES

  1. McBeth J, Chiu YH, Silman AJ, et al. Hypothalamic-pituitary-adrenal stress axis function and the relationship with chronic widespread pain and its antecedents. Arthritis Res Ther. 2005;7:R992-R1000.
  2. Adler GK, Geenen R. Hypothalamic-pituitary-adrenal and autonomic nervous system functioning in fibromyalgia. Rheum Dis Clin North Am. 2005;31:187-202.
  3. Gur K, Cevik R, Sarac AJ, Colpan L, Em S. Hypothalamic-pituitary-gonadal axis and cortisol in young women with primary fibromyalgia: the potential roles of depression, fatigue, and sleep disturbance in the occurrence of hypocortisolism. Ann Rheum Dis. 2004;63:1504-1506.
  4. Pillemer SR, Bradley LA, Crofford LJ, Moldofsky H, Chrousos GP. The neuroscience and endocrinology of fibromyalgia. Arthritis Rheum. 1997;40:1928-1939.
  5. Moldofsky H. Sleep and fibrositis syndrome. Rheum Dis Clin North Am. 1989;15:91-103.
  6. Russell IJ, Orr MD, Littman B, et al. Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis Rheum. 1994;37:1593-1601.
  7. Demitrack MA, Crofford LJ. Evidence for and pathophysiologic implications of hypothalamic–pituitary–adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. Ann N Y Acad Sci. 1998;840:684-697.
  8. 8. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990;33:160-172.
  9. Harding SM. Sleep in fibromyalgia patients: subjective and objective findings. Am J Med Sci. 1998;315:367-376.
  10. Cote KA, Moldofsky H. Sleep, daytime symptoms, and cognitive performance in patients with fibromyalgia. J Rheumatol. 1997;24:2014-2023.
  11. Brecher LS, Cymet TC. A practical approach to fibromyalgia. J Am Osteopath Assoc. 2001;101(suppl):S12-S17.
  12. Moldofsky H. Management of sleep disorders in fibromyalgia. Rheum Dis Clin North Am. 2002;28:353-365.
  13. Osorio CD, Gallinaro AL, Lorenzi-Filho G, Lage LV. Sleep quality in patients with fibromyalgia using the Pittsburgh Sleep Quality Index. J Rheumatol. 2006;33:1863-1865.
  14. Roizenblatt S, Moldofsky H, Benedito-Silva AA, Tufik S. Alpha sleep characteristics in fibromyalgia. Arthritis Rheum. 2001;44:222-230.
  15. Singh BB, Berman BM, Hadhazy VA, Creamer P. A pilot study of cognitive behavioral therapy in fibromyalgia. Altern Ther Health Med. 1998;4:67-70.
  16. Sandström MJ, Keefe FJ. Self-management of fibromyalgia: the role of formal coping skills training and physical exercise training programs. Arthritis Care Res. 1998;11:432-447.
  17. Martin DP, Sletten CD, Williams BA, Berher IH. Improvement in fibromyalgia symptoms with acupuncture: results of a randomized controlled trial. Mayo Clin Proc. 2006;81:749-757.
  18. Shupak NM, McKay JC, Nielson WR, Rollman GB, Prato FS, Thomas AW. Exposure to a specific pulsed low-frequency magnetic field: a double-blind placebo-controlled study of effects on pain ratings in rheumatoid arthritis and fibromyalgia patients. Pain Res Manag. 2006;11:85-90.