CLINICAL FEATURES OF FIBROMYALGIA
Fibromyalgia is more common in women than men, with an estimated prevalence of 2% in the general population (3.4% in women and 0.5% in men). Its prevalence increases with age, rising sharply in middle age and then dropping off after age 80.2
Fibromyalgia is seen most often in women ages 50 and older.2 It occurs in 5% to 6% of patients presenting to general medical and family practice clinics and in 15% to 20% of patients presenting to rheumatologists, making it one of the most common diagnoses in office-based rheumatology practices.
American College of Rheumatology criteria may require only widespread pain and tenderness for a diagnosis of fibromyalgia, but most patients (73% to 85%) also report fatigue, sleep disturbance, and morning stiffness. Many (45% to 69%) report “pain all over,” paresthesias, headache, and anxiety. Co-occurring irritable bowel syndrome, sicca symptoms, and Raynaud’s phenomenon are less common (<35%).1 Patients with fibromyalgia also have high lifetime rates of other comorbid disorders, including migraine, chronic fatigue syndrome, and mood and anxiety disorders. Some patients report weakness, forgetfulness, difficulties in concentration, urinary frequency, history of dysmenorrhea, and restless legs.
Fibromyalgia is chronic, debilitating, and often leads to substantial functional impairment.3 Most patients with fibromyalgia do not display significant improvement over an average of 7 years of treatment.4 Patients with fibromyalgia report lower quality of well-being than patients with diagnoses of chronic obstructive pulmonary disease, rheumatoid arthritis, atrial fibrillation, advanced cancer, and several other chronic diseases.5
Stress response Stress appears to precipitate or exacerbate fibromyalgia symptoms in many patients.16 For example, fibromyalgia appears to be associated with victimization (adult and childhood sexual, physical, and emotional trauma), and this stress may trigger the development of fibromyalgia in some patients.17
Patients with fibromyalgia appear to develop disturbances in the two major stress-response systems: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system.16 Although the interpretation of these disturbances is still debated, some researchers suggest that the available data point to reduction in CNS corticotropin releasing hormone (CRH), the key mediator in the HPA axis.18,19 CRH is also a behaviorally active peptide that leads to physiologic and behavioral arousal when administered centrally to animals.18 CRH reduction could contribute to the clinical features of fibromyalgia (e.g., fatigue) either directly or indirectly by causing a relative glucocorticoid deficiency.18,19
Table 2
DIFFERENTIAL DIAGNOSIS OF FIBROMYALGIA
| Rheumatic disorders | Nonrheumatic disorders |
|---|---|
| Rheumatoid arthritis | Hypothyroidism |
| Systemic lupus erythematosus | Sleep apnea |
| Polyarticular osteoarthritis | Hepatitis |
| Polymyalgia rheumatica | Cushing’s syndrome |
| Addison’s disease | |
| Hyperparathyroidism | |
| Adapted from Clauw DJ. Fibromyalgia syndrome: an update on current understanding and medical management. Rheumatol Grand Rds 2000;3:1-9. | |
Fibromyalgia is also associated with moderate basal hypocortisolism.18,19 A relative glucocorticoid deficiency could contribute to fibromyalgia’s characteristic fatigue, arthralgias, myalgias, and disturbances in mood and sleep.18 This deficiency may also cause some of the immunologic disturbances seen with fibromyalgia.18,19
Atypical depression, which shares such features of fibromyalgia as profound lethargy, is also associated with inappropriately normal or reduced activation of the HPA axis and a functional deficit in the release of hypothalamic CRH.18 The unifying feature of HPA axis activity in both atypical depression and fibromyalgia may be a shared hypofunctioning.18 A more complete understanding of the neuroendocrine changes in fibromyalgia awaits further study.
Pain processing Aberrant CNS processing of pain may also play a role in fibromyalgia.16,20 Fibromyalgia is sometimes precipitated by physical trauma.21 A traumatic injury may start a process in susceptible individuals that leads to an enhanced central processing of painful stimuli characteristic of central sensitization.22 Patients with fibromyalgia often develop an increased response to painful stimuli (hyeralgesia) and experience pain from normally nonnoxious stimuli (allodynia).20
Substance P, an important nociceptive neurotransmitter, may have a role in generating central sensitization.23 Elevated concentrations of substance P have been found in the cerebrospinal fluid (CSF) of individuals with fibromyalgia.24 Substance P also inhibits CRH release and may contribute to low CRH activity in fibromyalgia.16
Neurotransmitter defects A functional reduction in serotonergic activity has been demonstrated in patients with fibromyalgia. Schwarz et al25 found a strong negative correlation between serum concentrations of the primary serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and substance P, pain, and insomnia. Evidence also exists of reduced concentrations of the primary norepinephrine metabolite, 3-methoxy-4-hydroxyphenethylene (MHPG), in the CSF of patients with fibromyalgia.26 Reduced serotonin and norepinephrine levels in descending pain-inhibitory pathways may cause the allodynia and hyperalgesia of fibromyalgia.
Pharmacologic treatment
Most studies of pharmacologic treatment of fibromyalgia have examined antidepressants for three reasons:
- There is evidence of the successful use of antidepressants in other chronic pain conditions.27
- These agents are effective for treating mood and anxiety disorders, which frequently occur in patients with fibromyalgia and may share a common physiologic abnormality.28
- Antidepressants might enhance the activity of neurotransmitters such as serotonin and norepinephrine in the descending inhibitory pain pathways, leading to reduced pain perception.29