Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.

Fibromyalgia was almost completely absent from an urban affluent population compared with poor urban and rural communities. Seventeen percent of Gulf War veterans with soft tissue syndromes had fibromyalgia, a much higher rate than was seen in previous studies of rheumatic disease in the military population. A state of central hyperexcitability in the nociceptive system was reported in fibromyalgia. Altered functioning of the stress-response system has been further documented in fibromyalgia and chronic fatigue syndrome. Administration of growth hormone to patients with fibromyalgia who have low levels of insulin-like growth factor 1 resulted in improvement in their symptoms and tenderness. An association between chronic fatigue syndrome and initial infections was demonstrated. A correlation between particular immunologic abnormalities and measures of disease severity was documented in chronic fatigue syndrome. Concomitant fibromyalgia in other rheumatic diseases was a major contributor to poor quality of life. A favorable outcome of fibromyalgia in children was reported; the majority of patients improved over 2 to 3 years of follow-up. Treatment of patients with fibromyalgia continues to be of limited success.     

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome

There continues to be an emerging body of literature related to fibromyalgia and the related conditions chronic fatigue syndrome and myofascial pain. During the past year, the most notable contributions included a large multicenter study providing new diagnostic criteria for the classification of fibromyalgia and clinical studies describing the overlap of fibromyalgia, chronic fatigue syndrome, and myofascial pain. Pathophysiologic studies were often preliminary and uncontrolled but the focus of these studies on abnormal nociception, neurohormones, and muscle metabolism provides an exciting hypothesis to unify pain, fatigue, and sleep disturbances, the primary symptoms of fibromyalgia. Unfortunately, new therapeutic trials were neither innovative nor especially encouraging.     

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome

The prevalence of chronic widespread pain in the general population in Israel was comparable with reports from the USA, UK, and Canada. Comorbidity with fibromyalgia (FM) resulted in somatic hyperalgesia in patients with irritable bowel syndrome. One sixth of the subjects with chronic widespread pain in the general population were also found to have a mental disorder. Mechanisms involved in referred pain, temporal summation, muscle hyperalgesia, and muscle pain at rest were attenuated by the N-methyl-D-aspartate (NMDA) antagonist, ketamine, in FM patients. Delayed corticotropin release, after interleukin-6 administration, in FM was shown to be consistent with a defect in hypothalamic corticotropin-releasing hormone neural function. The basal autonomic state of FM patients was characterized by increased sympathetic and decreased parasympathetic systems tones. The severity of functional impairment as assessed by the Medical Outcome Survey Short Form (SF-36) discriminated between patients with widespread pain alone and FM patients. Chronic fatigue syndrome (CFS) occurred in about 0.42% of a random community-based sample of 28,673 adults in Chicago, Illinois. A significant clinical overlap between CFS and FM was reported. Cytokine dysregulation was not found to be a singular or dominant factor in the pathogenesis of CFS. A favorable outcome of CFS in children was reported; two thirds recovered and resumed normal activities. No major therapeutic trials in FM and CFS were reported over the past year.     

Primary fibromyalgia and the chronic fatigue syndrome

Summary Thirty-three primary fibromyalgia patients were investigated for chronic fatigue syndrome symptoms. Significant fatigue was reported by 21/33 patients (63.6%), and patients reported various flulike symptoms, yet only 7/33 patients (21.2%) fulfilled criteria for the chronic fatigue syndrome. Only one patient reported painful lymph glands and four patients reported fever. Thus, symptoms of painful glands or fever might serve as clinical indicators, distinguishing between fibromyalgia and the chronic fatigue syndrome.     

Fibromyalgia, chronic fatigue, and myofascial pain syndromes.

During the past year many studies have been published on fibromyalgia and chronic fatigue syndromes. Randomized clinical trials using current operational diagnostic criteria were reported, but no single therapy has been highly effective in either condition. The working case definition of chronic fatigue syndrome has been criticized and suggestions for a new case definition have been made. Further understanding of the overlap of these three common disorders will also require that uniform diagnostic criteria be tested in chronic fatigue syndrome and myofascial pain syndrome.     

Fibromyalgia syndrome in patients infected with human immunodeficiency virus. The Boston City Hospital Clinical AIDS Team.

PURPOSE: To prospectively assess rheumatic manifestations of human immunodeficiency virus (HIV) disease in a municipal hospital clinic population in which intravenous drug use was the most common risk factor for HIV infection. PATIENTS AND METHODS: Patients with documented HIV infection were evaluated for rheumatic disease using a standardized questionnaire and examination. Patients with fibromyalgia were compared with HIV-infected patients without fibromyalgia and with fibromyalgia patients without known risk factors for HIV infection. RESULTS: Thirty-seven of 140 patients with HIV infection had muskuloskeletal symptoms. Three of these 37 patients had arthritis, but none had Reiter's syndrome or psoriatic arthritis. Thirty (81%) of 37 patients had chronic musculoskeletal symptoms (for 3 months or longer). Twenty of 30 patients with chronic musculoskeletal symptoms had polyarthralgia, and of those, 15 (75%) were found to have either definite or probable fibromyalgia syndrome. Therefore, fibromyalgia syndrome was found in 41% of HIV-infected patients with musculoskeletal symptoms and in approximately 11% of all HIV-infected patients. Fibromyalgia patients with HIV infection had a longer duration of HIV infection (p = 0.01) and more frequently reported past depressed mood (p = 0.001) than HIV-infected patients without fibromyalgia. Compared with 301 patients with fibromyalgia syndrome and no known risk behavior for HIV, known HIV-infected patients with fibromyalgia were more commonly male (p = 0.001) and reported current depressed mood more frequently (p = 0.0001). CONCLUSION: Few patients with arthritis were noted among HIV-infected patients who had intravenous drug use as risk behavior. By comparison, fibromyalgia syndrome appeared to be a common cause of musculoskeletal symptoms in this patient population.     

Chronic diffuse musculoskeletal pain,fibromyalgia and co-morbid unexplained clinical conditions

This chapter reviews our current knowledge on the presence of overlapping syndromes in one form of chronic diffuse pain, fibromyalgia. Patients with fibromyalgia often present with signs and symptoms of other unexplained clinical conditions, including chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorders, and multiple chemical sensitivities. The high prevalence, impact on function and opportunities for treatment underscore the need for clinicians and researchers to screen routinely for co-morbid unexplained clinical conditions among persons with fibromyalgia. We, therefore, describe a simple approach to screening for such conditions in accordance with published criteria. Interventions should directly address both fibromyalgia symptoms and co-morbid unexplained clinical conditions, as well as the multiple factors that propagate pain, fatigue and limitations in function.     

Sleep, Epstein-Barr virus infection, musculoskeletal pain, and depressive symptoms in chronic fatigue syndrome.

Sleep physiology, viral serology and symptoms of 14 patients with chronic fatigue syndrome (CFS) were compared with 12 healthy controls. All patients described unrefreshing sleep and showed a prominent alpha electroencephalographic nonrapid eye movement (7.5-11.0 Hz) sleep anomaly (p less than or equal to 0.001), but had no physiologic daytime sleepiness. There were no group differences in Epstein-Barr virus (EBV) antibody titers. The patient group had more fibrositis tender points (p less than 0.0001), described more somatic complaints (p less than 0.0001), and more depressive symptoms (p less than 0.0001). Patients with CFS do not show evidence for a specific chronic EBV infection, but show altered sleep physiology, numerous tender points, diffuse pain, and depressive symptoms. These features are similar to those found in fibromyalgia syndrome.     

Comorbidity of fibromyalgia with medical and psychiatric disorders.

PURPOSE: Patients with fibromyalgia have been reported to display high rates of several concomitant medical and psychiatric disorders, including migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder. To test further these and other possible associations, we assessed the personal and family histories of a broad range of medical and psychiatric disorders in patients with fibromyalgia. PATIENTS AND METHODS: Subjects were 33 women (mean age 42.1 years) who each met American College of Rheumatology criteria for fibromyalgia and presented to a rheumatologist at a tertiary referral center. They received the Structured Clinical Interview for DSM-III-R (SCID); a supplemental interview, in SCID format, for other medical and psychiatric disorders, including migraine, irritable bowel syndrome, and chronic fatigue syndrome; and an interview for family history of medical and psychiatric disorders. RESULTS: Patients with fibromyalgia displayed high lifetime rates of migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder. They also exhibited high rates of familial major mood disorder. CONCLUSIONS: The finding that migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder are frequently comorbid with fibromyalgia is consistent with the hypothesis that these various disorders may share a common physiologic abnormality.     

Somatosensory conflicts in complex regional pain syndrome type 1 and fibromyalgia syndrome

The somatosensory system is an integral component of the motor control system that facilitates the recognition of location and experience of peripheral stimuli, as well as body part position and differentiation. In chronic pain, this system may be disrupted by alterations in peripheral and cortical processing. Clinical symptoms that accompany such changes can be difficult for patients to describe and health care practitioners to comprehend. Patients with chronic pain conditions such as complex regional pain syndrome or fibromyalgia typically describe a diverse range of somatosensory changes. This article describes how sensory information processing can become disturbed in fibromyalgia syndrome and complex regional pain syndrome and how symptoms can potentially be explained by the mechanisms that generate them.     

Hypothalamo-pituitary-adrenal axis dysfunction in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy

These neuroendocrine studies were part of a series of studies testing the hypotheses that 1) there may be reduced activity of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome and 2) low-dose augmentation with hydrocortisone therapy would improve the core symptoms. We measured ACTH and cortisol responses to human CRH, the insulin stress test, and D-fenfluramine in 37 medication-free patients with CDC-defined chronic fatigue syndrome but no comorbid psychiatric disorders and 28 healthy controls. We also measured 24-h urinary free cortisol in both groups. All patients (n = 37) had a pituitary challenge test (human CRH) and a hypothalamic challenge test [either the insulin stress test (n = 16) or D-fenfluramine (n = 21)]. Baseline cortisol concentrations were significantly raised in the chronic fatigue syndrome group for the human CRH test only. Baseline ACTH concentrations did not differ between groups for any test. ACTH responses to human CRH, the insulin stress test, and D- fenfluramine were similar for patient and control groups. Cortisol responses to the insulin stress test did not differ between groups, but there was a trend for cortisol responses both to human CRH and D-fenfluramine to be lower in the chronic fatigue syndrome group. These differences were significant when ACTH responses were controlled. Urinary free cortisol levels were lower in the chronic fatigue syndrome group compared with the healthy group. These results indicate that ACTH responses to pituitary and hypothalamic challenges are intact in chronic fatigue syndrome and do not support previous findings of reduced central responses in hypothalamic-pituitary-adrenal axis function or the hypothesis of abnormal CRH secretion in chronic fatigue syndrome. These data further suggest that the hypocortisolism found in chronic fatigue syndrome may be secondary to reduced adrenal gland output. Thirty-two patients were treated with a low-dose hydrocortisone regime in a double-blind, placebo-controlled cross-over design, with 28 days on each treatment. They underwent repeated 24-h urinary free cortisol collections, a human CRH test, and an insulin stress test after both active and placebo arms of treatment. Looking at all subjects, 24-h urinary free cortisol was higher after active compared with placebo treatments, but 0900-h cortisol levels and the ACTH and cortisol responses to human CRH and the insulin stress test did not differ. However, a differential effect was seen in those patients who responded to active treatment (defined as a reduction in fatigue score to the median population level or less). In this group, there was a significant increase in the cortisol response to human CRH, which reversed the previously observed blunted responses seen in these patients. We conclude that the improvement in fatigue seen in some patients with chronic fatigue syndrome during hydrocortisone treatment is accompanied by a reversal of the blunted cortisol responses to human CRH.     

Co-existence of chronic fatigue syndrome with fibromyalgia syndrome in the general population. A controlled study

OBJECTIVE: To determine the proportion of adults with fibromyalgia syndrome (FMS) in the general population who also meet the 1988 Centre for Disease Control (CDC) criteria for chronic fatigue syndrome (CFS). METHODS: Seventy-four FMS cases were compared with 32 non-FMS controls with widespread pain and 23 with localized pain, all recruited in a general population survey. RESULTS: Among females, 58.0% of fibromyalgia cases met the full criteria for CFS, compared to 26.1% and 12.5% of controls with widespread and localized pain, respectively (p=0.0006). Male percentages were 80.0, 22.2, and zero, respectively (p=0.003). Compared to those with FMS alone, those meeting the case definitions for both FMS and CFS reported a worse course, worse overall health, more dissatisfaction with health, more non-CFS symptoms, and greater disease impact. The number of total symptoms and non-CFS symptoms were the best predictors of co-morbid CFS. CONCLUSIONS: There is significant clinical overlap between CFS and FMS.     

Neuroendocrine mechanisms in fibromyalgia–chronic fatigue

Fibromyalgia and chronic fatigue syndrome are poorly understood disorders that share similar demographic and clinical characteristics. Because of the clinical similarities between both disorders it was suggested that they share a common pathophysiological mechanism, namely, central nervous system dysfunction. This chapter presents data demonstrating neurohormonal abnormalities, abnormal pain processing and autonomic nervous system dysfunction in fibromyalgia and chronic fatigue syndrome. The possible contribution of the central nervous system dysfunction to the development and symptomatology of these conditions is discussed. The chapter concludes by reviewing the effect of current treatments and emerging therapeutic modalities in fibromyalgia and chronic fatigue syndrome.     

Neuroendocrine mechanisms in fibromyalgia-chronic fatigue.

Fibromyalgia and chronic fatigue syndrome are poorly understood disorders that share similar demographic and clinical characteristics. Because of the clinical similarities between both disorders it was suggested that they share a common pathophysiological mechanism, namely, central nervous system dysfunction. This chapter presents data demonstrating neurohormonal abnormalities, abnormal pain processing and autonomic nervous system dysfunction in fibromyalgia and chronic fatigue syndrome. The possible contribution of the central nervous system dysfunction to the development and symptomatology of these conditions is discussed. The chapter concludes by reviewing the effect of current treatments and emerging therapeutic modalities in fibromyalgia and chronic fatigue syndrome.     

Narrative review: the pathophysiology of fibromyalgia

Primary fibromyalgia is a common yet poorly understood syndrome characterized by diffuse chronic pain accompanied by other somatic symptoms, including poor sleep, fatigue, and stiffness, in the absence of disease. Fibromyalgia does not have a distinct cause or pathology. Nevertheless, in the past decade, the study of chronic pain has yielded new insights into the pathophysiology of fibromyalgia and related chronic pain disorders. Accruing evidence shows that patients with fibromyalgia experience pain differently from the general population because of dysfunctional pain processing in the central nervous system. Aberrant pain processing, which can result in chronic pain and associated symptoms, may be the result of several interplaying mechanisms, including central sensitization, blunting of inhibitory pain pathways, alterations in neurotransmitters, and psychiatric comorbid conditions. This review provides an overview of the mechanisms currently thought to be partly responsible for the chronic diffuse pain typical of fibromyalgia.     

The prevalence of musculoskeletal pain and fibromyalgia in patients hospitalized on internal medicine wards

OBJECTIVES: To estimate the prevalence of nonarticular pain complaints (chronic widespread pain, chronic localized pain, transient pain) and fibromyalgia in hospitalized patients and to study utilization patterns of health services associated with pain related problems. METHODS: Five hundred twenty-two patients hospitalized on internal medicine wards were enrolled. Data were collected with a questionnaire covering demographic background, information on pain and other symptoms, utilization of health services, and drug consumption. All subjects were classified into four pain groups: those with no pain, transient pain, chronic regional pain, and chronic widespread pain. Tenderness was assessed by thumb palpation, and patients were diagnosed as having fibromyalgia if they met the 1990 American College of Rheumatology criteria. RESULTS: Sixty-two percent of the patients reported pain; 36% reported chronic regional pain, 21% reported chronic widespread pain, and 5% reported transient pain. Fifteen percent of all patients had fibromyalgia, most of whom (91%) were women. The prevalence of chronic widespread pain and of fibromyalgia in women increased with age. Sleep problems, headache, and fatigue were highly prevalent, especially among those with chronic widespread pain. Patients with chronic widespread pain reported more visits to family physicians (6.2 visits per year) and more frequent use of drugs. They also were more frequently referred to rheumatologists, and they reported more hospitalizations. CONCLUSIONS: Pain syndromes and related symptoms are prevalent among hospitalized patients on the medicine wards. The internist taking care of these patients should be aware of the presence of these syndromes and realize that some of the reported symptoms are partly related to these (undiagnosed) pain syndromes rather than to the cause of hospitalization.     

Autonomic dysfunction in fibromyalgia syndrome: Postural orthostatic tachycardia

Although fibromyalgia (FM) syndrome is defined by chronic widespread pain and tenderness, additional symptoms, including disabling fatigue and dizziness, are often reported by patients with this chronic illness. Although nonrestorative sleep may play an important role for chronic fatigue in FM, other mechanisms, including dysfunction of the autonomic nervous system (ANS), need to be considered. Many important biological functions, such as heart rate, blood pressure, respirations, and bowel function, are tightly regulated by the ANS. However, dysfunction of the ANS is common in FM and often becomes quite apparent after positional changes from supine to upright. Although such positional changes sometimes result in syncope, they are more often associated with palpitations and dizziness. Head-up tilt table testing can be used to evaluate autonomic dysfunction and is frequently helpful for the work-up of FM complaints, including fatigue, dizziness, and palpitations. One of the most common events experienced by FM patients during tilt table testing is postural orthostatic tachycardia syndrome, which is defined as a heart rate increase of more than 30 beats per minute after more than 3 minutes of standing upright.     

Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder

BACKGROUND: Patients with chronic fatigue syndrome (CFS), fibromyalgia (FM), and temporomandibular disorder (TMD) share many clinical illness features such as myalgia, fatigue, sleep disturbances, and impairment in ability to perform activities of daily living as a consequence of these symptoms. A growing literature suggests that a variety of comorbid illnesses also may commonly coexist in these patients, including irritable bowel syndrome, chronic tension-type headache, and interstitial cystitis. OBJECTIVE: To describe the frequency of 10 clinical conditions among patients with CFS, FM, and TMD compared with healthy controls with respect to past diagnoses, degree to which they manifested symptoms for each condition as determined by expert-based criteria, and published diagnostic criteria. METHODS: Patients diagnosed as having CFS, FM, and TMD by their physicians were recruited from hospital-based clinics. Healthy control subjects from a dermatology clinic were enrolled as a comparison group. All subjects completed a 138-item symptom checklist and underwent a brief physical examination performed by the project physicians. RESULTS: With little exception, patients reported few past diagnoses of the 10 clinical conditions beyond their referring diagnosis of CFS, FM, or TMD. In contrast, patients were more likely than controls to meet lifetime symptom and diagnostic criteria for many of the conditions, including CFS, FM, irritable bowel syndrome, multiple chemical sensitivities, and headache. Lifetime rates of irritable bowel syndrome were particularly striking in the patient groups (CFS, 92%; FM, 77%; TMD, 64%) compared with controls (18%) (P<.001). Individual symptom analysis revealed that patients with CFS, FM, and TMD share common symptoms, including generalized pain sensitivity, sleep and concentration difficulties, bowel complaints, and headache. However, several symptoms also distinguished the patient groups. CONCLUSIONS: This study provides preliminary evidence that patients with CFS, FM, and TMD share key symptoms. It also is apparent that other localized and systemic conditions may frequently co-occur with CFS, FM, and TMD. Future research that seeks to identify the temporal relationships and other pathophysiologic mechanism(s) linking CFS, FM, and TMD will likely advance our understanding and treatment of these chronic, recurrent conditions.     

Nongastrointestinal disorders in the irritable bowel syndrome

A large proportion of irritable bowel syndrome (IBS) patients also complain of other functional disorders, such as headache, noncardiac chest pain, low back pain, and dysuria. Some of these features, particularly headache, may have a negative influence on the outcome of IBS. In a large proportion of female IBS patients, sexual intercourse triggers the symptoms, and frequently IBS symptoms exacerbate during menses. These gynecological-type symptoms often mislead the patients to the gynecological clinic, which may imply unnecessary investigations and inappropriate treatments. The diagnostic criteria of the fibromyalgia syndrome include IBS, and hence, the apparent relationship of both syndromes is difficult to analyze. On the other hand, no convincing evidence has been produced to date to sustain an association between IBS and the chronic fatigue syndrome.     

Role of central sensitization in symptoms beyond muscle pain, and the evaluation of a patient with widespread pain

Patients with widespread pain or fibromyalgia syndrome have many symptoms besides musculoskeletal pain: e.g. fatigue, sleep difficulties, a swollen feeling in tissues, paresthesia, cognitive dysfunction, dizziness, and symptoms of overlapping conditions such as irritable bowel syndrome, headaches and restless legs syndrome. There is evidence for central sensitization in these conditions, but further studies are needed. Anxiety, stress and depression are also present in 30-45% of patients. Other factors that may contribute to symptoms include endocrine dysfunction, psychosocial distress, trauma, and disrupted sleep. Evaluation of a patient presenting with widespread pain includes history and physical examination to diagnose both fibromyalgia and associated or concomitant conditions. Fibromyalgia should be diagnosed by its own characteristic features. Some patients with otherwise typical symptoms of fibromyalgia may have as few as four to six tender points in clinical practice. Patients with rheumatoid arthritis and systemic lupus erythematosus should be evaluated for fibromyalgia, since 20-30% of them have associated fibromyalgia, requiring a different treatment approach.