The fibromyalgia family study: a genome-wide linkage scan study.

OBJECTIVE: Familial aggregation of fibromyalgia has been increasingly recognized. The goal of this study was to conduct a genome-wide linkage scan to identify susceptibility loci for fibromyalgia. METHODS: We genotyped members of 116 families from the Fibromyalgia Family Study and performed a model-free genome-wide linkage analysis of fibromyalgia with 341 microsatellite markers, using the Haseman-Elston regression approach. RESULTS: The estimated sibling recurrence risk ratio (λs ) for fibromyalgia was 13.6 (95% confidence interval 10.0-18.5), based on a reported population prevalence of 2%. Genome-wide suggestive evidence of linkage was observed at markers D17S2196 (empirical P [Pe ]=0.00030) and D17S1294 (Pe=0.00035) on chromosome 17p11.2-q11.2. CONCLUSION: The estimated sibling recurrence risk ratio (λs ) observed in this study suggests a strong genetic component of fibromyalgia. This is the first report of genome-wide suggestive linkage of fibromyalgia to the chromosome 17p11.2-q11.2 region. Further investigation of these multicase families from the Fibromyalgia Family Study is warranted to identify potential causal risk variants for fibromyalgia.

Cross-cultural adaptation and validation of a Bengali version of the modified fibromyalgia impact questionnaire.

BACKGROUND: Currently, no validated instruments are available to measure the health status of Bangladeshi patients with fibromyalgia (FM). The aims of this study were to cross-culturally adapt the modified Fibromyalgia Impact Questionnaire (FIQ) into Bengali (B-FIQ) and to test its validity and reliability in Bangladeshi patients with FM. METHODS: The FIQ was translated following cross-cultural adaptation guidelines and pretested in 30 female patients with FM. Next, the adapted B-FIQ was physician-administered to 102 consecutive female FM patients together with the Health Assessment Questionnaire (HAQ), selected subscales of the SF-36, and visual analog scales for current clinical symptoms. A tender point count (TPC) was performed by an experienced rheumatologist. Forty randomly selected patients completed the B-FIQ again after 7 days. Two control groups of 50 healthy people and 50 rheumatoid arthritis (RA) patients also completed the B-FIQ. RESULTS: For the final B-FIQ, five physical function sub-items were replaced with culturally appropriate equivalents. Internal consistency was adequate for both the 11-item physical function subscale (α = 0.73) and the total scale (α = 0.83). With exception of the physical function subscale, expected correlations were generally observed between the B-FIQ items and selected subscales of the SF-36, HAQ, clinical symptoms, and TPC. The B-FIQ was able to discriminate between FM patients and healthy controls and between FM patients and RA patients. Test-retest reliability was adequate for the physical function subscale (r = 0.86) and individual items (r = 0.73-0.86), except anxiety (r = 0.27) and morning tiredness (r = 0.64). CONCLUSION: This study supports the reliability and validity of the B-FIQ as a measure of functional disability and health status in Bangladeshi women with FM.

The concept of incomplete fibromyalgia syndrome: comparison of incomplete fibromyalgia syndrome with fibromyalgia syndrome by 1990 ACR classification criteria and its implications for newer criteria and clinical practice.

BACKGROUND: The 1990 American College of Rheumatology (ACR) classification criteria for fibromyalgia/fibromyalgia syndrome (FMS) has 2 components: (a) widespread pain (WSP) and (b) presence of 11 or more tender points (TP) among possible 18 sites. Some clinic patients fulfill 1 component but not the other. We have considered these patients to have incomplete FMS (IFMS). The purpose of this study was to examine the clinical and psychological differences between IFMS and FMS (by 1990 ACR criteria) because such comparison may be helpful to diagnose patients in the clinic. METHODS: Six hundred consecutive patients referred to our rheumatology clinic with a diagnosis of FMS were examined by a standard protocol to determine whether they fulfilled the 1990 criteria for FMS. Both IFMS and FMS groups were compared in demographic, clinical, and psychological variables using appropriate statistical methods. RESULTS: One hundred twelve (18.7%) patients did not satisfy the 1990 ACR criteria and were classified as IFMS. Symptoms in IFMS and FMS were similar, generally with less frequent and less severe symptoms in the IFMS group. In IFMS, no significant difference was found among the WSP and TP component subgroups. Both TP and WSP were correlated with important features of FMS. CONCLUSIONS: Fulfillment of the ACR 1990 criteria is not necessary for a diagnosis of FMS in the clinic. For diagnosis and management of FMS in the clinical setting, IFMS patients, along with consideration of the total clinical picture, may be considered to have FMS, albeit generally mild.

Central sensitivity syndromes: a new paradigm and group nosology for fibromyalgia and overlapping conditions, and the related issue of disease versus illness.

OBJECTIVES: To discuss the current terminologies used for fibromyalgia syndrome (FMS) and related overlapping conditions, to examine if central sensitivity syndromes (CSS) is the appropriate nosology for these disorders, and to explore the issue of disease versus illness. METHODS: A literature search was performed through PubMed, Web of Science, and ScienceDirect using a number of keywords, eg, functional somatic syndromes, somatoform disorders, medically unexplained symptoms, organic and nonorganic, and diseases and illness. Relevant articles were then reviewed and representative ones cited. RESULTS: Terminologies currently used for CSS conditions predominantly represent a psychosocial construct and are inappropriate. On the other hand, CSS seems to be the logical nosology based on a biopsychosocial model. Such terms as "medically unexplained symptoms," "somatization," "somatization disorder," and "functional somatic syndromes" in the context of CSS should be abandoned. Given current scientific knowledge, the concept of disease-illness dualism has no rational basis and impedes proper patient-physician communication, resulting in poor patient care. The concept of CSS is likely to promote research, education, and proper patient management. CONCLUSION: CSS seems to be a useful paradigm and an appropriate terminology for FMS and related conditions. The disease-illness, as well as organic/non-organic dichotomy, should be rejected.

Fibromyalgia and overlapping disorders: the unifying concept of central sensitivity syndromes.

OBJECTIVES: To discuss fibromyalgia syndrome (FMS) and overlapping conditions, eg, irritable bowel syndrome, headaches, and chronic fatigue syndrome, within the concept of central sensitivity syndromes (CSS). METHODS: A critical overview of the literature and incorporation of the author's own views. RESULTS: The concept of CSS seems viable. It is based on mutual associations among the CSS conditions as well as the evidence for central sensitization (CS) among several CSS members. However, such evidence is weak or not available in other members at this time, requiring further studies. The biology of CSS is based on neuroendocrine aberrations, including CS, that interact with psychosocial factors to cause a number of symptoms. CONCLUSIONS: CSS is an important new concept that embraces the biopsychosocial model of disease. Further critical studies are warranted to fully test this concept. However, it seems to have important significance for new directions for research and patient care involving physician and patient education. Each patient, irrespective of diagnosis, should be treated as an individual considering both the biological and psychosocial contributions to his or her symptoms and suffering.

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.

Editorial review: an update on central sensitivity syndromes and the issues of nosology and psychobiology.

Central sensitization (CS), simply defined as an amplified response of the central nervous system to peripheral input, is a concept of great importance in clinical medicine. It has helped to explain aspects of the pathophysiology of common diseases, e.g. fibromyalgia syndrome (FMS), irritable bowel syndrome, vulvodynia, headaches, chronic pelvic pain and other overlapping conditions (collectively called central sensitivity syndromes, or CSS). It also applies to pain of complex regional pain syndrome, osteoarthritis (OA), rheumatoid arthritis (RA) and post-operative pain. The pathology-pain gap in CSS is readily explained by CS. Many FMS and other CSS patients have peripheral pathology, e.g. nociceptive areas in the muscles, arthritis, small fiber neuropathy and inflammation. Pro-inflammatory cytokines are elevated in some patients. Identification of CS in patients with structural pathology, e.g. OA and RA, has helped to explain why not all patients benefit from nonsteroidal anti-inflammatory drugs or joint replacement surgery, and require therapy directed at CS. Glial cells are important in pain processing. Remarkable advances have been achieved in neuroimaging, including visualization of grey matter and white matter, not only during provoked pain but also pain at rest. Based on CS mechanisms, targeted individual therapy may now be possible. Appropriate nosology is important particularly for effective patient care. Dichotomy of neurochemical-structural ("functional") and structural ("organic") pathology should be abandoned; many patients have both. Psychobiology is also biology. Patient-blaming terms like somatization, somatizer and catastrophizing should be avoided. For therapy, both pharmacological and non- pharmacological approaches are important, including recognition of subgroups and person/patient-centered care.

Is chronic pain a variant of depressive disease? The case of primary fibromyalgia syndrome.

The responses of 45 primary fibromyalgia syndrome (PFS) patients, 29 rheumatoid arthritis (RA) patients and 31 healthy non-pain controls (NC) on the Zung Self-Rating Depression scale were compared. No difference between the PFS and RA groups was found, although the former has no known organic pathology, unlike the latter. Therefore, the hypothesis that the presentation of chronic pain in the absence of a known organic pathology is a variant of 'depressive disease' was not supported in the case of PFS. However, a subgroup of PFS (28.6%) and RA (31.0%) patients appeared to be experiencing significant depressive symptomatology.

The use of contemporary MMPI norms in the study of chronic pain patients.

In a previous study, Ahles et al. [1] compared the MMPI results of primary fibromyalgia, rheumatoid arthritis and non-pain control participants. The purpose of the present study was to reanalyze the original data using the contemporary norms of Colligan et al. [5]. The reanalysis revealed that the pattern of group differences remained the same; however, the number of primary fibromyalgia patients classified as 'psychologically disturbed' was appreciably reduced. These data have clinical relevance in that the incidence of psychopathology in chronic pain patients may be overestimated because of the use of outdated norms. Additionally the data have theoretical relevance in that a large number of patients who present with pain in the absence of a known organic pathology do not present evidence of psychopathology.

A comprehensive medical evaluation of patients with fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) is a common and distressful condition. It is imperative that all physicians do their best to help these suffering patients with understanding and respect, since the primary responsibility of a physician is to ameliorate suffering of a patient, irrespective of the type of the disease or the illness. (The authors use the terms "disease" and "illness" synonymously, since any distinction between these two terms are really pointless because the word "disease" means lack of ease or presence of suffering.) It is clear that a physician cannot optimize management of a patient with FMS without a thorough medical and psychologic evaluation. A good evaluation helps to make a proper diagnosis, assess severity, recognize aggravating and relieving factors of symptoms, appraise psychologic factors, evaluate relevant associated or concomitant conditions, document individualized problems in a given patient, and subsequently formulate proper and individualized management. This article focuses on the major elements of a comprehensive medical evaluation, with some reference to psychologic aspects--are covered in detail in the article by Turk et al in this issue.

The prevalence of fibromyalgia in other chronic pain conditions.

Central sensitivity syndromes (CSS) include fibromyalgia syndrome (FMS), irritable bowel syndrome, temporomandibular disorder, restless legs syndrome, chronic fatigue syndrome, and other similar chronic painful conditions that are based on central sensitization (CS). CSS are mutually associated. In this paper, prevalence of FMS among other members of CSS has been described. An important recent recognition is an increased prevalence of FMS in other chronic pain conditions with structural pathology, for example, rheumatoid arthritis, systemic lupus, ankylosing spondylitis, osteoarthritis, diabetes mellitus, and inflammatory bowel disease. Diagnosis and proper management of FMS among these diseases are of crucial importance so that unwarranted use of such medications as corticosteroids can be avoided, since FMS often occurs when RA or SLE is relatively mild.

The clinical concept of fibromyalgia as a changing paradigm in the past 20 years.

Fibromyalgia (FMS) is a valid clinical condition that affects 2%-4% of the population with a pivot symptom of widespread body pain. The cause and cure of FMS are as yet unknown. The concept of FMS has evolved over the past two decades to incorporate symptoms beyond pain as contributing to the global spectrum of suffering. FMS is now recognized to be grounded in the neurological domain with evidence of dysregulation of pain processing. Appreciation of the neurophysiologic mechanisms operative in FMS has contributed to rational treatment recommendations, although a "gold standard treatment" does not currently exist. Ideal treatments for FMS patients should be individualized with emphasis on active patient participation, good health practices, and multimodal intervention, incorporating nonpharmacologic and pharmacologic treatments. Predictors of outcome, which is favourable in over 50% of patients, are unknown, but those with better outcome do more physical activity and use fewer medications.

The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity.

OBJECTIVE: To develop simple, practical criteria for clinical diagnosis of fibromyalgia that are suitable for use in primary and specialty care and that do not require a tender point examination, and to provide a severity scale for characteristic fibromyalgia symptoms. METHODS: We performed a multicenter study of 829 previously diagnosed fibromyalgia patients and controls using physician physical and interview examinations, including a widespread pain index (WPI), a measure of the number of painful body regions. Random forest and recursive partitioning analyses were used to guide the development of a case definition of fibromyalgia, to develop criteria, and to construct a symptom severity (SS) scale. RESULTS: Approximately 25% of fibromyalgia patients did not satisfy the American College of Rheumatology (ACR) 1990 classification criteria at the time of the study. The most important diagnostic variables were WPI and categorical scales for cognitive symptoms, unrefreshed sleep, fatigue, and number of somatic symptoms. The categorical scales were summed to create an SS scale. We combined the SS scale and the WPI to recommend a new case definition of fibromyalgia: (WPI > or =7 AND SS > or =5) OR (WPI 3-6 AND SS > or =9). CONCLUSION: This simple clinical case definition of fibromyalgia correctly classifies 88.1% of cases classified by the ACR classification criteria, and does not require a physical or tender point examination. The SS scale enables assessment of fibromyalgia symptom severity in persons with current or previous fibromyalgia, and in those to whom the criteria have not been applied. It will be especially useful in the longitudinal evaluation of patients with marked symptom variability.

Gender differences in fibromyalgia and other related syndromes.

Fibromyalgia syndrome is characterized by widespread musculoskeletal pain, fatigue, poor sleep, and tenderness on palpation at multiple sites called tender points. It occurs mostly among women; only about 10% of patients are men. Two recent studies showed that women had significantly more common fatigue, morning fatigue, "hurt all over," a greater total number of symptoms, as well as a greater number of tender points. Gender differences have also been reported in other related syndromes such as tension headache, migraine, irritable bowel syndrome, chronic fatigue syndrome, and temporomandibular disorder. Although the mechanisms of gender differences in these illnesses are not fully understood, they are likely to involve an interaction between biology, psychology, and sociocultural factors.

History of fibromyalgia: past to present.

Fibromyalgia syndrome (FMS) is now a recognized clinical entity causing chronic and disabling pain. For several centuries, muscle pains have been known as rheumatism and then as muscular rheumatism. The term fibrositis was coined by Gowers in 1904 and was not changed to fibromyalgia until 1976. Smythe laid the foundation of modern FMS in 1972 by describing widespread pain and tender points. The first sleep electroencephalogram study was performed in 1975. The first controlled clinical study with validation of known symptoms and tender points was published in 1981. This same study also proposed the first data-based criteria. The important concept that FMS and other similar conditions are interconnected was proposed in 1984. The first American College of Rheumatology criteria were published in 1990 and neurohormonal mechanisms with central sensitization were developed in the 1990s. Serotonergic/norepinephric drugs were first shown to be effective in 1986.

Fibromyalgia in men: comparison of psychological features with women.

OBJECTIVE: To describe possible differences in psychological factors in men compared to women with fibromyalgia syndrome (FM). METHODS: Forty men and 160 women with FM were evaluated for anxiety, stress, and depression measured by ordinal scales and validated psychological instruments. Clinical and psychological variables were evaluated by a protocol. RESULTS: Both men and women scored high in the psychological variables measured but the results were not significantly different between them. CONCLUSION: There was no significant difference between men and women with FM in their psychological status.

Relationship between fibromyalgia features and smoking.

OBJECTIVE: The objective of this study was to examine a possible relationship between smoking and fibromyalgia features among 233 female patients with fibromyalgia syndrome. METHODS: Data on clinical and psychological features were collected by a protocol. Smoking status was evaluated by a question inquiring about the packs of cigarettes smoked per day. Differences between the smokers and non-smokers were tested by Mann Whitney U test. To adjust data for age and education, a partial correlation test was used. A p value of < or = 0.01 was accepted as the level of significance. RESULTS: Fifty-one patients (21.9%) smoked. After adjustment for age and education, significantly positive relationship was found between smoking and pain, patient global severity, functional disability, and numbness. There was no difference between smokers and non-smokers for fatigue, morning fatigue, sleep difficulties, tender points (TP), depression, anxiety and stress. CONCLUSIONS: Smokers reported significantly more pain, numbness, patient global severity, and functional difficulties than non-smokers. There was no significant difference between smokers and non-smokers for fatigue and TP.

Relationship between body mass index and fibromyalgia features.

OBJECTIVE: to evaluate the relationship between body mass index (BMI) and features of the fibromyalgia syndrome (FMS). METHODS: 211 female patients with FMS seen consecutively in our rheumatology clinic were analyzed. Spearman correlation was used. Further, FMS features were compared at different levels of BMI (kg/m2), e.g., < 25.00 vs > or = 25.00 (normal vs overweight). P value of < or = 0.01 was accepted as significant. RESULTS: A significant positive correlation was found between BMI and age (p<0.001) and a negative correlation between BMI and education (p<0.009). Health Assessment Questionnaire (HAQ) score was significantly correlated with BMI (p<0.001), whereas fatigue and number of tender points (TP) showed a trend (p=0.035 and 0.037, respectively). CONCLUSION: The HAQ score is significantly associated with BMI in FMS with a trend towards significance for fatigue and TP. Weight loss may improve physical functioning in this disorder.