Validating the revised Symptom Impact Questionnaire with a proposed fibromyalgia phenotype using experimentally-induced pain and patient self-reports.

OBJECTIVES: The Symptom Impact Questionnaire (SIQR), now used for over a decade, has strong psychometric properties based on patients' subjective questionnaire data and correlations with other general measures of severity. However, the construct validity of the SIQR in assessing the central features of fibromyalgia (FM) has not been tested specifically with more objective measures. This study examined the construct validity of the SIQR using clinical examination of prominent features of FM, as well as patient questionnaire data. METHODS: We determined if SIQR severity groups (low, moderate, high severity) in 158 chronic pain patients (50 FM, 108 Pain/No FM) predicted four central features of FM tenderness and pain: digital palpation tenderness, blood pressure cuff evoked pain, widespread pain locations, and a persistent deep ache question. RESULTS: Low, moderate, and high SIQR severity groups showed concomitant increases in tenderness in response to digital evoked palpation (F=23.5; p<0.0000; ηp2=0.23; MR=.54), blood pressure cuff evoked pain (F=17.0; p<0.0000; ηp2=0.18; MR=0.48) and number of pain location (F=38.8; p<0.0000; ηp2=0.33; MR.59). Strongest differences in SIQR severity were found in response to the question, "I have a persistent deep aching over most of my body" (F=87.5; p<0.0000; ηp2=0.53; MR=0.74). CONCLUSIONS: The SIQR strongly predicts the central features of FM tenderness and pain including its widespreadness and its multifaceted character. We propose that tenderness, both locally and over most of the body, attendant to the SIQR is the hallmark of the FM phenotype: tenderness is focal, diffuse, deep, and superficial.

Genome-wide expression profiling in the peripheral blood of patients with fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is a common pain disorder characterized by nociceptive dysregulation. The basic biology of FM is poorly understood. Herein we have used agnostic gene expression as a potential probe for informing its underlying biology and the development of a proof-of-concept diagnostic gene expression signature. METHODS: We analyzed RNA expression in 70 FM patients and 70 healthy controls. The isolated RNA was amplified and hybridized to Affymetrix® Human Gene 1.1 ST Peg arrays. The data was analyzed using Partek Genomics Suite version 6.6. RESULTS: Fibromyalgia patients exhibited a differential expression of 421 genes (p<0.001), several relevant to pathways for pain processing, such as glutamine/glutamate signaling and axonal development. There was also an upregulation of several inflammatory pathways and downregulation of pathways related to hypersensitivity and allergy. Using rigorous diagnostic modeling strategies, we show "locked" gene signatures discovered on Training and Test cohorts, that have a mean Area Under the Curve (AUC) of 0.81 on randomized, independent external data cohorts. Lastly, we identified a subset of 10 probesets that provided a diagnostic sensitivity for FM of 95% and a specificity of 96%. We also show that the signatures for FM were very specific to FM rather than common FM comorbidities. CONCLUSIONS: These findings provide new insights relevant to the pathogenesis of FM, and provide several testable hypotheses that warrant further exploration and also establish the foundation for a first blood-based molecular signature in FM that needs to be validated in larger cohorts of patients.

Sodium oxybate therapy provides multidimensional improvement in fibromyalgia: results of an international phase 3 trial.

BACKGROUND: Fibromyalgia is characterised by chronic musculoskeletal pain and multiple symptoms including fatigue, multidimensional function impairment, sleep disturbance and tenderness. Along with pain and fatigue, non-restorative sleep is a core symptom of fibromyalgia. Sodium oxybate (SXB) is thought to reduce non-restorative sleep abnormalities. This study evaluated effects of SXB on fibromyalgia-related pain and other symptoms. METHODS: 573 patients with fibromyalgia according to 1990 American College of Rheumatology criteria were enrolled at 108 centres in eight countries. Subjects were randomly assigned to placebo, SXB 4.5 g/night or SXB 6 g/night. The primary efficacy endpoint was the proportion of subjects with ≥30% reduction in pain visual analogue scale from baseline to treatment end. Other efficacy assessments included function, sleep quality, effect of sleep on function, fatigue, tenderness, health-related quality of life and subject's impression of change in overall wellbeing. RESULTS: Significant improvements in pain, sleep and other symptoms associated with fibromyalgia were seen in SXB treated subjects compared with placebo. The proportion of subjects with ≥30% pain reduction was 42.0% for SXB4.5 g/night (p=0.002) and 51.4% for SXB6 g/night (p<0.001) versus 26.8% for placebo. Quality of sleep (Jenkins sleep scale) improved by 20% for SXB4.5 g/night (p≤0.001) and 25% for SXB6 g/night (p≤0.001) versus 0.5% for placebo. Adverse events with an incidence ≥5% and twice placebo were nausea, dizziness, vomiting, insomnia, anxiety, somnolence, fatigue, muscle spasms and peripheral oedema. CONCLUSION: These results, combined with findings from previous phase 2 and 3 studies, provide supportive evidence that SXB therapy affords important benefits across multiple symptoms in subjects with fibromyalgia.

The effect of dietary glutamate on fibromyalgia and irritable bowel symptoms.

OBJECTIVES: To examine the effects of a challenge with monosodium glutamate (MSG) as compared to placebo on the symptoms of fibromyalgia (FM), in participants who initially experienced >30% remission of symptoms on an excitotoxin elimination diet. METHODS: Fifty-seven FM patients who also had irritable bowel syndrome (IBS) were placed on a 4-week diet that excluded dietary additive excitotoxins including MSG and aspartame. Thirty-seven people completed the diet and 84% of those reported that >30% of their symptoms resolved, thus making them eligible to proceed to challenges. Subjects who improved on the diet were then randomised to a 2-week double-blind placebo-controlled crossover challenge with MSG or placebo for 3 consecutive days each week. The primary outcome measure was total symptom score. Secondary outcome measures included visual analogue pain scales (VAS for FM and IBS), an IBS Quality of Life Questionnaire (IBS QOL) and the Fibromyalgia Impact Questionnaire-Revised (FIQR). Repeated measures ANOVA was used to analyse crossover challenge results. RESULTS: The MSG challenge, as compared to placebo, resulted in a significant return of symptoms (total symptom score, p<0.02); a worsening of fibromyalgia severity as determined by the FIQR (p<0.03); decreased quality of life in regards to IBS symptoms (IBS QOL, p<0.05); and a non-significant trend toward worsening FM pain based on visual analogue scale (VAS, p<0.07). CONCLUSIONS: These findings suggest that dietary glutamate may be contributing to FM symptoms in some patients. Future research on the role of dietary excitotoxins in FM is warranted.

A randomized placebo-controlled study of noninvasive cortical electrostimulation in the treatment of fibromyalgia patients.

OBJECTIVE: The aim of this multicenter study was to evaluate the efficacy, safety, and tolerability of noninvasive cortical electrostimulation in the management of fibromyalgia (FM). DESIGN: A prospective, randomized, double-blind, placebo-controlled design was used. Setting. Subjects received therapy at two different outpatient clinical locations. PATIENTS: There were 77 subjects meeting the American College of Rheumatology 1990 classification criteria for FM. Intervention. Thirty-nine (39) active treatment (AT) FM patients and 38 placebo controls received 22 applications of either noninvasive cortical electrostimulation or a sham therapy over an 11-week period. OUTCOME MEASURES: The primary outcome measures were the number of tender points (TePs) and pressure pain threshold (PPT). Secondary outcome measures were responses to the Fibromyalgia Impact Questionnaire (FIQ), Symptom Checklist-90 (SCL-90), Beck Depression Inventory-II, and a novel sleep questionnaire, all evaluated at baseline and at the end of treatment. RESULTS: Intervention provided significant improvements in TeP measures: compared with placebo, the AT patients improved in the number of positive TePs (-7.4 vs -0.2, P<0.001) and the PPT (19.6 vs -3.2, P<0.001). Most secondary outcomes also improved more in the AT group: total FIQ score (-15.5 vs -5.6, P=0.03), FIQ pain (-2.0 vs -0.6, P=0.03), FIQ fatigue (-2.0 vs -0.4, P=0.02), and FIQ refreshing sleep (-2.1 vs -0.7, P=0.02); and while FIQ function improved (-1.0 vs -0.2), the between-group change had a 14% likelihood of occurring due to chance (P=0.14). There were no significant side effects observed. CONCLUSIONS: Noninvasive cortical electrostimulation in FM patients provided modest improvements in pain, TeP measures, fatigue, and sleep; and the treatment was well tolerated. This form of therapy could potentially provide worthwhile adjunctive symptom relief for FM patients.

Long-term outcomes in fibromyalgia patients treated with noninvasive cortical electrostimulation.

OBJECTIVE: To evaluate long-term outcomes of a noninvasive cortical stimulation technology in the treatment of fibromyalgia (FM). DESIGN: After trial follow-up survey of subjects who had completed a randomized, controlled, double-blind study of noninvasive cortical stimulation therapy some 45 months previously. SETTING: General community. PARTICIPANTS: Patients with FM (N=69) who participated in the previous study, 39 of whom were mailed surveys. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Changes in the Fibromyalgia Impact Questionnaire. RESULTS: There was a 64% survey return rate. The total Fibromyalgia Impact Questionnaire score was 52.6 at baseline, 35.7 at end of study, and 31.8 at follow-up (P<.001). Subjects reported symptom improvements lasting at least 2 years, with a reduction or elimination of medicine use and need to see physicians for FM. CONCLUSIONS: A high percentage of patients with FM treated with noninvasive cortical stimulation continued to experience worthwhile improvement at follow-up.

Which symptoms best distinguish fibromyalgia patients from those with other chronic pain disorders?

RATIONALE, AIMS AND OBJECTIVES: The primary purpose of this study was to test both classic and novel FM pain and non-pain symptoms to determine their practical efficacy in aiding clinicians to distinguish FM pain from other chronic pain disorders. METHODS: 158 pain patients from two primary care clinics were evaluated with history, physical exam, chart review, and a questionnaire containing 26 exploratory symptoms (10 from the Symptom Impact Questionnaire (SIQR) and 16 from the FM literature)). The symptoms were rated on a 0-10 VAS for severity by those patients reporting pain over the past week. Somers' D and mean severity differences between FM and chronic pain patients without FM were used to rank the discriminatory and diagnostic contributions of symptoms. RESULTS: Fifty patients (14.2%) carried a chart diagnosis of FM, 108 (30.7%) had pain but not FM, and 192 (54.5%) who had neither pain nor FM. Comparing means between the two pain groups, the 5 best differentiating symptoms (all, P < .0001) were: a persistent deep aching over most of my body, poor balance (7.4 vs 3.1), environmental sensitivity (6.8 vs 3.0), tenderness to touch (6.8 vs 3.6) and pain after exercise (8.1 vs 4.1). Notably, VAS pain though significantly higher for FM was least discriminatory (6.5 vs 5.1, P < .001). The five best symptoms generated a ROC = 0.85 and Somers' D = 0.69, an accuracy of 81%, and an odd's ratio of 14.4. CONCLUSIONS: Our results herein suggest that clinicians may be well-served to consider symptoms in addition to those contained in current diagnostic criteria when recognizing FM in their chronic pain patients.

Central sensitivity syndromes: mounting pathophysiologic evidence to link fibromyalgia with other common chronic pain disorders.

The aim of this study was to review emerging data from the fields of nursing, rheumatology, dentistry, gastroenterology, gynecology, neurology, and orthopedics that support or dispute pathophysiologic similarities in pain syndromes studied by each specialty. A literature search was performed through PubMed and Ovid using the terms fibromyalgia, temporomandibular joint disorder, irritable bowel syndrome, irritable bladder/interstitial cystitis, headache, chronic low back pain, chronic neck pain, functional syndromes, and somatization. Each term was linked with pathophysiology and/or central sensitization. This paper presents a review of relevant articles with a specific goal of identifying pathophysiologic findings related to nociceptive processing. The extant literature presents considerable overlap in the pathophysiology of these diagnoses. Given the psychosomatic lens through which many of these disorders are viewed, demonstration of evidence-based links supporting shared pathophysiology between these disorders could provide direction to clinicians and researchers working to treat these diagnoses. "Central sensitivity syndromes" denotes an emerging nomenclature that could be embraced by researchers investigating each of these disorders. Moreover, a shared paradigm would be useful in promoting cross-fertilization between researchers. Scientists and clinicians could most effectively forward the understanding and treatment of fibromyalgia and other common chronic pain disorders through an appreciation of their shared pathophysiology.

Neurotherapy of fibromyalgia?

OBJECTIVE: To evaluate the efficacy of a novel variant of electroencephalograph biofeedback, the Low Energy Neurofeedback System (LENS), that utilizes minute pulses of electromagnetic stimulation to change brainwave activity for the amelioration of fibromyalgia (FM) symptoms. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: Tertiary referral academic medical center, outpatient. PATIENTS: Thirty-four patients diagnosed with FM according to 1990 American College of Rheumatology classification criteria. INTERVENTIONS: Active or sham LENS, depending on randomization, for 22 treatment sessions. OUTCOME MEASURES: Primary outcome measure was the Fibromyalgia Impact Questionnaire total score. Secondary outcome measures included number of tender points (TPs) and pressure required to elicit TPs on physical examination, quantitative sensory testing heat pain threshold, and self-reported cognitive dysfunction, fatigue, sleep problems, global psychological distress, and depression obtained at baseline, immediate post-treatment, and 3- and 6-month follow-up. RESULTS: Participants who received the active or sham interventions improved (Ps < 0.05) on the primary and a variety of secondary outcome measures, without statistically significant between group differences in evidence at post-treatment or 3- or 6-month follow-up. Individual session self-reported ratings of specific symptoms (cognitive dysfunction, fatigue, pain, and sleep, and overall activity level) over the course of the 22 intervention sessions indicated significant linear trends for improvement for the active intervention condition only (Ps < 0.05). CONCLUSION: LENS cannot be recommended as a single modality treatment for FM. However, further study is warranted to investigate the potential of LENS to interact synergistically with other pharmacologic and nonpharmacologic therapies for improving symptoms in FM.

Identification of symptom and functional domains that fibromyalgia patients would like to see improved: a cluster analysis.

BACKGROUND: The purpose of this study was to determine whether some of the clinical features of fibromyalgia (FM) that patients would like to see improved aggregate into definable clusters. METHODS: Seven hundred and eighty-eight patients with clinically confirmed FM and baseline pain > or =40 mm on a 100 mm visual analogue scale ranked 5 FM clinical features that the subjects would most like to see improved after treatment (one for each priority quintile) from a list of 20 developed during focus groups. For each subject, clinical features were transformed into vectors with rankings assigned values 1-5 (lowest to highest ranking). Logistic analysis was used to create a distance matrix and hierarchical cluster analysis was applied to identify cluster structure. The frequency of cluster selection was determined, and cluster importance was ranked using cluster scores derived from rankings of the clinical features. Multidimensional scaling was used to visualize and conceptualize cluster relationships. RESULTS: Six clinical features clusters were identified and named based on their key characteristics. In order of selection frequency, the clusters were Pain (90%; 4 clinical features), Fatigue (89%; 4 clinical features), Domestic (42%; 4 clinical features), Impairment (29%; 3 functions), Affective (21%; 3 clinical features), and Social (9%; 2 functional). The "Pain Cluster" was ranked of greatest importance by 54% of subjects, followed by Fatigue, which was given the highest ranking by 28% of subjects. Multidimensional scaling mapped these clusters to two dimensions: Status (bounded by Physical and Emotional domains), and Setting (bounded by Individual and Group interactions). CONCLUSION: Common clinical features of FM could be grouped into 6 clusters (Pain, Fatigue, Domestic, Impairment, Affective, and Social) based on patient perception of relevance to treatment. Furthermore, these 6 clusters could be charted in the 2 dimensions of Status and Setting, thus providing a unique perspective for interpretation of FM symptomatology.

Atypical depression is more common than melancholic in fibromyalgia: an observational cohort study.

BACKGROUND: It has been postulated that atypical and melancholic depression subtypes exist in depressed fibromyalgia (FM) patients, yet no study has empirically tested this hypothesis. The purpose of this study is to determine whether major depressive disorder (MDD) with atypical features and MDD with melancholic features occurs in a FM sample and to describe their demographic, clinical and diagnostic characteristics. METHODS: An observational cohort study using a descriptive cross-sectional design recruited a convenience sample of 76 outpatients with FM from an academic rheumatology clinic and a community mental health practice. Diagnoses of FM were confirmed using the 1990 ACR classification guidelines. Diagnoses of MDD and diagnostic subtypes were determined using the DSM-IV-TR criteria. Clinical characteristics were measured using the Fibromyalgia Impact Questionnaire, Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement and other standardized instruments. Odds ratios were computed on subtype-specific diagnostic criteria. Correlations assessed associations between subtype diagnoses and diagnostic criteria. RESULTS: Of the 76 subjects with FM, 11.8% (n = 9) were euthymic, 52.6% (n = 40) met diagnostic criteria for MDD with atypical features and 35.6% (n = 27) for MDD with melancholic features. Groups did not differ on demographic characteristics except for gender (p = 0.01). The non-depressed and atypical groups trended toward having a longer duration of FM symptoms (18.05 yrs. +/- 12.83; 20.36 yrs. +/- 15.07) compared to the melancholic group (14.11 yrs. +/- 8.82; p = 0.09). The two depressed groups experienced greater severity on all clinical features compared to the non-depressed group. The atypical group did not differ clinically from the melancholic group except the latter experienced greater depression severity (p = 0.001). The atypical group demonstrated the highest prevalence and correlations with atypical-specific diagnostic criteria: (e.g., weight gain/ increased appetite: OR = 3.5, p = 0.02), as did the melancholic group for melancholic-specific criteria: (e.g., anhedonia: OR = 20, p < 0.001). CONCLUSION: Depressed fibromyalgia patients commonly experience both atypical and melancholic depressive features; however, in this study, atypical depression was 1.5 times more common than melancholic depression. This finding may have significant research and clinical implications.

Fibromyalgia is associated with impaired balance and falls.

BACKGROUND/OBJECTIVE: The purpose of this study was to determine whether fibromyalgia (FM) patients differ from matched healthy controls in clinical tests of balance ability and fall frequency. METHODS: Thirty-four FM patients and 32 age-matched controls were administered the Balance Evaluation-Systems Test (BESTest), rated their balance confidence with the Activities-Specific Balance Confidence (ABC) Scale, and reported the number of falls in the last 6 months. The Fibromyalgia Impact Questionnaire was used to assess FM severity. RESULTS: FM patients had significantly impaired balance in all components of the BESTest compared with controls. They also scored more poorly on balance confidence. Overall FM severity (Fibromyalgia Impact Questionnaire) correlated significantly with the BESTest and the ABC scale. The BESTest and ABC correlated significantly with 6 commonly reported FM symptoms (excluding pain). FM patients reported a total of 37 falls over the last 6-months compared with 6 falls in healthy controls. CONCLUSION: FM is associated with balance problems and increased fall frequency. Patients were aware of their balance problems. These results suggest that FM may affect peripheral and/or central mechanisms of postural control. Further objective study is needed to identify the relative contributions of various neural and musculoskeletal and other impairments to postural stability in FM to provide clinicians with methods to maximize postural stability and help fall prevention.

AAPT Diagnostic Criteria for Fibromyalgia.

Fibromyalgia (FM) is a common chronic pain disorder that presents diagnostic challenges for clinicians. Several classification, diagnostic and screening criteria have been developed over the years, but there continues to be a need to develop criteria that reflect the current understanding of FM and are practical for use by clinicians and researchers. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration (FDA) and the American Pain Society (APS) initiated the ACTTION-APS Pain Taxonomy (AAPT) to develop a diagnostic system that would be clinically useful and consistent across chronic pain disorders. The AAPT established an international FM working group consisting of clinicians and researchers with expertise in FM to generate core diagnostic criteria for FM and apply the multidimensional diagnostic framework adopted by AAPT to FM. The process for developing the AAPT criteria and dimensions included literature reviews and synthesis, consensus discussions, and analyses of data from large population-based studies conducted in the United Kingdom. The FM working group established a revised diagnosis of FM and identified risk factors, course, prognosis, and pathophysiology of FM. Future studies will assess the criteria for feasibility, reliability, and validity. Revisions of the dimensions will also be required as research advances our understanding of FM. PERSPECTIVE: The ACTTION-APS FM taxonomy provides an evidence-based diagnostic system for FM. The taxonomy includes diagnostic criteria, common features, comorbidities, consequences, and putative mechanisms. This approach might improve the recognition of FM in clinical practice.

Conceptualizing and measuring illness self-concept: a comparison with self-esteem and optimism in predicting fibromyalgia adjustment.

Illness self-concept (ISC), or the extent to which individuals are consumed by their illness, was theoretically described and evaluated with the Illness Self-Concept Scale (ISCS), a new 23-item scale, to predict adjustment in fibromyalgia. To establish convergent and discriminant validity, illness self-concept was compared to self-esteem and optimism in predicting health status, illness intrusiveness, depression, and life satisfaction. The ISCS demonstrated good reliability (alpha = .94; test-retest r = .80) and was a strong predictor of outcomes, even after controlling for optimism or self-esteem. The ISCS predicted unique variance in health-related outcomes; optimism and self-esteem did not, providing construct validation. Illness self-concept may play a significant role in coping with fibromyalgia and may prove useful in the evaluation of other chronic illnesses.

Fibromyalgia: harmonizing science with clinical practice considerations.

UNLABELLED: This review summarizes the present and emerging knowledge base on the pathophysiology, diagnosis, and management of fibromyalgia. EPIDEMIOLOGY: Fibromyalgia is the most common chronic pain syndrome encountered in general medicine and rheumatology. Historically, contemporary concepts of fibromyalgia have evolved in terms of its clinical description and parallel advances in the understanding of its pathophysiology. PATHOPHYSIOLOGY: A generally accepted paradigm postulates that fibromyalgia is the clinical expression of a rheumatologic disorder in which the associated pain is driven primarily by central sensitization and possibly through changes in several neuronal systems but not necessarily reliant on peripheral processes. MANAGEMENT: Several agents, including serotonin-norepinephrine reuptake inhibitors (ie, duloxetine and milnacipran), opioids (ie, tramadol), and the alpha2-delta ligand pregabalin, which recently received U.S. regulatory approval for the treatment of fibromyalgia, have been evaluated in clinical trials, demonstrating benefit in terms of pain reduction and improvement in core symptoms (ie, fatigue and sleep disturbance). The European League Against Rheumatism has developed updated guidelines for the management of fibromyalgia.

Does familiarity with CDC guidelines, continuing education, and provider characteristics influence adherence to chronic pain management practices and opioid prescribing?

OBJECTIVES: (1) To assess providers' experience and knowledge of chronic noncancer pain (CNCP) management. (2) To assess providers' utilization of the Centers for Disease Control and Prevention (CDC) 2016 Guideline for Prescribing Opioids for Chronic Pain. (3) To assess the influence of the 2016 CDC guideline on provider confidence in managing CNCP and adherence to the CDC recommendations. METHODS: A cross-sectional, web-based survey conducted with 417 Oregon prescribing providers, divided into three continuing medical education (CME) groups composed of minimal (0-3), moderate (4-10), and high (≥11) hours of training. RESULTS: The three CME groups were associated with increased use of CDC opioid recommended practices (29.4, 34.2, 38.8; p = 0.001; scale 0-50), opioid conversion confidence (5.5, 6.5, 7.4; p < 0.001; scale 0-9), and confidence in pain management (5.5, 5.9, 6.9; p < 0.001, scale 0-9). Slightly more providers utilized CDC recommended practices than did not (57 vs 43 percent). However, CME groups differed substantially in utilization of CDC practices (42 vs 57 vs 72 percent; p < 0.001). Neither providers' profession (physician vs nurse practitioner [NP]) nor geographic setting (urban vs rural) showed differences in use of recommended practices or general confident in pain management (all p > 0.05); however, physicians were slightly more confident in opioid dose conversion than NPs (6.9 vs 5.9; p < 0. 001, scale 0-9). CONCLUSIONS: Higher hours of recent CME positively benefit provider confidence in pain management and utilization of CDC recommended practices. NPs and rural providers were equivalent to their physician and urban counterparts on confidence and adherence to CDC practices, with minor exceptions.

A simple screening test to recognize fibromyalgia in primary care patients with chronic pain.

RATIONALE, AIMS, AND OBJECTIVES: Primary care providers are increasingly expected to recognize and treat fibromyalgia (FM) without significant interaction with rheumatologists. The purpose of this study was to evaluate the potential usefulness of 3 simple measures (tenderness to digital pressure, BP cuff-evoked pain, and a single patient question) as a screening test for possible FM in a patient with chronic pain. METHODS: A total of 352 patients (mean age 50 ± 16.3 years, 70% female) scheduled for routine examination in 2 primary care practices were studied. They were comprised of 52 patients (14.8%) who carried a chart diagnosis of FM, 108 (30.7%) with chronic pain but not FM, and 192 who had neither pain nor FM (54.5%). Subjects were assessed for tenderness to digital pressure at 10 locations, BP cuff-evoked pain, and a single question, "I have a persistent deep aching over most of my body" (0-10). RESULTS: FM patients endorsed the single deep ache question substantially more than those with chronic pain but without FM (7.4 ± 2.9 vs 3.2 ± 3.4; P < .0001) and exhibited greater bilateral digital evoked tenderness (6.1 ± 3.1 vs 2.4 ± 2.4, P < 0.0001), and BP-evoked pressure pain (132.6 mmHg ±45.5 vs 169.2 mmHg ±48.0, P < 0.0001). However, on multivariate logistic regressions, the BP cuff-evoked pain became non-significant. On further analyses, a useful screening test was provided by: (1) pain on pinching the Achilles tendon at 4 kg/pressure over 4 seconds, and (2) and positive endorsement of the question "I have a persistent deep aching over most of my body". CONCLUSION: These results suggest that 2 tests, taking less than 1 minute, can indicate a probable diagnosis of FM in a chronic pain patient. In the case of a positive screen, a follow-up examination is required for confirmation or refutation.

Growth hormone perturbations in fibromyalgia: a review.

OBJECTIVE: Fibromyalgia (FM) is a syndrome characterized by chronic widespread pain, fatigue, disrupted sleep, depression, and physical deconditioning. In this article, we review the literature on the normal activity of the hypothalamic-pituitary-growth hormone-insulin-like growth factor-1 (HP-GH-IGF-1) axis and its perturbations in FM subjects. METHODS: Studies included in this review were accessed through an English language search of Cochrane Collaboration Reviews. Keyword MeSH terms included "fibromyalgia," "growth hormone" (GH), or "insulin-like growth factor-1" (IGF-1). RESULTS: Twenty-six studies enrolling 2006 subjects were reviewed. Overall, low levels of IGF-1 were found in a subgroup of subjects. Growth hormone stimulation tests often revealed a suboptimal response, which did not always correlate with IGF-1 levels. No consistent defects in pituitary function were found. Of the 3 randomized placebo controlled studies, only 9 months of daily injectable recombinant GH reduced FM symptoms and normalized IGF-1. CONCLUSIONS: These studies suggest that pituitary function is normal in FM and that reported changes in the HP-GH-IGF-1 axis are most likely hypothalamic in origin. The therapeutic efficacy of supplemental GH therapy in FM requires further study before any solid recommendations can be made.

Is further evaluation for growth hormone (GH) deficiency necessary in fibromyalgia patients with low serum insulin-like growth factor (IGF)-I levels?

OBJECTIVE: Fibromyalgia (FM) is characterized by diffuse pain, fatigue, and sleep disturbances; symptoms that resemble the adult growth hormone (GH) deficiency syndrome. Many FM patients have low serum GH levels, with a hypothesized aetiology of dysregulated GH/insulin-like growth factor (IGF)-I axis. The aim of this study was to assess the GH reserve in FM patients with low serum IGF-I levels using the GH-releasing hormone (GHRH)-arginine test. DESIGN: We retrospectively reviewed the GHRH-arginine data of 77 FM patients with low serum IGF-I levels referred to our tertiary unit over a 4-year period. RESULTS: Of the 77 FM patients, 13 patients (17%) failed the GHRH-arginine test. Further evaluation with pituitary imaging revealed normal pituitary glands (n=7), coincident microadenomas (n=4), empty sella (n=1) and pituitary cyst (n=1), and relevant medical histories such as previous head injury (n=4), Sheehan's syndrome (n=1), and whiplash injury (n=1). In contrast, the remaining 64 patients (83%) that responded to the GHRH-arginine test demonstrated higher peak GH levels compared to age and BMI-matched controls (n=24). CONCLUSION: Our data shows that a subpopulation of FM patients with low serum IGF-I levels will fail the GHRH-arginine test. We, thus, recommend that the GH reserve of these patients should be evaluated further, as GH replacement may potentially improve the symptomatology of those with true GH deficiency. Additionally, the increased GH response rates to GHRH-arginine stimulation in the majority of FM patients with low serum IGF-I levels further supports the hypothesis of a dysregulated GH/IGF-I axis in the pathophysiology of FM.

An internet survey of 2,596 people with fibromyalgia.

BACKGROUND: This study explored the feasibility of using an Internet survey of people with fibromyalgia (FM), with a view to providing information on demographics, sources of information, symptoms, functionality, perceived aggravating factors, perceived triggering events, health care utilization, management strategies, and medication use. METHODS: A survey questionnaire was developed by the National Fibromyalgia Association (NFA) in conjunction with a task force of "experts in the field". The questionnaire underwent several rounds of testing to improve its face validity, content validity, clarity and readability before it was mounted on the internet. The questionnaire consisted of 121 items and is available online at the website of the National Fibromyalgia Association. RESULTS: The questionnaire was completed by 2,569 people. Most were from the United States, with at least one respondent from each of the 50 states. Respondents were predominantly middle-aged Caucasian females, most of whom had FM symptoms for > or = 4 years. The most common problems were morning stiffness, fatigue, nonrestorative sleep, pain, concentration, and memory. Aggravating factors included: emotional distress, weather changes, insomnia, and strenuous activity. Respondents rated the most effective management modalities as rest, heat, pain medications, antidepressants, and hypnotics. The most commonly used medications were: acetaminophen, ibuprofen, naproxen, cyclobenzaprine, amitriptyline, and aspirin. The medications perceived to be the most effective were: hydrocodone preparations, aprazolam, oxycodone preparations, zolpidem, cyclobenzaprine, and clonazepam. CONCLUSION: This survey provides a snap-shot of FM at the end of 2005, as reported by a self-selected population of people. This descriptive data has a heuristic function, in that it identifies several issues for further research, such as the prescribing habits of FM health care providers, the role of emotional precipitants, the impact of obesity, the significance of low back pain and the nature of FM related stiffness.