Brian Walitt

The development of fibromyalgia--I: examination of rates and predictors in patients with rheumatoid arthritis (RA).

&NA; We determined rates and predictors of future development of fibromyalgia in patients with rheumatoid arthritis (RA). After excluding patients with fibromyalgia and those with high levels of fibromyalgia symptoms (fibromyalgianess score >10) at baseline, we studied fibromyalgia development in 9739 RA patients during 42,591 patient‐years of follow‐up. We defined fibromyalgia using a modification of the ACR 2010 fibromyalgia criteria. We used Cox regression to predict future fibromyalgia, and examined the accuracy of predictions using Harrell’s C concordance coefficient. At the last observation, 7.4% of patients satisfied criteria, although 19.8% satisfied criteria at some point during follow‐up, an incidence rate of 5.3 (95% CI 5.1, 5.6) per 100 patients years, and at rates that were similar in men (7.0%) and women (8.1%). Among those satisfying criteria, during 11,363 years of follow‐up from the time of first fibromyalgia diagnosis, half of follow‐up time was fibromyalgia+ and was associated with markedly abnormal RA variable and FM variable scores. Demographic factors were weak predictors of fibromyalgia (C = 0.604). Demographic plus RA variables (C = 0.720) and demographic plus fibromyalgia variables (C = 0.765), and all predictors (C = 0.782) increased accuracy. Clinically important hazard ratios were noted for cognition, depression, comorbidity, and high levels of RA and FM continuous variables Overall, study results indicate that multiple, inter‐correlated factors that include social disadvantage, psychological distress, comorbidity, RA severity, and fibromyalgia variables predict future development of fibromyalgia, but there is little evidence of the effect of underlying causes. After diagnosis, patients move in both directions across the diagnostic criteria cut points.

The Longitudinal Outcome of Fibromyalgia: A Study of 1555 Patients

Objective. To describe the diagnosis status and outcome of patients diagnosed with fibromyalgia (FM) by US rheumatologists. Methods. We assessed 1555 patients with FM with detailed outcome questionnaires during 11,006 semiannual observations for up to 11 years. At entry, all patients satisfied American College of Rheumatology preliminary 2010 FM criteria modified for survey research. We determined diagnosis status, rates of improvement, responder subgroups, and standardized mean differences (effect sizes) between start and study completion scores of global well-being, pain, sleep problems, and health related quality of life. (QOL) Results. The 5-year improvement rates were pain 0.4 (95% CI 0.2, 0.5), fatigue 0.4 (95% CI 0.2, 0.05), and global 0.0 (95% CI −0.1, 0.1). The standardized mean differences were patient global 0.03 (95% CI −0.02, 0.08), pain 0.22 (95% CI 0.16, 0.28), sleep problems 0.20 (95% CI 0.14, 0.25), physical component summary of the Short-form 36 (SF-36) 0.11 (95% CI −0.14, −0.07), and SF-36 mental component summary 0.03 (95% CI −0.07, 0.02). Patients switched between criteria-positive and criteria-negative states, with 716 patients (44.0%) failing to meet criteria at least once during 4228.5 patient-years (7448 observations). About 10% of patients had substantial improvement and about 15% had moderate improvement of pain. Overall, FM severity worsened in 35.9% and pain in 38.6%. Conclusion. Although we found no average clinically meaningful improvement in symptom severity overall, 25% had at least moderate improvement of pain over time. The result that emerged from this longitudinal study was one of generally continuing high levels of self-reported symptoms and distress for most patients, but a slight trend toward improvement.

Insecticide use and risk of rheumatoid arthritis and systemic lupus erythematosus in the Women's Health Initiative Observational Study.

Farming and agricultural pesticide use has been associated with 2 autoimmune rheumatic diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, risk associated with other residential or work place insecticide use is unknown.

Effects of Postmenopausal Hormone Therapy on Rheumatoid Arthritis: The Women's Health Initiative Randomized Controlled Trials

OBJECTIVE To study the effects of postmenopausal hormone therapy (PHT) on the incidence and severity of rheumatoid arthritis (RA). METHODS The Womens Health Initiative randomized controlled trials evaluated the effects of unopposed estrogen (E-alone) and estrogen plus progestin (E+P) compared with placebo on a diverse set of health outcomes over 7.1 and 5.6 years, respectively. RA cases were identified using historical and medication data. The hazard of developing RA was estimated using Cox proportional hazards regression models. Disease symptom severity was estimated using the Short Form 36 (SF-36) and self-reported joint pain scores at baseline and after 1 year. Mean changes in severity were compared using linear regression models. RESULTS Of the 27,347 participants, 63 prevalent cases and 105 incident cases of RA were identified. A nonsignificant reduction in the risk of developing RA (hazard ratio 0.74; 95% confidence interval [95% CI] 0.51, 1.10) was noted with PHT use. PHT use led to improved SF-36 scores in unadjusted analyses (percent change 12.5%; 95% CI -24.45, -0.57) but not after adjustment for relevant covariates (P = 0.33). Nonsignificant improvements in joint pain scores were seen with PHT use (odds ratio [OR] 4.10; 95% CI 0.83, 20.20). PHT did not improve swelling (OR 1.27; 95% CI 0.08, 19.63) or prevent new joint pains (OR 0.72; 95% CI 0.11, 4.68) in RA participants. CONCLUSION There were no statistically significant differences in the risk of developing RA or the severity of RA between the PHT and placebo groups.

The Prevalence and Characteristics of Fibromyalgia in the 2012 National Health Interview Survey

Background Most knowledge of fibromyalgia comes from the clinical setting, where healthcare-seeking behavior and selection issues influence study results. The characteristics of fibromyalgia in the general population have not been studied in detail. Methods We developed and tested surrogate study specific criteria for fibromyalgia in rheumatology practices using variables from the US National Health Interview Survey (NHIS) and the modification (for surveys) of the 2010 American College of Rheumatology (ACR) preliminary fibromyalgia criteria. The surrogate criteria were applied to the 2012 NHIS and identified persons who satisfied criteria from symptom data. The NHIS weighted sample of 8446 persons represents 225.7 million US adults. Results Fibromyalgia was identified in 1.75% (95% CI 1.42, 2.07), or 3.94 million persons. However, 73% of identified cases self-reported a physician’s diagnosis other than fibromyalgia. Identified cases had high levels of self-reported pain, non-pain symptoms, comorbidity, psychological distress, medical costs, Social Security and work disability. Caseness was associated with gender, education, ethnicity, citizenship and unhealthy behaviors. Demographics, behaviors, and comorbidity were predictive of case status. Examination of the surrogate polysymptomatic distress scale (PSD) of the 2010 ACR criteria found fibromyalgia symptoms extending through the full length of the scale. Conclusions Persons identified with criteria-based fibromyalgia have severe symptoms, but most (73%) have not received a clinical diagnosis of fibromyalgia. The association of fibromyalgia-like symptoms over the full length of the PSD scale with physiological as well as mental stressors suggests PSD may be a universal response variable rather than one restricted to fibromyalgia.

Arthritis Increases the Risk for Fractures---Results from the Women’s Health Initiative

Objective. To examine the relationship between arthritis and fracture. Methods. Women were classified into 3 self-reported groups at baseline: no arthritis (n = 83,295), osteoarthritis (OA; n = 63,402), and rheumatoid arthritis (RA; n = 960). Incident fractures were self-reported throughout followup. Age-adjusted fracture rates by arthritis category were generated, and the Cox proportional hazards model was used to test the association between arthritis and fracture. Results. After an average of 7.80 years, 24,137 total fractures were reported including 2559 self-reported clinical spinal fractures and 1698 adjudicated hip fractures. For each fracture type, age-adjusted fracture rates were highest in the RA group and lowest in the nonarthritic group. After adjustment for several covariates, report of arthritis was associated with increased risk for spine, hip, and any clinical fractures. Compared to the nonarthritis group, the risk of sustaining any clinical fracture in the OA group was HR 1.09 (95% CI 1.05, 1.13; p < 0.001) and HR 1.49 (95% CI 1.26, 1.75; p < 0.001) in the RA group. The risk of sustaining a hip fracture was not statistically increased in the OA group (HR 1.11; 95% CI 0.98, 1.25; p = 0.122) compared to the nonarthritis group; however, the risk of hip fracture increased significantly (HR 3.03; 95% CI 2.03, 4.51; p < 0.001) in the RA group compared to the nonarthritis group. Conclusion. The increase in fracture risk confirms the importance of fracture prevention in patients with RA and OA.

Mortality in fibromyalgia: A study of 8,186 patients over thirty‐five years

To determine if mortality is increased among patients diagnosed as having fibromyalgia.

Increased brain white matter axial diffusivity associated with fatigue, pain and hyperalgesia in Gulf War illness.

Background Gulf War exposures in 1990 and 1991 have caused 25% to 30% of deployed personnel to develop a syndrome of chronic fatigue, pain, hyperalgesia, cognitive and affective dysfunction. Methods Gulf War veterans (n = 31) and sedentary veteran and civilian controls (n = 20) completed fMRI scans for diffusion tensor imaging. A combination of dolorimetry, subjective reports of pain and fatigue were correlated to white matter diffusivity properties to identify tracts associated with symptom constructs. Results Gulf War Illness subjects had significantly correlated fatigue, pain, hyperalgesia, and increased axial diffusivity in the right inferior fronto-occipital fasciculus. ROC generated thresholds and subsequent binary regression analysis predicted CMI classification based upon axial diffusivity in the right inferior fronto-occipital fasciculus. These correlates were absent for controls in dichotomous regression analysis. Conclusion The right inferior fronto-occipital fasciculus may be a potential biomarker for Gulf War Illness. This tract links cortical regions involved in fatigue, pain, emotional and reward processing, and the right ventral attention network in cognition. The axonal neuropathological mechanism(s) explaining increased axial diffusivity may account for the most prominent symptoms of Gulf War Illness.

Toward development of a fibromyalgia responder index and disease activity score: OMERACT module update.

Following development of the core domain set for fibromyalgia (FM) in Outcome Measures in Rheumatology Clinical Trials (OMERACT) meetings 7 to 9, the FM working group has progressed toward the development of an FM responder index and a disease activity score based on these domains, utilizing outcome indices of these domains from archived randomized clinical trials in FM. Possible clinical domains that could be included in a responder index and disease activity score include pain, fatigue, sleep disturbance, cognitive dysfunction, mood disturbance, tenderness, stiffness, and functional impairment. Outcome measures for these domains demonstrate good to adequate psychometric properties, although measures of cognitive dysfunction need to be further developed. The approach used in the development of responder indices and disease activity scores for rheumatoid arthritis and ankylosing spondylitis represents heuristic models for our work, but FM is challenging in that there is no clear algorithm of treatment that defines disease activity based on treatment decisions, nor are there objective markers that define thresholds of severity or response to treatment. The process of developing candidate dichotomous responder definitions and continuous quantitative disease activity measures is described, along with participant discussions from OMERACT 10. Final results of this work will be published in a separate report pending completion of analyses.

Symptoms, the Nature of Fibromyalgia, and Diagnostic and Statistical Manual 5 (DSM-5) Defined Mental Illness in Patients with Rheumatoid Arthritis and Fibromyalgia

Purpose To describe and evaluate somatic symptoms in patients with rheumatoid arthritis (RA) and fibromyalgia, determine the relation between somatization syndromes and fibromyalgia, and evaluate symptom data in light of the Diagnostic and Statistical Manual-5 (DSM-5) criteria for somatic symptom disorder. Methods We administered the Patient Health Questionnaire-15 (PHQ-15), a measure of somatic symptom severity to 6,233 persons with fibromyalgia, RA, and osteoarthritis. PHQ-15 scores of 5, 10, and 15 represent low, medium, and high somatic symptom severity cut-points. A likely somatization syndrome was diagnosed when PHQ-15 score was ≥10. The intensity of fibromyalgia diagnostic symptoms was measured by the polysymptomatic distress (PSD) scale. Results 26.4% of RA patients and 88.9% with fibromyalgia had PHQ-15 scores ≥10 compared with 9.3% in the general population. With each step-wise increase in PHQ-15 category, more abnormal mental and physical health status scores were observed. RA patients satisfying fibromyalgia criteria increased from 1.2% in the PHQ-15 low category to 88.9% in the high category. The sensitivity and specificity of PHQ-15≥10 for fibromyalgia diagnosis was 80.9% and 80.0% (correctly classified = 80.3%) compared with 84.3% and 93.7% (correctly classified = 91.7%) for the PSD scale. 51.4% of fibromyalgia patients and 14.8% with RA had fatigue, sleep or cognitive problems that were severe, continuous, and life-disturbing; and almost all fibromyalgia patients had severe impairments of function and quality of life. Conclusions All patients with fibromyalgia will satisfy the DSM-5 “A” criterion for distressing somatic symptoms, and most would seem to satisfy DSM-5 “B” criterion because symptom impact is life-disturbing or associated with substantial impairment of function and quality of life. But the “B” designation requires special knowledge that symptoms are “disproportionate” or “excessive,” something that is uncertain and controversial. The reliability and validity of DSM-5 criteria in this population is likely to be low.