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Objectives To better investigate neurobiological heterogeneity in fibromyalgia for its symptom diversity and individual differences. Methods We collected structural MRI data and clinical characteristics of Chinese female fibromyalgia patients and healthy controls matched by age and educational level, then invited qualified patients to undergo either Ba‐Duan‐Jin or pregabalin intervention for 12 weeks randomly. Structural MRI was analyzed by CAT12 software, and the regional volume of gray matter (GMV) was calculated according to the Brainnetome atlas. Fibromyalgia patients were clustered using the HYDRA algorithm to detect disease subtypes. Results Two distinct neuroanatomical subtypes were found among 75 patients. Compared to 93 healthy controls, patients in subtype 1 (n = 38, 50.7%) showed widespread GMV increase, especially in some pain‐related brain regions, while no structural changes were observed in subtype 2 (n = 37, 49.3%). At the baseline before treatment, patients in subtype 1 showed a younger age (p = 0.037), longer illness duration (p = 0.042), and a severer psychological stress state evaluated by the Perceived Stress Scale (p = 0.008). After standardized treatment, subtype 1 patients showed less improvement in pain VAS score (p = 0.027) than subtype 2 patients. In addition, GMV of the bilateral dorsal caudate had negative correlations with stress level (Left r = −0.335, p = 0.040; Right r = −0.341, p = 0.036), and GMV of the left rostral temporal thalamus (r = 0.781, p = 0.038) and lateral amygdala (r = 0.761, p = 0.047) were positively related to the improvement of pain severity after treatment in subtype 1 patients. Conclusions These two neuroanatomical subtypes in fibromyalgia emphasize different underlying neuropathological processes and need future studies to optimize individualized treatment. Trial Registration ClinicalTrials.gov identifier: NCT03890133 This study reveals two distinct neuroanatomical subtypes of fibromyalgia. Differences in clinical symptoms and treatment responses between two subtypes validate the subtype classification and highlight variations in the underlying neuropathological processes of fibromyalgia, offering insights for individualized treatment strategies.

Fibromyalgia (FM) is mainly characterized by widespread pain and multiple accompanying symptoms, which hinder FM assessment and management. In order to reduce FM heterogeneity we classified clinical data into simplified dimensions that were used to define FM subgroups. 48 variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM criteria. A partitioning analysis was performed to find groups of variables similar to each other. Similarities between variables were identified and the variables were grouped into dimensions. This was performed in a subset of 559 patients, and cross-validated in the remaining 887 patients. For each sample and dimension, a composite index was obtained based on the weights of the variables included in the dimension. Finally, a clustering procedure was applied to the indexes, resulting in FM subgroups. VARIABLES CLUSTERED INTO THREE INDEPENDENT DIMENSIONS: \"symptomatology\", \"comorbidities\" and \"clinical scales\". Only the two first dimensions were considered for the construction of FM subgroups. Resulting scores classified FM samples into three subgroups: low symptomatology and comorbidities (Cluster 1), high symptomatology and comorbidities (Cluster 2), and high symptomatology but low comorbidities (Cluster 3), showing differences in measures of disease severity. We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. Our analysis stresses the importance of family and personal history of FM comorbidities. Also, the resulting patient clusters could indicate different forms of the disease, relevant to future research, and might have an impact on clinical assessment.

Fibromyalgia (FM) is a heterogeneous and complex syndrome; different studies have tried to describe subgroups of FM patients, and a 4-cluster classification based on the Fibromyalgia Impact Questionnaire-Revised (FIQR) has been recently validated. This study aims to cross-validate this classification in a large US sample of FM patients. A pooled sample of 6280 patients was used. First, we computed a hierarchical cluster analysis (HCA) using FIQR scores at item level. Then, a latent profile analysis (LPA) served to confirm the accuracy of the taxonomy. Additionally, a cluster calculator was developed to estimate the predicted subgroup using an ordinal regression analysis. Self-reported clinical measures were used to examine the external validity of the subgroups in part of the sample. The HCA yielded a 4-subgroup distribution, which was confirmed by the LPA. Each cluster represented a different level of severity: “Mild–moderate”, “moderate”, “moderate–severe”, and “severe”. Significant differences between clusters were observed in most of the clinical measures (e.g., fatigue, sleep problems, anxiety). Interestingly, lower levels of education were associated with higher FM severity. This study corroborates a 4-cluster distribution based on FIQR scores to classify US adults with FM. The classification may have relevant clinical implications for diagnosis and treatment response.

In the two decades between publication, in 1990 and 2010, of the American College of Rheumatology criteria for fibromyalgia, research proliferated and substantial headway was made in understanding this complex, chronic disorder. So what was learned in the wake of the 1990 criteria, and how are the 2010 criteria changing the landscape of research, understanding and management, in patients with fibromyalgia? Fibromyalgia is a disorder characterized by chronic widespread pain in the presence of widespread tenderness, and multiple somatic symptoms. Since the publication of the American College of Rheumatology (ACR) 1990 classification criteria for fibromyalgia, research has proliferated and, in a relatively short period, investigators have begun to unravel the etiology and long-term impact of this complex condition. Although the ACR 1990 criteria have been central to fibromyalgia research during the past two decades, a number of practical and philosophical objections have been raised in relation to them. Principally these objections have centered on the use (or lack thereof) of the tender point examination, the lack of consideration of associated symptoms, and the observation that fibromyalgia might represent the extreme end of a pain continuum. In developing the ACR 2010 criteria, experts have sought to address these issues and to simplify clinical diagnosis. An implicit aim was to facilitate more rigorous study of etiology. The purpose of this Review is to summarize research to date that has described the epidemiology, pathology and clinical course of fibromyalgia, and to assess the probable impact of the ACR 2010 criteria on future research efforts. Key Points Although the American College of Rheumatology (ACR) 1990 classification criteria for fibromyalgia have facilitated two decades of research, several practical and philosophical objections to them have been raised The ACR 2010 diagnostic criteria were developed to address obstacles and concerns presented in response to the 1990 criteria The ACR 2010 diagnostic criteria comprise a widespread pain index (WPI, measures pain distribution), and the symptom severity (SS) scale (assesses cognitive symptoms, sleep disturbances, fatigue and somatic symptoms) The maximum WPI score is 19, the SS score range is 0–12; WPI≥7 and SS≥5, or WPI 3–6 and SS≥9, classifies individuals as having fibromyalgia Use of the traditional tender-point count is not required in the ACR 2010 criteria The ACR 2010 criteria should facilitate more rigorous study of the etiology of fibromyalgia

The heterogeneity found in fibromyalgia (FM) patients has led to the investigation of disease subgroups, mainly based on clinical features. The aim of this study was to test the hypothesis that clinical FM subgroups are associated with different underlying pathophysiological mechanisms. Sixty-three FM patients were classified in type I or type II, according to the Fibromyalgia Impact Questionnaire (FIQ), and in mild/moderate versus severe FM, according to the severity of three cardinal symptoms considered in the American College of Rheumatology (ACR) 2010 criteria (unrefreshed sleep, cognitive problems and fatigue). To validate the subgroups obtained by these two classifications, we calculated the area under the receiver operating characteristic curves for various clinical variables and for two potential biomarkers of FM: Response to experimental pressure pain (algometry) and the amplitude/intensity slopes of the auditory evoked potentials (AEPs) obtained to stimuli of increasing intensity. The variables that best discriminated type I versus type II were those related to depression, while the indices of clinical or experimental pain (threshold or tolerance) did not significantly differ between them. The variables that best discriminated the mild/moderate versus severe subgroups were those related to the algometry. The AEPs did not allow discrimination among the generated subsets. The FIQ-based classification allows the identification of subgroups that differ in psychological distress, while the index based on the ACR 2010 criteria seems to be useful to characterize the severity of FM mainly based on hyperalgesia. The incorporation of potential biomarkers to generate or validate classification criteria is crucial to advance in the knowledge of FM and in the understanding of pathophysiological pathways.

As has been shown by a number of working groups, primary fibromyalgia syndrome does not represent a single clinical entity. It is possible to distinguish between a subgroup with high pain sensitivity and no associated psychiatric condition, a second and a third subgroup characterized by depression associated with fibromyalgia syndrome, and a fourth group with somatoform pain disorder of the fibromyalgia type. Mild inflammatory processes must be considered as the cause in the first group, while depression is combined with fibromyalgia in the second and the third group. In the fourth group, serious previous or still existing psychological problems or also insufficient coping with illness symptoms must be regarded as the reason for pain chronification. Group 1 benefits from a blocking of the 5-HT3 receptors by means of tropisetron, for example. This does not only affect pain chronification but also the inflammatory process itself. Group 2 and 3 needs antidepressant treatment, whereas the focus should be on psychotherapy in group 4. Groups 1, 2 and 3 will also profit from multimodal physical treatment programs, to a certain extent this applies to group 4 as well. So-called mixed types require a combination of therapeutic measures.

Fibromyalgia (FM), also known as fibromyalgia syndrome (FMS) and fibrositis, is a common form of nonarticular rheumatism that is associated with chronic generalized musculoskeletal pain, fatigue, and a long list of other complaints. Some have criticized the classification of FM as a distinct medical entity, but existing data suggest that individuals meeting the case definition for FM are clinically somewhat distinct from those with chronic widespread pain who do not meet the full FM definition. Clinic studies have found FM to be common in countries worldwide; these include studies in specialty and general clinics. The same is true of general population studies, which show the prevalence of FM to be between 0.5% and 5%. Knowledge about risk factors for FM is limited. Females are at greater risk, and risk appears to increase through middle age, then decline. Although some authors claim that an epidemic of FM has been fueled by an over-generous Western compensation system, there are no data that demonstrate an increasing incidence or prevalence of FM; moreover, existing data refute any association between FM prevalence and compensation. Claims that the FM label itself causes illness behavior and increased dependence on the medical system also are not supported by existing research. This article reviews the classification, epidemiology, and natural history of FM.

The aim of this study was to investigate the reliability and the validity of the Japanese version of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia (ACR 2010-J), and its quantification scale, the Fibromyalgia Symptom Scale (FS-J). In this study, we divided patients with chronic pain without psychiatric disorders other than depression into two groups according to the 1990 ACR Diagnostic Criteria for Fibromyalgia, a fibromyalgia group and a non-fibromyalgia group (rheumatoid arthritis, osteoarthritis, and gout). Patients in both groups were assessed using the ACR 2010-J and FS-J. Seventy-seven of 94 (82%) patients in the fibromyalgia group met the ACR 2010-J, whereas 9% (4/43) of the non-fibromyalgia group did so, with a sensitivity of 82%, specificity of 91%, positive predictive value of 95%, negative predictive value of 70%, and positive likelihood ratio of 8.8. Mean total scores on the FS-J significantly differentiated the fibromyalgia from the non-fibromyalgia group. The scale had high inter-rater reliability and high internal consistency. With a cutoff score of 10, the positive likelihood ratio was 10.1. Our findings indicate that the ACR 2010-J and FS-J have high reliability and validity, and are useful for assessing fibromyalgia in Japanese populations with chronic pain. As regards the positive likelihood ratio, that of the FS-J might be suitable as a positive test.

The aim of this study was to establish the cutoff points in the Combined Index of Fibromyalgia Severity (ICAF) questionnaire which allow classification of patients by severity and to evaluate its application in the clinical practice. The cutoff points were calculated using the area under the ROC curve in two cohorts of patients. Three visits, basal, fourth month and 15th month, were considered. The external criterion for grading severity was the number of drugs consumed by the patient. Sequential changes were calculated and compared. Correlations with drug consumption and comparisons of severity between patients with different types of coping were also calculated. Correlation between the number of drugs and the ICAF total score was significant. Three cutoff points were established: absence of Fibromyalgia (FM), <34; mild, 34–41; moderate, 41–50 and severe, >50, with the following distribution of severity: absence in 0.4 %, mild in 18.7 %, moderate in 32.5 % and severe in 48.4 % of the patients. There were significant differences between groups. The treatment under daily clinical conditions showed a significant improvement of the patients which was maintained at the end of follow-up. There was a 17 % reduction in the severe category. The patients with more passive coping factor showed highest punctuations in the remaining scores and were more prevalent in the severe category. The patients with a predominance of the emotional factor showed a better response at the end of follow-up. The established cutoff points allow the classification of FM patients by severity, to know the prognostic and to predict the response to the treatment.

INTRODUCTION: The present study aimed to replicate and validate the empirically derived subgroup classification based on the Multidimensional Pain Inventory (MPI) in a sample of highly disabled fibromyalgia (FM) patients. Second, it examined how the identified subgroups differed in their response to an intensive, interdisciplinary inpatient pain management program. METHODS: Participants were 118 persons with FM who experienced persistent pain and were disabled. Subgroup classification was conducted by cluster analysis using MPI subscale scores at entry to the program. At program entry and discharge, participants completed the MPI, Medical Outcomes Study Short Form‐36, Hospital Anxiety and Depression Scale and Coping Strategies Questionnaire. RESULTS: Cluster analysis identified three subgroups in the highly disabled sample that were similar to those described by other studies using less disabled samples of FM. The dysfunctional subgroup (DYS; 36% of the sample) showed the highest level of depression, the interpersonally distressed subgroup (ID; 24%) showed a modest level of depression and the adaptive copers subgroup (AC; 38%) showed the lowest depression scores in the MPI (negative mood), Medical Outcomes Study Short Form‐36 (mental health), Hospital Anxiety and Depression Scale (depression) and Coping Strategies Questionnaire (catastrophizing). Significant differences in treatment outcome were observed among the three subgroups in terms of reduction of pain severity (as assessed using the MPI). The effect sizes were 1.42 for DYS, 1.32 for AC and 0.62 for ID (P=0.004 for pairwise comparison of ID‐AC and P=0.018 for ID‐DYS). DISCUSSION: These findings underscore the importance of assessing individuals’ differences in how they adjust to FM.