Kirstine Amris

EULAR revised recommendations for the management of fibromyalgia

Objective The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were ‘expert opinion’. Methods A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia. A review, in May 2015, identified eligible publications and key outcomes assessed were pain, fatigue, sleep and daily functioning. The Grading of Recommendations Assessment, Development and Evaluation system was used for making recommendations. Results 2979 titles were identified: from these 275 full papers were selected for review and 107 reviews (and/or meta-analyses) evaluated as eligible. Based on meta-analyses, the only ‘strong for’ therapy-based recommendation in the guidelines was exercise. Based on expert opinion, a graduated approach, the following four main stages are suggested underpinned by shared decision-making with patients. Initial management should involve patient education and focus on non-pharmacological therapies. In case of non-response, further therapies (all of which were evaluated as ‘weak for’ based on meta-analyses) should be tailored to the specific needs of the individual and may involve psychological therapies (for mood disorders and unhelpful coping strategies), pharmacotherapy (for severe pain or sleep disturbance) and/or a multimodal rehabilitation programme (for severe disability). Conclusions These recommendations are underpinned by high-quality reviews and meta-analyses. The size of effect for most treatments is relatively modest. We propose research priorities clarifying who will benefit from specific interventions, their effect in combination and organisation of healthcare systems to optimise outcome.

Muscle fatigue in fibromyalgia is in the brain, not in the muscles: a case–control study of perceived versus objective muscle fatigue

Objective To investigate relationships between perceived and objectively measured muscle fatigue during exhausting muscle contractions in women with fibromyalgia (FM) compared with healthy controls (HC). Methods Women with FM and HC completed an isometric muscle exhaustion task at 90° shoulder abduction. Surface electromyographic (EMG) activity in the deltoid muscle was recorded together with self-reported level of muscle fatigue. Results 25 participants with FM and 23 HC were included. Average time to exhaustion was 254 s shorter in participants with FM than in HC. Participants with FM did not exhibit the same level of objective signs of muscle fatigue, seen as fewer changes in the EMG activity, as the HC during the exhaustion task. The task did not provoke pain in the HC, while participants with FM reported a doubling of pain. Conclusions Women with FM had shorter exhaustion times and showed fewer objective signs of muscle fatigue during an exhausting isometric shoulder abduction compared with younger HC. This indicates that perceived muscle fatigue may be of central origin and supports the notion of central nervous dysfunction as basic pathological changes in FM.

Concomitant fibromyalgia in rheumatoid arthritis is associated with the more frequent use of biological therapy: a cross-sectional study

Objectives: To compare the 28-joint Disease Activity Score (DAS28) and its components in patients with rheumatoid arthritis (RA) with and without concomitant fibromyalgia (FM), and to investigate the use of biological treatment in the two groups. Method: Questionnaires developed to diagnose FM were handed out among RA patients during their planned visits. Values for DAS28 were obtained from the DANBIO registry. Demographic data and data on patients’ medical treatment, disease duration, serological and radiological status were retrieved from patients’ files. The χ2 test and an unpaired t-test were applied to investigate group differences in the use of biological therapy, baseline characteristics, patient-reported outcomes, and DAS28 between groups when appropriate. Results: Questionnaires were completed by 162 out of 264 (61%) patients. Twenty-five patients (15.4%) with concomitant FM were identified. No group differences were found regarding disease duration, age, gender, and serological status. Of the RA patients with concomitant FM, 64% were treated with biological therapy vs. 32% of RA patients without concomitant FM (p = 0.002). The mean DAS28 in the FM group was 4.4 compared to 2.9 in the non-FM group (p < 0.001). Elevated DAS28 in the FM group resulted from a high tender joint count (p = 0.003) and a high visual analogue scale (VAS)-global score (p < 0.001). Erosions were more frequent in the non-FM group (p = 0.04). Conclusions: Concomitant FM in patients with RA is associated with a higher DAS28 due to subjective parameters and with the more frequent use of biological treatments. This raises the question of whether the more frequent use of biologics in these patients is justified by inflammation, or is instead due to persistent pain and other centrally mediated symptoms.

Interdisciplinary rehabilitation of patients with chronic widespread pain: primary endpoint of the randomized, nonblinded, parallel-group IMPROvE trial.

Summary Multicomponent treatment targeting patients with chronic widespread pain resulted in an objectively measured improvement of functional ability at 6‐month follow‐up, not reflected in patient‐reported outcomes. ABSTRACT This study examined the functional and psychological outcomes of a 2‐week, group‐based multicomponent treatment course that targeted patients with chronic widespread pain. Patients (192 included in the intention‐to‐treat population), all fulfilling the 1990 American College of Rheumatology classification criteria for fibromyalgia, were consecutively recruited from a tertiary care setting and randomized (1:1) to either the treatment course or a waiting list control group. Co‐primary outcomes were the Assessment of Motor and Process Skills (AMPS) and SF‐36 Mental Composite Score (MCS) evaluated at 6‐month follow‐up. Primary endpoints were partly achieved with a statistically significant improvement in AMPS activities of daily living motor (group mean difference: 0.20 [95% confidence interval (CI): 0.09 to 0.31] logits; P = .0003) and AMPS activities of daily living process (0.20 [95% CI: 0.12 to 0.27] logits, P < .0001) ability measures, whereas no difference in the SF‐36 MCS (1.14 [95% CI: −1.52 to 3.81], P = .40) was observed. Individual patient responses varied, and the proportion of patients achieving a clinically meaningful change of at least 0.3 logits on the AMPS seemed influenced by the reporting of a pending social welfare application at the time of enrollment. We conclude that even in fibromyalgia patients presenting with a substantial disability established over many years, the 2‐week multicomponent treatment course resulted in observable improvement of functional ability in a subgroup of patients at 6‐month follow‐up. This improvement, however, was not reflected in secondary patient reported outcomes, including scores of self‐reported functional ability on standardized questionnaires. We suggest including observation‐based assessments in future clinical trials focusing on functional outcomes in patients with fibromyalgia.

The Relationship between Mechanical Hyperalgesia Assessed by Manual Tender Point Examination and Disease Severity in Patients with Chronic Widespread Pain: A Cross-Sectional Study

The clinical utility of tender point (TP) examination in patients reporting chronic widespread pain (CWP) is the subject of contemporary debate. The objective of this study was to assess the relationship between mechanical hyperalgesia assessed by manual TP examination and clinical disease severity. 271 women with CWP were recruited from a clinical setting. Data collection included patient-reported symptoms, health-related quality of life variables, and observation-based measures of functional ability, muscle strength, 6-minute walk, and pressure pain thresholds measured by cuff algometry. TP examination was conducted according to ACR-guidelines. Relationships between disease variables and TP count (TPC) were analyzed with logistic regression in a continuum model, allowing the TPC to depend on the included disease variables and two regression models carried out for a TPC threshold level, varying between 1 and 17. The threshold analyses indicated a TPC threshold at 8, above which a large number of disease variables became consistently significant explanatory factors, whereas none of the disease variables reached a significance level in the continuum model. These results support the premise that the presence of mechanical hyperalgesia influences symptomatology in CWP and that the severity of clinical expression is related to a threshold of TPs, rather than being part of a continuum.

Association of physical fitness with depression in women with fibromyalgia

OBJECTIVE The aim of this study was to examine the association between physical fitness and depressive symptoms in women with fibromyalgia (FM). We also assessed whether different fitness components present independent relationships with depressive symptoms. DESIGN Cross-sectional study. SETTING University facilities and FM associations. SUBJECTS Four hundred and forty-four patients with FM according to the 1990 American College of Rheumatology criteria. METHODS Depressive symptoms were assessed using the Beck Depression Inventory (BDI-II). Physical fitness (aerobic fitness, muscle strength, flexibility, and motor agility) was assessed using the standardized Senior Fitness Test battery and the handgrip strength test. A standardized composite score for fitness was computed and divided into quintiles. RESULTS Overall, the fitness tests presented inverse associations with the total BDI-II score (P < 0.05). The patients in the highest fitness quintile had 8.4% lower depressive symptoms than the patients in the lowest fitness quintile (P = 0.014). The odds of severe symptoms of depression were between 3.7% and 16.9% lower for each performance unit in the back-scratch, handgrip, arm-curl, and eight-feet up-and-go tests. When all the fitness tests were simultaneously considered, the back-scratch test was the only one independently associated with the total BDI-II score (P = 0.001; R(2) = 0.023). CONCLUSIONS Although higher physical fitness was generally associated with lower symptoms of depression in women with FM, the observed associations were somewhat weak and inconsistent, differing from those previously observed in healthy adults. Further research to determine the clinical relevance of the association between physical fitness and depression in FM is warranted.

Diagnostic accuracy of heel pad palpation - a phantom study.

UNLABELLED Falanga torture involves repetitive blunt trauma to the soles of the feet and typically leaves few detectable changes. Reduced elasticity in the heel pads has been reported as characteristic sequelae and palpatory testing of heel pad elasticity is therefore part of medicolegal assessment of alleged torture victims. The goal was to test the accuracy of two experienced investigators in determining whether a heel pad model was soft, medium or hard. The skin-to-bone distance in the models varied within the human range. METHOD Two blinded investigators independently palpated nine different heel pad models with three different elasticities combined with three different skin-to-bone distances in five consecutive trials and categorized the models as soft, medium or hard. RESULTS Two experienced investigators were able to identify three known elasticities correctly in approximately two thirds of the cases. The skin-to-bone distance affected the accuracy. CONCLUSION The use of clinical examination in documenting alleged exposure to torture warrants a high diagnostic accuracy of the applied tests. The study implies that palpatory testing of the human heel pad may not meet this demand. It is therefore recommended that a device able to perform an accurate measurement of the viscous-elastic properties of the heel pad be developed.

Non-nociceptive pain in rheumatoid arthritis is frequent and affects disease activity estimation: cross-sectional data from the FRAME study

Background: The painDETECT questionnaire (PDQ) is a mechanism-based pain classification tool assigning patients to one of three categories depending on the quality of the experienced pain. Patients with non-nociceptive pain score high on the PDQ. The objective was to assess the proportions of the three PDQ classification groups in patients with rheumatoid arthritis (RA) and to explore differences in clinical characteristics. Method: RA patients initiating or escalating their RA therapy were included prospectively and underwent a thorough examination programme. Low (PDQ score < 13), medium (PDQ score 13–18), and high (PDQ score > 18) scores indicate nociceptive, unclear/possible neuropathic, or neuropathic pain mechanisms, respectively. Results: The 102 included patients were classified into the following PDQ classification groups: low = 65%, medium = 23%, and high = 12%. Patients in the medium and high PDQ groups scored worse on indicators of anxiety, depression, disability, mental health-related quality of life, pain, and fatigue. They also had more tender points and an RA disease activity score based on 28 joints (DAS28) where a higher fraction of the composite score pertained to non-inflammatory factors compared to patients in the low PDQ classification group. There were no differences in objective inflammatory indices across groups. Multiple regression analysis demonstrated that the tender joint count (TJC) and the 36-item Short Form Health Survey (SF36) mental component summary (MCS) score were independently associated with the PDQ score. Conclusions: In patients initiating or intensifying medical treatment for their RA, non-nociceptive pain (PDQ score ≥ 13) is common. In these patients, the pain mechanisms result in increased disease activity scores on a non-inflammatory basis.

The adaptation of a Danish version of the Pain Self-Efficacy Questionnaire: Reliability and construct validity in a population of patients with fibromyalgia in Denmark

The aim of this study was to translate, culturally adapt and evaluate the psychometric properties of the Pain Self-Efficacy Questionnaire (PSEQ) in a population of patients with fibromyalgia in Denmark. The study sample included 102 patients diagnosed with fibromyalgia referred to a specialist clinic. The PSEQ was translated and adapted to a Danish setting using a standard stepwise forward-backward translation procedure, followed by initial testing and focus group interview. Reliability was examined by analysing internal consistency and test-retest agreement. Construct validity was examined by investigating dimensionality, targeting, local independence, category functioning and differential item functioning (DIF). Reliability was high: Cronbachs alpha 0.88, test-retest correlation 0.93, intraclass correlation coefficient (ICC) 0.89 and item-total correlations 0.44-0.70. Factor analyses and item response (IRT) models indicated unidimensionality, and the PSEQ-DK was well targeted to the sample. High interitem correlation was observed between two items, indicating local dependence, and item misfit and DIF were observed for a few items. However, the overall fit of the scale to a single-factor model and IRT models supported acceptable construct validity. The PSEQ-DK showed acceptable psychometric properties and can therefore represent a reliable and valid measure for evaluating self-efficacy in patients with fibromyalgia in Denmark.

Temporal summation of pain and ultrasound Doppler activity as predictors of treatment response in patients with rheumatoid arthritis: protocol for the Frederiksberg hospitals Rheumatoid Arthritis, pain assessment and Medical Evaluation (FRAME-cohort) study

Introduction Chronic pain is common in rheumatoid arthritis (RA) and may still persist despite regression of objective signs of inflammation. This has led researchers to hypothesise that central pain sensitisation may play a role in the generation of chronic pain in RA. Application of the disease activity score DAS28 can classify some patients with active RA solely based on a high tender joint count and poor patient global health score. In such cases, intensified treatment with anti-inflammatory drugs would be expected to yield poorer results than in cases with DAS28 elevation due to a high score for swollen joints and C reactive protein (CRP). Evaluation of central pain sensitisation in patients with few inflammatory indices may be a predictive tool regarding the effect of anti-inflammatory treatment. Computerised pneumatic cuff pressure algometry (CPA) is a method for assessing temporal summation (ie, degree of central sensitisation). The main objective of this study was to examine the prognostic values of pressure pain-induced temporal summation, ultrasound Doppler activity and the interaction between them in relation to treatment response (DAS28-CRP change) in patients with RA initiating any anti-inflammatory therapy. Method and analysis 120 participants ≥18 years of age will be recruited. Furthermore, they must be either (1) diagnosed with RA, untreated with disease-modifying antirheumatic drugs for at least 6 months and about to initiate disease-modifying antirheumatic drug treatment or (2) about to begin or switch treatment with any biological drug for their RA. Data (clinical, imaging, blood samples, patient reported outcomes and CPA measurements) will be collected from each participant at baseline and after 4 months of anti-inflammatory treatment. Ethics and dissemination This study has been approved by the ethics committee for the Copenhagen region (H-4-2013-007). Dissemination will occur through presentations and publication in international peer-reviewed journals.