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Pain is a significant issue in rheumatoid arthritis (RA) and psoriatic arthritis (PSA) and can have a negative impact on patients' quality of life. Despite optimal control of inflammatory disease, residual chronic pain remains a major unmet medical need in RA. Pain in RA can be secondary to inflammation but can also generate neuroendocrine responses that initiate neurogenic inflammation and enhance cytokine release, leading to persistent hyperalgesia. In addition to well-known cytokines such as TNFα and IL-6, other cytokines and the JAK-STAT pathway play a role in pain modulation and inflammation. The development of chronic pain in RA involves processes beyond inflammation or structural damage. Residual pain is often observed in patients even after achieving remission or low disease activity, suggesting the involvement of non-inflammatory and central sensitization mechanisms. Moreover, fibromyalgia syndrome (FMS) is prevalent in RA patients and may contribute to persistent pain. Factors such as depression, sleep disturbance, and pro-inflammatory cytokines may contribute to the development of fibromyalgia in RA. It is essential to identify and diagnose concomitant FMS in RA patients to better manage their symptoms. Further research is needed to unravel the complexities of pain in RA. Finally, recent studies have shown that JAK inhibitors effectively reduce residual pain in RA patients, suggesting pain-reducing effects independent of their anti-inflammatory properties., Competing Interests: Declaration of competing interest None, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Fibromyalgia (FM) is difficult to diagnose and manage chronic pain condition whose symptoms have no clear pathophysiological cause, although it is thought that patient hypersensitivity to a range of stimuli may give rise to mechanical hyperalgesia as a result of altered central nociceptive processing. The 1990 American College of Rheumatology (ACR) classification criteria, which have been widely used in clinical practice, require the existence of chronic widespread pain (CWP) for >3months, and the presence of at least 11 out of 18 specified tender points upon digital palpation, although this latter criterion has long been criticised. The newer 2010 ACR diagnostic criteria state that FM can be defined as CWP associated with somatic symptoms, and recommend the use of a widespread pain index and a scale to rate symptom severity. A modified version of the 2010 criteria removed the physician assessment of the extent of somatic symptoms and replaced it by a summary score of three self-reported symptoms, thus making it easier to use while maintaining its sensitivity. This review discusses the advantages and limitations of all of these criteria., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To collect data on vitamin D (25(OH)D) serum levels in a large number of rheumatoid arthritis (RA) patients from different European countries, to investigate their relation with disease activity, disability, quality of life, and possibly to construct a new Patient Reported Outcome (PRO) questionnaire in order to self-estimate if they are at risk for vitamin D insufficiency/deficiency-related clinical implications (D-PRO)., Methods: This was a European League Against Rheumatism (EULAR) supported cross-sectional study (project No CLI064) which involved 625 RA patients (mean age 55±11years, mean disease duration 11±9years), 276 age and sex matched healthy subjects, and rheumatologists working in academic institutions or hospital centres, as well as PARE organizations (patient representatives) from 13 European countries. Serum samples for 25(OH)D level measurement were collected during winter time and analyzed in a central laboratory using chemiluminescence immunoassay (DiaSorin). Patient past medical history was recorded. RA patients were provided with three questionnaires: the Rheumatoid Arthritis Impact Diseases score (RAID), the Health Assessment Questionnaire (HAQ), and the new D-PRO questionnaire at the time of 25(OH)D serum sampling. D-PRO questionnaire consisted of three domains, Symptom Risk Score (SRS), Habitus Risk Score (HRS) and Global Risk Score (SRS+HRS=GRS), constructed with items possibly related to vitamin D deficiency. D-PRO was correlated with both clinical and PRO scores. DAS28-CRP was also evaluated. Statistical analysis was performed by non parametric tests., Results: Mean serum concentration of 25(OH)D in RA patients (17.62±9.76ng/ml) was found significantly lower if compared to the levels obtained in matched controls (18.95±9.45ng/ml) (p=0.01), with statistically significant differences among several European countries. Negative correlations were found between 25(OH)D serum levels and DAS28-CRP (p<0.001), RAID (p=0.05) and HAQ (p=0.04) scores in the RA patients group. Negative correlations were also found in the cohort of enrolled RA patients between 25(OH)D serum concentrations and SRS (p=0.04), HRS (p=0.02) and GRS (p=0.02) domains of the D-PRO questionnaire., Conclusions: This first multicentre European survey add new evidences that vitamin D insufficiency/deficiency is frequent in RA patients with statistically significant differences among several countries. Vitamin D serum concentrations seem to correlate negatively and significantly with the D-PRO Global Risk Score, clinimetric indexes for quality of life, disease activity and disability in present cohort of RA European patients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The assessment of chronic pain and its impact on physical, emotional and social functions requires the use of multidimensional qualitative and health-related quality of life instruments, but there is still little agreement concerning what these may be or which approach to adopt. Increasing focus on patient-reported outcomes in medicine has had the positive effect of giving prominence to the views and experiences of patients with chronic pain, and the ecological momentary assessment (EMA) approach allows patients' symptoms to be assessed in their natural environment in real time without the need for recall. Computerised EMA symptom diaries are now generally regarded as the 'gold standard' in the field of pain medicine, and they have recently attracted increasing attention as an essential component of health-care monitoring systems based on the information and communication technology. A web/Internet-based diary and patient terminal seem to provide a ubiquitous, easy-to-use and cost-efficient solution for patient-centred data acquisition. In addition, telemonitoring is increasingly seen as an effective means of supporting shared decision-making as it can inform patients about typical symptoms, treatment options and prognosis, and it is widely accepted as an additional source of information. This article reviews some of the instruments used to assess chronic pain, including newly developed and well-established validated multidimensional instruments and health-care monitoring systems based on information and communication technology, and it discusses their advantages and limitations., (Copyright © 2015. Published by Elsevier Ltd.)

The sometimes intense, persistent and disabling pain associated with rheumatoid arthritis (RA) and spondyloarthritis frequently has a multifactorial, simultaneously central and peripheral origin, and it may be due to currently active inflammation or joint damage and tissue destruction caused by a previous inflammatory condition. The symptoms of inflammatory pain symptoms can be partially relieved by non-steroidal anti-inflammatory drugs, but many patients continue to experience moderate pain due to alterations in central pain regulation mechanisms, as in the case of the chronic widespread pain (CWP) characterising fibromyalgia. The importance of distinguishing CWP from inflammatory pain is underlined by the fact that drugs such as tumour necrosis factor inhibitors are expensive, and direct costs are higher in patients with concomitant CWP than in those without. The management of pain requires a combination approach that includes pharmacological analgesia, and biological and non-biological treatments because, although joint replacement surgery can significantly improve RA-related pain, it may only be available to patients with the most severe advanced disease., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The introduction of anti-tumour necrosis factor (TNF) agents for the treatment of rheumatoid arthritis (RA), Crohn's disease (CD) or spondyloarthritis (SpA) has revolutionised the therapeutic approach to patients with active disease failing to respond to conventional therapy. However, some of the patients treated with selective TNF inhibitors may develop autoantibodies, such as antinuclear antibodies (ANAs) and anti-double-stranded DNA (anti-dsDNA) antibodies. Furthermore, anti-phospholipid antibodies, which are mainly detected by means of anti-cardiolipin assays, have been found in RA patients receiving TNF blockers. There have also been a number of reports of the development of anti-drug antibodies, of which those against infliximab can interfere with the drug's pharmacokinetics (and therefore its effects), and may also cause acute and delayed infusion and injection site reactions. The onset of autoimmune diseases during biological treatment is rare, but it needs to be promptly recognised in order to plan appropriate patient management. The addition of an immunosuppressive drug can reduce the induction of anti-TNF antibodies., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To evaluate the risk of serious infections (SIs) in RA patients receiving anti-TNF therapy on the basis of the data included in the GISEA register., Methods: The study involved 2769 adult patients with long-standing RA (mean age 53.2±13.4 years; mean disease duration 9.0±8.3 years) enrolled in the GISEA register, who had been treated for at least 6 months with TNF inhibitors or had discontinued therapy due to SI: 837 (30%) treated with infliximab (IFN), 802 (29%) with adalimumab (ADA), and 1130 (41%) with etanercept (ETN)., Results: 176 patients had experienced at least one of the 226 Sis during the 9 years of treatment with an anti-TNF agent, an overall incidence of 31.8/1000 patient-years (95% CI 25.2-38.3): 23.7/1000 patient-years (95% CI 13.1-34.2) on ADA; 12.8/1000 patient-years (95% CI 6.3-19.4) on ETN and 65.1/1000 patient-years (95% CI 48.4-81.8) on IFN. The risk was higher in the first than in the second year of treatment, but this difference was not statistically significant (p=0.08) (38.9% of the SIs were recorded in the first 12 months of treatment). The risk of SI was significantly different among the three treatment groups (p<0.0001). Multivariate models confirmed that the use of steroids (p<0.046), concomitant DMARD treatment during anti-TNF therapy (p=0.004), advanced age at the start of anti-TNF treatment (p<0.0001), and the use of IFN or ADA rather than ETN (respectively p<0.0001 and p=0.023) were strong and statistically significant predictors of infection., Conclusions: Anti-TNF therapy is associated with a small but significant risk of SI that is associated with the concomitant use of steroids, advanced age at the start of anti-TNF treatment, and the type of anti-TNF agent., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Fibromyalgia (FM) is a rheumatic disease that is characterised by chronic musculoskeletal pain, stiffness, fatigue, sleep and mood disorder. FM patients demonstrate dysregulation of pain neurotransmitter function and experience a neurohormone-mediated association with sleep irregularities. There are currently no instrumental tests or specific diagnostic markers for FM, and many of the existing indicators are only significant for research purposes. Anti-depressants, non-steroidal anti-inflammatory drugs (NSAIDS), opioids, sedatives, muscle relaxants and antiepileptics have all been used to treat FM with varying results. It has been shown that interdisciplinary treatment programmes lead to greater improvements in subjective pain and function than monotherapies. Physical exercise and multimodal cognitive behavioural therapy are the most widely accepted and beneficial forms of non-pharmacological therapy., (Copyright © 2011. Published by Elsevier Ltd.)

Assessing chronic widespread pain (CWP) and its impact on physical, emotional and social function requires multidimensional qualitative and health-related quality of life (HRQL) instruments. The recommendations of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) concerning outcome measurements for pain trials are useful for making routine assessments, the most significant of which include pain, fatigue, disturbed sleep, physical functioning, emotional functioning, patient global ratings of satisfaction and HRQL. However, despite the growing spread of instruments and theoretical publications devoted to measuring the various aspects of chronic pain, there is little widespread agreement, and no unified approach has yet been devised. There is therefore still considerable scope for the development of consensus around a core set of measures and response criteria, as well as for the development and refinement of the related instruments, standardised assessor training, the cross-cultural adaptation of health status questionnaires, electronic data capture and the introduction of valid, reliable and responsive standardised quantitative measurements into routine clinical care. Clinicians need to be aware of the psychometric properties of the instruments used, including their levels of imprecision and minimum clinically important differences (those indicating a meaningful change in clinical status). This article reviews a selection of the instruments used to assess CWP patients, including validated newly developed and well-established screening instruments, and discusses their advantages and limitations., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Fibromyalgia (FM) is a rheumatic disease characterised by musculoskeletal pain, chronic diffuse tension and/or stiffness in joints and muscles, fatigue, sleep and emotional disturbances and pressure pain sensitivity in at least 11 of 18 tender points. There are currently no instrumental tests or specific diagnostic markers, and the characteristic symptoms of the disease overlap those of many other conditions classified in a different manner. FM is often associated with other diseases that act as confounding and aggravating factors, including primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). It has been reported to coexist in 25% of patients with RA, 30% of patients with SLE and 50% of patients with pSS. Its clinical diagnosis is not easy because FM-like symptoms are frequent, and its differential diagnosis with other causes of chronic diffuse pain is difficult. This is even more true in the case of patients who are positive for antinuclear antibodies (ANAs) because, although sensitive, ANA positivity is not specific for SLE or connective tissue diseases, and can also be found in 10-15% of FM patients. Furthermore, composite indices such as the disease activity score (DAS)-28, which are widely used in everyday clinical practice and clinical trials, may be insufficient to evaluate real inflammatory activity in patients with RA associated with chronic pain syndromes such as FM, and can lead to an overestimate of disease activity in RA. The presence of diffuse pain in autoimmune rheumatic diseases compromises the quality of life of the patients, although overall mortality is not increased. A misdiagnosis harms the patients and the community. Rheumatologists should be able to recognise and distinguish primary and secondary FM, and need new guidelines and instruments to avoid making mistakes., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Over the last decade, several studies have highlighted the value of ultrasonography for both clinical and research purposes in rheumatology. Ultrasonography is a non-invasive, inexpensive and free-of-radiation-hazards imaging technique providing quick and useful information for the management of rheumatic diseases. Considerable evidence supporting the role of ultrasonography in rheumatological clinical practice has led many rheumatologists to want to become experienced with this imaging technique. The main indications of ultrasonography in rheumatology include the evaluation of patients with regional pain syndromes and chronic arthritis, short-term therapy monitoring and guidance for invasive procedures. Ultrasonography's long learning curve is the main obstacle that hinders its widespread use in rheumatology. Many technical aspects may affect the scanning process and a correct interpretation of sonographic images depends on several elements such as a deep knowledge of ultrasonography anatomy and pathology.

Regional musculoskeletal pain is one of the most common complaints in daily rheumatological practice. Conventional radiology remains the cornerstone of diagnostic imaging in these patients despite the advent of new, fascinating imaging techniques. Ultrasonography may have a relevant impact on final diagnosis or therapeutic choices. It is highly sensitive to the identification of fine, soft-tissue changes and it should be considered as an integral part of the clinical examination in most patients. Scintigraphy is indicated when multifocal processes have to be excluded and when high sensitivity is required. Computed tomography is an excellent tool for the assessment of osseous based abnormalities. Magnetic resonance has several characteristics of the ideal diagnostic tool. However, its appropriateness in the evaluation of many regional musculoskeletal conditions is a matter for discussion. An appropriate diagnostic programme for patients with regional musculoskeletal pain has to be focused on the strengths and weaknesses of various imaging techniques.