Chronic widespread pain in the spectrum of rheumatological diseases.

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.

Multidisciplinary approach to fibromyalgia: what is the teaching?

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.

Neuroendocrine therapy of fibromyalgia syndrome: an update.

Fibromyalgia (FM) is a chronic pain syndrome characterized by widespread pain, fatigue, sleep alterations, and distress. Emerging evidence points toward augmented pain processing within the central nervous system as having a primary role in the pathophysiology of this disorder. Recent studies have identified distinct FM subgroups on the basis of clinical, neurochemical, and neuroendocrinological abnormalities, including increased cerebrospinal fluid levels of substance P and excitatory amino acids and functional abnormalities in the hypothalamic-pituitary-adrenal axis, and sympathoadrenal (autonomic nervous) system. Pharmacological treatments have been gradually enriched by a variety of compounds. Antidepressants, nonsteroidal anti-inflammatory drugs, opioids, sedatives, muscle relaxants, and alpha2-delta agonists have all been used to treat FM with varying results. Physical exercise and multimodal cognitive-behavioral therapy seem to be the most widely accepted and beneficial forms of nonpharmacological therapy. Studies predicting treatment response indicate that it is useful if not essential to tailor the choice of treatment components to the needs of individual patients.

An open, randomized comparison study of cyclosporine A, cyclosporine A + methotrexate and cyclosporine A + hydroxychloroquine in the treatment of early severe rheumatoid arthritis.

PURPOSE: To determine whether a regimen of cyclosporine (CSA) and methotrexate (MTX), or CSA and hydroxychloroquine (HCQ) introduced in early rheumatoid arthritis (RA) can produce a significant improvement in clinical outcome and/or retard radiographic damage in comparison with standard monotherapy with CSA alone. METHODS: One hundred five patients with active RA of less than 36 months duration, who had never previously been treated with immunosuppressive agents, were included in a 12-month, multi-center, open, randomized trial. Patients who fulfilled the criteria for early severe RA were randomized to receive either combination therapy (CSA + MTX n = 34, CSA + HCQ n = 35) or CSA alone (n = 36). RESULTS: CSA + MTX was more effective than the other two treatment groups in controlling RA symptoms. CSA+MTX did not show a significant radiographic progression according to Larsen-Dale (0.90 +/- 3.89 compared to baseline values, P > 0.05); moreover, patients treated with CSA alone or CSA+HCQ showed a significant worsening of Larsen-Dale score (2.91 +/- 5.99 and 2.97 +/- 4.28 respectively vs baseline values, P < 0.05), although not significant when compared with the CSA + HCQ group (P = 0.56 and 0.39, respectively). CONCLUSIONS: This trial indicated that CSA+MTX was more effective than the other two treatments in improving clinical data and inhibiting radiographic progression, although the differences were not significant in this relatively small study. However, the difference was significant in favor of CSA + MTX regarding ACR 50% response.

Correlation of the score for subjective pain with physical disability, clinical and radiographic scores in recent onset rheumatoid arthritis.

BACKGROUND: To analyse the relationship between subjective pain score and other measures of clinical, radiographic and functional status; in particular Larsen radiographic scores and Health Assessment Questionnaire (HAQ); in patients with severe rheumatoid arthritis (RA) with a disease duration of less than 3 years. METHODS: In this cross sectional study of 105 patients with RA (76 women, 29 men: mean age 50.93; mean disease duration 15.86 months; 71% rheumatoid factor positive) subjective pain was assessed according to the Visual Analog Scale (VAS). Correlation coefficients between pain score and disease activity measures (patients' global assessment of disease by VAS, number of tender and swollen joints, morning stiffness, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP] and titre of rheumatoid factor, radiographic evaluations (Larsen-Dale scores for radiographic damage of the small joints of the hands, wrist and feet), disability measures (health assessment questionnaire [HAQ]), and demographic variables were calculated; hierarchical regression analysis was done with subjective pain score as the dependent variable. RESULTS: The Spearman's correlation coefficient comparing subjective pain and HAQ was 0.421 (p < 0.001), between subjective pain and global assessment of disease and morning stiffness was 0.573 (p < 0.001) and 0.427 (p < 0.001) respectively, and between pain and number of tender and swollen joints 0.037 and 0.050 respectively (p > 0.05). In regression analysis, global assessment of disease by patients explained 32.8% of the variation in pain intensity score, morning stiffness 10.7%, CRP 4.0%, HAQ 3.8% and Larsen-Dale scores explained 2.1%; other variables were not significant in the model. CONCLUSIONS: Pain scores of patients with early severe rheumatoid arthritis are correlated at higher levels with patients' global assessment of disease and with morning stiffness rather than with radiographic or other clinical variables such as number of tender and swollen joints.

Long-term safety and efficacy of low-dose cyclosporin A in severe psoriatic arthritis.

OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of long-term treatment with cyclosporin A (CsA) in patients with psoriatic arthritis (PsA). METHODS: Sixty patients with PsA were enrolled in a prospective, nonrandomised study of CsA. Patients with hypertension or hypercreatinemia were excluded. Disease activity was evaluated according to clinical activity measures and the Psoriasis Area Severity Index (PASI). Assessments were made at baseline and after 3, 6, 12, 18, and 24 months. Measurements. The primary endpoints were 20% and 50% improvement in disease activity according to American College of Rheumatology (ACR) responses at 6, 12, 18, and 24 months. Other endpoints were 70% ACR responses at 6, 12, 18, and 24 months and other measures of disease activity at 3, 6, 12, 18, and 24 months. RESULTS: Forty-nine patients completed the 24-month of treatment with CsA. When all the clinical variables throughout the study were compared with baseline results, they all showed significant improvement after 6 months of treatment. Erythrocyte sedimentation rates (ESR) reached a significant improvement after 12 months of treatment (P<0.05). The PASI scores decreased from 15.1+/-4.3 to 5.2+/-2.7 after 24 months of treatment (P<0.001). Side effects included hypertrichosis (24% of patients), gum hyperplasia (12%), gastrointestinal intolerance (9%), hypertension (21%), neurological disturbance (7%), and nephrotoxicity (17%). Three patients withdrew due to treatment failure. One patient was lost to follow-up, and seven patients withdrew due to side effects. CONCLUSIONS: Cyclosporin A represents a helpful second-choice treatment for patients with active psoriatic arthritis. Administration of CsA necessitates expert and careful follow-up of patients.