Search

Central nervous system (CNS) involvement is quite unusual in patients with rheumatoid arthritis (RA), although cerebral vasculitis, rheumatoid nodules and meningitis have all been reported, and patients with RA may also have CNS comorbidities such as stroke and neuro-degenerative and demyelinating syndromes. It has been found that biological drugs, especially anti-tumour necrosis factor-alpha (anti-TNF-α) drugs, slightly increase the risk of developing demyelinating diseases, and they are consequently discouraged in patients with multiple sclerosis and related disorders. Furthermore, the risk of opportunistic CNS infections is increased in immunosuppressed patients. To review the current literature concerning CNS involvement in patients with RA (including RA-related forms and comorbidities) and the incidence of new-onset CNS diseases in patients with RA undergoing biological treatment (anti-TNF or non-anti-TNF drugs), the Medline database was searched using the key words 'rheumatoid arthritis', 'central nervous system', 'anti-TNF', 'abatacept', 'tocilizumab', 'rituximab' and 'anakinra'. Abstracts not in English were excluded. We selected 76 articles published between 1989 and 2017, which were divided into four groups on the basis of whether CNS involvement was RA-related or not and according to the type of biological agent used (TNF inhibitors or other agents). The RA-related diseases included aseptic meningitis, vasculitis and cerebral rheumatoid nodules, which benefit from immunosuppressive treatments. CNS comorbidities included stroke, seizures, dementia and neuropsychiatric disorders, which have been frequently described in biological agent-naïve patients with RA, and other rarely reported neurological diseases, such as extra-pyramidal syndromes and demyelinating disorders. CNS comorbidities are relatively frequent among patients with RA and may be related to systemic inflammation or concomitant medications. The use of anti-TNF drugs is associated with the risk of developing demyelinating diseases, and CNS infections have been described in patients treated with anti-TNF and non-anti-TNF agents. Non-anti-TNF drugs may be preferred in the case of demyelinating diseases, cerebral vasculitis or neurolupus. Patients with RA may suffer from CNS involvement as a manifestation of RA or as a comorbidity. The treatment of such medical conditions should be guided on the basis of their etiopathogenesis: steroids and immunosuppressants are useful in the case of RA-related CNS diseases but are often detrimental in other situations. Similarly, the choice of biological agents in patients with RA with CNS complications should be guided by a correct diagnosis in order to prevent further complications., (Copyright © 2019 Elsevier Ltd. 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.)

Complex regional pain syndrome (CRPS) encompasses a wide range of painful conditions, but it is characterised by continuing (spontaneous and/or evoked) limb pain that is seemingly disproportionate in time or degree to the usual course of any known trauma or other lesion. The pain is regional, with distal predominance usually but not related to a specific nerve territory or dermatome, and it is usually associated with abnormal sensory, motor, sudomotor, vasomotor and/or trophic findings. The complexity of the aetiopathogenetic factors making up the clinical picture of CRPS is mirrored by the inconsistency of almost all of the monotherapies used to treat it so far. Motor and sensory symptoms significantly interfere with the patients' daily function and quality of life, and almost all of them report substantial disability in their working and recreational activities, mood and mobility., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Pain is frequent in patients with connective tissue diseases (CTDs), particularly those affected by systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) in which it is virtually ubiquitous and can have different causes. The SLE classification criteria include pain associated with musculoskeletal involvement, which are frequently the initial symptom of SLE and can include arthralgia, arthritis and/or myalgia. Chronic widespread pain, the cornerstone of fibromyalgia (FM), is also frequently associated with CTDs. Chronic pain has a considerable impact on mental health, and the professional and family lives of patients. It can be due to many disorders, but there are few reports concerning its prevalence during the course of other diseases. It is essential to identify the origin of pain in CTDs in order to avoid dangerous over-treatment in patients with co-existing widespread pain. Effective pain management is a primary goal of patient care, although it has not been investigated in detail in patients with SSc., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Cryoglobulinaemic syndrome (CS) includes clinical signs and symptoms that range from the classic triad of Meltzer and Franklin (purpura, weakness and arthralgias) to multiple organ involvement, and it may be characterised by nociceptive or neuropathic pain. Both types of pain use the same pathways and neurotransmitters, but nociceptive pain has an adaptive system and biological function whereas neuropathic pain does not. Managing CS means dealing with often very different clinical patterns, activity and severity with the aim of preventing irreversible organ damage, reducing pain, improving the patients' quality of life and reducing social costs. However, treatment is still largely empirical, and it is often delayed. The Italian Group for the Study of Cryoglobulinaemia (GISC) strongly recommended a low-antigen-content diet and colchicine for all symptomatic CS patients. Patients with mild-moderate symptoms (such as purpura, weakness, arthralgia and initial neuropathy) have been treated with low or medium doses of steroids, and, in the presence of chronic hepatitis C virus (HCV)-related hepatitis, an attempt has been made to eradicate HCV with pegylated interferon plus ribavirin. In the case of severe or rapidly progressive disease (glomerulonephritis, neuropathy, leg ulcers, widespread vasculitis or hyperviscosity syndrome), more aggressive treatment should be used (e.g., high doses of corticosteroids, plasma exchange plus cyclophosphamide or rituximab). Pain management in CS therefore depends on the type of pain (nociceptive, neuropathic or mixed), the characteristics of the patients and their co-morbidities. Drug therapy should be carefully monitored in order to obtain prompt and beneficial results., (Copyright © 2015 Elsevier Ltd. 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.)

Chronic pain can be classified as localised, regional or widespread, and its high prevalence in the general population seems to increase with age. The majority of cases present with musculoskeletal pain. The conditions associated with chronic widespread pain (CWP) are highly burdensome as their characteristic symptoms may include multifocal pain, fatigue, insomnia, memory difficulties and a higher rate of concomitant mood disorders. After many years of debate, it is still unclear whether CWP (central sensitisation) is an entirely explainable neurotransmitter-related process or is partially or totally due to individual cognitive experiences and evaluations. The two models (neurochemical and biopsychosocial) also affect our ability to find therapeutic answers., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

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.)