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Objective. To provide a comprehensive overview of peripheral spondyloarthritis (pSpA), focusing specifically on its occurrence and management in patients with inflammatory bowel disease (IBD). Methods. An exhaustive literature search was conducted in PubMed, Embase, Cochrane Database of Systematic Reviews, and Google Scholar to identify relevant studies on pSpA in IBD patients. Titles, abstracts, and full-text articles were screened for relevance. Data on study design, patient characteristics, diagnostic criteria, main findings, and conclusions were extracted from selected articles. Study quality was assessed using appropriate checklists. Information was synthesized narratively to summarize current understanding. Results. pSpA is the most common extraintestinal manifestation in IBD, with a median prevalence of 16%. It worsens quality of life and requires collaboration between gastroenterologists and rheumatologists for optimal diagnosis and treatment. Several “red flags” guide appropriate specialist referral of IBD patients with suspected pSpA. Once the diagnosis is confirmed, the choice of therapy depends on IBD phenotype and patterns of articular/axial involvement. Anti-tumor necrosis factor (TNF) drugs are first-line biologics, with interleukin (IL)-12/23 and IL-23 inhibitors as alternatives for anti-TNF failure. Small molecules like apremilast and Janus kinase inhibitors also have utility. Recommended treatment algorithms exist, but more randomized controlled trials are needed. Conclusions. Early identification of pSpA is crucial in IBD patients to enable timely intervention, prevent structural damage, and minimize disability. A multidisciplinary, holistic approach addressing musculoskeletal and extra-musculoskeletal manifestations is key to optimal patient outcomes.

Objective. Spondyloarthritis is a family of inflammatory diseases subdivided into those affecting the spine, called axial spondyloarthritis, and those involving peripheral joints, such as psoriatic arthritis (PsA). Several studies have reported differences in clinical manifestations, outcomes, and treatment responses between male and female PsA patients. The aim of our review was to evaluate if differences may also be identified in the context of cardiovascular (CV) risk factors and diseases. Methods. Patients with PsA have a higher CV risk than the general population. The increased CV risk associated with PsA is likely caused by the complex interplay of traditional CV risk factors, chronic systemic inflammation, and side effects related to the use of certain anti-rheumatic drugs. Results. Sex differences in CV risk factors in PsA patients, according to several studies, are controversial. However, the few studies that reported sex-stratified estimates did not find differences in the risk of stroke and myocardial infarction between sexes. The same also holds true for CV mortality. These mixed results may be related to the different study designs and case definitions, as well as genetic and geographical variability across the investigated populations. Conclusions. In conclusion, our review suggests that the evaluation of sex-gender aspects of CV comorbidities in PsA should be a central step in the context of personalized medicine in order to prevent and treat properly associated comorbidities.

Fungal endocarditis/aortitis is an uncommon yet emerging entity accounting for 2% to 4% of all cases of infective endocarditis and continues to be associated with a poor prognosis. We present the first case of polyethylene-terephthalate (PETE) graft aortitis caused by A. niger, a rare fungal agent. Early diagnosis with frequent transoesophageal echocardiography (TEE) and a prompt surgical intervention coupled with optimal antifungal therapy are still the only option to reduce the exceedingly high mortality and morbidity.

The aim was to evaluate the role of klotho in the pathogenesis of systemic sclerosis (SSc), through the measurement of its serum concentration in SSc patients compared to healthy controls, and to assess the association with cutaneous and visceral involvement. Blood samples obtained from both SSc patients and healthy controls were analysed by an ELISA assay for the detection of human klotho. SSc patients were globally evaluated for disease activity and assessed through the modified Rodnan’s Skin Score, Medsger’s scale, pulmonary function tests, 2D-echocardiography, nailfold capillaroscopy and laboratory tests. Our cohort consisted of 69 SSc patients (61 females, mean age 64.5±12.5 years, median disease duration 9.0 (IQR 8) years) and 77 healthy controls (28 females, mean age 49.7±10.2 years). In the group of SSc patients, 19 (27.5%) suffered from a diffuse form of SSc. All patients were receiving IV prostanoids, and some of them were concomitantly treated with immunosuppressive drugs (prednisone, hydroxychloroquine, mofetil mycophenolate, methotrexate, cyclosporin A and azathioprine). The median serum concentration of klotho was significantly lower in patients compared to controls (0.23 ng/mL vs 0.60 ng/mL; p

Klotho is a transmembrane and soluble glycoprotein that governs vascular integrity. Previous studies have demonstrated reduced serum klotho concentrations in patients with systemic sclerosis (SSc), and it is known that klotho deficiency can impair the healing of digital ulcers related to microvessel damage. The aim of this study was to evaluate the association between serum klotho levels and nailfold capillaroscopic abnormalities in SSc patients. We retrospectively enrolled 54 consecutive patients with SSc diagnosed on the basis of the 2013 EULAR/ACR criteria [11 with diffuse SSc; 47 females; median age 68.0 years (IQ 18); median disease duration 11.0 years (IQ 7)]. Serum klotho concentrations were determined by means of an enzyme-linked immunosorbent assay. On the basis of the 2000 classification of Cutolo et al., 14 patients had normal nailfold capillaroscopic findings, 8 had an early scleroderma pattern, 21 an active scleroderma pattern, and 11 a late scleroderma pattern. The median serum klotho concentration was 0.29 ng/mL (IQ 1). Regression analysis of variation showed an inverse correlation between serum klotho concentrations and the severity of the capillaroscopic pattern (p=0.02; t -2.2284), which was not influenced by concomitant treatment. Logistic regression did not reveal any significant association between the risk of developing digital ulcers and nailfold capillaroscopic patterns, serum klotho levels, or concomitant medications. The presence of avascular areas significantly correlated with calcinosis (p=0.006). In line with previous studies, our findings confirm that klotho plays a role in preventing microvascular damage detected with nailfold capillaroscopy.

The aim of this study was to determine the prevalence of T helper 9 (Th9) lymphocytes in rheumatoid arthritis (RA) patients and to identify a possible association between the percentage of Th9 and the discontinuation of a biological treatment with an anti-tumor necrosis factor (TNF) (infliximab). We collected peripheral blood mononuclear cells (PBMCs) from 55 consecutive RA outpatients and 10 healthy controls. Among RA patients, 15 were not receiving any immunosuppressive drug, 20 were successfully treated with infliximab and 20 discontinued infliximab because of adverse events or inefficacy and were treated with other biological agents. PBMCs were cultured with/without infliximab 50 mg/L for 18 h, and the percentage of Th9 cells was assessed by means of flow cytometry. Th9 lymphocytes were identified as interferon gamma, interleukin (IL)4-, IL17-, IL9-secreting cluster of differentiation 4 (CD4)+ T cells. Cytometric analysis revealed no significant decrease in the percentage of Th9 cells after infliximab exposure in any of the groups, although it was lower in healthy controls than RA patients either before and after the infliximab stimulation assay. Th9 cells are IL-9-secreting T helper lymphocytes whose role in RA is still poorly known. IL-9 levels are increased in RA patients, in whom this cytokine plays a crucial role. Th9 cells are the major producers of IL-9, and their prevalence is higher in RA patients than in healthy subjects; however our experiment in vitro does not demonstrate an association between Th9 lymphocytes and the response to infliximab. Further studies are required to evaluate the real involvement of Th9 population in the immunogenicity of anti-TNF agents.

It is still unknown whether there is an association between the use of certolizumab pegol (CZP) in rheumatic patients and the onset of cardiac arrhythmias. We describe the cases of two patients with rheumatoid arthritis (RA) treated with CZP as the first-line biological drug and methotrexate (MTX), who developed an arrhythmic event. The first was a 60-year-old, hypertensive male smoker, the second a 66-year-old dyslipidemic female non-smoker. Both were diagnosed as having RA in 2010, and started treatment with MTX plus CZP. The first patient developed undatable atrial fibrillation, which was resistant to pharmacological treatment and electrical cardioversion. The second patient developed an atrial flutter, which was treated with a betablocker. In both cases, we set a cautious interval between two consecutive administrations of CZP and, in the first case, also reduced the dose of MTX without any worsening of RA activity. Although many studies have shown that tumor necrosis factor (TNF)-alpha plays a pathogenetic role in inducing an arrhythmogenic substrate that is apparently rescued by anti-TNF drugs, there is still a lack of conclusive data. We suggest caution in any patient developing a cardiac event (including rhythm disorders) during treatment with a conventional or biological disease-modifying anti-rheumatic drug.

Temporomandibular joint (TMJ) involvement is common but usually delayed in patients with juvenile idiopathic arthritis (JIA). We describe the case of a JIA patient with bilateral TMJ involvement, mandibular retrognathia, bone erosion, and severely restricted mouth opening. The use of cone beam computed tomography and a 3D diagnostic protocol in young patients with JIA provides reliable, accurate and precise quantitative data and images of the condylar structures and their dimensional relationships. Analgesics and conventional disease modifying antirheumatic drugs were ineffective, but interdisciplinary treatment with etanercept and a Herbst functional appliance improved functional TMJ movement and bone resorption.

Chronic pain is a healthcare problem that significantly affects the mental health, and the professional and private life of patients. It can complicate many disorders and represents a common symptom of rheumatologic diseases, but the data on its prevalence is still limited. Pain is a ubiquitous problem in systemic sclerosis (SSc). SSc-related pain has been studied on the basis of biomedical models and is considered a symptom caused by the disease activity or previous tissue damage. Effective pain management is a primary goal of the treatment strategy, although this symptom in SSc has not yet been investigated in detail. However, these patients do not all respond adequately to pharmacological pain therapies, therefore in these cases a multimodal approach needs to be adopted.

Pain is the main manifestation of many rheumatic diseases (be they overtly inflammatory such as rheumatoid arthritis or dysfunctional such as fibromyalgia) but, at least initially, the mechanisms involved in the genesis, amplification and chronicisation of the persistent pain characterising the various conditions can be very different. The main peripheral mechanism underlying acute nociceptive pain is a change in the activity of the nociceptors located in the affected anatomical structures (joints, tendons and ligaments), which makes them more sensitive to normally painful stimuli (hyperalgesia) or normally non-painful stimuli (allodynia). This physiopathological mechanism of peripheral sensitisation plays a primary role in rheumatic diseases characterised by acute inflammation, such as the arthritides due to microcrystals. In the case of chronic rheumatic diseases that do not regress spontaneously, functional and structural central nervous system changes cause a generalised reduction in the pain threshold that is not limited to the anatomical structures involved, thus leading to the appearance of hyperalgesia and allodynia in many, if not all body districts. This is the physiopathological basis of chronic, widespread musculoskeletal pain.

Chronic pain has been identified as an important issue related to various rheumatic diseases. At the time of a major government spending review, it is appropriate to discuss the pain characterising rheumatic diseases and its related costs. It is clearly essential for healthcare authorities to rationalise their policies on the basis of the increasing expectations of the users of healthcare services while simultaneously balancing their books. There are few published studies concerning the costs of pain of any kind, and the same is true of the costs of the chronic pain associated with diseases such as rheumatoid arthritis, osteoarthritis, and fibromyalgia.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by heterogeneous clinical manifestations involving virtually the entire body. The pain in SLE can have different causes. The SLE classification criteria include mainly the musculoskeletal manifestations of pain, which are commonly reported as initial symptoms of SLE, such as arthralgia, arthritis and/or myalgia. Chronic widespread pain, which is typical of fibromyalgia (FM), is frequently associated with SLE. The aim of this review is to describe widespread pain and fatigue in SLE, and the association of SLE and FM. Although secondary FM is not correlated with the disease activity, it may interfere with the daily activities of SLE patients. Therefore it is necessary to identify its symptoms and treat them promptly to improve the quality of life of patients. In conclusion, it is essential to identify the origin of pain in SLE in order to avoid dangerous over-treatment in patients with co-existing widespread pain and FM.

Patients with rheumatoid arthritis (RA) are frequently afflicted by pain, which may be caused by joint inflammation (leading to structural joint damage) or secondary osteoarthritis, and may be increased by central sensitisation. Non-inflammatory pain may also confuse the assessment of disease activity, and so the aim of treatment is not only to combat inflammatory disease, but also relieve painful symptoms. In order to ensure effective treatment stratification, it is necessary to record a patients medical history in detail, perform a physical examination, and objectively assess synovitis and joint damage. The management of pain requires various approaches that include pharmacological analgesia and biological and non-biological treatments. Although joint replacement surgery can significantly improve RA-related pain, it may only be available to patients with the most severe advanced disease.

Medically unexplained symptoms are considered ‘somatoform disorders’ in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). The introduction of this nosographic category has been helpful in drawing attention to a previously neglected area, but has not been successful in promoting an understanding of the disorders’ biological basis and treatment implications, probably because of a series of diagnostic shortcomings. The newly proposed DSM-V diagnostic criteria try to overcome the limitations of the DSM-IV definition, which was organised centrally around the concept of medically unexplained symptoms, by emphasising the extent to which a patient’s thoughts, feelings and behaviours concerning their somatic symptoms are disproportionate or excessive. This change is supported by a growing body of evidence showing that psychological and behavioural features play a major role in causing patient disability and maintaining high level of health care use. Pain disorders is the sub-category of DSM-IV somatoform disorders that most closely resembles fibromyalgia. Regardless of the diagnostic changes recently brought about by DSM-V, neuroimaging studies have identified important components of the mental processes associated with a DSM- IV diagnosis of pain disorder.

Pain is the hallmark symptom of fibromyalgia (FM) and other related syndromes, but quite different from that of other rheumatic diseases, which depends on the degree of damage or inflammation in peripheral tissues. Sufferers are often defined as patients with chronic pain without an underlying mechanistic cause, and these syndromes and their symptoms are most appropriately described as “central pain”, “neuropathic pain”, “nonnociceptive pain” or “central sensitivity syndromes”. The pain is particular, regional or widespread, and mainly relates to the musculoskeletal system; hyperalgesia or allodynia are typical. Its origin is currently considered to be distorted pain or sensory processing, rather than a local or regional abnormality. FM is probably the most important and extensively described central pain syndrome, but the characteristics and features of FM-related pain are similar in other disorders of particular interest for rheumatologists, such as myofascial pain syndromes and temporo-mandibular joint disorders, and there is also an intriguing overlap between FM and benign joint hypermobility syndrome. This suggests that the distinctive aspects of pain in these idiopathic or functional conditions is caused by central nervous system hypersensitivity and abnormalities. Pharmacological and non-pharmacological therapies have been suggested for the treatment of these conditions, but a multidisciplinary approach is required in order to reduce the abnormal cycle of pain amplification and the related maladaptive and self-limiting behaviours.

The pain associated with spondyloarthritis (SpA) can be intense, persistent and disabling. It frequently has a multifactorial, simultaneously central and peripheral origin, and may be due to currently active inflammation, or joint damage and tissue destruction arising from a previous inflammatory condition. Inflammatory pain symptoms can be reduced by non-steroidal anti-inflammatory drugs, but many patients continue to experience moderate pain due to alterations in the mechanisms that regulate central pain, as in the case of the chronic widespread pain (CWP) that characterises fibromyalgia (FM). The importance of distinguishing SpA and FM is underlined by the fact that SpA is currently treated with costly drugs such as tumour necrosis factor (TNF) inhibitors, and direct costs are higher in patients with concomitant CWP or FM than in those with FM or SpA alone. Optimal treatment needs to take into account symptoms such as fatigue, mood, sleep, and the overall quality of life, and is based on the use of tricyclic antidepressants or selective serotonin reuptake inhibitors such as fluoxetine, rather than adjustments in the dose of anti-TNF agents or disease-modifying drugs.

Wegener’s granulomatosis or granulomatosis polyangiitis associated (GPA) is a granulomatous inflammation of the upper and lower respiratory tracts associated with necrotising vasculitis of small and medium-sized blood vessels and, frequently, necrotising glomerulonephritis. We describe the case of a 37 year old female patient presenting with upper respiratory tract involvement, chronic rhinosinusitis with green secretions, and bilateral hypoacusia. Ten months later, she suffered occipital headache and two episodes of lipothymia associated with nausea, photophobia, faintness with visual blurring. Magnetic resonance imaging (MRI) revealed aseptic meningitis. The patient was treated with steroids and cyclophosphamide without any effect on the neurological symptoms which, however, greatly improved after subsequent treatment with rituximab as confirmed by means of cerebral MRI. Rituximab is an optimal means of treating cyclophosphamide-resistant patients with GPA associated with meningeal involvement.

Objectives. To review the literature addressing the relationship between mood disorders and fibromyalgia/chronic pain and our current understanding of overlapping pathophysiological processes and pain and depression circuitry. Methods. We selectively reviewed articles on the co-occurrence of mood disorders and fibromyalgia/chronic pain published between 1990 and July 2012 in PubMed. Bibliographies and cross references were considered and included when appropriate. Results. Forty-nine out of 138 publications were retained for review. The vast majority of the studies found an association between depression and fibromyalgia. There is evidence that depression is often accompanied by symptoms of opposite polarity characterised by heights of mood, thinking and behaviour that have a considerable impact on pharmacological treatment. Recent developments support the view that the high rates of fibromyalgia and mood disorder comorbidity is generated by largely overlapping pathophysiological processes in the brain, that provide a neurobiological basis for the bidirectional, mutually exacerbating and disabling relationship between pain and depression. Conclusions. The finding of comparable pathophysiological characteristics of pain and depression provides a framework for understanding the relationship between the two conditions and sheds some light on neurobiological and therapeutic aspects.

This paper describes the techniques for controlling pain by the physical means that are most widely used clinically, particularly in the case of fibromyalgia. They are grouped on the basis of the physical energy used: mechanical, thermal (including magnetic and electromagnetic), and light (LASER). The main underlying neurophysiological mechanisms are gate activation, the stimulation of descending systems of pain control, and the endogenous opiate system.

Fibromyalgia (FM) is a chronic pain syndrome that affects at least 2% of the adult population. It is characterised by widespread pain, fatigue, sleep alterations and distress, and emerging evidence suggests a central nervous system (CNS) malfunction that increases pain transmission and perception. FM is often associated with other diseases that act as confounding and aggravating factors, such as rheumatoid arthritis (RA), spondyloarthritides (SpA), osteoarthritis (OA) and thyroid disease. Mechanism-based FM management should consider both peripheral and central pain, including effects due to cerebral input and that come from the descending inhibitory pathways. Rheumatologists should be able to distinguish primary and secondary FM, and need new guidelines and instruments to avoid making mistakes, bearing in mind that the diffuse pain of arthritides compromises the patients’ quality of life.

Fibromyalgia (FM) is a complex syndrome that, in Italy, affects at least 2% of the adult population. It is characterized by chronic widespread musculoskeletal pain often accompanied by multiple other symptoms. The aim of this study was to identify a set of clinical domains for FM considered relevant by both clinicians and patients using a consensus process. Consensus was achieved using the Delphi method based on questionnaires and systematic, controlled opinion feedback. The Delphi exercise involved a panel of 252 rheumatologists and 86 patients with FM as defined by the American College of Rheumatology criteria. All of the patients and clinicians were asked to rank the relative different domains of FM in order of priority. The content validity index (CVI) was used to establish the percentage agreement. The importance of each item was ranked on a 0-3 Likert scale. The frequency, mean relevance scores, and frequency importance product were also calculated. The Delphi exercise showed that the domains ranked highest by patients were similar to those of the clinicians, with the exception of tender point intensity (considered relevant by the clinicians but not by the patients) and environmental sensitivity (considered important by the patients but not by the clinicians). A final 8-item model was developed which was considered to demonstrate adequate validity. The Delphi exercises identified and ranked relevant key clinical domains that need to be assessed in FM research. On the basis of these results, a new patient-reported composite outcome index can be developed and used in clinical trials.

Psoriasis is a chronic, genetically determined and immunomediated inflammatory skin disease that affects 2-3% of the Caucasian population. A considerable proportion of these patients develop a form of inflammatory arthritis known as psoriatic arthritis (PsA), although the prevalence of this has not been well defined. Patients with PsA have a higher mortality rate than the general population and the risk of mortality is related to disease severity at the time of presentation. Endothelial dysfunction and early atherosclerosis have been found in patients with PsA without any cardiovascular disease (CVD) risk factors, and experts believe that CVD is one of the leading causes of death, as it is in patients with rheumatoid arthritis (RA). Various disease-related mechanisms may be involved in the development of premature vascular damage in both cases, including an increased synthesis of proinflammatory mediators (such as cytokines, chemokines and adhesion molecules), autoantibodies against endothelial cell components, perturbations in T-cell subsets, genetic polymorphisms, hyperhomocysteinemia, oxidative stress, abnormal vascular repair, and iatrogenic factors. In a recent study of 22 patients with PsA without any signs of CVD, we found that the plasma concentration of asymmetric dimethylarginine (ADMA) levels were significantly high and coronary flow reserve (CFR) was significantly reduced. Moreover, there was a significant correlation between CFR and plasma ADMA levels in the PsA group. The significant correlation between the reduced CRF and increased ADMA levels suggests that, like patients with early RA, PsA patients suffer from endothelial dysfunction and impaired coronary microcirculation. Active PsA is a risk factor for CVD, and so PsA patients should be screened for subclinical forms of the disease and its risk factors, and an early treatment approach should be adopted.

To fully answer the complex question of what modes of non pharmacological treatments are useful for fibromyalgia (FM) one should ask different layers of questions, and as with peeling layers of onions, be prepared to shed some tears. The first painful question, or layer of the onion, is related to understanding patients’ complaints. Patients who experience recurrent as well as persistent physical symptoms without any objective evidence are too often classified as “psychosomatic disorders” or worse as “non disease” (see Sarzi this issue)...

Use of complementary and alternative medicine (CAM) for chronic conditions has increased in recent years. CAM is immensely popular for musculoskeletal conditions and patients suffering from rheumatoid arthritis (RA) frequently try CAM. This review summarises the trial data for or against CAM as a symptomatic treatment for rheumatoid arthritis. Collectively the evidence demonstrates that some CAM modalities show significant promise, e.g. acupuncture, diets, herbal medicine, homoeopathy, massage, supplements. However, for the great majority of these therapies no evidencebased (clinical randomized trials) results are available. CAM is usually used in addition to, and not as a substitute for conventional therapies. The motivation of patients to try CAM is complex; the willingness to take control of their healthcare, the desire to try everything available, the mass-media pressure and the erroneous notion that CAM is without risks. In fact, none of these treatments is totally devoid of risks. While the use of complementary and alternative modalities for the treatment of RA continues to increase, rigorous clinical trials examining their efficacy are needed before definitive recommendations regarding the application of these modalities can be made.

Fibromyalgia (FM) is currently classified as chronic widespread pain with widespread allodynia/hyperalgesia to pressure pain and is categorized among the large group of soft-tissue pain syndromes. FM remains an elusive condition of unknown etiology in which patients report not only chronic widespread pain but also a variety of other complaints, so that it is one of several relatively common overlapping syndromes characterized by otherwise unexplained chronic pain and fatigue (1, 2)...

Fibromyalgia (FM), also known as fibromyalgia syndrome (FMS), is a frequently observed systemic disorder characterized by widespread musculoskeletal pain (1, 2). Its prevalence in the general population is 1-3%, and it is more common among females than males. The American College of Rheumatology (ACR) classification criteria defines it as widespread pain with patients endorsing at least 11 of 18 tender points as painful (3). Although its defining feature is chronic, widespread pain, FM patients may also have a number of other symptoms including sleep disturbance, fatigue, irritable bowel syndrome, headache and mood disorders (1)....

Fibromyalgia (FM) is a central pain syndrome that is characterized, in part, by specific tender points (TPs) in the musculoskeletal system which are exceptionally sensitive to pressure. Pain, specifically characterized as hyperalgesia and allodynia, is the cardinal symptom of FM; however, most patients also experience additional symptoms such as debilitating fatigue, disrupted or nonrestorative sleep, functional bowel disturbances, and a variety of neuropsychiatric problems, including cognitive dysfunction, anxiety and depressive symptoms (1)....

Fibromyalgia syndrome (FMS) is a common chronic condition of widespread pain with causal mechanisms that are largely unknown. It is characterized by moderate to severe musculoskel - etal pain and allodynia, but its pathogenesis appears confined to the nociceptive structures of the central nervous system. From a pathogenetic point of view, indeed, no clear muscle pathology has been demonstrated in FMS (1, 2), while increasing evidence suggests a disturbance in pain perception that is genetically conditioned. In our review we will consider five “keypoints” that we think determine the origin and maintenance of the pain syndrome that we define as fibromyalgia...

Fibromyalgia (FM) is a rheumatic disease characterized by musculoskeletal pain, chronic diffuse tension and/or stiffness from joints and muscles, easy fatigue, sleep and emotional disturbances, and pressure pain sensitivity in at least 11 of 18 tender points (TP) (1, 2). This disease has an incidence of 2% in the general population, but it is found more often in middle-aged women (3.4%) (3, 4). The etiopathogenesis of FM has not been clarified yet. FM patients have a dysregulation of pain neurotransmitters and neurohormone-mediated association with irregularities in the physiology of sleep...

Fibromyalgia syndrome (FM) is a condition of chronic and diffuse muscular pain affecting particularly middle aged women. The aetiology of FM is not completely understood and it is currently considered a disorder of pain regulation. The most efficacious compounds include the tricyclic drugs and mixed reuptake inhibitors. Recent works suggest that the anticonvulsant medications pregabalin and gabapentin are also effective. Moreover, two serotonin and norepinephrine- reuptake inhibitors-duloxetine and milnacipran show encouraging results in treating FM symptoms. The results of clinical trials of anti-inflammatory medications have been generally disappointing, but three RCTs have found that tramadol (with or without acetaminophen) is effective in FM.

Clinical trials have shown that anti-tumour necrosis factor (TNF)-α drugs are effective in patients with rheumatoid arthritis (RA) refractory to disease- modifying antirheumatic drugs (DMARDs) (1-4). At about the same time as the European approval of the third anti-TNFα agent (adalimumab) for treating RA patients, the Italian Society of Rheumatology (Società Italiana di Reumatologia [SIR]) started a database for the registration and active follow-up of RA patients treated with biological response modifiers, which contains all of the demographic and clinical parameters, as well as the therapeutic data, usually needed to follow RA patients...

Although the term “fibromyalgia” (FM) is relatively new, the condition characterised by chronic musculoskeletal pain that is accompanied by numerous extra-skeletal symptoms has been described in the medical literature for many years under different names. The term “fibrositis,” which was originally used in 1904 by Sir William Gowers to define a type of lumbalgia, became a synonym for diffuse musculoskeletal pain until 1976 (1). In the mid-1970s, Smythe and Moldofsky used the term “fibrositic syndrome” to describe the presence of tender points (TPs), sleep disturbances and other accompanying symptoms such as asthenia...

Rheumatoid arthritis (RA) is a systemic disease characterized by chronic inflammation of the synovial joints damage and loss of the function. The ultimate goal in managing RA is to prevent joint damage and to maintain functional ability. Consequently, early diagnosis and treatment is important, but predictive markers for RA are still confined to auto- antibodies and also magnetic resonance imaging (MRI) and sonography do not appear to sufficiently distinguish between early RA and non RA. Evidence shows that substantial and irreversible joint damage already occurs within the first 2 years after disease onset. This “window of opportunity” hypothesis for therapeutic intervention in RA is based on the existence of a time frame within which there is a potential for a greater response to therapy, resulting in sustained benefits or, perhaps most important, a chance of cure. There is increasing evidence for beneficial effects of early DMARDs (disease-modifying anti-rheumatic drugs) therapy over delayed treatment in patients who present with arthritis of recent onset. However, no universal consensus exists concerning the choice of initial drug or whether single drug or combination should be given as initial treatments. Most studies demonstrated superiority of aggressive over conventional approaches. Because the tumor necrosis factor (TNF)-α inhibitors have proved to stop joint damage progression in severe progressive RA, the achievement of these agents in early RA are currently of great interest.

Patients fear pain because it causes considerable suffering, and clinicians may not handle it appropriately because they fail to understand it (1). The International Association for the Study of Pain (IASP) defines it as “… is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (2). Individual patients perceive it differently, depending on the context of the stimulus, their previous experience, and their current psychological and physical condition. Furthermore, painful stimuli cannot be ignored, disturb behavioural and cognitive activities, and give rise to anxiety and/or depression (3, 4). Acute pain is one of the most frequent reasons for consulting a doctor in all parts of the world (5), and is often associated with already distressing...

Several studies demonstrated the efficacy of the B-cell depletion therapy with rituximab (RTX) in RA patients, including those unresponsive to anti- TNF therapy, underlying the important role of B cells in this disease (1-5). Several recent papers have demonstrated a differential effects of RTX in depleting B-cells and blocking plasma cell generation at the synovial and at the bone marrow level (7-9). This differential effect may explain why among patients who respond to RTX, some relapse while others show a very prolonged response, independently from the reappearance of B-cells in the peripheral blood (6). However, the efficacy of RTX may also depend on the individual genetic predisposition. At this regard, very few data were produced by now.

Rheumatoid arthritis (RA) is a systemic disease of unknown etiology characterized by a chronic inflammatory process mainly leading to destruction of synovial membrane of small and major diarthrodial joints. The prevalence of RA within the general adult population is about 1% and female subjects in fertile age result mostly involved. It’s an invalidating disease, associated with changes in life quality and a reduced life expectancy. Moreover, we can observe an increased mortality rate in this population early after the onset of the disease. The mortality excess can be partially due to infective, gastrointestinal, renal or pulmonary complications and malignancy (mainly lung cancer and non- Hodgkin lymphoma). Among extra-articular complications, cardiovascular (CV) involvement represents one of the leading causes of morbidity and mortality. Every cardiac structure can be affected by different pathogenic pathways: heart valves, conduction system, myocardium, endocardium, pericardium and coronary arteries. Consequently, different clinical manifestations can be detected, including: pericarditis, myocarditis, myocardial fibrosis, arrhythmias, alterations of conduction system, coronaropathies and ischemic cardiopathy, valvular disease, pulmonary hypertension and heart failure. Considering that early cardiac involvement negatively affects the prognosis, it is mandatory to identify high CV risk RA patients to better define long-term management of this population.

Patients with rheumatoid arthritis (RA) are at increased risk of manifestations such as serious infectious events (SIEs), malignancies and cardiovascular disease (1). Moreover, a long administration of drugs is required in this chronic disease, a condition that is responsible of a greater risk of side effects. As an example, there is an almost 2-fold greater risk on a SIE in patients with RA than in general population (2). Furthermore bacterial infection, one of the leading cause of morbidity and mortality in RA patients (3), is not an uncommon side effect of therapy. In addition, the use of corticosteroids, even at low doses (10 mg per day or less), utilized in approximately 65% of patients in randomized clinical trials is an important contributory factor to the increased prevalence of SIEs among RA patients (2, 4)...

Pain, a complex phenomenon influenced by a series of genetic, biological, psychological and social factors, is a major component of many rheumatological conditions and the result of physiological interactions between central and peripheral nervous system signalling. It may be acute or chronic (generally defined as lasting ≥ three months): acute pain is often primarily attributable to inflammation and/or damage to peripheral structures (i.e. nociceptive input), whereas chronic pain is more likely to be due to input from the central nervous system (CNS). The many different aspects of pain mean that rheumatologists and other clinicians need to have enough expertise to diagnose the type of pain correctly and treat it appropriately. However, most rheumatologists receive little formal training concerning contemporary theories of pain processing or management, and this may affect the clinical results of any specific target therapy.

This issue of “Reumatismo” deals with a variety of aspects of chronic widespread pain (CWP) and its rheumatological quasi-synonym of fibromyalgia (FM). The definitions of CWP and FM both have a long history. Chronic musculoskeletal pain conditions are universally prevalent in both genders and all age groups and, although their pathophysiology varies, they are inter-related anatomically and by their association with pain and impaired physical function. However, there is still no consensus as to whether FM should be considered a discrete entity or just the tip of the iceberg of CWP...

Il coinvolgimento cardiovascolare è frequente nei pazienti affetti da artrite reumatoide (AR) (1); un numero rilevante di studi hanno infatti dimostrato che la mortalità per eventi cardiovascolari (ECV) coinvolge il 40-50% dei pazienti affetti da AR e che aumenta in rapporto all’età e all’attività della malattia (1, 2). Tutte le strutture anatomiche del cuore possono essere interessate, ma in particolare le arterie coronariche (3). L’infarto acuto del miocardio (IMA) rappresenta la principale causa di morte per ECV nei pazienti affetti da AR (4). Il danno e di conseguenza la disfunzione endoteliale causata dagli alti livelli delle lipoproteine a bassa densità (LDL) ossidate, dall’omocisteina e da alcuni mediatori dell’infiammazione favoriscono il processo di aterosclerosi precoce e accelerata che si osserva nell’AR (5, 6). La disfunzione endoteliale aumenta la permeabilità cellulare, favorisce il rilascio di citochine, di sostanze vasoattive e il passaggio dei leucociti, che richiamano nel sottoendotelio i monociti, i quali inglobate le LDL ossidate si trasformano in “foam cells” (5)...

Objective. We aimed to compare a chemiluminescent immunoassay (CIA, QUANTA Flash) on BIO-FLASH with a multiplex flow immunoassay (MFI) on BioPlex 2200 for the detection of antibodies to Ro60, Ro52, and SS-B. Methods. The study included 241 samples, from patients suffering from systemic autoimmune diseases (n=108) as well as disease controls (n=133). All samples were tested for anti-Ro52, anti-Ro60, and anti-SS-B (La) antibodies on QUANTA Flash (INOVA Diagnostics, San Diego, USA) and BioPlex 2200 (Bio-Rad Laboratories Inc., Hercules, USA). Discrepant samples were tested by two independent methods: BlueDot/ANA and QUANTRIX Microarray (both D-tek, Belgium). Results. The overall qualitative agreements were 95.4% (95% confidence interval, CI 92.0–97.7%) for anti-Ro52, 98.8% (95% CI 96.4–99.7%) for anti-Ro60, and 91.7% (95% CI 87.5–94.9%) for anti-SS-B antibodies. There were 34 discrepant samples among all assays (20 anti-SS-B, 11 anti-Ro52, 3 anti-Ro60). 30/33 of retested samples (by D-tek dot blot) agreed with the QUANTA Flash results. Similar findings were obtained with QUANTRIX Microarray kit. Conclusion. QUANTA Flash and BioPlex 2200 show good qualitative agreement. The clinical performances were similar for anti-Ro52 and anti-Ro60 autoantibodies while differences were observed for anti-SS-B (La) antibodies.

Drug-induced lupus is a syndrome which share symptoms and laboratory characteristics with the idiopathic systemic lupus erythematosus (SLE). The list of medications implicated as etiologic agents in drug-induced lupus continues to grow. The terms used for this condition are lupus-like syndrome, drug-induced lupus erythematosus (DILE) and drug related lupus. More than 80 drugs have been associated with DILE. The first case of DILE was reported in 1945 and associated with sulfadiazin. In 1953 it was reported that DILE was related to the use of hydralazine. Drugs responsible for the development of DILE can divided into three groups, but the list of these drugs is quite long because new drugs are included yearly in the list. The syndrome is characterised by arthralgia, myalgia, pleurisy, rash and fever in association with antinuclear antibodies in the serum. Recognition of DILE is important because it usually reverts within a few weeks after stopping the drug.

Fibromyalgia (FM), a poorly-understood chronic condition, is characterized by widespread musculoskeletal pain, fatigue, non-restorative sleep, psychological distress, and specific regions of localized tenderness, all in the absence of otherwise apparent organic disease (1). While the etiology of FM is unclear, accumulating data suggests that disordered central pain processing likely plays a role in the pathogenesis of symptoms (2). Although various pharmacological treatments have been studied for treating FM, no single drug or group of drugs has proved to be particularly useful in treating FM patients as a whole; and to date, only two drugs (pregabalin and duloxetine) have earned U.S. Food and Drug Administration (FDA) approval for treating the syndrome in the United States (USA) (3, 4)...

L’idea che la deplezione dei B linfociti potesse essere utilizzata per il trattamento delle malattie reumatiche sistemiche deriva dall’ipotesi che, eliminando le cellule alterate dal circolo, si possa curare la malattia. In realtà, nelle malattie reumatiche sistemiche, contrariamente a quanto accade nei linfomi, la deplezione dei B linfociti persiste per alcuni mesi e successivamente si assiste alla riacutizzazione della malattia. Molteplici sono le ipotesi che possono spiegare tale evento: a) insufficiente deplezione dei cloni patogeni; b) persistenza di anticorpi patogeni; c) alterazione primaria o secondaria della tolleranza dei B linfociti; d) ricomparsa delle B cellule; e) reminiscenza della malattie da parte di cellule diverse dai B linfociti, probabilmente T linfociti (1, 2)...