Anti-tumor necrosis factor α: originators versus biosimilars, comparison in clinical response assessment in a multicenter cohort of patients with inflammatory arthropathies.

OBJECTIVE: To compare etanercept and adalimumab biosimilars (SB4 and ABP501) and respective bioriginators in terms of safety and efficacy in a real-life contest. METHODS: We consequently enrolled patients affected by rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with SB4, and ABP501, or with corresponding originators, belonging to the main biological prescribing centers in the Lazio region (Italy), from 2017 to 2020. Data were collected at recruitment and after 4, 8, 12, and 24 months of therapy. RESULTS: The multicenter cohort was composed by 455 patients treated with biosimilars [SB4/ABP501 276/179; female/male 307/146; biologic disease-modifying anti-rheumatic drug (b-DMARD) naïve 56%, median age/ interquartile range 55/46-65 years] and 436 treated with originators (etanercept/adalimumab 186/259, female/ male 279/157, b-DMARD naïve 67,2%, median age/interquartile range 53/43-62 years). No differences were found about safety, but the biosimilar group presented more discontinuations due to inefficacy (p<0.001). Female gender, being a smoker, and being b-DMARD naïve were predictive factors of reduced drug survival (p=0.05, p=0.046, p=0.001 respectively). The retention rate at 24 months was 81.1% for bioriginators and 76.5% for biosimilars (median retention time of 20.7 and 18.9 months, respectively) (p=0.002). Patients with remission/low disease activity achievement at 4 months showed a cumulative survival of 90% to biosimilar therapy until 24 months (p=0.001); early adverse reactions instead represented a cause of subsequent drug discontinuation (p=0.001). CONCLUSIONS: Real-life data demonstrated a similar safety profile between biosimilars and originators, but a reduced biosimilar retention rate at 24 months. Biosimilars could be considered a valid, safe, and less expensive alternative to originators, allowing access to treatments for a wider patient population.

Domestic violence detection amid the COVID-19 pandemic: the value of the WHO questionnaire in emergency medicine.

BACKGROUND: Gender-based violence affects 35-45% of women worldwide, mostly coming from domestic violence. A good screening procedure in clinical practice is useful, but WHO does not advise universal screening, recommending further research. AIM: (i) To report the frequency of domestic violence cases among admissions to the Emergency Room of a major Italian Hospital in 2020, including during complete 'Lockdown' period; (ii) to document acute and chronic health effects of domestic violence and (iii) to asses usefulness of the WHO screening as a tool for uncovering cases which would otherwise remain hidden. DESIGN AND METHODS: A database containing all the information recorded for each of 19 160 patients in the Emergency Room was constructed by a keyword search ('violence', 'assault', 'trauma') to filter the data and retrieve cases of violence in the period between 1 January and 2 June 2020. The self-administered questionnaire of the WHO Multi-country Study on Women's Health and Domestic Violence against Women was used in women referred to the emergency room for any cause, excluding trauma. RESULTS: A recent history of domestic violence was disclosed by 22.67%, after completing the WHO questionnaire. Of those not participating in the survey, diagnosis of domestic violence was only 0.6% (128/19 160). CONCLUSION: Power of detection of domestic violence by the WHO questionnaire is very high, while the frequency of occurrence of these events in this population was considerable. Seemingly, it elicits the responsiveness to the topic of the volunteer interviewees. Its use should be firmly recommended, reasonably, while Covid-19 pandemic is affecting health, rights and response.

Reduction of autophagy and increase in apoptosis correlates with a favorable clinical outcome in patients with rheumatoid arthritis treated with anti-TNF drugs.

BACKGROUND: Autophagy has emerged as a key mechanism in the survival and function of T and B lymphocytes, and its activation was involved in apoptosis resistance in rheumatoid arthritis (RA). To investigate whether the relationship between autophagy and apoptosis may impact the response to the therapy, we analyzed ex vivo spontaneous autophagy and apoptosis in patients with RA subjected to treatment with anti-tumor necrosis factor (TNF) drugs and in vitro the effects of TNFα and anti-TNF drugs on cell fate. METHODS: Peripheral blood mononuclear cells (PBMCs) from 25 RA patients treated with anti-TNF drugs were analyzed for levels of autophagy marker LC3-II by western blot and for the percentage of annexin V-positive apoptotic cells by flow cytometry. The same techniques were used to assess autophagy and apoptosis after in vitro treatment with TNFα and etanercept in both PBMCs and fibroblast-like synoviocytes (FLS) from patients with RA. RESULTS: PBMCs from patients with RA responsive to treatment showed a significant reduction in LC3-II levels, associated with an increased apoptotic activation after 4 months of therapy with anti-TNF drugs. Additionally, the expression of LC3-II correlated with DAS28. TNFα was able to induce autophagy in a dose-dependent manner after 24 h of culture in RA PBMCs and FLS. Moreover, etanercept caused a significant reduction of autophagy and of levels of citrullinated proteins. CONCLUSIONS: Our results show how the crosstalk between autophagy and apoptosis can sustain the survival of immune cells, thus influencing RA progression. This suggests that inhibition of autophagy represents a possible therapeutic target in RA.

Porphyromonas gingivalis in the tongue biofilm is associated with clinical outcome in rheumatoid arthritis patients.

Several studies have suggested a link between human microbiome and rheumatoid arthritis (RA) development. Porphyromonas gingivalis seems involved in RA initiation and progression, as supported by the high occurrence of periodontitis. In this case-control study, we analysed tongue P. gingivalis presence and quantification in a large healthy and RA cohort. We enrolled 143 RA patients [male/female (M/F) 32/111, mean ± standard deviation (s.d.), age 57·5 ± 19·8 years, mean ± s.d. disease duration 155·9 ± 114·7 months); 36 periodontitis patients (M/F 11/25, mean ± s.d., age 56 ± 9·9 years, mean ± s.d. disease duration 25·5 ± 20·9 months); and 57 patients (M/F 12/45, mean ± s.d., age 61·4 ± 10·9 years, mean ± s.d. disease duration 62·3 ± 66·9 months) with knee osteoarthritis or fibromyalgia. All subjects underwent a standard cytological swab to identify the rate of P. gingivalis/total bacteria by using quantitative real-time polymerase chain reaction. The prevalence of P. gingivalis resulted similarly in RA and periodontitis patients (48·9 versus 52·7%, P = not significant). Moreover, the prevalence of this pathogen was significantly higher in RA and periodontitis patients in comparison with control subjects (P = 0·01 and P = 0·003, respectively). We found a significant correlation between P. gingivalis rate in total bacteria genomes and disease activity score in 28 joints (DAS28) (erythrocyte sedimentation rate) (r = 0·4, P = 0·01). RA patients in remission showed a significantly lower prevalence of P. gingivalis in comparison with non-remission (P = 0·02). We demonstrated a significant association between the percentage of P. gingivalis on the total tongue biofilm and RA disease activity (DAS28), suggesting that the oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to more active disease.

Central sensitization as the mechanism underlying pain in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

BACKGROUND: Patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT) commonly suffer from pain. How this hereditary connective tissue disorder causes pain remains unclear although previous studies suggested it shares similar mechanisms with neuropathic pain and fibromyalgia. METHODS: In this prospective study seeking information on the mechanisms underlying pain in patients with JHS/EDS-HT, we enrolled 27 consecutive patients with this connective tissue disorder. Patients underwent a detailed clinical examination, including the neuropathic pain questionnaire DN4 and the fibromyalgia rapid screening tool. As quantitative sensory testing methods, we included thermal-pain perceptive thresholds and the wind-up ratio and recorded a standard nerve conduction study to assess non-nociceptive fibres and laser-evoked potentials, assessing nociceptive fibres. RESULTS: Clinical examination and diagnostic tests disclosed no somatosensory nervous system damage. Conversely, most patients suffered from widespread pain, the fibromyalgia rapid screening tool elicited positive findings, and quantitative sensory testing showed lowered cold and heat pain thresholds and an increased wind-up ratio. CONCLUSIONS: While the lack of somatosensory nervous system damage is incompatible with neuropathic pain as the mechanism underlying pain in JHS/EDS-HT, the lowered cold and heat pain thresholds and increased wind-up ratio imply that pain in JHS/EDS-HT might arise through central sensitization. Hence, this connective tissue disorder and fibromyalgia share similar pain mechanisms. WHAT DOES THIS STUDY ADD?: In patients with JHS/EDS-HT, the persistent nociceptive input due to joint abnormalities probably triggers central sensitization in the dorsal horn neurons and causes widespread pain.

Increased circulating osteopontin levels in adult patients with type 1 diabetes mellitus and association with dysmetabolic profile.

OBJECTIVE: Osteopontin (OPN) is a sialoprotein implicated in different immunity and metabolic pathways. Capable of activating dendritic cells and inducing Th1-Th17-mediated tissue damage, OPN plays a significant role in the development/progression of several autoimmune diseases; interestingly, it was also shown that OPN participates in the acute pancreatic islets response to experimentally induced diabetes in non-obese diabetic (NOD) mice. Furthermore, OPN promotes adipose tissue dysfunction, systemic inflammation and insulin resistance. Our aims of this study were to evaluate circulating OPN levels in adult patients with type 1 diabetes mellitus (T1DM) compared to non-diabetic control participants and to unravel clinical and biochemical correlates of OPN concentration. DESIGN: Case-control study. METHODS: We enrolled 54 consecutive T1DM patients referred to our diabetes outpatient clinic at Sapienza University of Rome and 52 healthy sex and age-comparable controls. The study population underwent clinical evaluation, blood sampling for biochemistry and complete screening for diabetes complications. Serum OPN levels were measured by MILLIPLEX Multiplex Assays Luminex. RESULTS: T1DM patients had significantly higher serum OPN levels than controls (17.2±12.9 vs 10.5±11.6 mg/ml, P=0.009). OPN levels correlated with T1DM, higher blood pressure, BMI, creatinine, γ-GT, ALP and lower HDL; the association between high OPN levels and T1DM was independent from all confounders. No correlation was shown between OPN and HbA1c, C-peptide, insulin requirement, co-medications and diabetes duration. CONCLUSIONS: This study demonstrates for the first time in a case-control study that adults with T1DM have increased serum OPN levels, and that higher OPN concentrations are associated with an unfavorable metabolic profile in these patients.

Anti-carbamylated protein antibodies in unaffected first-degree relatives of rheumatoid arthritis patients: lack of correlation with anti-cyclic citrullinated protein antibodies and rheumatoid factor.

OBJECTIVES: To investigate the prevalence of anti-carbamylated protein antibodies (anti-CarP) in the healthy first-degree relatives (HFDRs) of patients with rheumatoid arthritis (RA). METHODS: We enrolled 141 HFDRs of 63 patients with RA diagnosed accordingly to the 2010 ACR/EULAR criteria. Fifty-six normal healthy subjects (NHS), sex- and age-matched, served as controls. Anti-CarP IgG, anti-cyclic citrullinated peptide antibody (anti-CCP) IgG and rheumatoid factors (RF) isotypes (IgG, IgA, IgM) were assessed by solid-phase ELISA. RESULTS: Anti-CarP were detectable in 13 HFDRs (9.2%), anti-CCP in 9 (6.3%), IgG-RF in 10 (7%), IgA-RF in 17 (12%), and IgM-RF in 13 (9.2%) HFDRs. Twenty-nine (46%) RA patients were positive for anti-CarP, 31 (49.2%) for anti-CCP, and 34 (53.9%) for RF. One NHS (1.7%) resulted positive for anti-CarP, none for anti-CCP and RF. Anti-CarP showed significantly higher serum levels in RA and HFDRs than in NHS (p<0.0001 and p=0.0012, respectively). A significant correlation between anti-CCP and RF were found among RA patients (p=0.0002), whereas no correlations were reported between autoantibodies tested in the HFDRs. CONCLUSIONS: Anti-CarP can be found in the sera of HFDRs of RA patients and their prevalence is significantly higher than in NHS. No correlation of anti-CarP with anti-CCP and RF antibodies in RA HFDRs was found.

Distribution of interleukin-10 family cytokines in serum and synovial fluid of patients with inflammatory arthritis reveals different contribution to systemic and joint inflammation.

Evidence exists that interleukin (IL)-10 family cytokines may be involved in the pathogenesis of rheumatoid arthritis (RA). We sought to determine whether or not these cytokines are involved in psoriatic arthritis (PsA). We conducted a prospective study on patients with PsA, RA and osteoarthritis (OA); healthy controls (HC) were also included. We analysed IL-20, IL-24 and IL-19 serum and synovial fluid (SF) levels and change of serum levels following treatment with biological agents. IL-20 serum levels were increased in PsA and RA compared with OA patients and HC and with matched SF levels. IL-24 serum levels in PsA, RA and OA patients were higher than those in HC and also with respect to matched SF in PsA. IL-19 serum levels were higher in HC and OA compared with PsA and RA patients; IL-19 SF levels were higher in PsA and RA compared with OA patients, and in PsA compared with RA patients. PsA and RA patients showed a reduction of IL-19 serum levels after biological treatment. Therefore, IL-19 seems to be involved mainly in the joint inflammation, whereas IL-20 and IL-24 appear to participate mainly in the systemic responses. These findings may further the comprehension of the contribution of these cytokines to the inflammatory response involved in chronic arthritis, as well as to the development of novel therapeutic strategies.

Pain in rheumatoid arthritis: a critical review.

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.

Chronic widespread pain in spondyloarthritis.

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.

Pain and systemic lupus erythematosus.

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.

Effect of therapeutic inhibition of TNF on circulating endothelial progenitor cells in patients with rheumatoid arthritis.

Endothelial dysfunction has been detected in RA patients and seems to be reversed by control of inflammation. Low circulating endothelial progenitor cells (EPCs) have been described in many conditions associated with increased cardiovascular risk, including RA. The aim of this study was to investigate the effect of inhibition of TNF on EPCs in RA patients. Seventeen patients with moderate-severe RA and 12 sex and age-matched controls were evaluated. Endothelial biomarkers were tested at baseline and after 3 months. EPCs were identified from peripheral blood mononuclear cells by cytofluorimetry using anti-CD34 and anti-vascular endothelial growth factor-receptor 2. Asymmetric dimethylarginine (ADMA) was tested by ELISA and flow-mediated dilatation (FMD) by ultrasonography. Circulating EPCs were significantly lower in RA patients than in controls (P = 0.001). After 3 months EPCs increased significantly (P = 0.0006) while ADMA levels significantly decreased (P = 0.001). An inverse correlation between mean increase in EPCs number and mean decrease of DAS28 after treatment was observed (r = -0.56, P = 0.04). EPCs inversely correlated with ADMA (r = -0.41, P = 0.022). No improvement of FMD was detected. Short-term treatment with anti-TNF was able to increase circulating EPCs concurrently with a proportional decrease of disease activity suggesting that therapeutic intervention aimed at suppressing the inflammatory process might positively affect the endothelial function.

Biological therapies in rheumatic diseases.

The development of the biological drugs has revolutionized the therapeutic approach of the chronic inflammatory rheumatic diseases, particularly in patients resistant to standard treatment. These drugs are characterized by an innovative mechanism of action, based on the targeted inhibition of specific molecular or cellular targets directly involved in the pathogenesis of the diseases: pro-inflammatory cytokines (tumor necrosis factor, interleukin-1 and 6), CTLA-4, and molecules involved in the activation, differentiation and maturation of B cells. Their use has indeed allowed for a better prognosis in several rheumatic diseases (such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus) and to obtain a clinical remission. In the present review we give an overview of the biological drugs currently available for the treatment of the rheumatic diseases, analyzing the different mechanism of action, the therapeutic indications and efficacy data, and adverse events.

Fibromyalgia and arthritides.

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.

Preliminary identification of key clinical domains for outcome evaluation in fibromyalgia using the Delphi method: the Italian experience.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Psychometric properties of the Fibromyalgia Assessment Status (FAS) index: a national web-based study of fibromyalgia.

Fibromyalgia (FM) is a generalized chronic pain condition that is often accompanied by symptoms such as fatigue, sleep disturbances, psychological and cognitive alterations, headache, migraine, variable bowel habits, diffuse abdominal pain, and urinary frequency. Its key assessment domains include pain, fatigue, disturbed sleep, physical and emotional functioning, and patient global satisfaction and health-related quality of life (HRQL). A number of evaluation measures have been adapted from the fields of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, and others such as the Fibromyalgia Assessment Status (FAS) index and the Fibromyalgia Impact Questionnaire (FIQ) have been specifically developed. The aim of this study was to assess the impact of FM on HRQL by comparing the performance of the FAS index, the FIQ and the Health Assessment Questionnaire [HAQ] in 541 female and 31 male FM patients (mean age 50 years; mean disease duration 7.7 years) entered in the database of a web-based survey registry developed by the Italian Fibromyalgia Network (IFINET). Tests of convergent validity showed that the FAS index and FIQ significantly correlated with each other (rho=0.608, p<0.0001), but there were also significant correlations between the FAS index and other clinical measures of disability, including the HAQ (rho=0.423, p<0.0001), anxiety (rho=0.138, p=0.0009), depression (rho=0.174, p<0.0001) and, especially, the number of comorbidities (rho=0.147, p=0.0004). The FAS index revealed a statistically significant difference between males and females (p=0.048), analysed using the Mann-Whitney U-test for all pair wise comparisons. The FAS index is a valid three-item instrument (pain, fatigue and sleep disturbances) that performs at least as well as the FIQ in FM patients, and is simpler to administer and score. Both questionnaires may be useful when screening FM patients, with the choice of the most appropriate instrument depending on the setting.

Misdiagnosis in fibromyalgia: a multicentre study.

BACKGROUND: Fibromyalgia (FM) is the second most common cause of visits to rheumatologists after osteoarthritis, and may be difficult to diagnose in many patients. It is associated with various rheumatic disorders such as rheumatoid arthritis, spondyloarthropathies (SpA) and connective tissue disease (CTD), and a late diagnosis or misdiagnosis is a common and underestimated problem. OBJECTIVES: The aim of this study was to investigate the 'underdiagnosis' of FM, and which rheumatic diseases tend to be confused with it. METHODS: The following data were collected at baseline: symptoms, disease duration, physical examination findings, previous and current investigations and management, laboratory tests, tender point count, tender and swollen joint counts, and spinal pain. The clinimetric evaluation included the Fibromyalgia Impact Questionnaire (FIQ) and Fibromyalgia Assessment Status (FAS). RESULTS: The study population consisted of 427 outpatients (418 females and 9 males; mean age 49.3 years; mean disease duration 8.5 years). Fifty-seven patients (13.3%) had been previously misdiagnosed as having other musculoskeletal disorders (MSDs); 370 patients had been previous correctly diagnosed as having FM, or were diagnosed as having it during the course of the study. The FM and MSD groups were comparable in terms of demographic data and referral patterns. Disease duration was longer and the erythrocyte sedimentation rate was higher in the MSD patients, who also had less severe FIQ and lower pain visual analogue scale scores. Moreover, the FIQ and FAS scores correlated in the MS group. CONCLUSIONS: The findings of this study suggest that, although FM is a wellknown clinical entity, differential diagnosis with SpA, CTD and inflammatory arthritis can still be a challenge for rheumatologists and general practitioners.

Fatigue in Sjogren's syndrome: relationship with fibromyalgia, clinical and biologic features.

More than two third of patients with primary Sjögren's syndrome (SS) report fatigue. Despite its clinical relevance, only a few studies have examined the relationship of fatigue with the presence of an overlapping Fibromyalgia (FM) and other clinical and biological variables. The aim of this study was to assess the relationship between fatigue and SS disease activity and damage, FM, widespread pain, and mood disorders; finally, the possible correlation between fatigue and a panel of cytokines likely to drive the immunopathological process of the disease has been examined. Thirty-five female patients with primary SS were consecutively enrolled; for each patient the Sjögren's Syndrome Disease Damage Index (SSDDI) and the Sjögren's Syndrome Disease Activity Index (SSDAI) were calculated. Patients rated pain, fatigue and disease activity using a 100-mm VAS and completed Health Assessment Questionnaire (HAQ), the Zung depression (ZSDS) and anxiety scales (ZSAS). 30/35 patients (85.7%) felt unduly tired and the same percentage of patients suffered with pain in more than one area of the body. 7 patients satisfied ACR criteria for FM, representing 20% of the whole cohort and 23% of SS patients with fatigue. No differences were found in disease duration, SSDDI, SSDAI, ZSDS and ZSAS among SS patient with or without FM. In the whole group, fatigue VAS correlated with HAQ, ZSAS, ZSDS and pain VAS but not with age, disease duration, presence and severity of arthritis, SSDDI, SSDAI, or cytokines. In conclusion, an overlapping FM can contribute to, but does not entirely account for fatigue in Italian patients with primary SS.

Pharmacological treatment of fibromyalgia.

Fibromyalgia (FM) is a common syndrome characterised by widespread pain and at least 11/18 painful tender points that requires multimodal pharmacological treatment also combined with non-pharmacological therapy. Various drugs currently are available to control the complex and different symptoms reported by patients. Only three drugs (duloxetine, milnacipram, pregabalin) are approved by the American Food and Drug Administration (FDA) and none by the European Medicines Agency (EMEA), consequently, off-label use is habitual in Europe. Most of the drugs improve only one or two symptoms; no drug capable of overall symptom control is yet available. Furthermore, different classes of drugs with different mechanisms of action are used off-label, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), opioids, non-steroidal anti-inflammatory drugs (NSAIDs), growth hormone, corticosteroids and sedative hypnotics. As no single drug fully manages FM symptoms, multicomponent therapy should be used from the beginning. Various pharmacological treatments have been used to treat FM with inconclusive results, and gradually increasing low doses is suggested in order to maximise efficacy. The best treatment should be individualised and combined with patient education and non-pharmacological therapy.