Cardiovascular disease risk burden in primary Sjögren's syndrome: results of a population-based multicentre cohort study.

OBJECTIVE: Systemic autoimmune diseases, in particular systemic lupus erythematosus and rheumatoid arthritis, are characterized by a high risk of premature cardiovascular (CV) events. Disease-related characteristics and traditional CV disease risk factors may contribute to atherosclerotic damage. However, there are limited data on the risk of overt CV events in primary Sjögren's syndrome (pSS). METHODS: We retrospectively analysed a cohort of patients with 1343 pSS. Disease-related clinical and laboratory data, traditional CV disease risk factors and overt CV events were recorded. Prevalence of traditional CV disease risk factors and of major CV events was compared between a subgroup of 788 female patients with pSS aged from 35 to 74 years and 4774 age-matched healthy women. RESULTS: Hypertension and hypercholesterolaemia were more prevalent, whereas smoking, obesity and diabetes mellitus were less prevalent, in women with pSS than in control subjects. Cerebrovascular events (2.5% vs. 1.4%, P = 0.005) and myocardial infarction (MI) (1.0% vs. 0.4%, P = 0.002) were more common in patients with pSS. In the whole population, central nervous system involvement (odds ratio (OR) 5.6, 95% confidence interval (CI) 1.35-23.7, P = 0.02) and use of immunosuppressive therapy (OR 1.9, 95% CI 1.04-3.70, P = 0.04) were associated with a higher risk of CV events. Patients with leucopenia had a higher risk of angina (P = 0.01). CONCLUSIONS: pSS is associated with an increased risk of cerebrovascular events and MI. Disease-related clinical and immunological markers may have a role in promoting CV events.

Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients.

OBJECTIVES: To assess the prevalence of the main causes of morbi-mortality in the antiphospholipid syndrome (APS) during a 10-year-follow-up period and to compare the frequency of early manifestations with those that appeared later. METHODS: In 1999, we started an observational study of 1000 APS patients from 13 European countries. All had medical histories documented when entered into the study and were followed prospectively during the ensuing 10 years. RESULTS: 53.1% of the patients had primary APS, 36.2% had APS associated with systemic lupus erythematosus and 10.7% APS associated with other diseases. Thrombotic events appeared in 166 (16.6%) patients during the first 5-year period and in 115 (14.4%) during the second 5-year period. The most common events were strokes, transient ischaemic attacks, deep vein thromboses and pulmonary embolism. 127 (15.5%) women became pregnant (188 pregnancies) and 72.9% of pregnancies succeeded in having one or more live births. The most common obstetric complication was early pregnancy loss (16.5% of the pregnancies). Intrauterine growth restriction (26.3% of the total live births) and prematurity (48.2%) were the most frequent fetal morbidities. 93 (9.3%) patients died and the most frequent causes of death were severe thrombosis (36.5%) and infections (26.9%). Nine (0.9%) cases of catastrophic APS occurred and 5 (55.6%) of them died. The survival probability at 10 years was 90.7%. CONCLUSIONS: Patients with APS still develop significant morbidity and mortality despite current treatment. It is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications.

A retrospective, multicenter study evaluating the prognostic value of minor salivary gland histology in a large cohort of patients with primary Sjögren's syndrome.

OBJECTIVE: The objective of this report is to investigate the prognostic value of minor salivary glands (MSG) assessment, routinely performed with hematoxilin-eosin (H&E) staining, for the diagnosis of primary Sjögren's syndrome (pSS). METHODS: We retrospectively evaluated clinical, serological and histological features of 794 pSS patients. H&E-stained sections were assessed using the Chisholm and Mason grading system and/or the focus score (FS). RESULTS: FS allowed the identification of a number of differences in the disease spectrum, and its prognostic role was further confirmed by quantifying the association between FS value and clinical/serological variables with binary logistic regression. Moreover, hypocomplementemia and FS resulted the only variables associated with lymphoma at univariate analysis, and FS appeared to be associated with lymphoma independently on complement fraction concentrations. Conversely, when patients were divided according to the Chisholm and Mason grading system, we failed to observe any significant difference between subgroups. CONCLUSION: In addition to its diagnostic role, our data seem to support that the routine assessment of MSG-FS with H&E staining is useful to predict at the time of diagnosis the adverse outcomes, such as lymphoma and extraglandular manifestations, that complicate the pSS course. On this basis, it should be recommended that an MSG biopsy be performed even in those patients displaying clinical and serological criteria, allowing the diagnosis of pSS independent of histological status.

Clinical and biological differences between cryoglobulinaemic and hypergammaglobulinaemic purpura in primary Sjögren's syndrome: results of a large multicentre study.

OBJECTIVES: To determine the clinical and laboratory differences between cryoglobulinaemic and hypergammaglobulinaemic purpura in primary Sjögren's syndrome (pSS), in a large Italian multicentre cohort. METHOD: Patients were selected according to the following criteria: fulfilling the American-European classification criteria for pSS, serum cryoglobulin and gammaglobulin levels evaluated, and lack of hepatitis C virus (HCV) infection. Multinomial analyses were performed by distinguishing three groups of pSS: (i) purpura associated with cryoglobulinaemic vasculitis (CV), (ii) purpura associated with hypergammaglobulinaemic vasculitis (HGV), and (iii) pSS patients without purpura (pSS controls). Patients with purpura but without cryoglobulins or hypergammaglobulinaemia were excluded. RESULTS: A total of 652 patients were enrolled in this study. Group 1/CV comprised 23/652 patients (3.53%), group 2/HGV 40/652 patients (6.13%), and group 3/pSS controls 589/652 (90.34%). The three groups were found to be significantly different from each other (post-estimation test: group 1/CV vs. group 3/pSS controls: p < 0.0001; group 1/CV vs. group 2/HGV: p = 0.0001; group 2/HGV vs. group 3/pSS controls: p = 0.0003), thus confirming the different phenotypes of purpura in pSS.Multivariate analyses revealed that peripheral neuropathy (p < 0.001), low C4 (p < 0.001), leucopaenia (p = 0.01), serum monoclonal component (p = 0.02), and the presence of anti-SSB/La antibodies (p = 0.02) characterized CV whereas rheumatoid factor (p = 0.001), leucopaenia (p = 0.01), serum monoclonal component (p = 0.01), and anti-SSA/Ro antibodies (p = 0.049) were significantly associated with HGV. Lymphoma was associated only with CV. CONCLUSIONS: HGV is a cutaneous vasculitis, related to a benign B-cell proliferation, whereas CV is a systemic immune complex-mediated vasculitis with complement activation and a higher risk of lymphoma, thus confirming CV but not HGV as a prelymphomatous condition in pSS.

Relationship between SNPs and expression level for candidate genes in rheumatoid arthritis.

OBJECTIVES: The study of polymorphisms of genes differentially expressed may lead to the identification of putative causal genetic variants in multifactorial diseases such as rheumatoid arthritis (RA). Based on preceding transcriptomic results, we genotyped 10 single nucleotide polymorphisms (SNPs) belonging to six genes (S100A8, RNASE2, PGLYRP1, RUNX3, IL2RB, and LY96) showing the highest fold change (> 1.9) when level of expression was compared between RA patients and controls. These SNPs were then analysed to evaluate their role in RA. METHOD: The relationship between gene expression and genotypes of SNPs was first investigated by Kruskal-Wallis and Mann-Whitney tests in RA patients and controls. The genetic association of these SNPs with RA were then analysed using family-based association tests in trio families. RESULTS: We found that RNASE2 gene expression was related to rs2013109 genotypes in 14 RA patients (p = 0.030). The association study in a discovery sample of 200 French trio families revealed a significant association with RA for one SNP, PGLYRP1-rs2041992 (p = 0.019); this association was stronger in trios where RA patients carried the HLA-DRB1 shared epitope (SE) (p = 0.003). However, this association was not found in a replication sample of 240 European trio families (p = 0.6). CONCLUSIONS: Family-based association tests did not reveal an association between RA and any SNP of the candidate genes tested. However, RNASE2 gene expression was differentially expressed in RA patients considering a sequence polymorphism. This result led us to highlight the potential disease-specific regulation for this candidate gene in RA.

Poor sleep quality in systemic lupus erythematosus: does it depend on depressive symptoms?

OBJECTIVES: Sleep disturbances are frequently observed in rheumatic diseases including systemic lupus erythematosus (SLE). This study aimed at evaluating the prevalence of insomnia, poor sleep quality and their determinants in a cohort of SLE patients. METHODS: Eighty-one consecutive SLE female patients were evaluated in a cross-sectional study. The Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Beck Depression Inventory (BDI) and the Self-rating Anxiety Scale (SAS) were administered. Patients with previous diagnosis of obstructive sleep apnea or restless legs syndrome were excluded. Fifty-three women with hypertension (without SLE) were enrolled as control group (H). RESULTS: In the SLE cohort poor sleep quality (65.4% vs 39.6%, p < 0.01) and difficulty in maintaining sleep and/or early morning awakening (65.4% vs 22.6%, p < 0.001), but not insomnia (33.3% vs 22.6%, p = ns), were more prevalent than in H. Depressive symptoms were present in 34.6% of SLE vs 13.2% H patients (p < 0.001) while state anxiety was more common in H patients (H 35.8% vs SLE 17.3%, p < 0.005). SLE was associated with a 2.5-times higher probability of presenting poor sleep quality in comparison to H (OR 2.5 [CI 1.21-5.16]). After adjusting for confounders, both depressive symptoms (OR 4.4, [1.4-14.3]) and use of immunosuppressive drugs (OR 4.3 [CI 1.3-14.8]) were significantly associated with poor sleep quality in SLE patients. Furthermore, poor sleep quality was not associated either with disease duration or activity. CONCLUSIONS: In a cohort of SLE women, insomnia and poor sleep quality, especially difficulties in maintaining sleep, were common. Depressive symptoms might be responsible for the higher prevalence of poor sleep quality in SLE.

Sleep disorders and systemic lupus erythematosus.

OBJECTIVE: Sleep disturbances are often seen in rheumatic diseases, including systemic lupus erythematosus (SLE). However, the prevalence of sleep disorders in SLE as well as the contributing factors to their occurrence remain poorly understood. The aim of this paper is to review the clinical and psychobiological data on the relationship between sleep disturbances and SLE. METHOD: We performed a systematic search of MEDLINE, EMBASE and PsychINFO, using MeSH headings and keywords for "sleep disorders" and "SLE." RESULTS: Nine studies reporting the relationship between sleep disorders and SLE were found. Prevalence rates of sleep disorders ranged between 55% and 85%; differences in assessment techniques appeared to be a major source of this variability. In the majority of the studies an association between sleep disorders and disease activity, pain and fatigue has been reported. Psychosocial variables, depression, steroid use, and the role that sleep disruption has on pain, inflammation and cytokines, have been hypothesized as possible psychobiological factors. CONCLUSIONS: Sleep disorders appear to occur in more than half of patients with SLE and appear to be associated with disease activity. Pain and fatigue are also related to sleep disorders. Among the hypotheses on the possible mechanisms underlining the association between sleep disorders and SLE, psychosocial/psychological factors, especially depression, were the most frequently reported.

Neuropsychiatric questionnaires in systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) can be affected by a multitude of neurologic and psychiatric symptoms with a wide range of prevalence and severity. Irrespectively from attribution to SLE or other causes, neuropsychiatric (NP) symptoms strongly impact short-term and long-term outcomes, thus NP evaluation during routine clinical practice in SLE should be undertaken regularly. The assessment of NP involvement in SLE patients is challenging and the available diagnostic tools fail to guarantee optimal diagnostic accuracy, sensitivity to changes as well as feasibility in routine clinical care. Standardised questionnaires (both physician-administered and self-reported) can offer valuable help to the treating physician to capture all possible NP syndromes; few SLE-specific NP questionnaire have been developed but validation in large cohort or cross-cultural adaptations are still pending. On the other hand, general instruments have been largely applied to SLE patients. Both kinds of questionnaires can address all possible NP manifestations either globally or, more frequently, focus on specific NP symptoms. These latter have been mainly used in SLE to detect and classify mild and subtle symptoms, more likely to be overlooked during routine clinical assessment such as headache, cognitive impairment and psychiatric manifestations. In conclusion, this literature review highlights a clear case for validation studies in this area and the wider implementation of questionnaires to assess NP involvement is still warranted. The broader use of such instruments could have important consequences; first of all, by standardising symptom assessment, a better definition of the prevalence of NP manifestation across different centres could be achieved. Secondly, prospective studies could allow for the evaluation of clinical significance of mild symptoms and their impact on the patient's function and quality of life.

Annular subacute cutaneous lupus erythematosus lesions and polymyositis onset in a patient with primary Sjogren's syndrome: how should this unusual association be classified?

Classification of the wide variety of autoimmune diseases that can occur before or after the onset of Sjögren's syndrome (SS) is currently debated within the conventional SS criteria or as primary SS (pSS) developing autoimmune disease or as 'associated-overlap' with other systemic autoimmune diseases. There is also debate on whether or not to consider annular polycyclic subacute cutaneous lupus erythematosus (SCLE) and annular erythema associated with Sjögren's syndrome (AESS) as a spectrum linked to Ro-SSA and/or La-SSB auto-antibodies (SSA/SSB auto-ab). We present the case of a 55-year-old female patient, with pSS positive for SSA and SSB auto-ab, who developed chronic relapsing polymyositis and atypical annular non-polycyclic SCLE lesions resembling AESS, which seemed to suggest a common spectrum. While a chronic-progressive polymyositis may be generally accepted as a relatively rare myositis complicating pSS, interpretation of annular lesions of non-systemic SCLE in SS patients might actually be underestimated as pSS skin manifestation likely related to SSA/SSB auto-ab.

Depression and systemic lupus erythematosus: a systematic review.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic, relapsing-remitting autoimmune disorder that involves multiple organ systems including the central nervous system. Among the items included in the nomenclature for neuropsychiatric SLE, mood disorders have been identified. The aim of this paper is to review the clinical and psychobiological relationship between depression and SLE. METHOD: We performed a systematic search of MEDLINE, EMBASE, PsychINFO, using MeSH headings and keywords for 'depression' and 'SLE'. RESULTS: Seventeen studies reported depressive disorders, with prevalence rates in the range 17-75%. Three studies reported the most frequent symptoms, which may be represented by fatigue, weakness, somatic disorders and sleep disorders. Suicide ideation was much higher than in the general population. Nine studies analysed the relationship to SLE disease activity. The results of the available literature are contradictory. Psychobiological hypotheses have been considered in 13 studies. Among the psychobiological hypotheses which might underline the plausibility of their relationship, 'psychosocial factors' were the most frequently reported. CONCLUSIONS: Differences in assessment techniques appear to be the main explanation for the variability in findings and important methodological limitations are present in the available literature to definitively point to the prevalence of depression, type of depression and most prevalent symptoms. To date, the relationship between depression and SLE disease activity also appears controversial. Methodological limitations are present in the available literature and it would be necessary to develop evidence-based guidelines to improve the diagnosis of depression in SLE. Identification of SLE-specific biomarkers of depression also has high priority.

Systemic vasculitis: a critical digest of the recent literature.

Herewith we provide a critical digest of the recent literature on systemic vasculitis. In this manuscript, we reviewed all the articles published during the last 12 months on large-, medium- and small-vessel vasculitis and selected the most relevant studies regarding the epidemiology, pathogenesis and management of systemic vasculitis. In particular we focused the attention on giant cell arteritis, ANCA-associated vasculitis and cryoglobulinemia.

Health-related quality of life in severe cryoglobulinaemic vasculitis and improvement after B-cell depleting therapy.

OBJECTIVES: To study the health-related quality of life (HRQOL) in severe cryoglobulinaemic vasculitis (CV) associated with hepatitis C virus infection (HCV) and to describe the effect of rituximab on HRQOL. METHODS: HRQOL was evaluated with the Medical Outcomes Study Short Form 36 (SF-36). Health Survey questionnaire was submitted to 15 patients with severe CV. SF-36 questionnaire was evaluated at baseline and after rituximab. Physical Health Composite Summary (PCS) and Mental Health Composite Summary (MCS) scores were calculated according to standard protocols, and normalised to healthy controls. SF-36 summary scores were compared with those of HCV positive patients without CV, and other vasculitis published in the literature. European Quality of Life-5 dimensions (EQ5D) scores were also derived. RESULTS: Physical and mental domain scores were all reduced if compared with those of the healthy population, with physical domains being greatly affected. HRQOL of CV was comparable with HRQOL reported for the other small vessel vasculitis. The development of CV in HCV positive patients worsened PCS rather than MCS score. Birmingham Vasculitis Activity Score (BVAS) did not correlate with HRQOL, while the presence of peripheral neuropathy was associated with a worse HRQOL. Early rituximab treatment improved both PCS and MCS scores, with long-term effects. CONCLUSIONS: PCS rather than MCS was affected in HCV positive patients when CV is present. Rituximab improved both physical and mental domains, thus supporting its use before antiviral therapy in severe HCV-related CV. The cost/benefits ratio of a sequential therapy may be supported.

A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis.

OBJECTIVE: To conduct a long-term, prospective, randomized controlled trial evaluating rituximab (RTX) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis (CV). METHODS: Fifty-nine patients with CV and related skin ulcers, active glomerulonephritis, or refractory peripheral neuropathy were enrolled. In CV patients who also had hepatitis C virus (HCV) infection, treatment of the HCV infection with antiviral agents had previously failed or was not indicated. Patients were randomized to the non-RTX group (to receive conventional treatment, consisting of 1 of the following 3: glucocorticoids; azathioprine or cyclophosphamide; or plasmapheresis) or the RTX group (to receive 2 infusions of 1 gm each, with a lowering of the glucocorticoid dosage when possible, and with a second course of RTX at relapse). Patients in the non-RTX group who did not respond to treatment could be switched to the RTX group. Study duration was 24 months. RESULTS: Survival of treatment at 12 months (i.e., the proportion of patients who continued taking their initial therapy), the primary end point, was statistically higher in the RTX group (64.3% versus 3.5% [P < 0.0001]), as well as at 3 months (92.9% versus 13.8% [P < 0.0001]), 6 months (71.4% versus 3.5% [P < 0.0001]), and 24 months (60.7% versus 3.5% [P < 0.0001]). The Birmingham Vasculitis Activity Score decreased only after treatment with RTX (from a mean ± SD of 11.9 ± 5.4 at baseline to 7.1 ± 5.7 at month 2; P < 0.001) up to month 24 (4.4 ± 4.6; P < 0.0001). RTX appeared to be superior therapy for all 3 target organ manifestations, and it was as effective as conventional therapy. The median duration of response to RTX was 18 months. Overall, RTX treatment was well tolerated. CONCLUSION: RTX monotherapy represents a very good option for severe CV and can be maintained over the long term in most patients.

Systematic review of 2008-2012 literature and update of recommendations for the use of methotrexate in rheumatic diseases, with a focus on rheumatoid arthritis.

The objective of this review is to update the recommendations of the 2010 Italian Consensus on the use of methotrexate (MTX) in rheumatoid arthritis (RA) and other rheumatic diseases. The literature published between 2008 and 2012 was systematically reviewed and updated recommendations on MTX use in rheumatic diseases, particularly RA, were formulated. These recommendations were approved by a panel of expert Italian Rheumatologists. A total of 10,238 references were identified, among which 70 studies were selected for critical evaluation. Sufficient evidence had accumulated to warrant changes to several of the recommendations in the new version. A new recommendation for patients with RA who are in MTX-induced clinical remission was also proposed and approved by the panel. Updated recommendations for the use of MTX in patients with RA or other rheumatologic disease are proposed.

Cell surface expression of activating receptors and co-receptors on peripheral blood NK cells in systemic autoimmune diseases.

OBJECTIVES: A defined role for natural killer (NK) cells and their activating receptors in autoimmunity has not been clearly established. The aim of this study was to evaluate the levels of the CD3-CD56+ NK cells and their expression of receptors and co-receptors in the peripheral blood of patients with systemic autoimmune disorders. METHODS: Thirty-four subjects with systemic sclerosis (SSc), 14 with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), 14 with systemic lupus erythematosus (SLE), and 14 healthy donors were studied. The activating receptors NKp46, NKp44, NKp30, NKG2D, and DNAM-1 and the co-receptors NTB-A and 2B4 were analysed by flow cytometry on peripheral blood NK cells. RESULTS: In SSc, AAV, and SLE we detected a significant decrease in the percentage of CD3-CD56+ NK cells compared to healthy controls. No differences in the expression of NKp46, NKp44, and NKp30 were identified. On the contrary, NKG2D and DNAM-1 expression was decreased in SLE, but not in SSc and AAV, NTB-A was decreased in SLE, and 2B4 in both SLE and SSc. No differences were detected between active and inactive SLE patients. In SSc, only patients affected by pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) had a low expression of DNAM-1, 2B4, and NKp30. CONCLUSIONS: These data demonstrate that patients with different systemic autoimmune diseases differ in the expression of activating receptors and co-receptors on CD3-CD56+ NK cells. The down-regulation of receptors and co-receptors in SSc with lung involvement suggests their possible role in this manifestation of the disease.

Behçet's disease: features of neurological involvement in a dedicated centre in Italy.

OBJECTIVES: The aim of the present study was to retrospectively assess the prevalence of neurological involvement and the clinical patterns of presentation in a monocentric cohort of patients with BD, who have been followed in the last twenty years at our centre. METHODS: One hundred and seventeen patients were retrospectively studied. The male/female ratio was 1.6:1, with a mean disease duration of 11±5 years. Their mean age was 42±9 years (min:18, max:77), while the mean age at disease onset was 25±4 years (min:10, max:58). The mean ± SD duration of follow-up at our centre was 7±2 (min:1, max:11) years. RESULTS: Neurological involvement was observed in 38% (44 patients, 36 males and 8 females; mean age at onset 25±4 years). Organic brain involvement, demonstrated by MRI was due to ischaemic pons-mesencephalon lesions in 19 patients and to meningoencephalitis with brainstem involvement in 16. Peripheral nervous system involvement was confirmed by electroneuromyographic study in 4 patients, and consisted of peripheral neuropathy prominent in the lower extremities in all cases; we have also observed only 2 cases of endocranial hypertension and 3 BD patients suffering from pulsatile, severe headache, without abnormal neurological examination, responding only to medium-high doses of steroids. Excluding peripheral neuropathy and isolated headache, the onset of CNS involvement (total prevalence: 32% of the cohort) was observed in 2 patients within the first year from the onset of BD, in 4 cases between the first and the third year, in 24 between the third and the fifth year, 7 between the fifth and the tenth year; none presented a CNS involvement after the first 10 years of disease. CONCLUSIONS: Neuro-BD is more frequent in young males and it never represents a presenting feature of the disease. The most frequent time of onset of neurological involvement seems to be within the first 10 years of disease. Since neurological involvement may result in severe functional disability or be a life-threatening disease, a careful follow-up during the first years after onset is recommended.

Ultrasound imaging for the rheumatologist XXXVII. Sonographic assessment of the hip in ankylosing spondylitis patients.

OBJECTIVES: To investigate the prevalence of ultrasound (US) detectable inflammation in hips of patients with ankylosing spondylitis (AS) and the relationship between US and measures of disease activity and severity. METHODS: Consecutive patients with AS attending the rheumatology units involved in this study were enrolled. Clinical and demographical data were recorded. US examination of bilateral hips was performed at the same time, evaluating anterior longitudinal scan to search for synovial hypertrophy (SH), joint effusion (JE) or power Doppler (PD) positive synovitis. RESULTS: A total of 56 patients were included, median age (interquartile range, IQR) 49 (39, 59.5), median disease duration 98 (72, 204) months, 80.3% were treated with TNF-α inhibitors, median BASDAI 2.65 (1.96, 3.95), 30.3% had hip tenderness. US JE was found in 26.7% of patients, US SH in 16%, no patient had detectable PD. The concordance between clinical findings and US abnormalities was moderate, with a kappa of 0.44. Patients with detectable US abnormalities had higher median visual analogue scale (VAS) pain and C-reactive protein (CRP), while there was no significant association with other measures of disease activity and disability. In the subgroup of patients with no hip tenderness, US alterations were still significantly related to higher CRP levels, while in patients with hip tenderness and no US abnormalities CRP was not higher than in the asymptomatic patients. CONCLUSIONS: US assessment of hip joint in AS patients can be considered of value, as suggested by the correlation with relevant clinical and laboratory measures. In asymptomatic patients, US examination might provide further information on subclinical involvement.

Ultrasound imaging for the rheumatologist XXXIX. Sonographic assessment of the hip in fibromyalgia patients.

Fibromyalgia syndrome (FMS) is a common form of non-inflammatory rheumatism within the general population with symptoms often mimicking those of arthritis or muscle disorders. Arthralgic symptoms in the region of the hip are commonly mentioned by patients with FMS and one of the diagnostic trigger points for the condition is found around the greater trochanter. To date, no formal imaging studies using ultrasound (US) have been performed in FMS. This study describes the correlation between clinical and US findings in patients presenting with primary FMS to rheumatology clinics. In the majority of the patients, no significant pathological US abnormalities were detected.

Absence of xenotropic murine leukemia virus-related virus in Italian patients affected by chronic fatigue syndrome, fibromyalgia, or rheumatoid arthritis.

The xenotropic murine leukemia virus-related virus (XMRV) has been recently linked to chronic fatigue syndrome in a US cohort in whom the virus was demonstrated in 67% patients vs 3.7% healthy controls. Albeit this finding was not substantiated by subsequent reports and eventually considered a laboratory contamination, the matter is still the object of intense debate and scrutiny in various cohorts of patients. In this work we examined well-clinically characterized Italian patients affected by chronic fatigue syndrome, and also fibromyalgia and rheumatoid arthritis, two chronic illnesses of basically unknown etiology which show quite a few symptoms in common with chronic fatigue syndrome. Although we used recently updated procedures and controls, the XMRV was not found in 65 patients with chronic fatigue syndrome diagnosis, 55 with fibromyalgia, 25 with rheumatoid arthritis, nor in 25 healthy controls. These results add to the ever-growing number of surveys reporting the absence of XMRV in chronic fatigue syndrome patients and suggest that the virus is also absent in fibromyalgia and rheumatoid arthritis.

Thyroid autoimmunity may represent a predisposition for the development of fibromyalgia?

In our previous study, we observed that the presence of autoimmune thyroid disease worsens fibromyalgia (FM) symptoms. The aims of this study are to evaluate whether there is a predisposition for the development of FM in patients with Hashimoto's thyroiditis (HT) with or without subclinical hypothyroidism (SCH) and in patients with SCH alone and what is the weight of antithyroid antibody positivity and SCH on FM comorbidity. Fifty-two patients, 39 affected by HT with or without SCH and 13 by SCH, were matched with 37 patients affected by FM and 25 healthy subjects. Blood samples were collected from all study subjects for the determination of serum TSH, free triiodothyronine, free thyroxine, antithyroperoxidase antibody (TPOAb), antithyroglobulin antibody (TgAb) and non-organ-specific autoantibodies. Clinical assessment of patients and controls included the "Fibromyalgia Impact Questionnaire" (FIQ), while pain severity was evaluated using a visual analogue scale (VAS). Patients and controls were also characterized by the presence of diffuse pain, fatigue, paresthesiae, muscle spasms, non-restful sleep, tension headache and presence of mood disorders. FM comorbidity resulted in twelve HT subjects (31%) and none in SCH patient. In particular, FM comorbidity in HT patients without SCH was 33.3% and in HT patients with SCH was 28.5%. Based on our data, we speculate that maybe there is more than a hypothesis regarding the cause-effect relation between thyroid autoimmunity and the presence of FM, thus suggesting a hypothetical role of thyroid autoimmunity in FM pathogenesis.