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Immunoglobulin G4-related disease is an immune-mediated condition comprised of a number of various disorders sharing unique pathologic, serologic, and clinical features. Diagnosis of immunoglobulin G4-related sclerosing mastitis is challenging as the clinical and imaging findings mimic breast malignancies or other types of inflammatory mastitis. Herein, we describe a case of a female patient with a painless palpable mass in her right breast. An excisional core biopsy led to the rare diagnosis of immunoglobulin G4-related sclerosing mastitis, and the patient received steroid treatment for a month. To date, the patient has remained disease-free without any recurrence. As immunoglobulin G4-related sclerosing mastitis is a very rare disease, further studies are needed to reach conclusions about the pathogenesis, diagnosis, and treatment of this entity., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Background/aims: The high incidence of cardiovascular disease (CVD) in patients with autoimmune rheumatic diseases (ARDs) is the main driver towards increased mortality in this patient group. Cardiovascular magnetic resonance (CMR) can non-invasively and robustly detect CVD in ARD patients at an early stage of development. The review summarises the diagnostic information provided by CMR in ARD patients., Summary: CMR uses a strong magnetic field combined with radio-frequency pulses (pulse sequences) to generate images. Firstly, balanced steady-state free precession (bSSFP) can be used for evaluating cardiac anatomy, mass, wall motion, atrial/ventricular function. Secondly, T2-weighted imaging (T2-W) can be used for oedema detection, which appears as a high signal intensity area on STIR (short tau inversion recovery) images. T2 mapping is a newer T2-W technique that can provide more optimal identification of myocardial oedema. Lastly, late gadolinium enhanced (LGE) T1-W images, taken 15 min. after injection of contrast agent, allow the detection of myocardial replacement fibrosis, which appears as a bright area in a background of black myocardium. However, LGE has inherent disadvantages for the assessment of diffuse myocardial fibrosis. Therefore, T1 mapping and extracellular volume fraction (ECV) have been developed to quantify diffuse myocardial fibrosis., Results: Although multicentre studies are still missing, the CMR parameters have been extensively applied for the identification of oedema/fibrosis and treatment decision making in ARDs., Conclusions: Tissue characterisation with CMR allows early and robust identification of CVD in ARD patients and contributes to personalized management in the patients., (© 2021 The Mediterranean Journal of Rheumatology (MJR).)

Introduction: Patients with autoimmune rheumatic diseases (ARDs) are at increased risk for pneumococcal infections and should be vaccinated against Streptococcus pneumoniae. Data on the rates of pneumococcal vaccination among patients with ARDs in Southern Europe are scarce. Here, we estimate the pneumococcal vaccination rate in patients living in Greece with ARDs, explore the patients' awareness regarding vaccination, and try to recognize factors that influence the vaccine uptake., Methods: Between October 2015 and September 2016, a structured questionnaire was provided to all consecutive patients with ARDs attending one outpatient clinic of our department. The survey included parameters concerning patients' demographics, underlying ARD and immunosuppressive medications, other comorbidities, vaccine type, knowledge about infection risk and necessity of vaccination. Univariate and multivariate analyses were performed to study any association of these factors with the vaccination uptake., Results: Overall, 395 patients with ARDs (30.13% aged >65 years and 78.99% female) participated in our survey. The most frequent ARD was rheumatoid arthritis (43.04%); 40.51% of patients were receiving biologic agents and 44.56% steroids. Pneumococcal vaccination rate was 49.37%, while 45.06% of patients have been vaccinated during the last five years and only 8.21% of them had a second pneumococcal vaccine, as per national guidelines. The decision of vaccination was significantly influenced by the patient's age (>65 years) (p < 0.001) and the complete awareness of reasons for being vaccinated (p < 0.001), but not by presence of comorbidities, the type of ARD or administration of a biologic agent. The main reason for no vaccination was that it was not suggested by the caring physician (82.50%)., Conclusions: In our cohort of patients with ARDs the pneumococcal vaccination was suboptimal. Better understanding of the significance of vaccination by the patient and suggestion for vaccination by the caring physician will improve vaccination uptake and optimize the clinical benefits among patients with ARDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose of Review: Autoimmune rheumatic diseases (ARDs) affect 8% of the population and approximately 78% of patients are women. Myocardial disease in ARDs is the endpoint of various pathophysiologic mechanisms including atherosclerosis, valvular disease, systemic, myocardial, and/or vascular inflammation, as well as myocardial ischemia and replacement/diffuse fibrosis., Recent Findings: The increased risk of CVD in ARDs leads to excess comorbidity not fully explained by traditional cardiovascular risk factors. It seems that the chronic inflammatory status typically seen in ARDs, promotes both the development of myocardial inflammation/fibrosis and the acceleration of atherosclerosis. CMR (cardio-vascular magnetic resonance) is the ideal imaging modality for the evaluation of cardiac involvement in patients with ARDs, as it can simultaneously assess cardiac function and characterize myocardial tissues with regard to oedema and fibrosis. Due to its high spatial resolution, CMR is capable of identifying various disease entities such as myocardial oedema /inflammation, subendocardial vasculitis and myocardial fibrosis, that are often missed by other imaging modalities, notably at an early stage of development. Although generally accepted guidelines about the application of CMR in ARDs have not yet been formulated, according to our experience and the available published literature, we recommend CMR in ARD patientS with new-onset heart failure (HF), arrhythmia, for treatment evaluation/change or if there is any mismatch between patient symptoms and routine non-invasive evaluation.

Psoriatic arthritis (PsA) patients are at a higher risk of systemic inflammatory sequelae, leading to microalbuminuria, cardiovascular (CVD) and neuropsychiatric (NPD) disease. Our aim is to present the existing literature about the relationship between CVD, kidney and NPD in PsA. The literature evaluation of PsA revealed that chronic T-cell activation and increased levels of circulating immune complexes can cause glomerular injury leading to microalbuminuria, which predicts CVD and all-cause mortality in both diabetic and non-diabetic patients. Furthermore, it is a marker of preclinical brain damage and identifies patients at higher risk of NPD/CVD events. Among the currently used imaging modalities in PsA, magnetic resonance imaging (MRI) maintains a crucial role, because it is ideal for concurrent evaluation of brain/heart involvement and serial follow up assessment. There is increasing evidence regarding the relationship between kidneys, heart and brain in PsA. Although currently there are no official recommendations about a combined brain/heart MRI in PsA, it could be considered in PsA with microalbuminuria, arrhythmia, HF, cognitive dysfunction and/or depression.

Objectives: Cardiac rhythm disturbances constitute the most frequent cardiovascular cause of death in SSc. However, electrocardiographic findings are not a part of risk stratification in SSc. We aimed to translate 24 h Holter findings into a tangible risk prediction score using cardiovascular magnetic resonance., Methods: The Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS) was a prospective multicentre study including 150 consecutive SSc patients from eight European centres, assessed with 24 h Holter and cardiovascular magnetic resonance, including ventricular function, oedema (T2 ratio) and late gadolinium enhancement (%LGE). Laboratory/clinical parameters were included in multivariable corrections. A combined endpoint of sustained ventricular tachycardia requiring hospitalization and sudden cardiac death at a median (interquartile range) follow-up of 1 (1.0-1.4) year was generated., Results: Only T2 ratio and %LGE were significant predictors of ventricular rhythm disturbances, but not of supraventricular rhythm disturbances, after multivariable correction and adjustment for multiple comparisons. Using decision-tree analysis, we created the SAnCtUS score, a four-category scoring system based on T2 ratio and %LGE, for identifying SSc patients at high risk of experiencing ventricular rhythm disturbance at baseline. Increasing SAnCtUS scores were associated with a greater disease and arrhythmic burden. All cases of non-sustained ventricular tachycardia (n = 7) occurred in patients with the highest SAnCtUS score (=4). Having a score of 4 conveyed a higher risk of reaching the combined endpoint in multivariable Cox regression compared with scores 1/2/3 [hazard ratio (95% CI): 3.86 (1.14, 13.04), P = 0.029] independently of left ventricular ejection fraction and baseline ventricular tachycardia occurrence., Conclusion: T2 ratio and %LGE had the greatest utility as independent predictors of rhythm disturbances in SSc patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Purpose of Review: To present the interaction between brain/heart and emphasize the role of combined brain/heart magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) and other seronegative spondyloarthropathies (SNA)., Recent Findings: Both traditional cardiovascular disease (CVD) risk factors and intrinsic RA/SNA features contribute to the increased CVD-related morbidity/mortality. CVD in RA usually occurs a decade earlier than age- and sex-matched controls, and RA patients are twice more likely to develop myocardial infarction irrespective of age, history of prior CVD, and traditional CVD risk factors. RA also increases risk of non-ischemic heart failure (HF), valvular disease, and myo-pericarditis. CVD in SNA affects more commonly patients with long-standing disease. Ascending aortitis, aortic/mitral insufficiency, conduction defects, and diastolic dysfunction are the commonest findings in ankylosing spondylitis (AS). CVD is also the leading cause of death in psoriatic arthritis (PsA), due to myopericarditis, diastolic dysfunction, and valvular disease. Brain damage, due to either ischemic or hemorrhagic stroke and silent vascular damage, such as white matter hyperenhancement (WMH), is increased in both RA/SNA and may lead to cognitive dysfunction, depression, and brain atrophy. Magnetic resonance imaging (MRI) is ideal for serial brain/heart evaluation of patients with systemic diseases. RA/SNA patients are at high risk for brain/heart damage at early age, irrespectively of classic risk factors. Until more data will be obtained, a combined brain/heart MRI evaluation can be proposed in RA/SNA with new onset of arrhythmia and/or HF, cognitive dysfunction and/or depression.

Aims: T1-mapping is considered a surrogate marker of acute myocardial inflammation. However, in diffuse cutaneous systemic sclerosis (dcSSc) this might be confounded by coexisting myocardial fibrosis. We hypothesized that T1-based indices should not by themselves be considered as indicators of myocardial inflammation in dcSSc patients., Methods/results: A cohort of 59 dcSSc and 34 infectious myocarditis patients was prospectively evaluated using a 1.5-Tesla system for an indication of suspected myocardial inflammation and was compared with 31 healthy controls. Collectively, 33 (97%) and 57 (98%) of myocarditis and dcSSc patients respectively had ≥1 pathologic T2-based index. However, 33 (97%) and 45 (76%) of myocarditis and dcSSc patients respectively had ≥1 pathologic T2-based index. T2-signal ratio was significantly higher in myocarditis patients compared with dcSSc patients (2.5 (0.6) vs. 2.1 (0.4), p < 0.001). Early gadolinium enhancement, late gadolinium enhancement and T2-mapping did not differ significantly between groups. However, both native T1-mapping and extracellular volume fraction were significantly lower in myocarditis compared with dcSSc patients (1051.0 (1027.0, 1099.0) vs. 1120.0 (1065.0, 1170.0), p < 0.001 and 28.0 (26.0, 30.0) vs. 31.5 (30.0, 33.0), p < 0.001, respectively). The original Lake Louise criteria (LLc) were positive in 34 (100%) myocarditis and 40 (69%) dcSSc patients, while the updated LLc were positive in 32 (94%) and 44 (76%) patients, respectively. Both criteria had good agreement with greater but nonsignificant discordance in dcSSc patients., Conclusions: ~25% of dcSSc patients with suspected myocardial inflammation had no CMR evidence of acute inflammatory processes. T1-based indices should not be used by themselves as surrogates of acute myocardial inflammation in dcSSc patients.

Background: Autoimmune rheumatic diseases (ARDs) may affect both the heart and the brain. However, little is known about the interaction between these organs in ARD patients. We asked whether brain lesions are more frequent in ARD patients with cardiac symptoms compared with non-ARD patients with cardiovascular disease (CVD)., Methods: 57 ARD patients with mean age of 48 ± 13 years presenting with shortness of breath, chest pain, and/or palpitations, and 30 age-matched disease-controls with non-autoimmune CVD, were evaluated using combined brain-heart magnetic resonance imaging (MRI) in a 1.5T system., Results: 52 (91%) ARD patients and 16 (53%) controls had white matter hyperintensities ( p < 0.001) in at least one brain area (subcortical/deep/periventricular white matter, basal ganglia, pons, brainstem, or mesial temporal lobe). Only the frequency and number of subcortical and deep white matter lesions were significantly greater in ARD patients ( p < 0.001 and 0.014, respectively). ARD vs. control status was the only independent predictor of having any brain lesion. Specifically for deep white matter lesions, each increase in ECV independently predicted a higher number of lesions [odds ratio (95% confidence interval): 1.16 (1.01-1.33), p = 0.031] in ordered logistic regression. Penalized logistic regression selected only ARD vs. control status as the most important feature for predicting whether brain lesions were present on brain MRI (odds ratio: 5.46, marginal false discovery rate = 0.011)., Conclusions: Subclinical brain involvement was highly prevalent in this cohort of ARD patients and was mostly independent of the severity of cardiac involvement. However, further research is required to determine the clinical relevance of these findings., Competing Interests: The authors declare no conflict of interest.

Cardiovascular Disease (CVD) in Systemic Lupus Erythematosus (SLE) and Neuropsychiatric SLE (NPSLE) has an estimated prevalence of 50% and 40%, respectively and both constitute major causes of death among SLE patients. In this review, a combined brain/heart Magnetic Resonance Imaging (MRI) for SLE risk stratification has been proposed. The pathophysiologic background of NPSLE includes microangiopathy, macroscopic infarcts and accelerated atherosclerosis. Classic brain MRI findings demonstrate lesions suggestive of NPSLE in 50% of the NPSLE cases, while advanced MRI indices can detect pre-clinical lesions in the majority of them, but their clinical impact still remains unknown. Cardiac involvement in SLE includes myo-pericarditis, valvular disease/endocarditis, Heart Failure (HF), coronary macro-microvascular disease, vasculitis and pulmonary hypertension. Classic and advanced Cardiovascular Magnetic Resonance (CMR) indices allow function and tissue characterization for early diagnosis and treatment follow-up of CVD in SLE. Although currently, there are no clinical data supporting the combined use of brain/heart MRI in asymptomatic SLE, it may have a place in cases with clinical suspicion of brain/heart involvement, especially in patients at high risk for CVD/stroke such as SLE with antiphospholipid syndrome (SLE/APS), in whom concurrent cardiac and brain lesions have been identified. Furthermore, it may be of value in SLE with multi-organ involvement, NPSLE with concurrent cardiac involvement, and recent onset of arrhythmia and/or heart failure., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Acute cardiac events are a significant contributor to mortality in systemic sclerosis (SSc). However, echocardiographic evaluation may be deceptively normal during an acute presentation. We hypothesized that in diffuse SSc patients presenting with acute cardiac events and a normal echocardiogram, cardiovascular magnetic resonance (CMR) would have incremental diagnostic/prognostic value., Methods: 50 consecutive diffuse SSc patients with normal echocardiograms were evaluated using a 1.5T system. A total of 27 (63%) had experienced an acute cardiac event three to tendays before CMR evaluation (rhythm disturbances, angina pectoris, shortness of breath). Left/right ventricular (LV/RV) volumes and ejection fractions (EF), as well as LV mass, the T2-signal ratio, early/late gadolinium enhancement (EGE/LGE), native/post-contrast T1-mapping, T2-mapping and extracellular volume fraction (ECV) were compared between the event and no-event groups., Results: No differences were identified in LV/RV volumes/EF/mass. In logistic regression analyses, independent predictors of belonging to the event group were EGE (odds ratio (95% CI): 1.55 (1.06-2.26), p = 0.024), LGE (1.81 (1.23-2.67), p = 0.003), T2 mapping (1.20 (1.06-1.36), p = 0.004) and native/post-contrast T1 mapping (1.17 (1.04-1.32), p = 0.007 and 0.86 (0.75-0.98), p = 0.025). At a median follow-up of ~1.2 years, 42% vs. 11% of the event/no-event group respectively reached a combined endpoint of event occurrence/recurrence or cardiovascular mortality. Of the independent predictors resulting from logistic regression analyses, only LGE (hazard ratio (95% CI): 1.20 (1.11-1.30), p < 0.001), T2-mapping (1.07 (1.01-1.14), p = 0.025) and native T1-mapping (1.08 (1.01-1.15), p = 0.017) independently predicted the combined endpoint., Conclusions: A normal echocardiogram does not preclude myocardial lesions in diffuse SSc patients, which can be detected by CMR especially in symptomatic patients.

Background: Impaired myocardial deformation has been sporadically described in cardiac asymptomatic systemic sclerosis (SSc). We aimed to study myocardial deformation indices in cardiac asymptomatic SSc patients using cardiac magnetic resonance feature tracking (CMR-FT) and correlate these findings to the phenotypic and autoimmune background., Methods: Fifty-four cardiac asymptomatic SSc patients (44 females, 56±13 years), with normal routine cardiac assessment and CMR evaluation, including cine and late gadolinium enhancement (LGE) images, were included. SSc patients were compared to 21 sex- and age- matched healthy controls (17 females; 54±19 years). For CMR-FT analysis, a mid-ventricular slice for LV peak systolic radial and circumferential strain and a 4-chamber view for LV/RV peak systolic longitudinal strain were used., Results: Twenty-four patients had diffuse cutaneous SSc and 30 limited cutaneous SSc. Thirteen patients had digital ulcers. Median disease duration was 3.6 years. LV ejection fraction was higher in SSc patients compared to controls (62±6% vs. 59±5%, p = 0.01). Four patients had no LGE examination; in the remaining patients LGE was absent in 74%, while 18% had RV insertion fibrosis and 8% evidence of subendocardial infarction. LV longitudinal strain differed in those with insertion fibrosis (-18.0%) and infarction (-16.7%) compared to no fibrosis (-20.3%, p = 0.04). Patients with SSc had lower RV longitudinal strain and strain rate compared to controls (p<0.001 and p = 0.01, respectively). All other strain and strain rate measurements were non-significant between patients and controls., Conclusions: In cardiac asymptomatic SSc patients with normal routine functional indices, CMR-FT identifies subclinical presence of insertion fibrosis and/or myocardial infarction by impaired LV longitudinal strain. RV derived longitudinal indices were impaired in the patient group. CMR FT indices did not correlate to the patients' phenotypic and autoimmune features., Competing Interests: The authors have declared that no competing interests exist.

Autoimmune rheumatic diseases (ARDs) affect 8% of the population, and approximately 78% of them are women. Cardiovascular disease (CVD) in ARDs encompasses different pathophysiologic processes, such as endothelial dysfunction, myocardial/vascular inflammation and accelerated atherosclerosis with silent clinical presentation, leading to heart failure (HF), usually with preserved ejection fraction. Echocardiography and cardiovascular magnetic resonance (CMR) are the two most commonly used noninvasive imaging modalities for the evaluation of HF in patients with ARDs. Echocardiography currently represents the main diagnostic tool for cardiac imaging in clinical practice. However, the demand for more efficient and prompt diagnostic and therapeutic approach in this specific population necessitates the implementation of modalities capable of providing a more detailed and quantified information from the point of tissue characterization. Furthermore, echocardiography is an operator and acoustic window depended modality, with relatively low reproducibility and unable to perform tissue characterization. CMR is a noninvasive modality without radiation that can give reproducible and operator-independent information about both myocardial function and tissue characterization. By providing quantification of oedema, stress perfusion defects and fibrosis, CMR can diagnose myocardial inflammation, micro-macro-vascular myocardial ischemia and replacement or diffuse fibrosis, respectively. Tissue characterization allows for moving beyond the cardiac function to the assessment of intra- and inter-cellular alterations and promotes the development of personalized cardiac and anti-rheumatic treatment in ARDs with HF. ARDs are mainly female diseases. Cardiac involvement leading in HF is not unusual in ARDs and remains the main cause of death. Noninvasive, nonradiating imaging modalities such as echocardiography and CMR represent the main diagnostic tools. Specifically, echocardiography represents the first diagnostic approach; however, it is CMR that gives information about the pathophysiologic background behind HF in ARDs.

Background: Ventricular tachycardia/fibrillation (VT/VF) may occur in autoimmune rheumatic diseases (ARDs). We hypothesized that cardiovascular magnetic resonance (CMR) can identify arrhythmogenic substrates in ARD patients., Patients - Methods: Using a 1.5 T system, we evaluated 61 consecutive patients with various types of ARDs and normal left ventricular ejection fraction (LVEF) on echocardiography. A comparison of patients with recent VT/VF and those that never experienced VT/VF was performed. CMR parameters included left and right ventricular (LV and RV) end-systolic and end-diastolic volumes (ESV and EDV), T2 signal ratio of myocardium over skeletal muscle, early/late gadolinium enhancement (EGE and LGE), T1/T2-mapping and extracellular volume fraction (ECV)., Results: 21 (34%) patients had a history of recent, electrocardiographically identified, VT/VF. No demographic or functional CMR variables differed significantly between groups. The same was the case for T2 signal ratio and EGE/LGE. Median native T1 mapping values were significantly higher in patients with VT/VF compared to those without [1135.0 (1076.0, 1201.0) vs. 1050.0 (1025.0, 1078.0), p < 0.001], as was the case for mean T2 mapping [60.4 (6.6) vs. 55.0 (7.9), p = 0.009] and median ECV values [32.0 (30.0, 32.0) vs. 29.0 (28.0, 31.5), p = 0.001]. After multivariate corrections for age, LVEDV, LVEF, RVEDV, RVEF, T2 signal ratio, EGE and LGE, these remained significant predictors of having experienced VT/VF in the past., Conclusions: T1/T2-mapping and ECV offer incremental value as identifiers of arrhythmogenic substrates in ARD patients, beyond traditionally used indices. They can thus guide implantable cardiac defibrillator (ICD) implantation in ARD patients presenting with VT/VF and normal LVEF., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Sudden cardiac death (SCD) is due to ventricular tachycardia/fibrillation (VT/VF) and may occur with or without any structural or functional heart disease. The presence of myocardial edema, ischemia and/or fibrosis plays a crucial role in the pathogenesis of VT/VF, irrespective of the pathophysiologic background of the disease. Specifically, in autoimmune rheumatic diseases (ARDs), various entities such as myocardial/vascular inflammation, ischemia and fibrosis may lead to VT/VF. Furthermore, autonomic dysfunction, commonly found in ARDs, may also contribute to SCD in these patients. The only non-invasive, radiation-free imaging modality that can perform functional assessment and tissue characterization is cardiovascular magnetic resonance (CMR). Due to its capability to detect and quantify edema, ischemia and fibrosis in parallel with ventricular function assessment, CMR has the great potential to identify ARD patients at high risk for VT/VF, thus influencing both cardiac and anti-rheumatic treatment and modifying perhaps the criteria for implantation of cardioverter defibrillators.

Juvenile idiopathic arthritis (JIA) is the commonest rheumatic disease in childhood and presents several subtypes according to the ILAR classification. JIA, specifically in its systemic form, may seriously damage various structures of the cardiovascular system. Other JIA phenotypes are also of interest, as cardiovascular disease (CVD) is underestimated and understudied, but chronic systemic inflammation and risk factors remained important contributors for CVD development. The currently applied non-invasive modalities, although they are important for the initial evaluation of JIA patients, frequently fail to detect the silent, subclinical forms of CVD. Cardiovascular magnetic resonance (CMR), due to its multifaceted capability in the detection of cardiovascular disease, can offer early, reproducible, non-invasive information about cardiovascular disease in JIA, allowing risk stratification and timely initiation /modification of cardiologic and anti-rheumatic treatment. However, lack of availability/expertise and high cost still hamper its application in the clinical cardio-rheumatic practice. The aim of the current article is to present an overview of CVD in JIA emphasizing the emerging role of CMR in early diagnosis and treatment follow-up of CVD in JIA patients.

Life expectancy in autoimmune rheumatic diseases (ARDs) remains lower compared to the general population, due to various comoborbidities. Cardiovascular disease (CVD) represents the main contributor to premature mortality. Conventional and biologic disease-modifying antirheumatic drugs (DMARDs) have considerably improved long-term outcomes in ARDs not only by suppressing systemic inflammation but also by lowering CVD burden. Regarding atherosclerotic disease prevention, EULAR has recommended tight disease control accompanied by regular assessment of traditional CVD risk factors and lifestyle changes. However, this approach, although rational and evidence-based, does not account for important issues such as myocardial inflammation and the long asymptomatic period that usually proceeds clinical manifestations of CVD disease in ARDs before or after the diagnosis of systemic disease. Cardiovascular magnetic resonance (CMR) can offer reliable, reproducible and operator independent information regarding myocardial inflammation, ischemia and fibrosis. Some studies suggest a role for CMR in the risk stratification of ARDs and demonstrate that oedema/fibrosis visualisation with CMR may have the potential to inform cardiac and rheumatic treatment modification in ARDs with or without abnormal routine cardiac evaluation. In this review, we discuss how CMR findings could influence anti-rheumatic treatment decisions targeting optimal control of both systemic and myocardial inflammation irrespective of clinical manifestations of cardiac disease. CMR can provide a different approach that is very promising for risk stratification and treatment modification; however, further studies are needed before the inclusion of CMR in the routine evaluation and treatment of patients with ARDs.

Background Accurate diagnosis of cardiovascular involvement in systemic lupus erythematosus (SLE) remains challenging, due to limitations of echocardiography. We hypothesized that cardiovascular magnetic resonance can detect cardiac lesions missed by echocardiography in SLE patients with atypical symptoms. Aim To use cardiovascular magnetic resonance in SLE patients with atypical symptoms and investigate the possibility of silent heart disease, missed by echocardiography. Patients/methods From 2005 to 2015, 80 SLE patients with atypical cardiac symptoms/signs (fatigue, mild shortness of breath, early repolarization and sinus tachycardia) aged 37 ± 6 years (72 women/8 men), with normal echocardiography, were evaluated using a 1.5 T system. Left and right ventricular ejection fractions, T2 ratio (oedema imaging) and late gadolinium enhancement (fibrosis imaging) were assessed. Acute and chronic lesions were defined as late gadolinium enhancement-positive plus T2>2 and T2<2, respectively. Lesions were characterized according to late gadolinium enhancement patterns as: diffuse subendocardial, subepicardial and subendocardial/transmural, due to vasculitis, myocarditis and myocardial infarction, respectively. Results Abnormal cardiovascular magnetic resonance findings were identified in 22/80 (27.5%) of SLE patients with normal echocardiography, including 4/22 with recent silent myocarditis, 5/22 with past myocarditis (subepicardial scar in inferolateral wall), 9/22 with past myocardial infarction (six inferior and three anterior subendocardial infarction) and 4/22 with diffuse subendocardial fibrosis due to vasculitis. No correlation between cardiovascular magnetic resonance findings and inflammatory indices was identified. Conclusions Cardiovascular magnetic resonance in SLE patients with atypical cardiac symptoms/signs and normal echocardiography can assess occult cardiac lesions including myocarditis, myocardial infarction and vasculitis that may influence both rheumatic and cardiac treatment.

Systemic vasculitides (SVs) is a group of diseases characterised by inflammation/necrosis of the blood vessel wall in various organs. Simultaneous brain and heart involvement is a cause of increased morbidity/mortality in SV. We aimed to present evidence of concurrent brain/heart involvement in SV and the role of a combined brain/heart magnetic resonance imaging (MRI) in their risk stratification. Cerebral vasculitis (CV) can be presented as focal deficits, seizures, headache, neuropsychiatric manifestations or cognitive dysfunction and cardiovascular disease (CVD) as myocardial/vascular inflammation, perfusion/function defects and fibrosis. MRI is a non-invasive, non-radiating technique that allows the reliable identification of intraparenchymal brain lesions and the detection of myocardial/vascular inflammation and fibrosis. However, its use in SV is currently hampered by high cost, lack of availability/expertise and lack of awareness among the clinicians. Although there are no clinical data supporting the combined use of brain/heart MRI in asymptomatic SV, it would be called for in cases with clinical suspicion of brain/heart involvement, especially in those at high risk for CVD/stroke such as SLE/APS. Furthermore, it may be of value in SV with multi-organ involvement, cognitive dysfunction or other neuropsychiatric symptoms with concurrent cardiac involvement, presenting as typical or atypical symptoms with normal routine cardiac evaluation, new onset of arrhythmia and/or HF.

Inflammation, microvascular and macrovascular ischemia, valvular disease, and fibrosis are the main causes of cardiovascular disease (CVD) in autoimmune rheumatic diseases (ARDs). The silent presentation and the high mortality and/or morbidity of CVD in ARDs necessitate a reliable tool for early diagnosis. Noninvasive cardiovascular imaging, including echocardiography, nuclear imaging, cardiovascular computed tomography (CT), cardiac magnetic resonance (CMR), and hybrid imaging modalities, constitutes the main tool for monitoring of CVD in ARDs. Echocardiography is the cornerstone for CVD evaluation, but it is operator-dependent and cannot perform tissue characterization. Nuclear imaging and CT, although promising, have the disadvantage of ionizing radiation. CMR can assess inflammation, ischemia, and fibrosis without ionizing radiation, thus making it a necessary adjunct, which is especially relevant for ARDs with new-onset heart failure, conflicting data from other imaging modalities, and recent onset of chest pain and/or arrhythmias. Recently, hybrid imaging with positron emission tomography (PET)/CT and PET/CMR has shown promise in ARDs, although these modalities currently have prohibitive costs., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by microvascular abnormalities, inflammation and fibrosis. We hypothesized that myocarditis may be diagnosed in asymptomatic SSc, undergoing routine cardio-vascular magnetic resonance (CMR) for fibrosis assessment, using the Lake Louise criteria: T2 ratio, early (EGE) and late gadolinium enhanced (LGE) images., Methods: Eighty-two asymptomatic SSc, diagnosed according to American College of Rheumatology criteria, aged 43 ± 5 yrs., 62 with diffuse (dSSc) and 20 with localized (lSSc) systemic sclerosis were evaluated by CMR, performed at 1.5 T scanner, according to Lake Louise criteria., Results: CMR documented normal biventricular function in all SSc. However, 7/62 (11.2%) with dSSc and 2/20 (10%) with lSSc, had CMR signs of myocarditis according to Lake Louise criteria, without any clinical cardiac symptom. In these 9 patients, T2 ratio, EGE ratio and LGE (positive in all 9 SSc) were 2.8 ± 0.5%, 8 ± 3% and 5 ± 3% of LV mass, respectively. No correlation between CMR and blood inflammatory indices (C-reactive protein and erythrocyte sedimentation rate), cardiac troponin T, disease characteristics or type of SSc was identified. A repeat CMR at 6 months, after treatment with prednisone and azathioprine, showed normalisation of the acute inflammation CMR indices., Conclusions: Silent myocarditis may be diagnosed using the Lake Louise paper criteria in SSc patients without cardiac symptoms, has no correlation with blood inflammatory indices, cardiac troponin or disease characteristics. CMR is a promising tool to diagnose silent myocarditis in SSc and monitor the response to immunosuppressive treatment.

Background-Aim: Cardiac involvement at diagnosis of connective tissue disease (CTD) has been described by echocardiography. We hypothesized that cardio-vascular magnetic resonance (CMR) detects occult lesions at CTD diagnosis., Patients-Methods: CMR was performed early after diagnosis in 78 treatment-naïve CTDs (aged 43±11, 59F/19M) without cardiac involvement [5 Takayasu arteritis (TA), 4 Churg Strauss syndrome (CSS), 5 Wegener granulomatosis (WG), 16 systemic lupus erythematosus (SLE), 12 rheumatoid arthritis (RA), 8 mixed connective tissue diseases (MCTD), 12 ankylosing spondylitis (AS), 3 polymyalgia rheumatica (PMR), 8 systemic sclerosis (SSc) and 5 dermatomyositis (DM)]. Acute and chronic lesions were assessed by T2>2 with positive LGE and T2<2 with positive LGE, respectively., Results: In 3/5 TA, 3/4 CSS, 4/5 WG, 10/16 SLE, 9/12 RA, 6/8 MCTD, 4/12 AS, 1/3 PMR, 2/8 SSc and 2/5 DM, the T2 ratio was higher compared to normal (2.78±0.25 vs 1.5±0.2, p<0.01). Myocarditis was identified in 1 TA, 1 SLE, 1 RA, 1 SSc and 2 DM patients; diffuse, subendocardial fibrosis in 1 CSS and 1 RA patient, while subendocardial myocardial infarction in 3 SLE, 1 MCTD, 1 PMR and 2 RA patients. CMR re-evaluation after 6 and 12months of rheumatic and cardiac treatment, available in 28/52 CTDs with increased T2 ratio, showed significant improvement in T2 ratio (p<0.001), non-significant change in LGE extent and normalisation of those with impaired LV function., Conclusions: Occult CMR lesions, including oedema, myocarditis, diffuse subendocardial fibrosis and myocardial infarction are not unusual in treatment naïve CTDs and may be reversed with appropriate treatment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Cardiovascular magnetic resonance imaging is a recently developed noninvasive, nonradiating, operator-independent technique that has been successfully used for the evaluation of congenital heart disease, valvular and pericardial diseases, iron overload, cardiomyopathies, great and coronary vessel diseases, cardiac inflammation, stress-rest myocardial perfusion, and fibrosis. Rheumatoid arthritis and other spondyloarthropathies, systemic lupus erythematosus, inflammatory myopathies, mixed connective tissue diseases (CTDs), systemic sclerosis, vasculitis, and sarcoidosis are among CTDs with serious cardiovascular involvement; this is due to multiple causative factors such as myopericarditis, micro/macrovascular disease, coronary artery disease, myocardial fibrosis, pulmonary hypertension, and finally heart failure. The complicated pathophysiology and the high cardiovascular morbidity and mortality of CTDs demand a versatile, noninvasive, nonradiative diagnostic tool for early cardiovascular diagnosis, risk stratification, and treatment follow-up. Cardiovascular magnetic resonance imaging can detect early silent cardiovascular lesions, assess disease acuteness, and reliably evaluate the effect of both cardiac and rheumatic medication in the cardiovascular system, due to its capability to perform tissue characterization and its high spatial resolution. However, until now, high cost; lack of interaction between cardiologists, radiologists, and rheumatologists; lack of availability; and lack of experts in the field have limited its wider adoption in the clinical practice., Competing Interests: Disclosure The authors report no conflicts of interests in this work.

Background Cardiovascular disease (CVD) has been documented in >50% of systemic lupus erythematosus (SLE) patients, due to a complex interplay between traditional risk factors and SLE-related factors. Various processes, such as coronary artery disease, myocarditis, dilated cardiomyopathy, vasculitis, valvular heart disease, pulmonary hypertension and heart failure, account for CVD complications in SLE. Methods Electrocardiogram (ECG), echocardiography (echo), nuclear techniques, cardiac computed tomography (CT), cardiovascular magnetic resonance (CMR) and cardiac catheterization (CCa) can detect CVD in SLE at an early stage. ECG and echo are the cornerstones of CVD evaluation in SLE. The routine use of cardiac CT and nuclear techniques is limited by radiation exposure and use of iodinated contrast agents. Additionally, nuclear techniques are also limited by low spatial resolution that does not allow detection of sub-endocardial and sub-epicardial lesions. CCa gives definitive information about coronary artery anatomy and pulmonary artery pressure and offers the possibility of interventional therapy. However, it carries the risk of invasive instrumentation. Recently, CMR was proved of great value in the evaluation of cardiac function and the detection of myocardial inflammation, stress-rest perfusion defects and fibrosis. Results An algorithm for CVD evaluation in SLE includes clinical, laboratory, ECG and echo assessment as well as CMR evaluation in patients with inconclusive findings, persistent cardiac symptoms despite normal standard evaluation, new onset of life-threatening arrhythmia/heart failure and/or as a tool to select SLE patients for CCa. Conclusions A non-invasive approach including clinical, laboratory and imaging evaluation is key for early CVD detection in SLE.

Background: Peripheral Raynaud's phenomenon (RP) is either primary (PRP), without any coexisting disease or secondary (SRP), due to connective tissue diseases (CTD). We hypothesized that adenosine stress cardiovascular magnetic resonance (CMR) can assess myocardial perfusion in a population of PRP and SRP., Patients-Methods: Twenty CTDs, aged 30.6±7.5yrs., 16F/4M, including 9 systemic sclerosis (SSc), 4 systemic lupus erythematosus (SLE), 3 mixed connective tissue disease (MCTD), 2 polymyositis (PM) and 2 rheumatoid arthritis (RA), with SRP, under treatment with calcium blockers, were evaluated by stress CMR and compared with age-sex matched PRP and controls. All RP patients were under treatment with calcium blockers. Stress perfusion CMR was performed by 1.5T system using 140mg/kg/min adenosine for 4min and 0.05mmol/kg Gd-DTPA for first-pass perfusion. A rest perfusion was performed with the same protocol. Late gadolinium enhanced (LGE) images were acquired after another dose of Gd-DTPA., Results: In both PRP, SRP, the myocardial perfusion reserve index (MPRI) was significantly reduced compared with the controls (1.7±0.6 vs 3.5±0.4, p<0.001 and 0.7±0.2 vs 3.5±0.4, p<0.001, respectively). Furthermore, in SRP, MPRI was significantly reduced, compared with PRP (0.7±0.2 vs 1.7±0.6, p<0.001). Subendo-cardial LGE=8.2±1.7 of LV mass was revealed in 1 SLE, 1MCTD and 2 SSc, but in none of PR patients., Conclusions: MPRI reduction is common in both PRP and SRP, but it is more severe in SRP, even if RP patients are under treatment with calcium blockers. Occult fibrosis may coexist with the reduced MPRI in SRP but not in PRP., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Targeted therapies in connective tissue diseases (CTDs) have led to improvements of disease-associated outcomes, but life expectancy remains lower compared to general population due to emerging co-morbidities, particularly due to excess cardiovascular risk. Cardiovascular magnetic resonance (CMR) is a noninvasive imaging technique which can provide detailed information about multiple cardiovascular pathologies without using ionizing radiation. CMR is considered the reference standard for quantitative evaluation of left and right ventricular volumes, mass and function, cardiac tissue characterization and assessment of thoracic vessels; it may also be used for the quantitative assessment of myocardial blood flow with high spatial resolution and for the evaluation of the proximal coronary arteries. These applications are of particular interest in CTDs, because of the potential of serious and variable involvement of the cardiovascular system during their course. The International Consensus Group on CMR in Rheumatology was formed in January 2012 aiming to achieve consensus among CMR and rheumatology experts in developing initial recommendations on the current state-of-the-art use of CMR in CTDs. The present report outlines the recommendations of the participating CMR and rheumatology experts with regards to: (a) indications for use of CMR in rheumatoid arthritis, the spondyloarthropathies, systemic lupus erythematosus, vasculitis of small, medium and large vessels, myositis, sarcoidosis (SRC), and scleroderma (SSc); (b) CMR protocols, terminology for reporting CMR and diagnostic CMR criteria for assessment and quantification of cardiovascular involvement in CTDs; and (c) a research agenda for the further development of this evolving field., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Diffuse systemic sclerosis (dSSc) is characterized by vascular lesions and fibrosis. Cardiac involvement, although silent, accounts for 36% of deaths. We hypothesized that cardiovascular magnetic resonance (CMR) can clarify the pathophysiology of Q waves in dSSc patients., Patients-Methods: 105 dSSc, aged 48±2years, with atypical symptoms and normal routine assessment, were evaluated by ECG and CMR using a 1.5 T system. Biventricular function was assessed by steady-state free-precession sequence (SSFP). To identify fibrosis, late gadolinium enhanced areas (LGE) were evaluated 15min after injection of 0.2mmol/kg gadolinium-DTPA and expressed as % of LV mass., Results: Q waves in V1-V5 (Group A), II, III, AVF (Group B) and I, AVL, II, III, AVF, V1-V5 (Group C) were found in 25/105, 8/105 and 5/105 dSSc, respectively. In 25 dSSc with Q in V1-V6, patchy intramyocardial LGE was detected in 24/25 and involved 8±2% of LV mass. LGE involved the intraventricular septum (IVS) in 11/24 and the lateral wall (LAT) in 5/24 dSSc. Only in 1/25 dSSc, an anterior, transmural LGE, due to LAD occlusion, was identified. In 8 dSSc with Q in II, III, AVF, patchy intramyocardial LGE was detected in the inferior wall and involved 5±2% of LV mass. In 5 dSSc with Q in V1-V5, II, III, AVF, patchy intramyocardial LGE was detected in anterior and inferolateral wall and involved 9±2% of LV mass., Conclusion: CMR unveiled that the pattern of myocardial fibrosis in dSSc with Q waves is due to the systemic disease and not to CAD., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To evaluate the cardiovascular magnetic resonance (CMR) findings in a paediatric population with systemic lupus erythematosus (SLE) and cardiac symptoms., Methods: Twenty-five SLE children, aged 10.2 ± 2.6 years, with cardiac symptoms and normal routine non-invasive evaluation were examined by CMR, using a 1.5 T system and compared with sex-matched SLE adults. Left ventricular (LV) volumes, ejection fraction, T2 ratio, early (EGE) and late (LGE) gadolinium enhancement were assessed. Acute and chronic lesions were characterised as LGE-positive plus T2 > 2, EGE > 4 or T2 < 2, EGE < 4, respectively. According to LGE, lesions were characterized as: (a) diffuse subendocardial, (b) subepicardial and (c) subendocardial/transmural, due to vasculitis, myocarditis and myocardial infarction, respectively., Results: LV ejection fraction (LVEF) was normal in all SLEs. T2 > 2, EGE > 4 and positive epicardial LGE wall was identified in 5/25 children. Diffuse subendocardial fibrosis was documented in 1/25. No evidence of myocardial infarction was identified in any children. In contrast, in SLE adults, LGE indicative of myocardial infarction was identified in 6/25, myocarditis in 3/25, Libman-Sacks endocarditis in 1/25 and diffuse subendocardial fibrosis in 2/25. The incidence of heart disease in SLE children was lower compared to SLE adults (p < 0.05), with a predominance of myocarditis in children and myocardial infarction in adults. A significant correlation was documented between disease duration and CMR lesions (p < 0.05)., Conclusion: CMR identifies a predominance of myocarditis in paediatric SLE with cardiac symptoms and normal routine non-invasive evaluation. However, the incidence of cardiac lesions is lower compared to SLE adults, probably due to shorter disease duration., Significance and Innovation: CMR identifies heart involvement in a significant percentage of SLE children with cardiac symptoms and normal routine noninvasive evaluation.The incidence of heart disease is lower in SLE children compared with SLE adults.Predominance of myocarditis and myocardial infarction is observed in SLE children and SLE adults, respectively., (© The Author(s) 2015.)

Background: Myopericardial inflammation, perfusion's defects and fibrosis are major causes of cardiac disease in scleroderma (SSc). We hypothesized that using inflammation and stress perfusion-fibrosis cardiovascular magnetic resonance (CMR), we can identify the pathophysiology of heart disease in asymptomatic diffuse SSc., Patients-Methods: 46 recently diagnosed, asymptomatic patients with diffuse SSc had a CMR examination using a 1.5T system. ECG gated breath hold cine and short tau inversion recovery (STIR) T2 images were initially acquired. If T2 ratio<2 a stress perfusion-fibrosis protocol was applied. If T2>2 a myocarditis protocol including early (EGE) and late (LGE) gadolinium imaging was applied. SSc patients' results were compared with age and sex-matched controls and patients with coronary artery disease (CAD)., Results: In 2/46 SSc with T2 ratio>2, the myocarditis protocol was positive for acute myocardial inflammation, who developed clinical signs of acute myocarditis shortly after the CMR evaluation. In the rest 44/46 with T2 ratio<2 the stress perfusion-fibrosis CMR identified a significant reduction in Myocardial Perfusion Reserve Index (MPRI) compared with matched controls (0.6±0.4 vs 3.2±0.8, p<0.001), but not with CAD (0.6±0.4 vs 0.86±0.46, p=NS) and correlated only with the presence of digital ulcers (p<0.05). The scar was diffused and greater compared to controls, but did not differ from that assessed in CAD. Two years follow up, available in 11/44 SSc, showed further asymptomatic MPRI deterioration in all and diffuse subendocardial LGE in 8/11, without any change in LV, RV volumes and ejection fractions., Conclusion: CMR may reveal severe cardiac involvement in early, asymptomatic diffuse SSc with normal routine cardiac evaluation, presenting either as myocardial inflammation or as severe reduction of MPRI and diffuse fibrosis with further deterioration in the long term follow up.

Background: To clarify the imaging patterns of cardiovascular lesions in patients with mixed connective tissue disease (MCTD) and cardiovascular symptoms with or/ without abnormal routine non-invasive evaluation., Patients-Methods: Twenty-two MCTD patients (19F/3M), aged 38±4 yrs with cardiovascular symptoms were evaluated using a 1.5 T scanner. Of them, 8/22 had systemic lupus erythematosus (SLE), 5/22 rheumatoid arthritis (RA), 5/22 scleroderma (SSc) and 4/22 myositis (MY) overlap syndromes; 10/22 patients with MCTD presented with Raynaud phenomenon (RP) and all were positive for Anti-RNP antibodies. The cardiovascular magnetic resonance study (CMR) included evaluation of function, inflammation and fibrosis. Myocardial stress perfusion-fibrosis evaluation was performed only in MCTD patients with RP., Results: A positive CMR study was identified in 4/8 with SLE, 1/5 with RA, 4/5 with SSc and in 1/4 with MY like MCTD. The CMR lesions were subendocardial or transmural LGE following the distribution of coronary arteries, intramyocardial LGE and diffuse subendocardial LGE in SLE-RA, MY and SSc like MCTD, respectively. Although no evidence of fibrosis was identified in patients with RP, adenosine stress myocardial perfusion revealed diffuse subendocardial perfusion defects. No correlation between disease duration and/or inflammatory indices and cardiac lesions was identified., Conclusion: CMR can reveal myocardial lesions in MCTD patients with cardiac symptoms including myocardial infarction, inflammation, diffuse subendocardial fibrosis and diffuse perfusion defects, necessitating further cardiac investigation and/or treatment.

Objectives: Fibromyalgia (FM) is one of the most common chronic pain syndromes. Various pathogenetic mechanisms have been implicated but none is proven. Our scope was to determine if Intraepidermal Nerve Fiber Density (IENFD) is reduced in the skin of FM patients, as observed in patients with painful small fiber sensory neuropathy (SFSN)., Design, Setting and Participants: We prospectively studied 46 FM patients (5 men and 41 women), aged 29 to 76 (mean: 52.5) years, diagnosed according to the ACR 2010 criteria, and 34 controls (18 women and 16 men) aged 19 to 84 (mean: 31.7) years. IENFD was measured using published guidelines and immune markers were sought immunocytochemically. In 30 FM patients, pain intensity was assessed with the Neuropathic Pain Symptom Inventory (NPSI), a scale validated for neuropathic pain., Results: 15 of 46 (32.6%) FM patients had reduced IENFD [range: 0.6-12.5 fibers/mm (mean: 4.83 SD: 2.5)], compared to healthy controls [2.8-11.5 fibers/mm (mean: 7.35, SD: 1.85)] (p<0.0001). No significant correlation was noticed between NPSI scores and IENFD. No difference in the Langerhans cells, the major Antigen Presenting Cells (APCs) in the epidermis, or in IL-6 staining, was noted between FM and controls. IENFD was equally reduced in a subset of FM patients who also had another autoimmune disease., Conclusion: This is one of the largest series of FM patients demonstrating a significant reduction of IENFD in their skin biopsies. The findings indicate that in a subset of FM patients, the pain syndrome is, at least partially, of neuropathic origin. Skin biopsy may prove a useful tool and a potential biomarker in future studies of FM patients., (Copyright © 2014. Published by Elsevier B.V.)

Dietary interventions have been suggested to be a safe cost-efficient way to control hyperuricemia. The aim of the study is to assess the potential of mediterranean diet as intervention to control the level of urate in patients with hyperuricemia in a small sample of patients. Patients with asymptomatic hyperuricemia were recruited from outpatient clinics and were enrolled into personal Mediterranean diet-based programs. Body mass index (BMI), serum urate, lipid profile and indirect calorimetry were measured at the beginning and then monthly for the first 3 months and then at the sixth month. At the same time, patients' compliance with the Mediterranean diet was assessed by a formal interview and standard questionnaire. Only six out of twelve patients managed to complete the diet (dropout rate 50 %). Their BMI remained constant during the trial period in the level of 1st degree obesity (BMI = 31.46). The mean value of serum urate at the beginning of the study was 9.12 mg/dl. After the first month, there was a reduction in urate by 20 % with mean urate at 6.92 mg/dl. The second, third and sixth month mean urate levels were 6.32, 6.1 and 6.4 mg/dl, respectively. The effect of the mediterranean diet was rapid at the first month and remained constant throughout the dietary intervention, suggesting that it might have a clinically significant effect on urate level thus providing a cost-efficient and safe alternative to pharmaceutical intervention as first-line treatment of hyperuricemia.

The history of the Greek rheumatology from ancient world to the modern era. Emphasis is given to the contribution of the Greek vocabulary to rheumatologic terminology.

The cytotoxic effects of opiates, cocaine and their metabolites on peripheral blood mononuclear cells from healthy volunteers, concerning cell viability, were studied in a wide range of concentrations (ranging from 10-(2) to 10-(8) M), by 2 colorimetric in vitro assays, the neutral red uptake assay and thiazolyl blue tetrazolium bromide assay. All tested drugs of abuse and their metabolites were non-cytotoxic at concentrations lower than 10-(5) M. The possible immunomodulative effects of these substances were evaluated through phytohemagglutinin-induced lymphocyte proliferation ([3H]-thymidine DNA incorporation assay) as well as by a 51Cr release natural killer assay. The results showed immunomodulative effects of all the opiates tested. Cocaine, freebase cocaine and benzoylecgonine produced a statistically non-significant decrease of phytohemagglutinin proliferation. Cocaine induced a statistically non-significant increase, whereas freebase cocaine and benzoylecgonine showed a non-significant decrease of natural killer cell activity.

We describe a sensitive and reproducible microassay model using human peripheral blood lymphocytes (PBL) for discrimination between the cytotoxic and immunosuppressive effects of food colorants such as amaranth and tartrazine. The cytotoxic effects of a wide range of concentrations of these substances were studied on human PBL by the colorimetric in vitro cytotoxicity assays, neutral red uptake (NR) and thiazolyl blue tetrazolium bromide (MTT). The immunotoxic properties of these 2 substances were determined by a [3H]-thymidine DNA incorporation assay on phytohemagglutinin stimulated or non-stimulated lymphocytes, as well as by a Cr51 release Natural Killer assays. The results showed clear immunosuppressive effects from the 2 substances tested, although the concentrations chosen for this study proved to be non-cytotoxic by NR and MTT cytotoxic endpoints.

We investigated the antagonist immunomodulative properties of aflatoxin B1 and selenium on human peripheral blood lymphocytes by 2 colorimetric in vitro cytotoxicity assays, the neutral red uptake and the thiazolyl blue tetrazolium bromide assay. Immunotoxic properties of these substances were determined by a (3H)-thymidine DNA incorporation assay on phytohemagglutinin (PHA) stimulated and non-stimulated lymphocytes. Aflatoxin B1 and selenium, when studied separately, had an immunosuppressive effect on PHA stimulated and non-stimulated human peripheral blood lymphocytes. When they were studied together, they had an antagonistic effect on this immunological parameter.