The Genetic Landscape of Systemic Rheumatic Diseases: A Comprehensive Multigene-Panel Study Identifying Key Gene Polymorphisms.

Systemic rheumatic diseases, including conditions such as rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, and systemic lupus erythematosus, represent a complex array of autoimmune disorders characterized by chronic inflammation and diverse clinical manifestations. This study focuses on unraveling the genetic underpinnings of these diseases by examining polymorphisms in key genes related to their pathology. Utilizing a comprehensive genetic analysis, we have documented the involvement of these genetic variations in the pathogenesis of rheumatic diseases. Our study has identified several key polymorphisms with notable implications in rheumatic diseases. Polymorphism at chr11_112020916 within the IL-18 gene was prevalent across various conditions with a potential protective effect. Concurrently, the same IL18R1 gene polymorphism located at chr2_103010912, coding for the IL-18 receptor, was observed in most rheumatic conditions, reinforcing its potential protective role. Additionally, a further polymorphism in IL18R1 at chr2_103013408 seems to have a protective influence against the rheumatic diseases under investigation. In the context of emerging genes involved in rheumatic diseases, like PARK2, a significant polymorphism at chr6_161990516 was consistently identified across different conditions, exhibiting protective characteristics in these pathological contexts. The findings underscore the complexity of the genetic landscape in rheumatic autoimmune disorders and pave the way for a deeper understanding of their etiology and the possible development of more targeted and effective therapeutic strategies.

Chimeric antigen receptor T cell therapy for the treatment of systemic rheumatic diseases: a comprehensive review of recent literature.

Systemic rheumatoid diseases (SRDs) are autoimmune and inflammatory disorders that affect multiple organ systems, impacting patients' quality of life, and survival rates. Standard treatment requires continuous drug therapy and immunosuppression. Chimeric antigen receptor (CAR) T cell therapy has the potential to target and eliminate pathologically activated immune cells and re-establish tolerance in organs affected by dysregulated immunity, making them a promising treatment option for autoimmune diseases. In autoimmune diseases, CAR T cells have the advantage of being able to kill B cells effectively without the need for an accessory cell type. Additionally, CAR T cells targeting CD19 have shown promise in comprehensive B cell aplasia, preserving pre-existing humoral immunity, and specifically eliminating pathogenic B cells. CAR T cell therapy's limited use in SRDs is due to its inability to effectively target the various autoreactive lymphocytes present. Researchers are developing a universal CAR T cell therapy that detects and targets autoreactive lymphocytes using major epitope peptides, though further studies are required. Moreover, adoptive transfer of CAR-Tregs has shown promise for effectively reducing inflammation and treating autoimmunity. Through this exploration, the authors hope to provide a comprehensive understanding of the current state of research on this topic, identify areas for further study, and promote the advancement of CAR T cell therapy as a treatment option for SRDs.

Mesenchymal Stem/Stromal Cell-Based Therapies in Systemic Rheumatic Disease: From Challenges to New Approaches for Overcoming Restrictions.

Systemic rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, are chronic autoimmune diseases affecting multiple organs and tissues. Despite recent advances in treatment, patients still experience significant morbidity and disability. Mesenchymal stem/stromal cell (MSC)-based therapy is promising for treating systemic rheumatic diseases due to the regenerative and immunomodulatory properties of MSCs. However, several challenges need to be overcome to use MSCs in clinical practice effectively. These challenges include MSC sourcing, characterization, standardization, safety, and efficacy issues. In this review, we provide an overview of the current state of MSC-based therapies in systemic rheumatic diseases, highlighting the challenges and limitations associated with their use. We also discuss emerging strategies and novel approaches that can help overcome the limitations. Finally, we provide insights into the future directions of MSC-based therapies for systemic rheumatic diseases and their potential clinical applications.

The SPROUT study: A survey on current management practice of reproductive aspects in women of childbearing age with systemic autoimmune rheumatic diseases.

The SPROUT (Survey on reproduction in RheUmaTology) study explored current practice in women of childbearing age with systemic autoimmune rheumatic diseases, investigating the counselling on contraception, the prescription of low dose acetylsalicylic acid (LDASA) to pregnant patients and the management of disease activity in the post-partum period. The SPROUT questionnaire was designed ad hoc and promoted in the three months before the "11th International Conference on Reproduction, Pregnancy and Rheumatic Disease". Between June and August 2021, 121 physicians responded to the survey. Even though 66.8% of the participants declared themselves to be confident in counselling surrounding birth control, only 62.8% of physicians always discuss contraception and family planning with women of childbearing age. Approximately 20% of respondents do not prescribe LDASA to pregnant women with rheumatic diseases, and wide heterogeneity exists in the dose and timing of LDASA prescription. Most respondents (43.8%) restart treatment with biological agents soon after delivery to prevent disease flares, opting for a drug compatible with breastfeeding while 41.3% of physicians continue biologics throughout pregnancy and post-partum. The SPROUT study highlighted the necessity to further foster physicians' education and identified the management of disease activity after delivery as a matter for discussion between all the clinicians involved in the care of pregnant women with rheumatic conditions.

Clinical course and prognostic factors of COVID-19 infection in patients with chronic inflammatory-rheumatic disease: A retrospective, case-control study.

Objectives: This study aims to investigate the prognosis of novel coronavirus disease-2019 (COVID-19) infection in patients with the chronic inflammatory-rheumatic disease and evaluate the effects of immunosuppressive drugs on the prognosis, clinical characteristics, laboratory findings and hospitalization periods of the rheumatic patients with COVID-19 infection. Patients and methods: Between April 2020 and March 2021, a total of 101 patients (30 males, 71 females; mean age: 48±14.4 years; range, 46 to 48 years) with the rheumatic diseases diagnosed with COVID-19 infection were included. A total of 102 age- and sex-matched patients (35 males, 67 females; mean age: 44±14.4 years; range, 28 to 44 years) who were diagnosed with COVID-19 infection and had no history of rheumatic disease in the same period were included as the control group. Data including demographic characteristics of the patients, presence of any symptoms of COVID-19 disease, laboratory data at the time of diagnosis, and treatments administered were collected. Results: The rate of hospitalization was higher in 38 (37%) patients without rheumatic diseases than in 31 (31%) patients with rheumatic diseases (p=0.324). The rate of lung infiltration on radiographic examination was higher in patients without rheumatic diseases (40% vs. 49%) (p=0.177). COVID-19 infection symptoms such as anosmia 45 (45%), ageusia 51 (50%), shortness of breath 45(45%), nausea 29 (29%), vomiting 16 (16%), diarrhea 25 (25%) and myalgia-arthralgia 81 (80%) were higher in patients with rheumatic diseases. In terms of laboratory values, lymphocyte count (p=0.031) was statistically higher in patients without rheumatic diseases. Hydroxychloroquine (35%), oseltamivir 10 (10%), antibiotics 27 (26%), acetylsalicylic acid 52 (51%), and supplementary oxygen 25 (25%) treatments which used to cure COVID 19 infection were administered more in patients without rheumatic diseases. The number of treatments administered was higher in patients without rheumatic diseases (p<0.001). Conclusion: Patients with the chronic inflammatory-rheumatic disease have more symptoms due to COVID-19 infection, but the disease course is not poor and hospitalization rates are lower.

Association between systemic rheumatic diseases and dementia risk: A meta-analysis.

Background and aims: Epidemiological studies have been conducted on the relationship between systemic rheumatic diseases (SRDs) and dementia. Therefore, we focused on determining the extent of alliances bounded by SRDs, along with the risk of dementia. Materials and methods: Two independent reviewers assessed all studies retrieved from the PubMed, EMBASE, Scopus, and Web of Science databases between January 1, 2000 and November 30, 2021. Only observational studies that estimated the possibility of dementia in participants with SRD were considered. The random-effects model was applied to forecast pooled risk ratios (RRs) and 95% confidence intervals (CI). Heterogeneity among the studies was evaluated using the Q and I2 statistics. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Funnel plots were used to calculate the risk of bias. Results: Seventeen observational studies with 17,717,473 participants were recruited. Our findings showed that among the participants with SRDs, those with osteoarthritis, systemic lupus erythematosus, and Sjogren's syndrome were highly related to an elevated risk of dementia (pooled RR: 1.31; 95% CI: 1.15-1.49, p<0.001; pooled RR: 1.43; 95% CI: 1.19-1.73, p<0.001; and pooled RR: 1.26; 95% CI: 1.14-1.39, p<0.001, respectively). However, participants with rheumatoid arthritis (RA) were not associated with an increased risk of dementia (pooled RR: 0.98; 95% CI: 0.90-1.07, p<0.001). Conclusion: This systematic review and meta-analysis demonstrated an increased dementia risk among SRDs participants, except for RA.

Determination of the main causes, outcome, and prognostic factors of patients with rheumatologic diseases admitted to the medical intensive care unit in Southern Iran.

BACKGROUND: Systemic rheumatic diseases (SRD) are a heterogeneous group of diseases that can involve several organ systems and occasionally requires intensive care unit (ICU) admission because of severe systemic disease, life-threatening organ involvement, or complication of treatment. The objective of this study is to determine the causes, outcome, and prognostic factors of patients with rheumatologic diseases admitted in teaching medical ICUs in southern Iran. METHODS: A retrospective case review of all patients with rheumatologic diseases admitted in the academic medical ICUs in two referral hospitals in southern Iran, from March 2015 to January 2020. Patients' data were documented from their hospital records and the cause of admission, in-hospital outcome, and prognostic factors was evaluated. RESULTS: Ninety-one patients were included, of which 71.4% were female. Systemic lupus erythematosus (54.9%) was the most common disease. Nineteen (20.9%) patients were new cases of rheumatological disease. The most frequent symptom for admittance was dyspnea (54.9%) and hemoptysis (20.9%). The in-hospital mortality rate was 48%, and the leading cause of death was infection (29 patients; 65.5%) followed by disease activity (18 patients; 40.9%). Also, the death of 29.5% of patients was presumed due to both disease activity and infection. Factors associated with mortality included renal insufficiency (p < 0.028), infection (p < 0.001), pneumonia (p < 0.042), dyspnea (p < 0.042), loss of consciousness (p < 0.046), azathioprine consumption (p < 0.004) during 1 month before ICU admission, mechanical ventilation (p < 0.001), renal replacement therapy (p < 0.001), CNS involvement (p < 0.009), and ICU medications such as cyclosporine and azathioprine (0.03 and 0.03, respectively) or treatments such as plasmapheresis (p < 0.018). CONCLUSION: The ICU mortality rate of patients with SRD was high. Infection and disease exacerbation are the leading reasons for ICU admission in systemic rheumatic diseases. Intensivists must keep in mind that SRD exacerbation may require immunosuppressive agents along with lifesaving interventions, more particularly in newly diagnosed SRDs. Key Points • The ICU mortality rate of patients with SRD was high. • Infection and disease exacerbation are the leading reasons for ICU admission in systemic rheumatic diseases. • 63.8% of our patients fall into this category of new cases of rheumatologic disease and disease flare-up.

Different systemic rheumatic diseases as risk factors for COVID-19-related mortality.

COVID-19 has been associated with increased morbidity and mortality, globally. Whether COVID-19-related mortality is increased in patients with systemic rheumatic diseases (SRDs) is still debatable. Although results are somewhat conflicting, there are a handful of nationwide studies published indicating that, in individuals with SRD, there is signal for increased adverse COVID-19-related outcomes and higher mortality. It appears that there are differences in COVID-19-related mortality across various SRDs. Besides, certain disease-specific (disease activity, disease duration, medication received) and/or other features (e.g. comorbidities) seem to also affect COVID-19-related mortality in SRD patients. Herein, we wanted to highlight that a more individualized approach taking into consideration the effect of the aforementioned factors into the risk calculation for COVID-19 adverse outcomes, including mortality, in SRD patients is warranted. A multinational study based on nationwide data, examining all common SRDs and stratifying accordingly, would be of interest, toward this direction. Key Points • It is still debatable whether Covid-19-related mortality is increased in patients with sytemic rheumatic diseases (SRD). • Disease-specific risk factors (e.g. type of SRD, disease activity) should be taken into account in risk assessment for Covid-19-releted outcomes in SRD patients.

Baseline factors associated with self-reported disease flares following COVID-19 vaccination among adults with systemic rheumatic disease: results from the COVID-19 global rheumatology alliance vaccine survey.

OBJECTIVE: To examine the frequency of, and risk factors for, disease flare following COVID-19 vaccination in patients with systemic rheumatic disease (SRD). METHODS: An international study was conducted from 2 April to 16 August 2021, using an online survey of 5619 adults with SRD for adverse events following COVID-19 vaccination, including flares of disease requiring a change in treatment. We examined risk factors identified a priori based on published associations with SRD activity and SARS-CoV-2 severity, including demographics, SRD type, comorbidities, vaccine type, cessation of immunosuppressive medications around vaccination and history of reactions to non-COVID-19 vaccines, using multivariable logistic regression. RESULTS: Flares requiring a change in treatment following COVID-19 vaccination were reported by 4.9% of patients. Compared with rheumatoid arthritis, certain SRD, including systemic lupus erythematosus (OR 1.51, 95% CI 1.03, 2.20), psoriatic arthritis (OR 1.95, 95% CI 1.20, 3.18) and polymyalgia rheumatica (OR 1.94, 95% CI 1.08, 2.48) were associated with higher odds of flare, while idiopathic inflammatory myopathies were associated with lower odds for flare (OR 0.54, 95% CI 0.31-0.96). The Oxford-AstraZeneca vaccine was associated with higher odds of flare relative to the Pfizer-BioNTech vaccine (OR 1.44, 95% CI 1.07, 1.95), as were a prior reaction to a non-COVID-19 vaccine (OR 2.50, 95% CI 1.76, 3.54) and female sex (OR 2.71, 95% CI 1.55, 4.72). CONCLUSION: SRD flares requiring changes in treatment following COVID-19 vaccination were uncommon in this large international study. Several potential risk factors, as well as differences by disease type, warrant further examination in prospective cohorts.

Nintedanib in the treatment of systemic rheumatic disease-associated interstitial lung disease.

Systemic rheumatoid diseases form a large group of entities with variable clinical picture and different involvement and degree of organ impairment. Respiratory tract represents major site of damage, with lung interstitium, pleura, pulmonary vasculature and airways possibly affected. In systemic sclerodermia and rheumatoid arthritis, lung disease is the most significant cause of morbidity and mortality. Breathing difficulties may either present as first symptoms of underlying rheumatoid disease or may appear at any time during the course of the disease. Rheumatologists should routinely screen their patients for possible lung impairment. Similarly, extrapulmonal signs should be assessed by pulmonologists in patients referred for dyspnea. Currently, novel antifibrotic therapy is available not only for patients with idiopathic pulmonary fibrosis (IPF), but also for selected group of patients with non-IPF progressive fenotype associated interstitial lung disease having solid evidence-based background. Interdisciplinary approach in terms of collaboration between pulmonologist and rheumatologist is of key importance as proper identification of possible candidates and early onset of therapy is crucial.

Blocking IL-17: A Promising Strategy in the Treatment of Systemic Rheumatic Diseases.

Systemic rheumatic diseases are a heterogeneous group of autoimmune disorders that affect the connective tissue, characterized by the involvement of multiple organs, leading to disability, organ failure and premature mortality. Despite the advances in recent years, the therapeutic options for these diseases are still limited and some patients do not respond to the current treatments. Interleukin-17 (IL-17) is a cytokine essential in the defense against extracellular bacteria and fungi. Disruption of IL-17 homeostasis has been associated with the development and progression of rheumatic diseases, and the approval of different biological therapies targeting IL-17 for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) has highlighted the key role of this cytokine. IL-17 has been also implicated in the pathogenesis of systemic rheumatic diseases, including systemic lupus erythematosus (SLE), Sjögren's syndrome (SS) and systemic sclerosis (SSc). The aim of this review is to summarize and discuss the most recent findings about the pathogenic role of IL-17 in systemic rheumatic and its potential use as a therapeutic option.

How to investigate: Suspected systemic rheumatic diseases in patients presenting with muscle complaints.

Muscular symptoms, which may be due to multiple causes, are one of the most common early complaints in a rheumatology practice. Musculoskeletal symptoms in rheumatic conditions are very varied, ranging from mechanical problems to muscular symptoms derived from inflammatory and systemic autoimmune diseases. Several drugs commonly used by different specialists and certain drugs used in rheumatology can also cause a wide variety of muscle symptoms. A description of different systemic autoimmune diseases follows to describe the different forms of involvement of the musculoskeletal system that they cause, as well as the main causes with which a differential diagnosis should be made. In this chapter, we will try to give some clues to reach an early diagnosis using clinical criteria, particularly based on a directed anamnesis and physical examination, discussing possible guidelines for the complimentary tests that may be required in patients with muscle complaints.

The Prevalence of Systemic Rheumatic Diseases Among Breast Cancer Patients and Its Relationship With Survival.

OBJECTIVES: This study aims to investigate the prevalence of systemic rheumatic diseases (SRDs) among patients with breast cancer (BC) and to identify the clinicopathological characteristics of these patients. PATIENTS AND METHODS: A total of 3,744 female patients with BC (mean age 49±11.7 years; range, 18 to 92 years) followed in Hacettepe University Faculty of Medicine, Medical Oncology Department between January 2006 and December 2015 were retrospectively assessed. Patients with or without SRD were compared in terms of clinicopathological features including age, menopausal state, smoking status, Body Mass Index (BMI), age of menarche, age at first labor, and number of children. The groups were also evaluated regarding tumor grade, stage, estrogen receptor and progesterone receptor expression, human epidermal growth factor receptor 2 overexpression, and survival. RESULTS: Of the patients analyzed, 68 (1.81%) had concomitant SRD. Among these patients, 33 (48.6%) had rheumatoid arthritis, eight (11.8%) had familial Mediterranean fever, eight (11.8%) had Behçet's disease, four (5.8%) had Sjögren's syndrome, four (5.8%) had systemic lupus erythematosus, six (8.8%) had ankylosing spondylitis, three (4.4%) had systemic sclerosis, one (1.4%) had polymyositis, and one (1.4%) had temporal arteritis. The groups with or without SRDs were similar in terms of age, smoking status, BMI, menopausal state, breast feeding duration, age at menarche and first birth. Stage 1 and 2 BC was more prevalent in SRD patients (74.6% vs. 64.5%, p=0.018). The rate to receive chemotherapy was significantly lower in patients with SRD. However, there was no significant difference in five-year overall survival rates between patients with or without SRD. CONCLUSION: Among patients with BC, 1.81% had concomitant SRD. These patients were diagnosed at early stages and given chemotherapy less frequently. However, they had similar survival rates compared to those without SRDs.

Effectiveness and safety of lower dose sulfamethoxazole/trimethoprim therapy for Pneumocystis jirovecii pneumonia in patients with systemic rheumatic diseases: A retrospective multicenter study.

OBJECTIVES: To evaluate the effectiveness and safety of lower-dose sulfamethoxazole/trimethoprim therapy (SMX/TMP) for Pneumocystis jirovecii pneumonia (PCP) in patients with systemic rheumatic diseases. METHODS: In this multicenter retrospective study, we compared effectiveness and safety of SMX/TMP for the treatment of PCP among patients divided into three groups according to the initial dosage of SMX/TMP: the low, ≤10 mg/kg/day; the intermediate, 10-15 mg/kg/day; and the high and conventional, 15-20 mg/kg/day for TMP dose. RESULTS: Eighty-one patients, including 22, 30, and 29 patients in the low-, the intermediate- and the high-dose group could be analyzed and the 30-day survival rate were 100%, 93.3%, and 96.7%, respectively (P = 0.28). There were significant dose-dependent increasing trends of severe adverse drug reactions (ADRs) for SMX/TMP that were graded as ≥3 according to the Common Terminology Criteria for Adverse Events. When stratified by presence of severe hypoxemia defined by alveolar-arterial O2 gradient ≥45 mmHg, the 30-day survival and treatment modification rate were similar among the three groups, but frequency of severe ADRs were significantly decreased in the low-dose group. The low-dose group was independently and negatively associated with treatment modification within 14 days and severe ADRs. CONCLUSIONS: Lower dose SMX/TMP therapy with ≤10 mg/kg/day for TMP was as effective as higher dose therapy for the treatment of PCP and associated with lower rates of treatment modification and severe ADRs in patients with systemic rheumatic diseases.

Cardiovascular Imaging Techniques in Systemic Rheumatic Diseases.

The risk of cardiovascular (CV) events and mortality is significantly higher in patients with systemic rheumatic diseases than in the general population. Although CV involvement in such patients is highly heterogeneous and may affect various structures of the heart, it can now be diagnosed earlier and promptly treated. Various types of assessments are employed for the evaluation of CV risk such as transthoracic or transesophageal echocardiography, magnetic resonance imaging (MRI), and computed tomography (CT) to investigate valve abnormalities, pericardial disease, and ventricular wall motion defects. The diameter of coronary arteries can be assessed using invasive quantitative coronarography or intravascular ultrasound, and coronary flow reserve can be assessed using non-invasive transesophageal or transthoracic ultrasonography (US), MRI, CT, or positron emission tomography (PET) after endothelium-dependent vasodilation. Finally, peripheral circulation can be measured invasively using strain-gauge plethysmography in an arm after the arterial infusion of an endothelium-dependent vasodilator or non-invasively by means of US or MRI measurements of flow-mediated vasodilation of the brachial artery. All of the above are reliable methods of investigating CV involvement, but more recently, introduced use of speckle tracking echocardiography and 3-dimensional US are diagnostically more accurate.

Patients with systemic rheumatic diseases admitted to the intensive care unit: what the rheumatologist needs to know.

Patients with systemic rheumatic diseases (SRDs) may require admission to the intensive care unit (ICU) throughout the course of their disease. Therefore, the rheumatologist needs an understanding of the factors which may influence the course of patients with SRDs who are admitted to ICU. These include the causes for admission, patient characteristics including comorbidities and drug therapies, outcome (in-ICU mortality and causes of death), and prognostic factors. Infections and exacerbation/complications of SRDs are the most common (and potentially reversible) reasons for both admission and death on ICU. Mortality in patients with SRDs admitted to ICU has been reported to be either no different or higher than 'general' ICU patients. Reported prognostic factors included patient and disease characteristics, as well as ICU factors, including scoring systems. Rheumatologists need to be aware of the factors surrounding admission of patients with SRDs to ICU, including the need for strong links with critical care medicine.

The fact not to ignore: Mean blood pressure is the main predictor of increased arterial stiffness in patients with systemic rheumatic diseases.

PURPOSE: We aimed to evaluate the association between carotid-radial pulse wave velocity (PWV), augmentation index (AIx), and flow-mediated dilatation (FMD) of the brachial artery and factors potentially influencing them in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). MATERIAL AND METHODS: 316 patients diagnosed with RA (32%), SLE (20%), SSc (16%) and 156 controls (32%) were included in the study. Parameters of arterial stiffness AIx and PWV were obtained using applanation tonometry. FMD reflecting endothelial function was measured by ultrasound. RESULTS: AIx was increased in all three diseases (p<0.0001), but no differences were found between rheumatic diseases. In most of the RA cases PWV values were abnormal (on average by 0.52m/sec higher than in controls), while in SSc patients FMD values were diminished (p=0.006). Mean blood pressure (MBP) was the most consistent predictive factor in all three diseases, influencing both PWV and AIx, although patient age was also important in variation of AIx. The disease activity score (DAS28) was relevant only in RA patients. Furthermore, SLE disease activity index in SLE or Rodnan skin thickness score had no statistical significance in SSc and inflammatory markers. CONCLUSIONS: Both, PWV and AIx are dependent on MBP and age DAS28 may affect AIx in RA patients, while other disease or inflammatory markers are unlikely to have any effect. MBP is one of the main cardiovascular risk factors affecting the arterial stiffness in RA, SLE and SSc patients therefore controlling MBP in systemic rheumatic disease patients is mandatory.

The impact of pain on systemic rheumatic diseases.

Pain is associated with the different types of rheumatic syndromes because it is often the most troubling symptom of patients affected by any of these diseases. Some risk factors clearly play a major role in the clinical expression of pain and related syndromes, including genetics, age, gender, co-morbidities, traumas and psychological patterns, but there are no specific clinical, laboratory or neuroimaging markers that can indicate why and when a patient's localised pain will become chronic and widespread. Any type of pain must be treated not only appropriately, but also rapidly because the likelihood of developing some form of chronic pain is related to the duration of the peripheral pain stimulus. Chronic pain inevitably has a major impact on patients' quality of life because the loss of function undermines their ability to do everyday activities. Pain can be most effectively treated by carefully selecting various pharmacological and non-pharmacological interventions based on the characteristics of the pain itself, disease factors, psychological coping abilities, and lifestyle.

Evaluation of differences in carotid intima-media thickness in patients affected by systemic rheumatic diseases.

The objective of this study is to investigate whether rheumatic autoimmune diseases, systemic sclerosis (SSc) in particular, are associated with increased carotid intima-media thickness (C-IMT). A total of 108 clinical outpatients (93 females), mean age 51 ± 14 years suffering from CTD were consecutively enrolled. Patients were subdivided into the following two groups: (1) Systemic Sclerosis (SSc, 60 patients); (2) non-Systemic Sclerosis (NoSSc, 48 patients). No randomization was managed. All patients underwent structured clinical interview, physical examination, laboratory evaluation and two-dimensional echo-color Doppler of the carotid arteries to measure C-IMT and atherosclerotic plaques. Framingham risk score was also calculated. We also enrolled 108 healthy controls (HC), matched by sex and age. The primary outcome was to stratify cardiovascular risk of CTD patients. There were no significant differences between SSc and NoSSc patients regarding any of the demographics and traditional cardiovascular risk factors. Mean C-IMT was not significantly different between the whole CTD patients (0.86 ± 0.13 mm) and HC (0.83 ± 0.13 mm). C-IMT was significantly higher in SSc than in NoSSc group (0.91 ± 0.1 mm vs 0.80 ± 0.14 mm, p < 0.001). Furthermore, C-IMT in SSc group was significantly higher than C-IMT in controls (0.91 ± 0.1 mm vs 0.83 ± 0.13 mm, p < 0.001). C-IMT did correlate neither with disease activity nor with drug intake. SSc patients had a significant increase in C-IMT as compared to NoSSc patients and healthy controls.