Subclinical Atherosclerosis in Systemic Sclerosis: Not Less Frequent Than Rheumatoid Arthritis and Not Detected With Cardiovascular Risk Indices.

OBJECTIVE: To determine the frequency of subclinical atherosclerosis in patients with systemic sclerosis (SSc; scleroderma) compared to healthy subjects (HS) and rheumatoid arthritis (RA) patients and to determine the ability of cardiovascular (CV) risk indices in detecting SSc patients with subclinical atherosclerosis. METHODS: A total of 110 SSc patients (102 females and 8 males, mean ± SD age 50.5 ± 11.9 years), 110 age- and sex-matched RA patients, and 51 HS without CV disease were examined with ultrasonography (US). Carotid intima-media thickness (cIMT) >0.90 mm and/or carotid plaques were used as the gold standard for subclinical atherosclerosis (US+). Systematic Coronary Risk Evaluation (SCORE), QRisk II, and 2013 American College of Cardiology (ACC)/American Heart Association (AHA) CV risk indices were calculated. RESULTS: Twenty-one (19.1%) SSc patients, 24 (21.8%) RA patients, and 3 (5.9%) HS had subclinical atherosclerosis (SSc versus RA: P = 0.62, SSc versus HS: P = 0.029). cIMT in SSc was higher compared to HS (0.68 ± 0.15 mm versus 0.61 ± 0.10 mm; P = 0.008) but similar to RA patients (0.66 ± 0.14 mm; P = 0.82). Subclinical atherosclerosis in SSc was associated with age (odds ratio [OR] 1.07, P = 0.013), elevated erythrocyte sedimentation rate (OR 3.4, P = 0.045), and pulmonary arterial hypertension (OR 4.27, P = 0.012). Concerning CV risk indices, of the 21 US+ SSc patients only 0, 3 (14.2%), and 6 (28.6%) were classified as high CV risk according to SCORE, QRisk II, and ACC/AHA risk indices, respectively. CONCLUSION: Subclinical atherosclerosis in SSc patients is more frequent than in HS, but is as frequent as in RA patients in which accelerated atherosclerosis is clearly defined. CV risk indices for the general population are considerably insufficient to detect SSc patients with atherosclerosis.

Effectiveness of Thoracic Ultrasonography in the Evaluation of the Severity of Pulmonary Involvement in Patients With Systemic Sclerosis.

OBJECTIVES: This study aims to investigate the effectiveness of thoracic ultrasonography (USG) in a single session in the evaluation of the severity of pulmonary involvement in systemic sclerosis. PATIENTS AND METHODS: A total of 48 consecutive systemic sclerosis patients (2 males, 46 females; mean age 50.8±11.9 years; range 21 to 76 years) followed-up in our center were included. A thoracic USG using a linear probe was performed for each patient to evaluate the parenchymal involvement by two pulmonary disease specialists. The number of B-lines (B-lines described USG sign of interstitial lung fibrosis) was recorded. Systolic pulmonary artery pressure was measured by means of using a phase probe to evaluate pulmonary hypertension in the same sequence. The same day, pulmonary function tests were conducted. Warrick score was calculated according high resolution computed tomography (HRCT) images which were evaluated independently from each other by a radiologist and a pulmonary disease specialist. Medsger severity scale was calculated for each patient according to the results of HRCT findings, pulmonary function test, and systolic pulmonary artery pressure. RESULTS: The number of B-lines detected on thoracic USG was correlated with the Warrick score (r=0.89; p=0.0001) and Medsger disease scale (r=0.55; p=0.0001) and negatively correlated with diffusing capacity of carbon monoxide (r= -0.56; p=0.0001) and forced vital capacity (r= -0.46; p=0.001). When HRCT was accepted as the gold standard; the sensitivity, specificity, positive predicted value, and negative predicted value for thoracic USG were 100%, 84.2%, 90.6%, and 100%, respectively. If thoracic USG was used instead of HRCT for the evaluation of Medsger scale, the results changed in only one of the 48 patients. CONCLUSION: Thoracic USG showed good correlation with HRCT findings for the evaluation of pulmonary parenchymal involvement in systemic sclerosis. Therefore, USG might be a noninvasive and useful tool for the long-term follow-up of systemic sclerosis patients after initial examination with USG and HRCT.

Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome-Wide Association Study.

OBJECTIVE: Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome-wide association analysis of Takayasu arteritis. METHODS: Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis. RESULTS: We identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10(-9)), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10(-8)), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10(-10)). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 × 10(-8)). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 × 10(-5)) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B. CONCLUSION: Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.

Increased frequency of restless leg syndrome in patients with ankylosing spondylitis.

OBJECTIVE: To assess the prevalence of restless leg syndrome (RLS) in patients with ankylosing spondylitis (AS) and to investigate factors potentially associated with RLS. METHODS: One hundred and thirty patients diagnosed with AS according to modified New York criteria and 91 age- and sex-matched healthy control subjects were included in this study. The diagnosis of RLS was made according to the criteria of the International RLS Study Group. The factors associated with RLS were evaluated. Electrophysiological procedures were performed in a group of patients with RLS. RESULTS: RLS was significantly more common in patients with AS (30.8%) than in healthy controls (13.2%). When AS patients with RLS were compared with AS patients without RLS, it was seen that peripheral arthritis, uveitis, anemia, smoking and polyneuropathy were significantly higher in the former group. CONCLUSION: RLS is common in patients with AS and iron deficiency, smoking and small fiber neuropathy seem to be possible causes.

Impact of rheumatoid arthritis in Turkey: a questionnaire study.

OBJECTIVES: Unmet needs of rheumatoid arthritis (RA) patients regarding physician/patient communication, treatment preferences and quality of life issues were investigated in a Turkish survey study. METHODS: The study was conducted with the contribution of 33 rheumatologists, and included 519 RA patients. The study population included patients who had been on biologic therapy for >6 months and were still receiving biologic therapy (BT group), and those who were biologic naive, but found eligible for biologic treatment (NBT group). Of the RA patients, 35.5% initially had a visit to an internal disease specialist, 25.5% to a physical therapy and rehabilitation specialist, and 12.2% to a rheumatology specialist for their RA complaints. The diagnosis of RA was made by a rheumatologist in 48.2% of patients. RESULTS: The majority of RA patients (86.3%) visit their doctor within 15-week intervals. Most of the physician-patient communication focused on disease symptoms (99.0%) and impact of the disease on quality of life (61.8%). The proportion of RA patients who perceived their health status as good/very good/excellent was higher in the BT group than in the NBT group (74.3% vs. 51.5%, p<0.001). However, of those RA patients in the NBT group, only 24.8% have been recommended to start a biologic treatment by their doctors. With respect to dose frequency options, once-monthly injections were preferred (80%) to a bi-weekly injection schedule (8%). CONCLUSIONS: In conclusion, RA patients receiving biologic therapy reported higher rates of improved symptoms and better quality of life and seemed to be more satisfied with their treatment in our study.

A case of granulomatosis with polyangiitis and pyoderma gangrenosum successfully treated with infliximab and rituximab.

Here, we present a young male patient who was admitted with alveolar hemorrhage, arthritis and cutaneous lesions, who later developed bilateral orbital involvement and pyoderma gangrenosum (PG). He also had pathergy test positivity. The patient was refractory to conventional immunosuppressive therapy. Therefore, multiple devastating PG lesions and disease activity in granulomatosis with polyangiitis (GPA) were controlled with infliximab. Later, rituximab was used with success to prevent recurrence of symptoms. The relationship of PG with various autoimmune diseases is known; however, PG in GPA has been only rarely reported. Biologic agents might prove to be effective in GPA and PG patients who are refractory to standard immunosuppressive therapy.

Diagnostic dilemma of paraneoplastic arthritis: case series.

OBJECTIVES: Paraneoplastic arthritis (PA) may mimic rheumatic diseases. While presenting the demographic and laboratory features of the patients diagnosed with PA, this study also aims to provide possible appropriate tools to differentiate the PA cases from early rheumatoid arthritis (ERA). METHODS: Sixty-five patients with PA (male/female: 43/22) from 15 different rheumatology clinics and 50 consecutive patients with ERA (male/female: 13/37) fulfilling the 2010 American College of Rheumatology (ACR) criteria for the diagnosis if the RA from Gaziantep Rheumatology Early Arthritis Trial (GREAT) as controls who were diagnosed at least 12 months before, were enrolled into study. RESULTS: Mean ages of the patients with PA and ERA were 50.2 ± 15.3, and 42.7 ± 12.3, respectively, and the mean ages of the patients with PA were significantly higher than the ERA. Unlike the ERA patients, in our case series PA was predominantly observed among males. Oligoarthritis was significantly higher in solid tumors in contrast to ERA (P = 0.001). Polyarthritis and symmetric arthritis were significantly higher in the ERA group in contrast to all malignancies (P = 0.001). Rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) positivity were significantly higher in the ERA group (each P = 0.001). Lactic dehydrogenase levels of hematologic malignancies were significantly higher than other groups (each, P = 0.001). CONCLUSIONS: ERA patients had more symmetric joint involvement than PA; laboratory markers could be also an alternative where there is high RF and anti-CCP positivity with antibody levels among the ERA patients. Finally, the demographic features can be used as differentiating factors; ERA was seen predominantly among females aged 40-59 years which refers to young adults.

Spleen tyrosine kinase inhibition in the treatment of autoimmune, allergic and autoinflammatory diseases.

Spleen tyrosine kinase (Syk) is involved in the development of the adaptive immune system and has been recognized as being important in the function of additional cell types, including platelets, phagocytes, fibroblasts, and osteoclasts, and in the generation of the inflammasome. Preclinical studies presented compelling evidence that Syk inhibition may have therapeutic value in the treatment of rheumatoid arthritis and other forms of arthritis, systemic lupus erythematosus, autoimmune cytopenias, and allergic and autoinflammatory diseases. In addition, Syk inhibition may have a place in limiting tissue injury associated with organ transplant and revascularization procedures. Clinical trials have documented exciting success in the treatment of patients with rheumatoid arthritis, autoimmune cytopenias, and allergic rhinitis. While the extent and severity of side effects appear to be limited so far, larger studies will unravel the risk involved with the clinical benefit.

A case of cervical spine meningioma following etanercept use in a patient with RA.

BACKGROUND: A 70-year-old female with active rheumatoid arthritis (RA) was administered etanercept to treat active disease that persisted despite therapy with conventional DMARDs. After 18 months of etanercept therapy, her RA symptoms had improved; however, she developed quadriparesis. She presented to a specialist rheumatology clinic with weakness and numbness in her arms and legs; she also had difficulty in standing up and walking. INVESTIGATIONS: Physical examination, neurological examination, nerve conduction studies, measurement of serum inflammatory markers and autoantibodies, MRI of the cranium and cervical spine, and X-rays of the chest and hands. DIAGNOSIS: The patient underwent neurosurgery to resect a 1 x 2 cm mass in the cervical spine at C6-C7. Histopathologic examination of the excised mass revealed it to be a meningioma. MANAGEMENT: Etanercept was discontinued because of a possible association between the drug and development of meningioma; however, shortly afterwards the patient experienced a flare of RA symptoms. High-dose NSAIDs and prednisolone were administered, but the patient died because of gastric perforation. To our knowledge, this is the first report in the literature of meningioma developing following use of tumor necrosis factor inhibitor therapy, and the first to suggest a cause-effect relationship.