Thoracic Complications in Behçet's Disease: Imaging Findings.

Behçet's disease (BD) causes vascular inflammation and necrosis in a wide range of organs and tissues. In the thorax, it may cause vascular complications, affecting the aorta, brachiocephalic arteries, bronchial arteries, pulmonary arteries, pulmonary veins, capillaries, and mediastinal and thoracic inlet veins. In BD, chest radiograph is commonly used for the initial assessment of pulmonary symptoms and complications and for follow-up and establishment of the response to treatment. With the advancement of helical or multislice computed tomography (CT) technologies, such noninvasive imaging techniques have been employed for the diagnosis of vascular lesions, vascular complications, and pulmonary parenchymal manifestations of BD. CT scan (especially, CT angiography) has been used to determine the presence and severity of pulmonary complications without resorting to more invasive procedures, in conjunction with gadolinium-enhanced three-dimensional (3D) gradient-echo magnetic resonance (MR) imaging with the subtraction of arterial phase images. These radiologic methods have characteristics that are complementary to each other in diagnosis of the thoracic complications in BD. 3D ultrashort echo time (UTE) MR imaging (MRI) could potentially yield superior image quality for pulmonary vessels and lung parenchyma when compared with breath-hold 3D MR angiography.

Relationship between prevalence and severity of restless legs syndrome and anemia in patients with systemic lupus erythematosus.

AIM: Our aim was to evaluate the relationship between the prevalence and severity of restless legs syndrome (RLS) and the anemia in patients with systemic lupus erythematosus (SLE). METHODS: This was a case-control study which was conducted at the rheumatology clinic of a university affiliated hospital, including 62 patients with SLE and 62 age- and sex-matched healthy controls. The patients were divided into two groups in terms of their hemoglobin levels. The criterion for anemia was hemoglobin level lower than 12 g/dL in females and 13 g/dL in males. RESULTS: Nineteen patients (30.6%) in the patient group were diagnosed with RLS, and International RLS Study Group Rating Scale (IRLSSG-RS) score was 10.7 ± 9.5 (median:10.0 [range:0.0-30.0]). Three subjects (4.8%) in the control group had RLS, and the IRLSSG-RS score was 0.7 ± 3.3 (median:0.0 [range:0.0-18.0]). The prevalence of RLS and the IRLSSG-RS score were higher in the patient group than those in the control group (P < 0.001). Ten SLE patients (50%) with anemia had RLS, and their IRLSSG-RS score was 14.5 ± 9.9 (median:21.0 [range:11.0-30.0]). Nine SLE patients (21.4%) without anemia had RLS and their IRLSSG-RS was 9.0 ± 8.9 (median:21.0 [range:11.0-24.0]). Significant differences were present in the prevalence of RLS and the IRLSSG-RS score between SLE patients with and without anemia (P = 0.024, P = 0.044, respectively). CONCLUSION: The present study demonstrated that the prevalence of RLS was higher in patients with SLE than that of the normal population. Results of this study also suggested that anemia was associated with higher frequency of and more severe RLS in patients with lupus.

The evaluation of cochlear functions in Familial Mediterranean Fever.

Familial Mediterranean Fever (FMF) is a progressive disease characterized by chronic inflammation, which also has negative effects on cochlear functions and hearing levels. We investigated whether the cochlear functions and hearing levels of FMF patients were different than healthy controls and also evaluated the relationship of hearing levels with the age at diagnosis, duration without treatment, and inflammation and lipid parameters in this study. A total of 60 patients diagnosed with FMF and 48 age, gender and body mass index (BMI)-matched healthy controls were included in the study. The hemogram, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lipid parameters of the subjects were studied and they all underwent pure tone audiometry and Transient evoked otoacoustic emission tests after an otologic examination. The hearing levels of the FMF group were significantly higher than those of the control group. The TEOAE signal/noise (S/N) ratios were similar in both groups. A positive relationship was present between the audiometric test results and the age, BMI, low-density lipoprotein and triglyceride levels and a negative relationship with the high-density lipoprotein levels. A negative relationship was present between the TEOAE S/N ratios and the age of the patients, duration without treatment, lipid parameters, inflammation markers and the creatinine level. FMF patients are exposed to chronic inflammation and this can influence their hearing levels. The age at diagnosis, duration without treatment, chronic inflammation, unfavorable lipid parameters, and obesity can affect hearing tests negatively.

Apremilast for Behçet's syndrome--a phase 2, placebo-controlled study.

BACKGROUND: Oral ulcers, the hallmark of Behçet's syndrome, can be resistant to conventional treatment; therefore, alternative agents are needed. Apremilast is an oral phosphodiesterase-4 inhibitor that modulates several inflammatory pathways. METHODS: We conducted a phase 2, multicenter, placebo-controlled study in which 111 patients with Behçet's syndrome who had two or more oral ulcers were randomly assigned to receive 30 mg of apremilast twice daily or placebo for 12 weeks. This regimen was followed by a 12-week extension phase in which the placebo group was switched to apremilast and a 28-day post-treatment observational follow-up phase. The patients and clinicians were unaware of the study assignments throughout the trial. The primary end point was the number of oral ulcers at week 12. Secondary outcomes included pain from these ulcers (measured on a 100-mm visual-analogue scale, with higher scores indicating worse pain), the number of genital ulcers, overall disease activity, and quality of life. RESULTS: The mean (±SD) number of oral ulcers per patient at week 12 was significantly lower in the apremilast group than in the placebo group (0.5±1.0 vs. 2.1±2.6) (P<0.001). The mean decline in pain from oral ulcers from baseline to week 12 was greater with apremilast than with placebo (-44.7±24.3 mm vs. -16.0±32.5 mm) (P<0.001). Nausea, vomiting, and diarrhea were more common in the apremilast group (with 22, 9, and 12 incidents, respectively, among 55 patients) than in the placebo group (with 10, 1, and 2 incidents, respectively, among 56 patients), findings that were similar to those in previous studies of apremilast. There were two serious adverse events in patients receiving apremilast. CONCLUSIONS: Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Behçet's syndrome. This preliminary study was neither large enough nor long enough to assess long-term efficacy, the effect on other manifestations of Behçet's syndrome, or the risk of uncommon serious adverse events. (Funded by Celgene; ClinicalTrials.gov number, NCT00866359.).

Mood, anxiety and personality disorders in patients with systemic lupus erythematosus.

OBJECTIVE: This study presents the current prevalence of mood, anxiety and personality disorders and factors associated with the existence of psychiatric disorders in patients with systemic lupus erythematosus (SLE). METHODS: The study sample was comprised of 45 patients with SLE and 60 control subjects. Mood and anxiety disorders were ascertained by means of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition/Clinical Version. Personality disorders were diagnosed with the Structured Clinical Interview for DSM, Revised Third Edition Personality Disorders. The disease activity was assessed with SLE Disease Activity Index. RESULTS: Of the 45 patients, 21 (46.7%) had at least one mood or anxiety disorder, and 16 (35.6%) had at least one personality disorder. The most common Axis I and Axis II diagnoses in the patient group were major depression (22.2%) and obsessive-compulsive personality disorder (20.0%), respectively. Specifically, major depression, generalized anxiety disorder and obsessive-compulsive personality disorder were more prevalent in the SLE group compared to the control group. The existence of Axis I disorders was associated with a more severe disease activity of SLE. CONCLUSION: Mood and anxiety disorders, particularly major depression and generalized anxiety disorder, are frequently observed in patients with SLE.

HLA-B27 subtypes in Turkish patients with ankylosing spondylitis and healthy controls.

The aim of this study was to determine human leukocyte antigen (HLA)-B27 subtypes frequency in ankylosing spondylitis (AS) and related spondyloartropathy (SpA) patients. Therefore, we investigated the differences in HLA-B27 subtypes between HLA-B27-positive patients and controls. Sixty six patients were included in this study (51 AS and 15 SpA). Thirty-five individuals were diagnosed with leukemia or chronic renal failure, and their donors without any rheumatological problem (no SpA history) were selected as the control group. HLA-B27 subtyping was performed by PCR-SSP (polymerase chain reaction with sequence-specific primer) method in serologically HLA-B27-positive 46 AS patients, 9 SpA patients and control group. When the frequency of HLA-B27 was 4.5% in Turkish population, this frequency was 90.2% in AS patients. Four different HLA-B27 subtypes found in AS patients were B 2705 (65.2%), B 2702 (26.1%), B 2704 (6.5%) and B 2707 (2.2%). In SpA patients, B 2705 and B 2702 found in equal frequency. Five B27 alleles were identified in our control group: B 2705 (54.3%), B 2702 (31.4) %, B 2703 (2.9%), B 2704 (2.9%) and B 2702/B 2705 (8.5%). Both in the patient group and in the control group, we also observed B 2705 as most frequent allele, and B 2702 was second common allele. Our results show that the frequency of HLA-B27 subtypes is not significantly different between patients and controls (P > 0.10).

Remission and rheumatoid arthritis: data on patients receiving usual care in twenty-four countries.

OBJECTIVE: To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). METHODS: The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). RESULTS: The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >or=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. CONCLUSION: The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.

Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study.

INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. METHODS: The study involved a clinical assessment by a rheumatologist and a self-report questionnaire by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were hypertension, hyperlipidemia, diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity were calculated using Cox proportional hazard regression models. RESULTS: Between January 2005 and October 2006, the QUEST-RA project included 4,363 patients from 48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the mean age was 57 years. The prevalence for lifetime CV events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event. The prevalence for CV risk factors was 32% for hypertension, 14% for hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical inactivity, and 18% for obesity. Traditional risk factors except obesity and physical inactivity were significantly associated with CV morbidity. There was an association between any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0.59; 95% CI 0.43 to 0.79), sulfasalazine (HR 0.92; 95% CI 0.87 to 0.98), glucocorticoids (HR 0.95; 95% CI 0.92 to 0.98), and biologic agents (HR 0.42; 95% CI 0.21 to 0.81; P < 0.05) was associated with a reduction of the risk of CV morbidity; analyses were adjusted for traditional risk factors and countries. CONCLUSION: In conclusion, prolonged use of treatments such as methotrexate, sulfasalazine, leflunomide, glucocorticoids, and tumor necrosis factor-alpha blockers appears to be associated with a reduced risk of CV disease. In addition to traditional risk factors, extra-articular disease was associated with the occurrence of myocardial infarction in patients with RA.

Intraobserver and interobserver agreements of leg circumference measurements by tape measure based on 3 reference points.

The objective of this study was to evaluate the intraobserver and interobserver agreements in tape measurements of the ankle and calf circumference with due emphasis on the 3 main reference points, the patella, the tibial tuberosity, and the medial malleolus. The leg circumference at 2 locations was measured in 66 patients in the mornings of 2 consecutive days by 6 observers. Finally, a blinded couple measured leg circumferences at a line created on calves with a ballpoint pen of 68 outpatients to calculate interobserver agreement for lined regions. Leg circumference measurement was accepted as correct when the difference was less than 0.6 cm in 2 occasions. Intraobserver and interobserver agreements were calculated as the percentage of correct measurements. Chi-square test was used to compare intraobserver and interobserver agreements for each reference point. At the calf region, intraobserver and interobserver agreements based on the tibial tuberosity (88% and 81%) were better than those of the patella (65% and 57%) and the medial malleolus (73% and 65%). On the other hand, at above the ankle region, the agreements (79% and 62%) were also better than those of the patella (60% and 43%) and nearly the same as those of the medial malleolus (86% and 65%). Finally, interobserver agreement of the measurements at the created line with ballpoint pen (96%) was better when compared to those of the tibial tuberosity (81%), the patella (57%), and medial malleolus (65%) (p = 0.005, p < 0.001, and p < 0.001, respectively). The results of this study suggest that the tibial tuberosity as a reference point for leg circumference measurement has better intraobserver and interobserver agreements than those of the patella and the medial malleoli.

Systemic onset juvenile rheumatoid arthritis presenting with absence of B lymphocytes.

Juvenile rheumatoid arthritis (JRA) is a complex disease involving the interactions of several cell populations with different mediators. Herein, we report a five-year-old girl with systemic-onset JRA. At admission, peripheral blood flowcytometric analysis showed the percentages of CD19(+) and CD20(+) B cells were <1%. These values returned to normal on the tenth day of steroid treatment. This is the first report of JRA presented with absence of B lymphocytes in the literature and suggested that lymphocytes subset analysis could change with treatment in patients with JRA. Different clinical signs and symptoms reflecting aspects of JRA are critical for the etiology of the disease and to identify new strategies for treatment.

Prevalence of Behçet's disease in Istanbul, Turkey.

BACKGROUND: The prevalence of Behçet's disease (BD) is much higher in countries along the ancient Silk Route, extending from Japan to Mediterranean countries including Turkey, than in northern Europe and the USA. Three previous epidemiologic surveys have been carried out in different regions of Turkey. PATIENTS AND METHODS: This study investigated the cross-sectional prevalence of BD in individuals aged > 12 years in Istanbul, Turkey, in two stages. The first stage aimed to identify individuals with recurrent oral ulcers (ROUs) by visiting them in their homes, and the second stage aimed to further examine those with ROUs for the presence of other BD-related manifestations under hospital conditions. The sample size was determined to be 24,000 with an expected BD prevalence rate of 1/1000 and a sampling error of 4/10,000, with a 95% confidence interval (CI) of 6-14/10,000. The number of individuals to be screened in each district was determined in proportion to the population of all districts in Istanbul. RESULTS: The standard questionnaire was applied to a total of 23,986 individuals at their homes. A history of ROU was recorded in 2289 individuals (9.5%), and a previous diagnosis of BD was recorded in 47. The diagnosis of ROU was confirmed in 700, and the diagnosis of BD was established in 101 according to the International Study Group criteria. The prevalence rate of BD was estimated as 42/10,000 (95% CI, 34-51/10,000) in Istanbul, Turkey. CONCLUSIONS: This survey conducted in Istanbul, the largest cosmopolitan city in Turkey with immigrants from all over the country, has a larger sample size than other previous studies, and therefore the reported prevalence rate of BD has a more acceptable confidence interval. This study aids in the estimation of the prevalence of BD in Turkey, and supports previous findings that Turkey has the highest prevalence rate of the disease in the world.

Rhabdomyolysis in a patient with hypothyroidism.

We describe a case of rhabdomyolysis associating hypothyroidism. Hypothyroidism frequently leads to myalgias, muscle stiffness, cramps and sometimes elevated levels of muscle enzymes, but rhabdomyolysis is quite rare. This report describes a case of rhabdomyolysis associating hypothyroidism in a 19-year old man. Muscle enzyme levels were typical of rhabdomyolysis. Muscle biopsy and electromyographic findings were compatible with hypothyroid myopathy. Muscle functions completely recovered with levothyroxine therapy. The present case represents rhabdomyolysis secondary to undiagnosed hypothyroidism in a developed stage which manifests itself with rhabdomyolysis.

Bone and calcium metabolism in subclinical autoimmune hyperthyroidism and hypothyroidism.

Bone turnover is reported to increase in favour of resorption in overt hyperthyroidism and the rate of resorption is associated with the levels of thyroid hormones. Hypothyroidism, on the other hand, was shown to cause no disturbance of calcium kinetics and found to associate lower trabecular resorption surfaces and increased bone cortical thickness. Similar studies are very rare in subclinical thyroid disorders and consequently we aimed to examine calcium and bone metabolism in subclinical thyroid disorders. Thirteen patients with subclinical hyperthyroidism secondary to untreated Graves' disease, 20 patients with subclinical hypothyroidism and 10 healthy subjects participated in this survey. Briefly calcium, phosphorus, and creatinine (Cre), urinary deoxypyridinoline (U-DPD) and serum osteocalcin (OC) were measured as biochemical markers for calcium metabolism. Concerning serum Ca and phosphorus levels, there were no differences between three of the groups, but urinary Ca excretion was higher in subclinical hyperthyroid patients compared to control and hypothyroid subjects. Hypothyroid patients had similar U-DPD levels with control subjects (p = 0.218). Serum OC and U-DPD were higher in subclinical hyperthyroid compared to control subjects (p<0.001 and p<0.001 respectively). We demonstrated a higher bone turnover and greater calcium excretion in subclinical hyperthyroid patients. Additionally, we found that subclinical hypothyroidism is not associated with disturbed calcium metabolism. As persistent increase in bone turnover is responsible for accelerated bone loss, patients with Graves' disease may have increased risk for osteoporosis.

Target organ associations in Turkish patients with Behçet's disease: a cross sectional study by exploratory factor analysis.

OBJECTIVE: To look for target organ associations in Turkish patients with Behçet's disease (BD). METHODS: We studied target organ associations in 272 consecutive patients with BD. The occurrence of any of the clinical manifestations related to BD within the previous 3 months was sought by history questionnaire completed by a rheumatologist and by physical examination. Factor analysis was used to analyze the data. RESULTS: Four factors were identified by factor analysis of variables oral and genital ulcers, erythema nodosum, papulopustular skin lesions, uveitis, superficial and deep vein thrombosis, joint, arterial, neurological, and gastrointestinal involvement; the 4 identified factors explained 69% of the original information of the matrix. There was an association between oral ulcers, genital ulcers, and erythema nodosum (Factor 1); and between superficial and deep vein thrombosis (Factor 2). Uveitis was identified as a distinct feature, and was negatively associated with erythema nodosum (Factor 3) only among the females. There was also an association between papulopustular skin lesions and joint involvement (Factor 4). Factors 2 and 3 had higher scores in males (p = 0.001 and p = 0.009, respectively) versus females. CONCLUSION: We studied clinical features of BD in Turkish patients. The 4 factors we identified by factor analysis differ from a previous study from Israel, probably due to different methodologies used in the 2 studies. One factor described in our study, the association between papulopustular lesions and arthritis, supports findings of our recent study. A recognized association between superficial and deep vein thrombosis was also confirmed.