New inflammatory markers in early rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is the most common chronic inflammatory disorder and is associated with progressive destruction of synovial joints and physical disability. Therapies with known benefits include disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, as well as more recent biologic agents, such as tumor necrosis factor inhibitors (anti-TNF therapy). METHOD: This was a retrospective study, which included 205 RA and 112 early RA (ERA) patients from the Rheumatology Clinic at Gaziantep University School of Medicine Research Center as well as 104 healthy controls. RESULTS: The mean neutrophil to lymphocyte ratio (NLR) was found to be 3.15 ± 2.64 in the patient group and 2.03 ± 0.94 in the control group. The mean platelet to lymphocyte ratio (PLR) was 162.39 ± 107.76 in the patient group and 131.23 ± 48.09 in the control group. There was a significant difference in both the NLR and PLR between the patient and control groups (both p < 0.01). There was a significant difference in both the NLR and PLR between patients with active disease and remission (both p < 0.001) in RA, including anti-TNF therapy and DMARDs groups. There was a significant difference in NLR (p = 0.001) but not in PLR (p = 0.051) between active disease and remission in ERA. CONCLUSION: The results of the present study suggest that the NLR may be considered a useful marker of disease activity in RA and one that can aid the diagnosis of ERA. The PLR can be used in the assessment of disease activity in RA patients undergoing anti-TNF therapy but is not suitable for diagnosing ERA.

Identification of multiple genetic susceptibility loci in Takayasu arteritis.

Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ~200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r(2) < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10(-9); and rs189754752, OR = 2.47, p = 4.22 × 10(-9)). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10(-12)). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10(-8)).

Validity and reliability of the Lupus QoL index in Turkish systemic lupus erythematosus patients.

BACKGROUND: Systemic lupus erythematosus (SLE) patients have seriously impaired quality of life (QoL). In addition to activity and damage indices used in the past, tools to evaluate QoL in SLE have been developed in recent years. In this study, we test the validity of the Turkish version of the Lupus-QoL (LupusQoL-TR) score, and investigate its association with clinical findings and activity indices. METHODS: A total of 132 patients diagnosed with SLE according to ACR 1997 criteria were included. The clinical and demographic features, and biochemical data were retrieved from hospital records. SLE Disease Activity Index (SLEDAI) and damage score (SLICC-ACR) were determined at the time of administration of Lupus-QoL questionnaire. The Lupus-QoL includes 34 questions divided into eight domains. We reevaluated the LupusQoL-TR and pretested its understandability. SLE patients were concomitantly administered the LupusQoL-TR and generic SF-36. Internal consistency, test-retest reliability, convergent and discriminant validity were calculated. RESULTS: The mean age of our SLE patients was 37.9 ± 12.8 years. Internal consistency reliability ranged from 0.88 to 0.93, and test-retest reliability from 0.84 to 0.94. LupusQoL-related domains in SF-36 were correlated (from 0.66 to 0.74). Most LupusQoL-TR domains, except planning, were able to discriminate between active and inactive SLE groups. Scores in all domains of the LupusQoL-TR were found to be discriminative for patients with and without damage according to SLICC-ACR score. CONCLUSION: The LupusQoL-TR was found to be a valid patient-reported outcome measure method when evaluating QoL in Turkish SLE patients.

Cardiovascular and all-cause mortality in relation to various anthropometric measures of obesity in Europeans.

BACKGROUND AND AIMS: Cardiovascular and all-cause mortality in relation to various anthropometric measures of obesity is still controversial. METHODS AND RESULTS: Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), A Body Shape Index (ABSI) and waist-to-hip-to-height ratio (WHHR) were measured at baseline in a cohort of 46,651 European men and women aged 24-99 years. The relationship between anthropometric measures of obesity and mortality was evaluated by the Cox proportional hazards model with age as a time-scale and with threshold detected by a piecewise regression model. Over a median follow-up of 7.9 years, 2381 men and 1055 women died, 1071 men (45.0%) and 339 women (32.1%) from cardiovascular disease (CVD). BMI had a J-shaped relationship with CVD mortality, whereas anthropometric measures of abdominal obesity had positive linear relationships. BMI, WC and WHtR showed J-shaped associations with all-cause mortality, whereas WHR, ABSI and WHHR demonstrated positive linear relationships. Accordingly, a threshold value was detected at 29.29 and 30.98 kg/m(2) for BMI, 96.4 and 93.3 cm for WC, 0.57 and 0.60 for WHtR, 0.0848 and 0.0813 m(11/6) kg(-2/3) for ABSI with CVD mortality in men and women, respectively; 29.88 and 29.50 kg/m(2) for BMI, 104.3 and 105.6 for WC, 0.61 and 0.67 for WHtR, 0.95 and 0.86 for WHR, 0.0807 and 0.0765 for ABSI in men and women, respectively, and 0.52 for WHHR in women with all-cause mortality. CONCLUSION: All anthropometric measures of abdominal obesity had positive linear associations with CVD mortality, whereas some showed linear and the others J-shaped relationships with all-cause mortality. BMI had a J-shaped relationship with either CVD or all-cause mortality. Thresholds detected based on mortality may help with clinical definition of obesity in relation to mortality.

Systemic vasculitis in a patient with rhupus syndrome.

Rhupus is a rare syndrome characterized by overlap of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Previous reports mentioned that rhupus patients have prominent RA associated clinical manifestations and only mild organic damage related to SLE. Progressive or life-threatening manifestations are rare in rhupus patients. Our patient diagnosed as rhupus was a young women, presented with multi-organ involvement of systemic vasculitis. Rheumatologists should be aware of possibility that rhupus may be accompanied by progressive or life-threatening conditions such as vasculitis.

Effects of periodontal therapy on disease activity and systemic inflammation in rheumatoid arthritis patients.

OBJECTIVE: This observational prospective cohort study aimed to evaluate the effects of non-surgical periodontal treatment on clinical periodontal measurements and systemic inflammatory mediator levels in low or moderate to highly active rheumatoid arthritis (RA) patients with chronic periodontitis. SUBJECTS AND METHODS: Rheumatoid arthritis activity was assessed with disease activity score test (DAS28). Thirty patients with RA with moderate to high disease activity (DAS28 ≥ 3.2) and chronic periodontitis (MHDA group) and thirty patients with RA with low disease activity (DAS28 < 3.2) and chronic periodontitis (LDA group) were enrolled in the study. The patients were monitored at the beginning and 3 months after undergoing periodontal therapy. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α) levels in serum, DAS28 and periodontal parameters were evaluated. RESULTS: Erythrocyte sedimentation rate, CRP, TNF-α levels in serum, DAS28 and periodontal parameters exhibited similar and significant reduction 3 months after the non-surgical periodontal treatment. CONCLUSION: Non-surgical periodontal treatment may prove beneficial in reducing RA severity as measured by ESR, CRP, TNF-α levels in serum and DAS28 in low or moderate to highly active RA patients with chronic periodontitis.

Are clinical features in Löfgren's syndrome-related erythema nodosum different from idiopathic erythema nodosum?

BACKGROUND AND OBJECTIVES: We retrospectively evaluated acute sarcoidosis (Löfgren's syndrome) patients diagnosed at 2 centers and compared the clinical features of Löfgren's syndrome (LS) related erythema nodosum (EN) to patients with idiopathic IEN who were diagnosed within the same time frame. METHODS: Thirty patients (10 males, 20 females) who were diagnosed with LS and were being followed up for the last 8 years at 2 centers were included. Thirty patients (4 males, 26 females) who were admitted to the rheumatology outpatient clinics for IEN during that time period were taken as controls. The clinical and laboratory features at the initial admission, treatment modalities and response were recorded. RESULTS: Twentyfour (80%) patients with LS related EN had arthritis and/or arthralgia. Fifteen of them had only findings of periarticular ankle inflammation and 4 had polyarthritis. When LS related EN patients were compared to IEN patients, the former group had more arthritis and/or arthralgia (p < 0.001), leucocytosis (p = 0.02), lymphopenia (p = 0.005) and thrombocytosis (p = 0.05), and higher ESR (p = 0.02). Twentyfive (83.3%) patients with LS related EN were administered oral corticosteroids. In 21 patients, hilar lymphadenopathy disappeared on control chest x-ray and CT; in 3 patients, minimal residual lymph node enlargement was persistent. During a median follow-up of 54 months (range: 10-84 months), none of the LS related EN patients had clinical relapse. CONCLUSIONS: Apart from BHL, arthritis and/or arthralgia especially periarticular ankle inflammation is the feature which could be used to differentiate LS related EN from IEN. There is more need for steroids in LS patients and the symptoms quickly resolve with steroids.

Serum cytokine levels and periodontal parameters in ankylosing spondylitis.

BACKGROUND AND OBJECTIVE: Multiple studies support the role of periodontal disease in contributing to the chronic systemic inflammatory burden in a variety of diseases, including ankylosing spondylitis (AS), in the progression which the inflammatory process plays an important role. We assume that patients with AS are more likely to have periodontal disease than healthy individuals. The aim of this study was to determine the possible relationship between inflammatory periodontal diseases and AS by evaluating clinical periodontal parameters and serum cytokine levels. MATERIAL AND METHODS: Forty-eight adults with AS (35 women and 13 men; age range 18-56 years; mean age 34.27 years) and 48 age- and sex-matched systemically healthy control subjects participated in the study. The clinical periodontal parameters, venous blood and Bath Ankylosing Spondylitis Disease Activity Score were obtained, and serum C-reactive protein, tumour necrosis factor-α and interleukin-6 (IL-6) levels were evaluated. RESULTS: There was statistically no significant difference in the frequency of periodontitis between AS patients and the control group. Furthermore, there was no significant difference in probing depth, clinical attachment level and plaque index, and the only significant clinical difference between groups was in levels of bleeding on probing (p < 0.001). Serum concentrations of IL-6, tumour necrosis factor-α and C-reactive protein in the AS group were significantly higher than those in the control group (p < 0.001). In the AS group, there was a correlation between serum IL-6 levels and clinical attachment level (p < 0.001). CONCLUSION: The results of present study suggest that bleeding on probing was the only different periodontal parameter between the AS and the control group, and the periodontal status of patients with AS may be affected by IL-6 levels.

Coronary disease risk prediction algorithm warranting incorporation of C-reactive protein in Turkish adults, manifesting sex difference.

BACKGROUND AND AIM: An algorithm is needed for predicting coronary heart disease (CHD) risk in Turkish adults who have a high prevalence of metabolic syndrome (MetS). METHODS AND RESULTS: Ten-year risk of CHD was estimated in 2232 middle-aged adults free of CHD at baseline, followed over 7.6-years. Cox proportional hazard regression was used to predict CHD. Discrimination was assessed with area under receiver operating characteristics curve (AROC). CHD developed in 302 subjects. In multivariable analysis, high-density lipoprotein (HDL)-cholesterol levels were borderline predictive in men; smoking status and HDL-and low-density lipoprotein (LDL)-cholesterol levels were not predictive in women. Age, presence of diabetes, systolic blood pressure and C-reactive protein (CRP) were predictors in both sexes, while smoking status and LDL-cholesterol were so in men only. AROC of the model was 0.789 in men, and 0.806 in women (p < 0.001 each). An algorithm using the stated seven variables was derived separately for each sex. After age adjustment, men and women in the highest quintile of risk score were significantly and 20-27-fold more likely to develop CHD than those in the lowest quintile. CONCLUSIONS: In a population with prevalent MetS, low-grade inflammation is independently relevant for CHD, as are serum lipoproteins and smoking status. The derived algorithm is effective in estimating CHD risk among Turkish adults.

An algorithm to predict risk of type 2 diabetes in Turkish adults: contribution of C-reactive protein.

BACKGROUND AND AIM: An algorithm for predicting Type 2 diabetes (DM) risk in a population with prevalent metabolic syndrome (MetS) is needed since ethnicity influences the pathogenesis of DM. MATERIAL AND METHODS: The 8- yr risk of DM was estimated in 2261 middle-aged Turkish adults free of DM at baseline who were followed for over 7.6 yr. DM newly developed in 212 subjects. Cox proportional hazard regression and 15 variables were used to predict DM. Discrimination was assessed with area under receiver operating characteristics curve (AROC). RESULTS: In multivariable analysis, height, family income brackets, systolic blood pressure, smoking status, alcohol usage, and HDL-cholesterol levels were not predictive in either sex. In addition to sex, family history of DM, fasting glucose, and waist circumference were predictors, in men, age and non-HDL-cholesterol, while in women physical inactivity and serum C-reactive protein were so. AROC of the final model was 0.783 in men, 0.772 in women (p<0.001 each). An algorithm using the stated 7 variables was developed separately for each sex. Men and women in the top quintile of risk score were, respectively, 20 and 50 times and significantly more likely to develop DM than those in the bottom quintile. The predictive value of the algorithm was validated in 2 split samples. CONCLUSIONS: A marker of low grade inflammation provides useful predictive ability beyond other simple predictors in a female population with MetS prevailing. The derived simple algorithm may be useful in estimating the 8-yr risk of DM among middle-aged Turkish men and women.

Health-related quality of life and its associations with mood condition in familial Mediterranean fever patients.

The aim of the present study was to investigate the health-related quality of life (HRQOL) and mood conditions in familial Mediterranean fever (FMF) patients. Ninety FMF patients (F/M 60/30, median age 29) and 67 control subjects (F/M 46/21, median age 30) were included in this study. HRQOL was assessed with short form-36 (SF-36) and mood conditions were assessed with hospital anxiety depression scale (HADS). FMF patients had significantly lower mean scores on SF-36 physical components compared to the control group. However, mental components were comparable between groups. FMF patients were significantly more likely to have depression and anxiety compared to the control group [30 (33%) vs. 8 (12%), respectively, χ (2) = 9.58, OR (95% CI) = 3.7 (1.5-8.7), p < 0.01 for depression and 48 (53%) and 11 (16%), respectively, χ (2) = 22.31, OR (95% CI) = 5.8 (2.7-12.5), p < 0.001 for anxiety]. When frequency of anxious subjects was adjusted for the presence of concomitant depressive status as a confounding factor, the difference between the groups remained statistically significant [χ (2) = 11.86, OR (95% CI) = 5.4 (2.1-13.7), p < 0.01]. However, the difference of depression status between groups was not statistically significant when adjusted for the presence of concomitant anxiety status [χ (2) = 0.08, OR (95% CI) = 1.3 (0.5-3.8), p = 0.78] and FMF was found to be independently associated with only anxiety [OR (95% CI) = 7.1 (2.3-20.3)]. In addition, pure anxious FMF subgroup had significantly lower scores of mental health and mental component summary when compared to normal mood subgroup. In conclusion, FMF might adversely affect HRQOL. Depression and anxiety are more frequent in FMF patients than healthy subjects.

Serum apolipoprotein C-III in high-density lipoprotein: a key diabetogenic risk factor in Turks.

AIMS: We studied determinants of serum apolipoprotein C-III (apoC-III) and whether levels of apoC-III or its fractions predict metabolic syndrome (MetS), Type 2 diabetes and coronary heart disease (CHD). METHODS: The predictive value of apoC-III, measured by immunoturbimetric immunoassay in 802 tracked individuals of a Turkish general population in determining cardiometabolic risk was assessed over 4.4 +/- 1.2 years' follow-up. Patients with MetS, Type 2 diabetes and CHD at baseline were excluded. RESULTS: Total apoC-III, as well as both fractions, was significantly, linearly and inversely related to smoking status, positively to alcohol usage and to levels of complement C3. Mid and high tertiles of total or non-high density lipoprotein (HDL) apoC-III predicted significantly and independently incident MetS; they predicted CHD with risk ratios of 1.6 [95% confidence intervals (CI) 1.02-2.5], for 1 sd increment, after adjustments that included HDL cholesterol and body mass index (BMI). The highest tertile of HDL apoC-III was a major independent predictor of new-onset diabetes with a 2.5-fold risk ratio for 1 sd increment (95% CI 1.5-4.0) in combined sexes, after adjustment for waist circumference, HDL cholesterol and other confounders and was a better predictor than waist girth. CONCLUSIONS: Serum total apoC-III or its fractions are linearly and inversely associated with smoking, positively with alcohol usage and serum complement C3. The presumably dysfunctional HDL apoC-III is a stronger predictor of Type 2 diabetes than waist girth in Turks. Non-HDL apoC-III predicts strongly the development of MetS as well as incident CHD, independent of HDL cholesterol, BMI and non-lipid factors. The atherogenicity of apoC-III and dysfunctionality of HDL apoC-III carry huge public health implications in Turks.

Takayasu's arteritis in Turkey - clinical and angiographic features of 248 patients.

OBJECTIVE: Takayasu's arteritis (TA) is a chronic, inflammatory vasculitis affecting the aorta and its major branches. Although it is more prevalent in Far-East Asia, the distribution of the disease is worldwide with different vascular involvement patterns and clinical manifestations. The objective of this study was to evaluate the demographic, clinical, angiographic and prognostic features of TA patients in Turkey. METHODS: Clinical and angiographic findings of 248 TA patients (228 female, 27 male) followed at 15 Rheumatology Centers were prospectively evaluated according to a predefined protocol. RESULTS: The mean age was 40.1 years (30.2 years at the clinical onset). Clinical manifestations included constitutional symptoms in 66%, absent or diminished pulses in 88%, bruits in 77%, extremity pain in 69%, claudication in 48%, hypertension in 43% and cerebrovascular accidents (CVA) in 18% of the patients. Renal artery stenosis, aortic regurgitation and pulmonary hypertension were present in 26%, 33% and 12%, respectively. According to the new angiographic classification, type V (50.8%) and Type I (32%) were the most frequent types of involvement. Corticosteroids were the main treatment in 93% of the patients alone (9%) or in combination with immunosuppressive agents (84%). Most frequently preferred immunosuppressive agents were methotrexate (63%), azathioprine (22%) and cyclophosphamide (13%). Remission was observed at least once in 94% of the patients and sustained remission in 71% during follow-up. CONCLUSION: The demographical, clinical and angiographic findings of TA patients in our series were similar to those reported from Japan, Brazil and Colombia. Combination therapies with immunosuppressive agents were the preferred choice of treatment in Turkey.

PTPN22 gene polymorphism in Takayasu's arteritis.

OBJECTIVE: Takayasu's arteritis (TA) is a chronic, rare granulomatous panarteritis of unknown aetiology involving mainly the aorta and its major branches. In this study, genetic susceptibility to TA has been investigated by screening the functional single nucleotide polymorphism (SNP) of PTPN22 gene encoding the lymphoid-specific protein tyrosine phosphatase. METHODS: Totally, 181 patients with TA and 177 healthy controls are genotyped by PCR-RFLP method for the SNP rs2476601 (A/G) of PTPN22 gene. Polymorphic region was amplified by PCR and digested with Xcm I enzyme. RESULTS: Detected frequencies of heterozygous genotype (AG) were 5.1% (9/177) in control group and 3.8% (7/181) in TA group (P = 0.61, odds ratio: 0.75, 95% CI: 0.3, 2.0). No association with angiographic type, vascular involvement or prognosis of TA was observed either. CONCLUSION: The distribution of PTPN22 polymorphism did not reveal any association with TA in Turkey.

Autoimmune polyendocrine syndrome with atrial septal defect.

Atrial septal defect is frequently reported with genetic syndromes. But, to the best of our knowledge, it has not been reported with autoimmune polyendocrine syndrome. Here, the case of a 44-year-old-woman with concomitant involvement of the salivary gland, thyroid, intestines, and, possibly endocrine pancreas, diagnosed with autoimmune polyendocrine syndrome type II, is reported with accompanying atrial septal defect. Celiac disease, Hashimoto thyroiditis, and Sjögren syndrome were symptomatic and laboratory confirmed diagnosis; anti-glutamic acid decarboxylase antibody was positive but asymptomatic for type-1 diabetes. She was known to have sinus venosus type atrial septal defect diagnosed at 38 years old, when she had tiredness and chest pain.

Vascular endothelial growth factor and carotid intima-media thickness in patients with Behçet's disease.

There is morphologic evidence of subclinical atherosclerosis in Behçet's disease (BD) patients obtained by high-resolution B-mode ultrasonography (US). Vascular endothelial growth factor (VEGF) is a potent angiogenetic factor and a marker for endothelial dysfunction. VEGF could contribute to the pathological events in BD. VEGF could also be an important factor in the progression of atherosclerosis. In this study, we investigated whether there is correlation between intima-media thickness (IMT) of the carotid arteries and serum VEGF levels in BD patients and healthy controls. Twenty-one patients with BD (male/female: 15/6, mean age: 35.8 +/- 8.6 years) were individually matched to control subjects on the basis of age (within 3 years) and sex. Carotid IMT of the subjects was measured by high-resolution B-mode US. Mean IMT values of common carotid arteries were 0.86 +/- 0.18 mm for patients with BD, and 0.57 +/- 0.14 mm for healthy controls (p < 0.001). Mean VEGF levels were 130.41 +/- 58.28 pg/ml for patients with BD and 82.69 +/- 25.03 pg/ml for healthy controls (p < 0.001). There was no correlation between VEGF levels in the control group and in the BD group, but there was a significant correlation between VEGF levels and mean carotid IMT in the whole group (r = 0.317, p < 0.05). In conclusion, elevation of VEGF appears as a feature of the inflammatory reaction during the course of BD, not a direct determinant of subclinical atherosclerosis. On the other hand, the significant correlation between carotid IMT and serum VEGF levels in the whole group suggests that association between VEGF levels and carotid IMT warrants further investigation with larger sample sizes.

Plasma and platelet serotonin levels in familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever (FMF) is the most common auto-inflammatory syndrome with exaggerated acute phase and inflammatory response. After revealing the MEFV gene mutation with the finally disturbed end product pyrin, some of the mechanisms were explained. However it is still unknown what triggers or ends these periodical attacks. Moreover, the treatment of up to 30% of the patients, that are resistant to colchicine is still a problem. In this study we investigated the role of serotonin in colchicine-resistant FMF patients. METHODS: Twenty-four FMF patients (male/female: 15/9) and 32 age- and sex-matched healthy controls (male/female: 17/15) were included into the study. Patients were subdivided into two groups. Thirteen had FMF attacks despite regular colchicine (colchicine-resistant group), other 11 had disease under control with colchicine for at least 6-months. Sampling was done both during the attack and ten days after its cessation. Plasma and platelet serotonin levels and acute phase reactants were studied in patients and controls. RESULTS: Colchicine-resistant patients had plasma serotonin (5-HT) levels of 7.85 +/- 1.0 nmol/l during acute attacks which significantly reduced to the levels of 6.3 +/- 0.6 nmol/l (p < 0.001), after 10 days of acute attacks and these levels were significantly lower than those of attack-free patients' and controls' (10.7 +/- 0.2 nmol/l and 10.1 +/- 0.3 nmol/l, respectively). Platelet 5-HT level was 6.4 +/- 0.3 nmol/10(9) platelets during acute attack, and this level was increased to 9.8 +/- 0.5 nmol/10(9) platelets on the 2(nd) sampling, 10 days after the cessation of the acute attack (p < 0.001). They were both significantly higher than those of attack-free FMF patients (5.9 +/- 0.1 nmol/10(9) platelets) and healthy controls (5.7 +/- 0.3 nmol/10(9) platelets). There was a negative correlation between plasma and platelet 5-HT levels (r=-0.77, p < 0.001). CONCLUSION: Changes in plasma and platelet 5-HT levels may be related to the disturbances in 5-HT transport mechanisms or may also be attributed to the potential role of serotonin in the inflammatory cascade. Last but not least, serotonin may have a role in the pathogenesis of FMF.

Extra-articular manifestations of rheumatoid arthritis: results of a university hospital of 526 patients in Turkey.

OBJECTIVE: Presence of extra-articular manifestations (EAM) in rheumatoid arthritis (RA) is associated with more severe disease and increased mortality. Prevalence of EAM may vary in different geographic areas and in different ethnic populations. In this study we investigated the frequency of EAM in 526 RA patients from a single university hospital in Turkey. METHODS: The hospital records of patients who had been diagnosed as RA in Hacettepe University Department of Rheumatology between the years 1988 and 2003 were retrospectively evaluated. There were 73 males and 453 females, and mean age of the patients was 48.0 +/- 12.3 years. The mean follow-up period was 4.8 +/- 4.1 years. Three hundred and fifty-nine patients were rheumatoid factor (RF) positive (68.3%). RESULTS: The overall frequency of EAM was 38.4% (202 patients). The most common EAM was rheumatoid nodules (18.1%). Sicca symptoms, pulmonary findings, Raynaud's phenomenon, livedo reticularis, carpal tunnel syndrome, vasculitis, amyloidosis, and Felty syndrome were present in 11.4%, 4.8%, 3%, 4.8%, 2.8%, 1.3%, 1.1%, and 0.3% of the patients, respectively. Overall EAM and rheumatoid nodules were significantly more common in RF positive patients than RF negative patients. The frequency of rheumatoid nodules was significantly higher in males than in females. CONCLUSION: The prevalence of EAM in Turkey is higher than East Asia and Africa, and lower than UK and North America. Excluding secondary Sjögren's syndrome, our results are similar to other Mediterranean populations like Italy.

Circulating thrombomodulin levels in familial Mediterranean fever.

Increments in circulating thrombomodulin levels reflect endothelial cell injury. Thrombomodulin can also be synthesized by several inflammatory cells including monocytes, neutrophils, and thrombomodulin itself can modulate the inflammatory response. In this study, we assessed circulating thrombomodulin concentrations in patients with familial Mediterranean fever (FMF). Twenty-five patients with FMF (F/M: 14/11) (mean age: 31.1 +/- 9.7 years) and 25 healthy controls (F/M: 13/12) (mean age: 34.6 +/- 7.0 years) were involved in the study. Thrombomodulin levels were measured by commercially available enzyme-linked immunosorbant assay (ELISA) (Immunoassay of thrombomodulin Diagnostica Stago, Asnieres-Sur-Seine, France). Twenty of the patients were in attack-free period and the remaining five had been during acute FMF attacks. Thrombomodulin levels were higher in the study group (20.9 +/- 12.1 ng/ml) than healthy controls (14.1 +/- 8.4 ng/ml) (p < 0.05). Circulating thrombomodulin levels were also higher in attack-free FMF patients (22.4 +/- 12.9 ng/ml) than controls. This study disclosed for the first time significantly higher increments in the circulating levels of thrombomodulin in FMF. This observation could be a consequence of injured endothelium and/or activated inflammatory cells.

Evaluation of choroidal thickness in patients with scleroderma.

PURPOSE: To investigate the choroidal thickness in patients with scleroderma and to compare them with healthy control subjects. METHODS: Forty-six patients with scleroderma (3 male and 43 female) and 31 healthy controls (6 male and 25 female) were included in the study. Twenty-five patients had limited-type and 21 patients had diffuse-type scleroderma. Only left eyes of the patients and control subjects were used in the analysis. Demographic features of all the patients and control subjects were recorded. Each subject underwent ophthalmological examinations including refraction, visual acuity, intraocular pressure, axial length (AXL) measurement, slit-lamp biomicroscopy, and fundus examination. Body mass index (BMI) was estimated for all participants. RESULTS: There were no significant differences between the patients with scleroderma and the control subjects in terms of age, gender, BMI, mean AXL, and mean spherical equivalent refractive error (SE) (P=0.1, P=0.086, P=0.37, P=0.55, and P=0.072 respectively). The patients with scleroderma had significantly thinner nasal, temporal, and subfoveal choroid than the healthy control subjects (P1=0.012, P2=0.046, and P3<0.001, respectively). There were no significant differences between the patients with limited-type and diffuse-type scleroderma in terms of age, gender, BMI, mean AXL, mean SE, nasal, temporal, and subfoveal choroidal thicknesses (all P>0.05). CONCLUSIONS: Choroidal thickness in patients with scleroderma was significantly less than healthy control subjects. Vasculopathy in scleroderma is characterized by obliteration of arterioles and reduced capillary density may cause atrophy of choroid in patients with scleroderma.