Neuropsychiatric lupus in late- and early-onset systemic lupus erythematosus patients: a systematic review and meta-analysis.

OBJECTIVES: Late-onset SLE is usually milder and associated with lower frequency of LN and neuropsychiatric manifestations. The diagnosis of NPSLE is especially challenging in older patients because of increased incidence of neurological comorbidities. We performed a systematic review and meta-analysis to evaluate the differences in NPSLE manifestations in early-onset (<50-year-old) vs late-onset (≥50-year-old) SLE patients. METHODS: A literature search was performed using the PubMed, Web of Science and Cochrane Library databases. Studies available in English (1959-2022) including a late-onset SLE comparison group and evaluating the frequency of NPSLE were eligible. A forest plot was used to compare odds ratios (95% CI) of incidence and manifestations of NPSLE by age groups. Study heterogeneity was assessed using I2 statistics. RESULTS: A total of 44 studies, including 17 865 early-onset and 2970 late-onset SLE patients, fulfilled our eligibility criteria. CNS involvement was reported in 3326 patients. Cumulative NPSLE frequency was higher in the early-onset group than in the late-onset group (OR: 1.41, 95% CI: 1.24, 1.59, P < 0.0001). In early-onset SLE patients, seizures (OR: 1.68, 95% CI: 1.27, 2.22) and psychosis (OR: 1.72, 95% CI: 1.23, 2.41) were more common than in late-onset SLE patients (P values, 0.0003 and 0.0014, respectively). Peripheral neuropathy was more commonly reported in the late-onset SLE group than in the early-onset SLE group (OR: 0.64, 95% CI: 0.47, 0.86, P = 0.004). CONCLUSION: Our meta-analysis revealed that the frequencies of overall NPSLE, seizures, and psychosis were less common in late-onset SLE patients than in early-onset SLE patients. In contrast, peripheral neuropathy was more common in the late-onset SLE group.

Thrombocytopenia in Patients with Systemic Lupus Erythematosus.

Thrombocytopenia can be one of the first manifestations of systemic lupus erythematosus and occurs in up to 40% of patients. Additionally, approximately 2% of patients with primary immune thrombocytopenia may develop systemic lupus erythematosus. Systemic lupus erythematosus is a highly heterogeneous disease, and in some patients, it may present mainly with hematological findings. Thrombocytopenia associated with systemic lupus erythematosus is also diverse, ranging from asymptomatic to severe, acute, or chronic cases. Several studies suggest that the coexistence of immune thrombocytopenia and systemic lupus erythematosus may be linked to a shared genetic background among various autoimmune diseases. Studies have reported correlations between thrombocytopenia and increased disease activity as well as kidney and central nervous system involvement in systemic lupus erythematosus. Severe thrombocytopenia is considered a poor prognostic factor in systemic lupus erythematosus. Despite this knowledge, the exact cause of reduced platelet count in systemic lupus erythematosus remains relatively unknown. Mainly, an excess of platelet destruction and/or reduced production from megakaryocytes are considered the primary factors contributing to systemic lupus erythematosus-associated thrombocytopenia. Given the prognostic significance of thrombocytopenia, there is a possibility of a pathogenic mechanistic role of thrombocytopenia and platelets in systemic lupus erythematosus. In systemic lupus erythematosus, platelets are activated and play a role in promoting autoimmune and inflammatory responses by interacting with both the innate and adaptive immunity. There is no randomized clinical trial in the treatment of systemic lupus erythematosus-related thrombocytopenia. Treatment approach of thrombocytopenia in lupus is almost similar to the treatment of immune thrombocytopenia. Considering the role of platelets in both inflammation and tissue injury, platelet activation and platelet-immune cell interaction might be important therapeutic strategies in the treatment of systemic lupus erythematosus.

Development of systemic lupus erythematosus in patients with immune thrombocytopenic purpura: A systematic meta-analysis.

BACKGROUND: Recent population-based cohort studies suggest that the incidence of systemic lupus erythematosus (SLE) is increased in patients with immune thrombocytopenic purpura (ITP). We performed a systematic review and meta-analysis to evaluate the development of SLE in patients with ITP. METHODS: Literature search was performed in PubMed, Web of Science and Cochrane Library for studies published prior to October 2022. Studies were included that reported development of SLE in ITP patients. Forest plot was used to detect overall SLE frequency in ITP and compare risk ratios for SLE development in different ITP subgroups. Study heterogeneity was assessed by using I2 statistics. RESULTS: 26 eligible studies comprising 14867 ITP patients were included in analysis. 311 ITP patients developed SLE during the follow-up period (range: 1.1-14 years) (2.09%, 95%CI: 1.87-2.33). Relative risk (RR) for developing SLE was significantly higher in female ITP patients (RR: 4.23, 95%CI: 2.52-7.12, p < 0.0001). Anti-nuclear antibody (ANA) was reported in 23 studies, there were 766/4377 ANA positive patients with ITP (17.5%). The risk of SLE development in ANA positive ITP patients was significant (RR: 26.29, 95%CI: 14.45-47.81, p < 0.0001). CONCLUSIONS: Our study suggests ITP patients are at high risk of developing SLE in future. Pooled data revealed that females and patients with a positive ANA titer are at a significantly high risk of developing SLE.

Small fiber neuropathy and related factors in patients with systemic lupus erythematosus; the results of cutaneous silent period and skin biopsy.

INTRODUCTION: Evaluating small nerve fibers in patients with systemic lupus erythematosus (SLE) using cutaneous silent period (CSP) and skin biopsy and assesssing the relationship between clinical signs, autoantibodies and neuropathic pain score. OBJECTIVE - METHODS: Fifty one SLE patients and 46 healthy volunteers were included in this study. Nerve conduction studies and CSP were performed both on upper and lower limbs in subjects. Skin biopsy was performed and the number of epidermal nerve density and IL-6 staining were evaluated. RESULTS: In SLE patients, CSP latencies were significantly prolonged both in lower and upper limbs and lower and upper extremity CSP durations were significantly shorter when compared to controls (p < 0.001). The number of epidermal nerve was significantly lower in SLE patients when compared to healthy controls (p < 0.001). CONCLUSION: We detected marked small nerve fiber damage in both lower and upper limbs in SLE patients using CSP. Decreased epidermal nerve density also supports this finding.

Small fiber neuropathy and related factors in patients with systemic lupus erythematosus; the results of cutaneous silent period and skin biopsy

Abstract Introduction Evaluating small nerve fibers in patients with systemic lupus erythematosus (SLE) using cutaneous silent period (CSP) and skin biopsy and assesssing the relationship between clinical signs, autoantibodies and neuropathic pain score. Objective - methods Fifty one SLE patients and 46 healthy volunteers were included in this study. Nerve conduction studies and CSP were performed both on upper and lower limbs in subjects. Skin biopsy was performed and the number of epidermal nerve density and IL-6 staining were evaluated. Results In SLE patients, CSP latencies were significantly prolonged both in lower and upper limbs and lower and upper extremity CSP durations were significantly shorter when compared to controls ( p < 0.001). The number of epidermal nerve was significantly lower in SLE patients when compared to healthy controls ( p < 0.001). Conclusion We detected marked small nerve fiber damage in both lower and upper limbs in SLE patients using CSP. Decreased epidermal nerve density also supports this finding.(AU)

Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin. MEFV, an FMF-associated gene, is also a candidate gene for AS. We aimed to identify AS susceptibility loci and also examine the association between MEFV and AS in Turkish and Iranian cohorts. We performed genome-wide association studies in 1001 Turkish AS patients and 1011 Turkish controls, and 479 Iranian AS patients and 830 Iranian controls. Serum IL-1ß, IL-17 and IL-23 cytokine levels were quantified in Turkish samples. An association of major effect was observed with a novel rare coding variant in MEFV in the Turkish cohort (rs61752717, M694V, OR = 5.3, P = 7.63×10(-12)), Iranian cohort (OR = 2.9, P = 0.042), and combined dataset (OR = 5.1, P = 1.65×10(-13)). 99.6% of Turkish AS cases, and 96% of those carrying MEFV rs61752717 variants, did not have FMF. In Turkish subjects, the association of rs61752717 was particularly strong in HLA-B27-negative cases (OR = 7.8, P = 8.93×10(-15)), but also positive in HLA-B27-positive cases (OR = 4.3, P = 7.69×10(-8)). Serum IL-1ß, IL-17 and IL-23 levels were higher in AS cases than controls. Among AS cases, serum IL-1ß and IL-23 levels were increased in MEFV 694V carriers compared with non-carriers. Our data suggest that FMF and AS have overlapping aetiopathogenic mechanisms. Functionally important MEFV mutations, such as M694V, lead to dysregulated inflammasome function and excessive IL-1ß function. As IL-1 inhibition is effective in FMF, AS cases carrying FMF-associated MEFV variants may benefit from such therapy.

CXCL12 rs18011157 polymorphism in patients with non-Hodgkin's lymphoma: Is it associated with poor outcome?

OBJECTIVE: We studied CXCL12-related rs18011157 polymorphism in non-Hodgkin lymphoma (NHL) patients. We also determined the effect of this polymorphism on clinical features and outcome of NHL. METHODS: We included 90 NHL patients (54 males, 36 females) and 88 healthy controls (54 males, 34 females). CXCL12-related rs18011157 polymorphism was determined by polymerase chain reaction. RESULTS: rs18011157 polymorphism was significantly more frequent in NHL patients with GA genotype than in healthy controls (37.8% vs. 20.5%, P = 0.011). The frequency of patients with initially high lactate dehydrogenase (LDH) level (65.8% vs. 38.5%) and extranodal involvement (61.1% vs. 43.8%) was significantly higher in the GA plus AA genotype groups when considered altogether (P = 0.01 and 0.09). Poor prognostic factors in univariate analysis were the presence of B symptoms, initially high International Prognostic Index (IPI), splenomegaly, nonresponse to first-line therapy, the presence of early relapse, and carrying A allele (GA plus AA genotypes). The independent prognostic factors in multivariate analysis were only early relapse and an initially high IPI score. DISCUSSION: CXCL12 rs1801157 polymorphism which was found to be associated with extranodal involvement and increased LDH in NHL might be a marker of poor prognosis in patients with GA and AA genotypes. CONCLUSIONS: CXCL12-related rs18011517 polymorphism was more frequent in NHL patients: it might be associated with NHL pathogenesis and outcome.

Nationwide Experience With Off-Label Use of Interleukin-1 Targeting Treatment in Familial Mediterranean Fever Patients.

OBJECTIVE: Approximately 30-45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine-unresponsive or colchicine-intolerant FMF patients are limited; the most promising alternatives seem to be anti-interleukin-1 (anti-IL-1) agents. Here we report our experience with the off-label use of anti-IL-1 agents in a large group of FMF patients. METHODS: In all, 21 centers from different geographical regions of Turkey were included in the current study. The medical records of all FMF patients who had used anti-IL-1 treatment for at least 6 months were reviewed. RESULTS: In total, 172 FMF patients (83 [48%] female, mean age 36.2 years [range 18-68]) were included in the analysis; mean age at symptom onset was 12.6 years (range 1-48), and the mean colchicine dose was 1.7 mg/day (range 0.5-4.0). Of these patients, 151 were treated with anakinra and 21 with canakinumab. Anti-IL-1 treatment was used because of colchicine-resistant disease in 84% and amyloidosis in 12% of subjects. During the mean 19.6 months of treatment (range 6-98), the yearly attack frequency was significantly reduced (from 16.8 to 2.4; P < 0.001), and 42.1% of colchicine-resistant FMF patients were attack free. Serum levels of C-reactive protein, erythrocyte sedimentation rate, and 24-hour urinary protein excretion (5,458.7 mg/24 hours before and 3,557.3 mg/24 hours after) were significantly reduced. CONCLUSION: Anti-IL-1 treatment is an effective alternative for controlling attacks and decreasing proteinuria in colchicine-resistant FMF patients.

The epidemiology of dermatomyositis in northwestern Thrace region in Turkey: epidemiology of dermatomyositis in Turkey.

Dermatomyositis (DM) is a rare disease that may affect the skeletal muscles and the skin. Literature data on its incidence and prevalence are limited. There are no data on its incidence or prevalence in Turkey. Patients diagnosed with DM at the Trakya University Medical Faculty, Department of Rheumatology from November 2004 to November 2014 were reviewed retrospectively. Patients' clinical and demographic features, laboratory data, treatment modalities, follow-up durations, disease courses, outcomes, and complications were evaluated. Our study included 23 patients with DM; 14 were females and 9 were males (female/male: 1.55). Over the course of the study, the annual incidence of DM was 3.7 per million (95% CI 0-18.8) person years, and the overall prevalence was 32.2 per million (95% CI 18.1-46.3). Incidence in women was higher (4.6/1,000,000 person years) compared to men (2.9/1,000,000 person years). The frequencies of most common findings were as follows: heliotrope rash (82.6%), Gottron papules (87%), proximal myopathy (78.3%), and facial erythema (60.9%). In our hospital-based study, the frequency of DM was lower than those reported in North America; however, they were similar to European countries.

Development of Atherosclerotic Cardiovascular Mortality in Gouty Arthritis and Rheumatoid Arthritis Patients: Are They Associated With Mean Platelet Volume and Neutrophil-Lymphocyte Ratio? A Comparative Study.

OBJECTIVES: This study aims to evaluate the mean platelet volume (MPV) and neutrophil-lymphocyte ratio (NLR) in gouty arthritis (GA) and rheumatoid arthritis (RA) patients, as well as their relationship with atherosclerotic cardiovascular mortality (ACVM). PATIENTS AND METHODS: The study included 122 GA patients (96 males, 26 females; mean age 64.6±13.4 years; range 34 to 82 years), 82 RA patients (40 males, 42 females; mean age 62.1±12.1 years; range 29 to 83 years), and 61 healthy controls (34 males, 27 females; mean age 65.3±4.8 years; range 33 to 80 years). Clinical and ACVM data were obtained from medical charts. Erythrocyte sedimentation rate, C-reactive protein, MPV, and NLR were recorded at the time of diagnosis and one month after therapy. RESULTS: Mean platelet volume in GA (8.49±1.5) and RA (7.98±0.99) groups were significantly lower than in healthy controls (9.8±15) (p<0.001). NLR in healthy controls (1.9±0.74) was significantly lower than in GA (3.6±2.3) and RA (3.7±2.5) groups (p<0.001). After treatment, MPV did not change significantly in GA and RA groups (p values >0.05); however, NLR decreased in both groups (p<0.001). Nine GA and 12 RA patients died from ACVM during follow-up. GA patients with ACVM were older and had more frequent hypertension, higher MPV, and higher intercritical CRP level. In multivariate analysis, MPV was an independent poor prognostic factor for ACVM in GA patients. CONCLUSION: Gouty arthritis and RA patients had significantly lower MPV and significantly higher NLR than controls. MPV might be used as a potential biomarker for the development of ACVM in GA.

BLK pathway-associated rs13277113 GA genotype is more frequent in SLE patients and associated with low gene expression and increased flares.

We aimed to evaluate the relationship between some important genetic variations and expressions of these genes in our SLE population. We also determined their association with clinical parameters. Eighty-four SLE patients (79 F, 5 M) and 105 healthy controls (98 F, 7 M) were included in the study. rs13277113, rs2736340, rs7829816, rs6983130, rs2613310, and rs704853 polymorphisms, gene expressions of Src family kinases (Blk, Hck, Lck, and Lyn), and Syk kinases (Syk, ZAP70) were studied by real-time PCR. The heterozygous genotypic pattern (GA) for rs13277113 polymorphism was more frequent in patients with SLE when compared to that in controls (48.8 vs. 31.4%, p = 0.035). Other genotype variants were similar in SLE patients and controls. In the SLE group, the heterozygous genotype for rs13277113 was significantly less frequent in active SLE patients (58.8 vs. 26.7%, p = 0.01). SLE flares according to the SELENA-SLEDAI flare index were significantly more frequent in GA (rs13277113) (70 vs. 37%) and CT (rs2736340) genotypes (66.7 vs. 35.2%) than those in other genotypes (p values <0.01). The relative expression of Blk gene was significantly decreased in the SLE group as compared to that in controls (0.52 times, 95%CI 0.19-0.85). The gene expressions of Blk and ZAP70 were significantly lower in SLE patients who had flares according to the SELENA-SLEDAI flare index when compared to those in others (p values 0.01 and 0.017). We observed more frequent heterozygous GA genotypic pattern (rs13277113) in our SLE patients compared to that in controls; and it was associated with disease flares. Blk gene expression in SLE was lower, especially in relapsing patients.

High apelin levels could be used as a diagnostic marker in multiple myeloma: A comparative study.

BACKGROUND: Apelin/APJ system regulates angiogenesis and is overexpressed in some malignancies. Apelin can induce lymphangiogenesis and lymph node metastasis. OBJECTIVE: We evaluated apelin levels in multiple myeloma (MM) and non-Hodgkin lymphoma (NHL); and analyzed the association between apelin levels and clinical findings. METHODS: We included consecutive 29 MM, 31 NHL patients, and 19 healthy controls. Patients' demographic and clinical features, treatment modalities, and responses were recorded from hospital records. Plasma apelin was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: MM patients had significantly higher plasma apelin level than NHL and healthy control groups (p< 0.001). Apelin level in NHL group was similar to controls (p> 0.05). ROC curve analysis showed that the area under the curve value for apelin level in MM was 0.842 ng/ml (95%CI: 0.739-0.945, p< 0.001). Plasma apelin level ≥ 0.827 ng/ml had 76% sensitivity and 86% specificity for the diagnosis of MM. Multivariate Cox regression analysis showed that MM patients with high apelin level had better prognosis and patients with advanced stage of disease (ISS-3) had significantly poor prognosis when compared to others. In the MM group, apelin level correlated negatively with LDH (r = -0.39, p= 0.038). CONCLUSIONS: In MM, plasma apelin level was significantly higher than in NHL and control groups. Apelin could be playing a role in MM pathogenesis; and apelin level could be used as a diagnostic and prognostic biomarker in MM.

A multicenter report of biologic agents for the treatment of secondary amyloidosis in Turkish rheumatoid arthritis and ankylosing spondylitis patients.

In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy-based on creatinine level, proteinuria and disease activity-was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.

The investigation of killer cell immunoglobulin-like receptor genotyping in patients with systemic lupus erytematosus and systemic sclerosis.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the production of autoantibodies and the involvement of multiple organ systems. Systemic sclerosis (SSc) is another autoimmune disease that causes fibrosis. We will aim to analyse the role of killer cell immunoglobulin-like receptor (KIR) genotypes and their existence with the respective HLA ligands in patients with SLE and SSc. Forty-five SLE, 25 SSc and 40 healthy controls were included. We examined the presence/absence of KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5A, 2DL5B, 2DS1, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1, 2DP1, 3DP1 and their known HLA ligands. In the SLE group, the KIR2DL5, KIR2DL5B and KIR2DS3 genes were significantly more frequent, and KIR2DL3 gene was significantly less than in controls (p values <0.05). In SSc patients, the KIR2DS3 gene was more frequent than in controls (p = 0.032). The KIR2DL3 gene was detected more frequently in controls while KIR2DS3 gene was more frequent in the patient group when SLE and SSc patients were combined (p values < 0.05). The KIR2DS2/HLA-C and KIR2DS2/HLA-C combinations were significantly more in both SLE and SSc groups than in controls. The KIR2DL2 and KIR2DL5B genes were protective from neurologic involvement in SLE patients (p values <0.05). The variations of some KIR genes such as KIR2DL5, KIR2DL5B, KIR2DS3 and KIR2DL3 may have a role in the pathogenesis of SLE and SSc. Also, the presence of KIR2DL2 and KIR2DL5B may cause major organ involvement, like neurologic involvement, in SLE.

Response rate of initial conventional treatments, disease course, and related factors of patients with adult-onset Still's disease: Data from a large multicenter cohort.

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare condition, and treatment choices are frequently dependent on expert opinions. The objectives of the present study were to assess treatment modalities, disease course, and the factors influencing the outcome of patients with AOSD. METHODS: A multicenter study was used to reach sufficient patient numbers. The diagnosis of AOSD was based on the Yamaguchi criteria. The data collected included patient age, gender, age at the time of diagnosis, delay time for the diagnosis, typical AOSD rash, arthralgia, arthritis, myalgia, sore throat, lymphadenopathy, hepatomegaly, splenomegaly, pleuritis, pericarditis, and other rare findings. The laboratory findings of the patients were also recorded. The drugs initiated after the establishment of a diagnosis and the induction of remission with the first treatment was recorded. Disease patterns and related factors were also investigated. A multivariate analysis was performed to assess the factors related to remission. RESULTS: The initial data of 356 patients (210 females; 59%) from 19 centers were evaluated. The median age at onset was 32 (16-88) years, and the median follow-up time was 22 months (0-180). Fever (95.8%), arthralgia (94.9%), typical AOSD rash (66.9%), arthritis (64.6%), sore throat (63.5%), and myalgia (52.8%) were the most frequent clinical features. It was found that 254 of the 306 patients (83.0%) displayed remission with the initial treatment, including corticosteroids plus methotrexate with or without other disease-modifying antirheumatic drugs. The multivariate analysis revealed that the male sex, delayed diagnosis of more than 6 months, failure to achieve remission with initial treatment, and arthritis involving wrist/elbow joints were related to the chronic disease course. CONCLUSION: Induction of remission with initial treatment was achieved in the majority of AOSD patients. Failure to achieve remission with initial treatment as well as a delayed diagnosis implicated a chronic disease course in AOSD.

The epidemiology of antineutrophil cytoplasmic antibody-associated vasculitis in northwestern Turkey.

Epidemiological data about antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is very limited. Until now, there has been no study about the epidemiology of AAV in Turkey. In this study, we evaluated the frequency of AAV in the northeastern part of Turkey. The general clinical features of patients diagnosed with AAV at our center within the last 10 years (2004-2014) were retrospectively recorded down. The incidence rates and the prevalence per 1,000,000 population aged ≥16 years were calculated. In addition, we evaluated the clinical features and survival rates of AAV patients. There were 30 patients with granulomatous polyangiitis (GPA), 15 with microscopic polyangiitis (MPA), and 5 with eosinophilic polyangiitis (EGPA). The overall prevalence of AAV in our region was 69.3/1,000,000 in individuals ≥16 years. Males had a similar prevalence (73.2/1,000,000) with females (65.4/1,000,000). The mean annual incidence rate was 8.1/million for all AAV. The annual incidence of AAV in females was 6.9/million; in males, it was 9.2/million. The annual incidence for GPA was calculated as 4.8/1,000,000, the incidence for MPA was 2.4/1,000,000, and the incidence for CSS was 0.8/1,000,000. Ten-year survival of patients with AAV was 65.3 %. The only independent poor prognostic factor in Cox's multivariate analysis was advanced age at the time of diagnosis (OR 7.5, 95 % CI 10.6-526, p = 0.043). The frequency of all AAV in northwestern Turkey was similar to that in southern Europe; however, it was lower than the frequency in Northern Europe.

The epidemiology of Takayasu arteritis: a hospital-based study from northwestern part of Turkey.

Takayasu arteritis (TA) is a chronic, inflammatory large vessel vasculitis that affects aorta and its main branches. We aimed to evaluate the incidence and prevalence of TA in the northwestern part of Turkey. We retrospectively evaluated 23 TA patients followed by our clinic. Clinical features, treatments and responses were recorded. Our hospital is the single tertiary referral center for rheumatic diseases for a mixed rural and urban population of 620,447 people for >16 years (306,036 males, 314,411 females). Nineteen of the 23 patients were females (82.6 %) and four were males (17.4 %). The annual incidence rate for TA was 0.34/100,000. The overall prevalence of TA in our region was 3.3/100,000 (95 % CI 1.9-4.8) in individuals >16 years. The most common findings at the time of presentation were blood pressure difference (73 %) and headache (60.4 %). The most common angiographic type was type 1 (12 patients, 52.2 %). Median follow-up period was 48 months (range 10-132). Three (13 %) of the patients had stent replacements to different vascular sites. One patient had an operation for aortic aneurysm, and aortic valve replacement surgery has been made. One patient had renal artery bypass operation. Eleven patients (47.8 %) had recurrency at follow-up period and two patients (8.7 %) died. In northwestern part of Turkey, the annual incidence and prevalence of TA were higher than western population, but similar to East Asian data.

Assessment of the New 2012 EULAR/ACR Clinical Classification Criteria for Polymyalgia Rheumatica: A Prospective Multicenter Study.

OBJECTIVE: To assess the performance of the new 2012 provisional European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) polymyalgia rheumatica (PMR) clinical classification criteria in discriminating PMR from other mimicking conditions compared with the previous 5 diagnostic criteria in a multicenter prospective study. METHODS: Patients older than 50 years, presenting with new-onset bilateral shoulder pain with elevated acute-phase reactants (APR), were assessed for the fulfillment of the new and old classification/diagnostic criteria sets for PMR. At the end of the 1-year followup, 133 patients were diagnosed with PMR (expert opinion) and 142 with non-PMR conditions [69 rheumatoid arthritis (RA)]. Discriminating capacity, sensitivity, and specificity of the criteria sets were estimated. RESULTS: Discriminating capacity of the new clinical criteria for PMR from non-PMR conditions and RA as estimated by area under the curve (AUC) were good with AUC of 0.736 and 0.781, respectively. The new criteria had a sensitivity of 89.5% and a specificity of 57.7% when tested against all non-PMR cases. When tested against all RA, seropositive RA, seronegative RA, and non-RA control patients, specificity changed to 66.7%, 100%, 20.7%, and 49.3%, respectively. Except for the Bird criteria, the 4 previous criteria had lower sensitivity and higher specificity (ranging from 83%-93%) compared with the new clinical criteria in discriminating PMR from all other controls. CONCLUSION: The new 2012 EULAR/ACR clinical classification criteria for PMR is highly sensitive; however, its ability to discriminate PMR from other inflammatory/noninflammatory shoulder conditions, especially from seronegative RA, is not adequate. Imaging and other modifications such as cutoff values for APR might increase the specificity of the criteria.

The IL-33 gene is related to increased susceptibility to systemic sclerosis.

Systemic sclerosis (SSc) is a chronic inflammatory disease characterized by widespread fibrosis of the skin and several visceral organs. The pro-fibrotic potential of interleukin (IL)-33 has been demonstrated by in both in vitro and in vivo settings; moreover, increased level of IL-33 has also been reported in patients with SSc. Therefore, the aim of the present study was to detect the potential association of IL-33 gene polymorphisms on the susceptibility of SSc. A total of 300 SSc patients and 280 healthy controls (HC) were enrolled in this multicentric preliminary candidate gene study. DNA samples were harvested using an appropriate commercial DNA isolation kit. Four single nucleotide polymorphisms (SNPs) of IL-33 gene (rs7044343, rs1157505, rs11792633 and rs1929992) were genotyped using the appropriate commercial primer/probe sets on real-time PCR. There was no significant difference in terms of the allelic distributions and minor allele frequencies of evaluated four IL-33 polymorphisms between the SSc and HC groups (P > 0.05 for all). Moreover, the genotypic distributions of rs1157505, rs11792633 and rs1929992 polymorphisms were not significantly different (P > 0.05 for all). However, CC genotype of rs7044343 SNP was significantly higher in the SSc group compared to the HC group (P = 0.013, OR 1.75, 95 % CI 1.12-2.72). This preliminary candidate gene study demonstrates that rs7044343 polymorphism of IL-33 gene is associated with the susceptibility to the SSc in Turkish population. It may be suggested that IL-33 gene may be a candidate gene to research in SSc.