Gozde Yildirim Cetin

Amyloidosis and its related factors in Turkish patients with familial Mediterranean fever: a multicentre study

OBJECTIVE The primary aim of this study was to investigate the prevalence of amyloidosis and its related factors in a large number of FMF patients. METHODS Fifteen centres from the different geographical regions of Turkey were included in the study. Detailed demographic and medical data based on a structured questionnaire and medical records were collected. The diagnosis of amyloidosis was based on histological proof of congophilic fibrillar deposits in tissue biopsy specimens. RESULTS There were 2246 FMF patients. The male/female ratio was 0.87 (1049/1197). The mean age of the patients was 34.5 years (S.D. 11.9). Peritonitis was the most frequent clinical finding and it was present in 94.6% of patients. Genetic testing was available in 1719 patients (76.5%). The most frequently observed genotype was homozygous M694V mutation, which was present in 413 (24%) patients. Amyloidosis was present in 193 patients (8.6%). Male sex, arthritis, delay in diagnosis, M694V genotype, patients with end-stage renal disease (ESRD) and family history of amyloidosis and ESRD were significantly more prevalent in patients with amyloidosis compared with the amyloidosis-negative subjects. Patients with homozygous M694V mutations had a 6-fold higher risk of amyloidosis compared with the other genotypes (95% CI 4.29, 8.7, P < 0.001). CONCLUSION In this nationwide study we found that 8.6% of our FMF patients had amyloidosis and homozygosity for M694V was the most common mutation in these patients. The latter finding confirms the association of homozygous M694V mutation with amyloidosis in Turkish FMF patients.

Characteristics Predicting Tuberculosis Risk under Tumor Necrosis Factor-α Inhibitors: Report from a Large Multicenter Cohort with High Background Prevalence

Objective. Screening strategies for latent tuberculosis (TB) before starting tumor necrosis factor (TNF)-α inhibitors have decreased the prevalence of TB among patients who are treated with these agents. However, despite vigilant screening, TB continues to be an important problem, especially in parts of the world with a high background TB prevalence. The aim of this study was to determine the factors related to TB among a large multicenter cohort of patients who were treated with anti-TNF. Methods. Fifteen rheumatology centers participated in this study. Among the 10,434 patients who were treated with anti-TNF between September 2002 and September 2012, 73 (0.69%) had developed TB. We described the demographic features and disease characteristics of these 73 patients and compared them to 7695 patients who were treated with anti-TNF, did not develop TB, and had complete data available. Results. Among the 73 patients diagnosed with TB (39 men, 34 women, mean age 43.6 ± 13 yrs), the most frequent diagnoses were ankylosing spondylitis (n = 38) and rheumatoid arthritis (n = 25). More than half of the patients had extrapulmonary TB (39/73, 53%). Six patients died (8.2%). In the logistic regression model, types of anti-TNF drugs [infliximab (IFX), OR 3.4, 95% CI 1.88–6.10, p = 0.001] and insufficient and irregular isoniazid use (< 9 mos; OR 3.15, 95% CI 1.43–6.9, p = 0.004) were independent predictors of TB development. Conclusion. Our results suggest that TB is an important complication of anti-TNF therapies in Turkey. TB chemoprophylaxis less than 9 months and the use of IFX therapy were independent risk factors for TB development.

Sonographic Evaluation of Subclinical Entheseal Involvement in Patients With Behçet Disease

OBJECTIVE The aim of the current study was to determine the prevalence of subclinical entheseal involvement in patients with Behçet disease via ultrasound using a newly developed method, the Madrid sonography enthesitis index. SUBJECTS AND METHODS The study was conducted with 36 patients with Behçet disease and 46 healthy sex- and age-matched control subjects. All patients with Behçet disease who had no clinical evidence of arthritis or enthesitis underwent an ultrasound examination. All sonographic findings were identified according to the Madrid sonography enthesitis index. Madrid sonography enthesitis index values of patients and control subjects were compared by Student t test and Mann-Whitney U test. Validity was analyzed by receiver operating characteristic curve. RESULTS Total enthesitis score was 12.16 ± 6.16 among patients with Behçet disease and 2.06 ± 2.18 among healthy control subjects (p < 0.001). The receiver operating characteristic curve established an ultrasound score greater than 4.5 in the Behçet disease group as the best cut-off point differentiating case subjects from control subjects. This cutoff was exceeded by 88.8% of the patients with Behçet disease. When the Madrid sonography enthesitis index score in each affected enthesis was evaluated, patients with Behçet disease had significantly higher scores than did control subjects when all entheseal sites were compared (all p values < 0.05). CONCLUSION This is the first study to our knowledge to show significant subclinical enthesopathy of the triceps tendon enthesis in patients with Behçet disease who had no arthritic involvement. These data suggest that the Madrid sonography enthesitis index scoring system for sonographic detection of enthesopathy should be incorporated into the clinical protocol for evaluating patients with Behçet disease in routine clinical practice.

Association Between Thr21Met and Ser89Asn Polymorphisms of the Urotensin II Gene and Systemic Sclerosis

Objective. Systemic sclerosis (SSc) is an autoimmune chronic fibrotic disorder. Urotensin II (U-II) is predominantly a vasoactive peptide with fibrotic and prothrombotic features. Like endothelin-1 (ET-1), U-II could play an important role in SSc pathogenesis. We evaluated the possible role of the U-II gene polymorphisms (Thr21Met and Ser89Asn) in the genetic susceptibility to SSc in a Turkish population. Methods. A total of 189 patients with SSc and 205 healthy controls were enrolled in our study. We analyzed the genotype and allele frequencies of the U-II (UTS2) gene polymorphisms Thr21Met and Ser89Asn in patients with SSc and in controls. Results. We found that the Thr21Met polymorphism of the UTS2 gene was markedly associated with the risk of developing SSc (p < 0.0001), but there was no relationship between the Ser89Asn polymorphism and SSc (p > 0.05). Two haplotypes (MS and TS) were markedly associated with SSc (p < 0.05). There were significant associations between the genotype and allele frequencies of UTS2 gene Thr21Met polymorphism and cases with diffuse or limited SSc, systemic or lung involvement, finger flexion deformity, pitting scars at the fingertips, positive anticentromere, or positive antitopoisomerase 1 antibody groups. Conclusion. Our study shows the association between Thr21Met, but not Ser89Asn, in the UTS2 gene and SSc. The results strongly suggest that this single-nucleotide polymorphism may be an important risk factor in the development of SSc, and a powerful indicator of severe skin and lung involvement in patients with SSc.

Increased Enthesopathy in Patients With Familial Mediterranean Fever Evaluation With a New Sonographic Enthesitis Index

The aim of this study was to determine the frequency of enthesopathy in familial Mediterranean fever by using a newly developed sonographic method, the Madrid Sonographic Enthesitis Index (MASEI).

Evaluation of the Mean Platelet Volume and Red Cell Distribution Width in FMF: Are They Related to Subclinical Inflammation or Not?

In this paper we want to demonstrate whether higher than normal levels of RDW, and lower than normal levels of MPV can be used as indicators of subclinical inflammation and tools for treatment decision in FMF or not. The participants in this study included 89 patients with FMF during attack-free periods and 30 healthy controls. The RDW and platelet counts were significantly higher, while the MPV was significantly lower in the patients with FMF group than healthy control group (P < 0.001; P = 0.005; P < 0.001, resp.). In the attack-free FMF group, a negative correlation was found between the MPV and RDW values (P < 0.001, r = −0.40). The positive correlation was found between the RDW and ESR (r = 0.23, P = 0.028). And the negative correlation was found between the MPV and CRP (r = −0.216, P = 0.042). Consequently, our results suggest that low MPV and high RDW levels may provide additional information about subclinical inflammation in FMF patients. But other strong predisposing factors affecting subclinical inflammation in FMF should be considered. Further studies with large numbers of patients are needed. Treatment of FMF should include not only prevention of acute attacks but also decreasing of the subclinical inflammation.

Thiol/disulfide homeostasis in patients with ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease. In many inflammatory diseases, increased production of pro-inflammatory cytokines is associated with an increase in oxidative stress mediators. Thiol/disulfide homeostasis is a marker for oxidative stress. The aim of this study was to examine the dynamic thiol/disulfide homeostasis in AS. Sixty-nine patients with AS and 60 age- and sex-matched controls were included in the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and visual analogue scale (VAS) were used to determine the disease activity. Native thiol, total thiol, and disulfide levels were measured with a novel automated method recently described by Erel and Neselioglu. The aforementioned method is also optionally manual spectrophotometric assay. The total thiol levels were significantly lower in the AS group compared with the control group (p = 0.03). When the patients were divided into active (n = 35) and inactive (n = 34) subgroups using BASDAI scores, the native plasma thiol and total thiol levels were significantly lower in the active AS patients compared to the inactive AS patients (p = 0.02, p = 0.03 respectively). There was a negative correlation between the plasma native thiol levels and VAS, BASDAI scores. Thiol/disulfide homeostasis may be used for elucidating the effects of oxidative stress in AS. Understanding the role of thiol/disulfide homeostasis in AS might provide new therapeutic intervention strategies for patients.Ankylosing spondylitis (AS) is a chronic inflammatory disease. In many inflammatory diseases, increased production of pro-inflammatory cytokines is associated with an increase in oxidative stress mediators. Thiol/disulfide homeostasis is a marker for oxidative stress. The aim of this study was to examine the dynamic thiol/disulfide homeostasis in AS. Sixty-nine patients with AS and 60 age- and sex-matched controls were included in the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and visual analogue scale (VAS) were used to determine the disease activity. Native thiol, total thiol, and disulfide levels were measured with a novel automated method recently described by Erel and Neselioglu. The aforementioned method is also optionally manual spectrophotometric assay. The total thiol levels were significantly lower in the AS group compared with the control group (p = 0.03). When the patients were divided into active (n = 35) and inactive (n = 34) subgroups using BASDAI scores, the native plasma thiol and total thiol levels were significantly lower in the active AS patients compared to the inactive AS patients (p = 0.02, p = 0.03 respectively). There was a negative correlation between the plasma native thiol levels and VAS, BASDAI scores. Thiol/disulfide homeostasis may be used for elucidating the effects of oxidative stress in AS. Understanding the role of thiol/disulfide homeostasis in AS might provide new therapeutic intervention strategies for patients.

Avaliação de entesopatia em pacientes com fibromialgia por meio do novo índice ultrassonográfico de entesite

OBJECTIVE: The aim of the present study is to determine the frequency of enthesopathy in fibromyalgia (FM) by using a newly developed ultrasonography (US) method, the Madrid Sonography Enthesitis Index (MASEI). METHODS: This study was conducted on 38 consecutive patients with FM and 48 healthy sex- and age-matched controls. Six entheseal sites (olecranon tuberosity, superior and inferior poles of patella, tibial tuberosity, superior and inferior poles of calcaneus) on both lower limbs were evaluated. All US findings were identified according to MASEI. Scores of patients and controls were compared by Students t-test and Mann-Whitney U-test. Validity was analysed by receiver operating characteristic curve. Values of P 3.5 in the FM group as the best cut-off point to differentiate between cases and controls. No statistically significant correlation was found between the MASEI score and the FM disease duration, and the location of the tender points. CONCLUSIONS: Misdiagnoses of FM are harmful to patients and the community, and the presence of enthesopathy among FM patients increases. Its detection with the MASEI score may help to discriminate FM patients presenting with ill-defined symptoms and signs, in order to prevent mistreatment.

Avaliação da frequência e aspectos dos ataques de pacientes com resistência à colchicina em febre familiar do Mediterrâneo (FFM)

INTRODUCTION Colchicine is the mainstay for the treatment of FMF, which is an auto-inflammatory disease mainly with relapsing polyserositis. Despite daily doses of 2mg or more each day, approximately 5% to 10% of the patients continue to suffer from its attacks. In this study, we aimed to investigate the depression and attack features in patients with FMF who have colchicine resistance (CR). PATIENTS E METHODS CR was defined for FMF patients with 2 or more attacks within the last 6 months period while using 2mg/day colchicine. Eighteen patients (9 Female/9 Male) were enrolled into the CR group and 41 patients were enrolled into the control group (12 Male/29 Female). Demographic, clinical e laboratory findings, treatment adherence, and the Beck Depression Inventory (BDI) scores were evaluated. RESULTS The age of onset of FMF was significantly lower in the CR group (12.3 yrs vs. 16.9 yrs, P=0.03). Disease duration was longer in the CR group (P=0.01). Abdominal and leg pain due to exercise were significantly more frequent in the CR group versus controls (83% vs. 51%; P=0.02 e 88% vs. 60%; P=0.04, respectively). Patients with BDI scores over 17 points were more frequent in the CR group compared to controls (50% vs. 34.1%; P<0.001). DISCUSSION We found that: (1) the age of disease onset was lower and (2) the disease duration was longer in CR group. Pleuritic attacks, hematuria e proteinuria were more frequent in CR patients. We propose that depression is an important factor to consider in the susceptibility to CR.

Bilateral tubo-ovarian abscess and sepsis caused by Salmonella in patients with systemic lupus erythematosus

A 39-year-old woman was admitted to the emergency department due to abdominal pain. Her history included systemic lupus erythematosus (SLE) and use of immunosuppressive drugs. The patients general condition was poor with fever and tenderness in the abdomen. Laboratory tests revealed leukopenia (3800/mm3), elevated C reactive protein (112 mg/dL) and international noramalised ratio (INR 11). In contrast-enhanced CT, bilateral tubo-ovarian abscess was observed sized 86×44 …