Mehmet Sayarlioglu

Tuberculosis in Turkish patients with systemic lupus erythematosus: increased frequency of extrapulmonary localization

The objectivewas to investigatethe frequencyand characteristicsof tuberculosis(TB) in patients with systemic lupus erythematosus (SLE). We reviewed the charts of 556 patients with SLE who were followed up between 1978 and 2001 in our lupus clinic. Patientswho developedTB after the diagnosis of SLE were identified (SLE/TB). Ninety-six consecutive patients with SLE who did not develop TB during the follow-up were evaluated as a control group (SLE/TB-). Clinical, laboratory and management characteristics of these two groups of patients were recorded according to a predefined protocol, and compared. Of the 556 patients evaluated, 20 patients (3.6%) with TB were identified. Nine of the 20 patients (45%) had extrapulmonary TB (vertebral involvement in three patients, meningeal in two, and joint and soft tissue in four). Arthritis and renal involvement were significantly high in the SLE/TB group (P 0.045, P 0.009, respectively). The mean daily dose of prednisolonebefore the diagnosis of TB and the cumulative dose of prednisolonewere significantly higher in the SLE/TB group compared to the SLE/TB- group (27 + 22 g versus 16 + 16 g, 24 + 45 mg versus 11 + 8.5 mg, respectively). In conclusion, we found an increased frequency of TB infection and a high prevalence of extrapulmonary TB in a large cohort of SLE patients. The mean daily dose of prednisolonebefore the diagnosisof TB and the cumulativedose of prednisolone, which possibly related to disease severity, were important determinants for the increased risk of TB in these patients with SLE.

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.

Fibrosing mediastinitis and thrombosis of superior vena cava associated with Behçet's disease

We present CT, MRI and venography findings in 13-year boy with mediastinal fibrosis and superior vena cava (SVC) thrombosis associated with Behçets disease. Fibrosing mediastinitis is an excessive fibrotic reaction that occurs in the mediastinum and may lead to compression of mediastinal structures (especially vascular). This condition is usually idiopathic, though many (and perhaps most) cases in the USA are thought to be caused by an abnormal immunologic response to Histoplasma capsulatum infection. SVC syndrome secondary to extrinsic compression by mediastinal fibrosis combined with Behçets disease has rarely been described. Radiological investigations of this syndrome are necessary to avoid a useless anticoagulant therapy.

Initial diagnosis of lumbar disc herniation is associated with a delay in diagnosis of ankylosing spondylitis.

Objective. There is often a considerable delay in diagnosis of ankylosing spondylitis (AS). In this multicenter study, we analyzed the delay and possible associated factors, including an initial diagnosis of lumbar disc herniation (LDH), which we frequently encounter in daily clinical practice. Methods. The study included 393 consecutive patients [258 men (65.6%), mean age 39.3 ± 10.8 yrs] with AS according to the modified New York criteria. Face-to-face interviews were done using a structured questionnaire, addressing all the potentially relevant factors. Results. The mean diagnostic delay was 8.1 ± 8.6 years in the whole study population. The shortest delay was observed when rheumatologists were the first physicians consulted (2.9 ± 5.3 yrs). An initial diagnosis of LDH was reported by 33% of the patients. The diagnostic delays in patients with an initial diagnosis of LDH and those without were 9.1 ± 8.5 years and 6.2 ± 7.4 years, respectively (p = 0.002). In a regression model, predictive factors for delay in diagnosis were age at onset of spondyloarthritic symptoms, back pain, education level, prior diagnosis of LDH, and surgical history for LDH. Conclusion. These results indicate the need to increase awareness of the concept of axial spondyloarthritis among specialists who might be the first physicians consulted by patients with AS for their back pain. There is also a need to develop strategies for early referral of such patients to rheumatologists.

Incidence of Cyclophosphamide-induced Urotoxicity and Protective Effect of Mesna in Rheumatic Diseases

Objective. To assess bladder toxicity of cyclophosphamide (CYC) and uroprotective effect of mesna in rheumatic diseases. Methods. Data of 1018 patients (725 women/293 men) treated with CYC were evaluated in this retrospective study. All of the following information was obtained: the cumulative CYC dose, route of CYC administration, duration of therapy, concomitant mesna usage, and hemorrhagic cystitis. Cox proportional hazard model was used for statistics. Results. We identified 17 patients (1.67%) with hemorrhagic cystitis and 2 patients (0.19%) with bladder cancer in 4224 patient-years. The median time for diagnosis to hemorrhagic cystitis was 10 months (4–48) and bladder cancer was 8 years (6–10.9). There were 583 patients (57.2%) who received mesna with intravenous CYC therapy. We observed similar incidence rate for hemorrhagic cystitis in both patient groups concomitantly treated with or without mesna [9/583 (1.5%) vs 8/425 (1.8%) respectively, p = 0.08]. Cumulative CYC dose (HR for 10-g increments 1.24, p < 0.001) was associated with hemorrhagic cystitis. Conclusion. Cumulative dose was the only risk factor for hemorrhagic cystitis in patients treated with CYC. No proof was obtained for the uroprotective effect of mesna in our cohort.

A case of toxic epidermal necrolysis-like skin lesions with systemic lupus erythematosus and review of the literature.

Objective Subepidermal bullous lesions and toxic epidermal necrolysis-like (TEN-like) lesions can occur in patients with systemic lupus erythematosus (SLE). In this report, we describe a case of a patient previously diagnosed with SLE who experienced TEN-like skin lesions with unusual subacute progression in the context of the current literature. Methods We present a recent case of TEN-like lupus erythematosus and review of studies published in English identifying SLE cases mimicking TEN, accessed via PubMed and Google Scholar databases. The keywords used in the search were: TEN, SLE, TEN-like SLE, and TEN-like lesions. The search covered all articles from January 1980 to November 2011. Results A 52-year-old male presented with fatigue, weakness, and weight loss (23 kg in two months). Skin redness started across nose and cheeks six months before admission. Bilateral pleural effusions were observed in a thorax tomography taken in the referral hospital two months prior to admission. Because of articular involvement, antinuclear antibody (ANA), and anti-dsDNA positivity, the patient was diagnosed with SLE. We initiated a punch skin biopsy, and the findings were consistent with Stevens-Johnson syndrome. There was marked basal layer necrosis in the epidermis, and there was predominantly lymphohistiocytic infiltrate in the dermis. A total of 22 cases, including our case, with TEN-like lupus erythematosus were reported in the literature. In addition, cutaneous lupus had positive ANAs in 18 of 22 patients (81.8%). The patients were aged 12 to 76 years; 21 cases were women and only one patient was male. Discussion Skin involvement, including the rare variant of TEN-like acute cutaneous SLE, is very common among SLE patients. The acute syndrome of pan-epidermolysis or apoptotic pan-epidermolysis may become a useful designation when considering a clinical diagnosis of drug-induced TEN or SLE. Further studies are required to verify our findings.

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.

Diagnostic dilemma of paraneoplastic arthritis: case series.

Paraneoplastic arthritis (PA) may mimic rheumatic diseases. While presenting the demographic and laboratory features of the patients diagnosed with PA, this study also aims to provide possible appropriate tools to differentiate the PA cases from early rheumatoid arthritis (ERA).

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.