Salim Dönmez

A case of granulomatosis with polyangiitis and pyoderma gangrenosum successfully treated with infliximab and rituximab

Here, we present a young male patient who was admitted with alveolar hemorrhage, arthritis and cutaneous lesions, who later developed bilateral orbital involvement and pyoderma gangrenosum (PG). He also had pathergy test positivity. The patient was refractory to conventional immunosuppressive therapy. Therefore, multiple devastating PG lesions and disease activity in granulomatosis with polyangiitis (GPA) were controlled with infliximab. Later, rituximab was used with success to prevent recurrence of symptoms. The relationship of PG with various autoimmune diseases is known; however, PG in GPA has been only rarely reported. Biologic agents might prove to be effective in GPA and PG patients who are refractory to standard immunosuppressive therapy.

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).

The clinical manifestations and survival of systemic lupus erythematosus patients in Turkey: report from two centers

Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a variety of clinical features. Survival has become longer as a result of better treatment modalities and better supportive care. There is no information on survival of SLE patients in Turkey. We evaluated clinical features and survival in SLE patients in two rheumatology departments. Methods All SLE patients being followed up by the Department of Rheumatology, Trakya University Medical Faculty, and the Department of Rheumatology, Marmara University Medical Faculty, over the 1996–2012 period were included. Patients were diagnosed with SLE if they fulfilled at least four American College of Rheumatology (ACR) criteria. The clinical and laboratory features, mortality data were obtained from medical charts. Results We had 428 SLE patients, and women (399 patients, 93.2%) far outnumbered men (29 patients, 6.8%). The mean age at the time of SLE diagnosis was 40.3 ± 12.4 years. The most frequent clinical manifestations were arthritis (76.9%) and photosensitivity (70.1%). Renal disease was present in 32.9% of patients and neurological involvement in 12.9% of patients. After a median follow-up of 60 months, 19 patients died. The most frequent causes of death were ischemic heart disease, chronic renal failure and sepsis. The rate of five-year survival was 96%; 10-year survival, 92%; and 15-year survival, 88.8%. Multivariate Cox analysis showed that serositis at the time of diagnosis, SLE disease activity index (SLEDAI) score 6, and autoimmune hemolytic anemia were independent prognostic factors. Conclusions Data from two centers in Northwestern Turkey show that the mortality rate for SLE is similar to the rate in Western countries.

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.

Protective effects of irbesartan and alpha lipoic acid in STZ-induced diabetic nephropathy in rats

The aim of this study was designed to investigate the possible beneficial effects of the angiotensin (ang) II T1 (AT1) receptor blocker, irbesartan (Irb), and the alpha lipoic acid (ALA) in streptozotocin (STZ)-induced diabetic nephropathy (DNP) in rats. The rats were randomly allotted into one of five experimental groups: A, control; B, diabetic untreated; C, diabetic treated with Irb; D, diabetic treated with ALA; and E, diabetic treated with Irb + ALA; each group contains 10 animals. B, C, D, and E groups received STZ. Diabetes was induced in four groups by a single intraperitoneal injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). The rats in Irb-, ALA-, and Irb + ALA-treated groups were given Irb (5 mg/kg), ALA (in a dose of 3 mg/kg), and Irb + ALA (in a dose of 2.5 + 1.5 mg/kg) once a day orally by using intragastric intubation for 12 weeks starting 2 days after STZ injection, respectively. Treatment with ALA and especially Irb reduced the glomerular size; thickening of capsular, glomerular, and tubular basement membranes; increased amounts of mesangial matrix and tubular dilatation as compared with diabetic-untreated rats. Notably, the better effects were obtained when Irb and ALA were given together. We conclude that Irb, ALA, and especially Irb + ALA therapy causes renal morphologic improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of Irb and ALA treatment, alone or its combination, may indicate its usefulness as a potential treatment in DNP.

Subclinical Atherosclerosis in Systemic Sclerosis: Not Less Frequent Than Rheumatoid Arthritis and Not Detected With Cardiovascular Risk Indices.

To determine the frequency of subclinical atherosclerosis in patients with systemic sclerosis (SSc; scleroderma) compared to healthy subjects (HS) and rheumatoid arthritis (RA) patients and to determine the ability of cardiovascular (CV) risk indices in detecting SSc patients with subclinical atherosclerosis.

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.

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.

The incidence and prevalence of systemic lupus erythematosus in Thrace, 2003-2014: A 12-year epidemiological study.

Background We estimated the prevalence and incidence, clinical features, treatment, and prognosis of systemic lupus erythematosus (SLE) patients in the Thrace region of Turkey. Methods We retrospectively evaluated 331 patients (307 female, 24 male, mean age 38.5 years) diagnosed with SLE between 2003 and 2014. Clinical features, treatments, and response to various treatment modalities were recorded. Our hospital has been the only tertiary referral center for rheumatological diseases for a mixed rural and urban population of 620,477 people (306,036 females, 314,411 males) for more than 16 years. Results The mean annual incidence of SLE was 4.44/100,000 (females, 8.4/100,000; males, 0.6/100,000). The overall prevalence of SLE was 51.7/100,000 (females, 97.7/100,000; males, 7/100,000). Major organ involvement was present in the following percentages: neurologic involvement: 20.1%; renal involvement: 28.2%; autoimmune hemolytic anemia: 9.6%; thrombocytopenia: 14.7%. Seventeeen SLE patients (13 females, four males) died at a median follow-up of 48 months. The five-year survival was 94.5%, and the ten-year survival was 89.9%. According to Kaplan–Meier survival analysis, poor prognostic factors were: male gender (p = 0.015); smoking (p = 0.02); pleural involvement (p = 0.011); thrombocytopenia (p = 0.021); myocarditis (p = 0.028); renal involvement (p = 0.037); treatment with cyclophosphamide (p = 0.011); and an initial high SLEDAI score (>4) (p = 0.02). Lymphopenia at the time of diagnosis appeared as a favorable prognostic factor (p = 0.008). Cox regression analysis revealed myocarditis (OR: 20.4, p = 0.018) and age at diagnosis (OR: 1.11, p = 0.035) to be poor, and lymphopenia at the time of diagnosis to be good prognostic factors (OR:0.13, p = 0.031). Conclusions The annual incidence and prevalence of SLE in the Thrace region of Turkey is lower than those reported in North America, however they are similar to those reported for European countries. Clinical manifestations appear to be milder, whereas survival was similar to those recorded in Western countries.

PECAM-1 gene polymorphisms and soluble PECAM-1 level in rheumatoid arthritis and systemic lupus erythematosus patients: any link with clinical atherosclerotic events?

Genetic polymorphisms of platelet endothelial cell adhesion molecule-1 (PECAM-1) were found to play roles in atherosclerotic events. We determined PECAM-1 polymorphisms, soluble PECAM-1, and CD40L levels in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and evaluated their associations with clinical atherosclerotic complications. We included 100 RA patients, 81 SLE patients, and 94 healthy controls. The clinical features about the patients were obtained from medical records. Past cardiovascular complications were recorded. The most frequent gene polymorphisms of PECAM-1 were studied in our genetics laboratory. Soluble PECAM-1 and CD40L levels in serum were determined with ELISA. The frequencies of 373C (rs668) and 1688A (rs12953) alleles were higher in RA patients when compared to controls (p values, 0.028 and 0.016). RA and SLE patients had significantly higher allele frequencies for 2008A (rs1131012) when compared to controls (p values, 0.016 and 0.001). SLE patients had significantly more frequent AA genotype for rs1131012 polymorphism than RA patients and controls (p values, 0.007 and <0.001). Soluble PECAM-1 level was significantly higher in RA patients than in SLE patients and healthy controls (p values <0.001). Atherosclerotic complications were more frequent in SLE patients with AG genotype (rs12953) than those with AA genotype (p = 0.021). SLE patients with CC genotype (rs668) had a significantly lower frequency of atherosclerotic complications than those with CG genotype (p = 0.045). Nevertheless, in multivariate analysis, there was no association between genotype and atherosclerotic complications. We found associations between various PECAM-1 polymorphisms in RA and SLE; PECAM-1 and soluble CD40 ligand (sCD40L) levels were significantly higher in RA patients than in SLE and control groups. PECAM-1 polymorphisms in SLE were protective against atherosclerotic complications.