Ismail Simsek

Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database

Objectives To determine the causes and predictors of mortality in systemic sclerosis (SSc). Methods Patients with SSc (n=5860) fulfilling the American College of Rheumatology criteria and prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. EUSTAR centres completed a structured questionnaire on cause of death and comorbidities. Kaplan–Meier and Cox proportional hazards models were used to analyse survival in SSc subgroups and to identify predictors of mortality. Results Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths, 35% were attributed to pulmonary fibrosis, 26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the non-SSc-related causes, infections (33%) and malignancies (31%) were followed by cardiovascular causes (29%). Of the non-SSc-related fatalities, 25% died of causes in which SSc-related complications may have participated (pneumonia, sepsis and gastrointestinal haemorrhage). Independent risk factors for mortality and their HR were: proteinuria (HR 3.34), the presence of PAH based on echocardiography (HR 2.02), pulmonary restriction (forced vital capacity below 80% of normal, HR 1.64), dyspnoea above New York Heart Association class II (HR 1.61), diffusing capacity of the lung (HR 1.20 per 10% decrease), patient age at onset of Raynauds phenomenon (HR 1.30 per 10 years) and the modified Rodnan skin score (HR 1.20 per 10 score points). Conclusion Disease-related causes, in particular pulmonary fibrosis, PAH and cardiac causes, accounted for the majority of deaths in SSc.

Optic neuritis occurring with anti-tumour necrosis factor α therapy

Objective: Various demyelinating disorders have been reported in association with anti-tumour necrosis factor α (TNFα) agents. The objective of this study was to review the occurrence, clinical features and outcome of optic neuritis (ON) during treatment with anti-TNFα agents. Methods: A PubMed search was conducted to identify literature addressing the potential association between anti-TNFα agents and ON, following our experience with a patient having rheumatoid arthritis in whom ON developed while being treated with infliximab. Results: 15 patients including the case presented here with ON in whom the symptoms developed following TNFα antagonist therapy were evaluated. Eight of these patients had received infliximab, five had received etanercept and two patients had received adalimumab. Among them, nine patients experienced complete resolution, and two patients had partial resolution, while four patients continued to have symptoms. Discussion: Patients being treated with a TNFα antagonist should be closely monitored for the development of ophthalmological or neurological signs and symptoms. Furthermore, consideration should be given to avoiding such therapies in patients with a history of demyelinating disease. If clinical evaluation leads to the diagnosis of ON, discontinuation of the medication and institution of steroid treatment should be a priority.

Serum interleukin-18 levels in patients with Behçet’s disease. Is its expression associated with disease activity or clinical presentations?

Interleukin (IL)-18 is a proinflammatory cytokine which plays a crucial role in T helper (Th)1 type immune response. The aim of this study is to investigate the relationship of serum levels of IL-18 with disease activity and clinical presentations in patients with Behcet’s disease (BD). Sixty patients with BD and 20 healthy controls were included in the study. Patients were grouped as having active or inactive disease according to the Leeds activity score. They were also separated as a systemic involvement or mucocutaneous symptoms only. Patients with systemic involvement were further grouped according to the presence of ocular, articular and vascular involvement. IL-18 levels were significantly higher in all patient subgroups as compared to healthy controls and found to be correlated with the activity score in patients having active disease. In conclusion, this cytokine participates in the pathogenesis of BD and its levels are correlated with the disease activity. Detection of increased levels of IL-18 in patients with inactive disease implies that Th1 activation and subclinical inflammation persist during the inactive period of the disease.

Synovial proinflammatory cytokines and their correlation with matrix metalloproteinase-3 expression in Behçet’s disease. Does interleukin-1β play a major role in Behçet’s synovitis?

The objective of this study has been the well established fact that proinflammatory cytokines and metalloproteinases play a crucial role in the pathogenesis of chronic arthritis as well as the development of pannus, with the eventual erosive changes. Among the proinflammatory cytokines, interleukin-18 (IL-18) has been shown to contribute to the pathogenesis of chronic synovitis by increasing the secretion of interleukin-1beta (IL-1β) and the tumor necrosis factor-alpha (TNF-α) and also stimulating angiogenesis. The aim of this study is to investigate the synovial IL-18, IL-1β, TNF-α and matrix metalloproteinase-3 (MMP-3) levels in patients with Behçet’s disease (BD), and compare them with the levels of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). 30 patients with BD, 20 with RA, and 20 with OA were included in the study. The synovial levels of IL-18, IL-1β, TNF-α and MMP-3 were detected using the two-step sandwich ELISA method. The synovial IL-18, TNF-α and MMP-3 levels were significantly higher in RA patients than patients with BD (P=0.004, 0.019, 0.025, respectively) and with OA (P=0.004, 0.045, 0.032, respectively). There were no differences, with respect to the cytokine levels, when patients with BD were compared with those with OA. Patients with RA and BD had higher IL-1β levels than patients with OA (P=0.017, 0.013, respectively). However, no such difference was found for IL-1β between BD and RA patients. Among patients with RA, positive correlations were found between TNF-α and MMP-3 (r=0.683, P=0.001). Our results showed that MMP-3 and proinflammatory cytokines, except IL-1β, were expressed in relatively small quantities in Behçet’s synovitis. Detection of the lower levels of these cytokines and metalloproteinases might explain the non-erosive character of Behçet’s arthritis. We suggest that IL-1β may be involved in the pathogenesis of Behçet’s synovitis.

Inhibition of inducible nitric oxide synthase reduces bacterial translocation in a rat model of acute pancreatitis

Introduction Translocation of bacteria from the gut into pancreatic necrosis is an important factor in the development of septic complications and mortality in acute pancreatitis. S-methylisothiourea (SMT) is an inducible nitric oxide synthase inhibitor that has been shown to decrease bacterial translocation in sepsis and thermal injury. Aim To investigate whether SMT could affect bacterial translocation in acute necrotizing pancreatitis. Methodology Forty-five Sprague-Dawley rats were studied. Acute pancreatitis was induced in Group I and Group II by injection of taurocholate and trypsin into the common biliopancreatic duct. Group III underwent laparotomy with the manipulation (but not cannulation) of the pancreas and received saline injection. Group I rats received normal saline as a placebo, and Group II rats received SMT after surgery for 2 days. At 48 hours, blood was drawn for serum amylase determinations. Bacterial translocation to mesenteric lymph nodes and distant sites (pancreas, liver, and peritoneum) were examined. A point scoring system of histologic features was used to evaluate the severity of pancreatitis. Results Plasma amylase levels and pancreatic histologic score were significantly reduced in Group II rats given SMT compared with those in Group I rats given saline (p < 0.01, p < 0.05, respectively). All Group I rats had bacterial translocation to mesenteric lymph nodes compared with 7 of 12 rats in Group II (p < 0.05). There was no difference in bacterial translocation to distant organs between the two groups, although rates tended to be lower in Group II compared with Group I (p > 0.05). Bacterial counts in the pancreas were significantly reduced in Group II rats compared with those in Group I rats (p < 0.05). Conclusion Treatment with SMT appears to have ameliorated the course of acute pancreatitis; however, mortality was not affected.

The close association between dental and periodontal treatments and oral ulcer course in behcet’s disease: a prospective clinical study

OBJECTIVE The aim of the study was to evaluate the influence of dental and periodontal treatments to the course of oral ulcers in patients with Behcets disease (BD). METHODS Fifty-eight consecutive BD patients with oral ulcers were studied. Twenty-nine patients were in the intervention group (F/M: 15/14, mean age: 39.6 +/- 6.9 years) and 29 (F/M: 15/14, 39.4 +/- 10.6 years) were followed with a conventional treatment approach. In addition to oral hygiene education, dental and periodontal treatments were carried out in the intervention group, whereas the control group was only given oral hygiene education. Patients were evaluated in the pre-treatment observation period (1 month), treatment period (1 month) and 6 months after treatment. RESULTS An increase in the number of new oral ulcers (4.1 +/- 3.5) was observed within 2 days during the treatment compared with 3-30 days during treatment month (2.3 +/- 1.2) (P = 0.002). However, 6 months after the treatment, the number of oral ulcers (1.9 +/- 1.5) was significantly lower compared with the pre-treatment observation (4.8 +/- 3.2) (P = 0.000) and treatment periods (6.4 +/- 2.3) in the intervention group (P = 0.05), whereas a similar oral ulcer presence was observed in the control group (2.8 +/- 2.4, 3.7 +/- 2.3 and 4.8 +/- 4.3, respectively) (P > 0.05). Dental and periodontal indices were also better in the intervention group during the 6-month follow-up. CONCLUSION Our results suggest that, in BD patients, dental and periodontal therapies could be associated with a flare-up of oral ulcers in the short term, but may decrease their number in longer follow-up. They also lead to a better oral health.

Penetration of Meropenem and Cefepim into Pancreatic Tissue During the Course of Experimental Acute Pancreatitis

Introduction Recent data from experimental and clinical studies suggest that the antibiotics showing good penetration into the pancreas may reduce mortality by preventing pancreatic infection, which is the most important prognostic factor in acute pancreatitis. Aim To determine and compare pancreatic tissue concentrations of meropenem and cefepime at different stages of acute necrotizing pancreatitis in an animal model that has been shown to closely mimic severe human pancreatitis. Methodology Acute necrotizing pancreatitis was induced in rats by a standardized intraductal infusion of glycodeoxycholic acid and intravenous cerulein. Six hours (n = 30) and 48 hours (n = 30) after induction of pancreatitis, the rats were randomized to receive an intravenous 20 mg/kg injection of either meropenem or cefepime. Blood and the head of the pancreas were collected for determining antibiotic concentrations by high-performance liquid chromatography. Results Meropenem concentrations in the pancreas at 6 hours of acute pancreatitis increased significantly and decreased at 48 hours of the disease, but were still higher than that in controls. Concentrations of cefepime in necrotic pancreatic tissue were significantly low either during the initial or later phase, but lower in latter, in which the necrosis was more evident. Tissue/serum concentration ratios of meropenem were significantly higher than those of cefepime. However, tissue concentrations of both antibiotics are much higher than the minimum inhibitory concentration values for the common microorganisms involved in pancreatic infections. Conclusion Although both antibiotics penetrate into the necrotic tissue in sufficient therapeutic concentrations, penetration of meropenem is much better than cefepime. However, good tissue penetration may not solely indicate efficacy of that antibiotic. Therefore, further experimental and clinical studies are needed to determine the therapeutic and prognostic efficacy of these agents.

A Case of Churg-Strauss Syndrome Presenting with Cortical Blindness

Abstract: A 46-year-old woman with a sudden sight loss due to infarction of the occipital lobes is reported. The association of pulmonary disease, digital ischaemia, polyneuropathy and peripheral eosinophilia led to a diagnosis of Churg–Strauss syndrome. Her vision partially improved by a treatment with steroids and monthly i.v. cyclophosphamide. To our knowledge, this is the first case of CSS with a sudden loss of vision due to bilateral occipital infarction.

Living with scleroderma: patients’ perspectives, a phenomenological study

In this study, it is aimed to determine the daily life experiences of patients on the basis their own way of statement. Sixteen patients with scleroderma were enrolled to this qualitative study. Data were collected using both a demographic data form and a semi-structured interview form. Study was made on individual patient interview by face-to-face manner. Data were evaluated using Colaizzi’s phenomenological data analysis method. Data analysis revealed four categories and nine topics. These categories were (1) physical impact of disease, (2) emotional impact of disease, (3) social impact of disease and (4) patient behaviours for the cope with the disease. As emotional impact, patients imply that they have experienced disappointment, hope to get well and have fears about the future. In the physical impact category, tight skin, limitations of hand skills, swelling of the hands and feet, fatigue, swallowing difficulties and deformation of their bodies were the prominent features. In patients with recognizable disease, difficulty to join to social activities increases and eventually leads to isolation. There was also some evidence that patients who have been supported by their family and close relatives seem to be more optimistic about their disease. Most patients are not willing to communicate with other patients, particularly in an advanced stage. Scleroderma patients imply that they experience several difficulties regarding emotional, physical and social aspects. Individual abilities to cope with the disease were much more improved among patients who have a sustained social support. For advanced patients with apparent deformations, an effective social support system should be introduced.

Osteopoikilosis coexistent with ankylosing spondylitis and familial Mediterranean fever.

Osteopoikilosis (OPK) is a rare benign sclerosing disease of the skeleton and inherited as an autosomal dominant trait. OPK is associated with inflammatory rheumatic disorders, such as rheumatoid arthritis, scleroderma, reactive arthritis and familial Mediterranean fever (FMF). We report a rare case of OPK coexistent with ankylosing spondylitis and FMF. The patient presented multiple sclerotic lesions within and around the sacroiliac joints and a series of radiological diagnostic challenges.