Meral Calguneri

Mean platelet volume (MPV) as an inflammatory marker in ankylosing spondylitis and rheumatoid arthritis

AIMS The aim of this retrospective study was to investigate the correlation between MPV and the clinical disease activity indices of rheumatoid arthritis and ankylosing spondylitis. METHODS The study consisted of 32 active RA patients (males/females: 7/25, mean age: 49+/-13) and 30 active AS patients (males/females: 15/15, mean age: 36+/-12) along with 26 osteoarthritis (OA) patients (males/females: 4/22, mean age: 52+/-8) and 29 age-matched healthy subjects (males/females: 5/24, mean age: 41+/-7) as control groups for RA and AS, respectively. RESULTS MPV was significantly lower in both AS patients and RA patients with active disease as compared to controls (RA vs OA p<0.001, AS vs healthy subjects p<0.001). After treatment MPV values significantly increased in AS and RA (p<0.001 for all). However, MPV values remained somewhat lower in RA patients than OA patients (p=0.019). There was a negative correlation between MPV values and BASDAI scores in AS patients after two months of treatment (r=-0.507; p=0.004). CONCLUSION Our results suggest that assessment of MPV may provide additional information about inflammation in AS and RA.

Pathological haemostasis and ‘prothrombotic state’ in Behçet's disease

Behçets disease (BD) is a widespread occlusive-type vasculitis with life-threatening manifestations. The vasculopathy of BD is unique and any type of vessel can be involved. Moreover, vascular lesions in BD represent an occlusive nature suggesting a hypercoagulable/prothrombotic state. The data concerning the genetic defects of the coagulation cascade are expanding. There is evidence of universal activation of haemostatic system in BD. Procoagulant markers of thrombosis are elevated reflecting intravenous excessive thrombin formation. Defective fibrinolysis with impaired fibrinolytic kinetics may have a role in the hypercoagulable/prothrombotic state of BD. Endothelial cell injury and/or pathological activation is well documented in BD. The aim of this paper is to review current literature knowledge and our experience regarding the unresolved complicated issues of genetic thrombotic defects, in vivo haemostatic markers, coagulation inhibitors, impaired fibrinolysis, and endothelial injury/dysfunction of the hypercoagulable/prothrombotic state of BD. The clinical aspects of vascular thrombosis, the genetic basis of coagulation, coagulation inhibitors, fibrinolysis inhibitors, and endothelial dysfunction are reviewed. Challenges and future prospects regarding the prothrombotic state of BD are discussed together with new promising antithrombotic and antiplatelet treatment strategies. Better understanding of the exact pathogenesis of the hypercoagulable/prothrombotic state of this disease may help to develop novel therapeutic approaches offering a better outcome for Behçets patients with thrombosis.

Anti-Interleukin 1 Treatment for Patients with Familial Mediterranean Fever Resistant to Colchicine

Objective. Familial Mediterranean fever (FMF) is a recessively inherited autoinflammatory disorder characterized by recurrent attacks of fever and serositis. Although colchicine is the standard therapy for preventing attacks and suppressing inflammation, 5%–10% of compliant patients are colchicine-resistant. We report the effect of anti-tumor necrosis factor therapy (etanercept) and anti-interleukin 1 (IL-1) treatment (anakinra) in 6 cases resistant to colchicine therapy. Methods. Five children and an adult patient (3 female, 3 male) who were experiencing at least 2 attacks per month and had consistently elevated C-reactive protein levels despite regular colchicine therapy were given either etanercept or anakinra. Results. Although etanercept lowered the number of attacks (from 3–4 attacks per month to 2 attacks per month), attacks still recurred and acute-phase reactants remained high in 2 patients; thus etanercept was considered ineffective. All 4 patients were switched to anakinra. In 2 patients anakinra completely resolved clinical and laboratory findings. The other 4 patients have been switched to anakinra recently; to date anakinra has reduced the number of attacks (to < 1 per month) and lowered the levels of acute-phase reactants. Conclusion. In this small series, anakinra was succesful in suppressing inflammation and decreasing the number of attacks in FMF. This may be explained by the role of pyrin in the regulation of IL-1ß activation.

Effects of interferon α treatment on the clinical course of refractory Behçet’s disease: an open study

Interferon α (IFNα) has recently been introduced in the treatment of uveitis, mucocutaneous lesions, and arthritis of Behcet’s disease (BD).1–6 To our knowledge, there is currently no clinical trial which has evaluated the efficacy of IFNα treatment in the vascular or neurological involvement in BD. In this open study we evaluated the efficacy, toxicity, and tolerability of IFNα in the management of BD with ocular, articular, vascular, or neurological manifestations which had previously been unsuccessfully treated conventionally. A total of 29 patients (17 men, 12 women; mean age 33.2 months, range 16–51) who were resistant to conventional treatments were treated with systemic IFNα. Previous conventional treatments had been colchicine, aspirin, and penicillin plus sulfasalazine for patients with arthritis; or colchicine, aspirin, and penicillin plus steroids and/or immunosuppressive agents, azathioprine, cyclosporin A, or cyclophosphamide for ocular, vascular, and/or neurological involvement. The mean duration of the disease was 8.86 years (range 1–30). Four patients were excluded from the statistical analysis because of the short duration of treatment (<4 months). Seventeen patients had ocular inflammation. Eleven patients had arthritis. Ten patients had vascular disease (aneurisms in the internal cerebral and ophthalmic arteries; thrombosis of popliteal veins and left anterior descending coronary artery causing myocardial infarction; organised thrombus in superior and inferior caval, …

Echocardiographic Evidence of Cardiac Involvement in Ankylosing Spondylitis

Abstract: Aortic insufficiency, myocardial fibrosis and conduction disturbances are known complications of ankylosing spondylitis (AS). However, few studies have assessed left ventricular diastolic function and no data are available about P-wave analysis. In this study 88 AS patients and 31 healthy volunteers underwent clinical examination, electrocardiography, echocardiography and signal-averaged P-wave analysis for the evaluation of asymptomatic cardiac involvement. The aortic root in AS patients was larger and this was correlated with the duration of the disease. Five of 88 AS patients (5.7%) had evidence of mitral valve prolapse, six (6.8%) had thick and redundant mitral valves without prolapse, five (5.7%) had mild mitral regurgitation, two had moderate (2.3%) and two had mild (2.3%) aortic regurgitation. Examination of diastolic function revealed a lower peak of E-wave velocity (E) and E/A ratio, a higher peak of A-wave velocity (A) and acceleration rate of the A wave, a longer deceleration time of E-wave velocity and isovolumic relaxation time in the AS group compared to controls. Mean filtered P-wave duration (PWD) in AS was similar to that of controls. However, PWD in AS patients was positively correlated with left atrial dimension and acceleration rate of the A wave and negatively correlated with E and E/A ratio. In conclusion, cardiac involvement may be seen in AS patients in the absence of clinical manifestations. Echocardiographic examination of diastolic function can be used in this asymptomatic period. Further studies are needed to clarify the prognostic significance of diastolic abnormalities and the value of P-wave analysis in cardiac evaluation of these patients.

A multicenter study of patients with adult-onset Still’s disease compared with systemic juvenile idiopathic arthritis

Adult-onset Still’s disease (AOSD) has often been regarded as the adult spectrum of systemic juvenile idiopathic arthritis (sJIA). The present study aims to compare the clinical and laboratory features, the disease course and the response to treatment in patients having AOSD with those having sJIA. Retrospective review of all available data that were filled out by adult and paediatric rheumatologists from six centers using a standard data extraction form was performed. A total of 95 patients with AOSD and 25 patients with sJIA were recruited for the study. The frequency of fever, rash, myalgia, weight loss and sore throat was higher in patients with AOSD. The pattern of joint involvement differed slightly. Laboratory findings were similar in both groups, except that liver dysfunction and neutrophilia were more common among adults. A multiphasic pattern dominated the childhood cases, whereas the most frequent course was a chronic one in adults. Corticosteroids and methotrexate were the most commonly employed therapy; however, chloroquine was another popular therapy in the adult group. We showed a difference in the rate of clinical and laboratory features between patients with AOSD and those with sJIA. AOSD and sJIA may still be the same disease, and children may simply be reacting differently as the result of the first encounter of the putative antigens with the immune system.

Pathologic thrombopoiesis of rheumatoid arthritis

Rheumatoid arthritis (RA) is frequently complicated by thrombocytosis correlated with disease activity. The exact pathogenetic mechanism(s) that cause increased platelet counts in RA are still unknown. Recent investigations indicate that proinflammatory pleiotropic cytokines of RA also have megakaryocytopoietic/thrombopoietic properties. Moreover, several lineage-dominant hematopoietic cytokines can also act as acute phase responders and contribute to the inflammation. This review focuses on the current literature and our experience regarding the dual relationships of the pathologic thrombopoiesis of RA. Growth factors contributing to it, namely interleukin (IL)-6, IL-11, stem cell factor, leukemia inhibitory factor, granulocyte colony stimulating factor, thrombopoietin (TPO), and the regulation of megakaryocytopoiesis during the inflammatory cascade are reviewed. Some data indicate that thrombopoietin could contribute to the reactive thrombocytosis of RA. In the non-lineage-specific gp130 cytokine family, IL-6 appears to predominate for the induction of megakaryopoiesis. However, other cytokines and growth factors may also contribute to the pathologic megakaryocytopoiesis of RA. Those pleiotropic mediators seem to act in concert to regulate this enigmatic process. Clarification of the pathobiologic basis of thrombopoiesis in RA may improve understanding of the disease pathogenesis and management of the inflammatory thrombocytosis.

Detection of Subclinical Cardiac Involvement in Systemic Sclerosis by Echocardiographic Strain Imaging

Background: Cardiac involvement is one of the major problems in systemic sclerosis (SSc). Subclinical cardiac involvement has a higher frequency than thought previously. In this study we investigated whether subclinical cardiac involvement can be detected by using echocardiographic strain imaging in SSc patients without pulmonary hypertension. Methods: Echocardiographic examinations were performed to 27 SSc patients and 26 healthy controls. Left ventricular strain parameters were obtained from apical views and average strain value was calculated from these measurements. Results: There were no significant differences between patients and controls regarding two‐dimensional (2D), conventional Doppler and tissue Doppler velocity measurements. Strain was reduced in 6 of 12 segments of the left ventricle (LV) and in 1 of 2 segments of the right ventricle (RV). Strain rate (SR) was reduced in 2 of 12 segments of the LV and 1 of 2 segments of the RV in SSc patients as compared to controls (P < 0.05 for all). These involvements did not match any particular coronary artery distribution. More important differences were detected by average strain and SR values of the LV between patients and controls (19.78 ± 3.00% vs 23.41 ± 2.73%, P < 0.001; 2.01 ± 0.41 vs 2.23 ± 0.27/sec, P = 0.026, respectively). Furthermore, carbon monoxide diffusion capacity (DLCO) in scleroderma patients significantly correlated with LV average strain (r = 0.59; P = 0.001). Conclusion: Evaluation of ventricular function by using echocardiographic strain imaging appears to be useful to detect subclinical cardiac involvement in SSc patients with normal standard echocardiographic and tissue Doppler velocity findings.

Frequency of Lymphadenopathy in Rheumatoid Arthritis and Systemic Lupus Erythematosus

This study aimed to assess the frequency of all palpable lymph nodes during active disease and remission in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Hospital records of 100 SLE patients, 100 RA patients, 100 spondyloarthropathy patients, and 150 osteoarthritis patients, treated in our rheumatology department, were evaluated retrospectively. Overall frequencies of enlarged lymph nodes in patients with active RA and SLE were 82% and 69%, respectively. Enlarged lymph nodes associated with RA were mostly located in the axillary region, and in SLE the nodes were smaller and lymphadenopathy was more generalized compared with RA. Palpable lymph nodes disappeared in the majority of patients during remission. Lymphadenopathy was significantly less frequent in patients treated with steroids before admission. Lymph node enlargement is an important physical finding associated with RA and SLE disease activity. Atypical locations and unusually large lymph nodes should raise clinical suspicion of another underlying disease.

Alterations in left ventricular function in patients with Behçet's disease using radionuclide ventriculography and Doppler echocardiography.

Behçets syndrome is a multisystem disease; however, cardiac involvement in this disorder has been relatively less recognized. Noninvasive imaging methods may reveal a cardiac disorder which has not manifested itself clinically. In this study, radionuclide ventriculography and Doppler echocardiography were performed in 24 patients with Behçets disease to assess the left ventricular systolic and diastolic function. Patients had neither known heart disease nor cardiac symptoms. Radionuclide ventriculography was performed using 99mTc-labeled red blood cells. Ejection fraction (EF), EF fraction in the first 100 ms (EFV), peak ejection rate, time to peak ejection, 1/3 EF, time to end systole, peak filling rate (PFR), time to peak filling and 1/3 filling fraction (1/3 FF) values were computed using Fourier analysis of the time activity curve of the left ventricle with 3 harmonics. Doppler echocardiography (DE) has described impairment of diastolic compliance using analysis of mitral flow. The mean EF (54.7 +/- 9%), EFV (11.6 +/- 3.6%), PFR (2.49 +/- 0.58 EDC/s) and 1/3 FF (33.64 +/- 14%) values were significantly lower in patients than those of the control group. Nine (37.5%) patients demonstrated an impairment of diastolic function and 3 (12.5%) had abnormal systolic function observed by the radionuclide method. DE showed abnormal ventricular compliance in 13.6% of patients. As a conclusion, noninvasive imaging methods such as radionuclide ventriculography and DE may be valuable to detect diastolic impairment as an early sign of cardiac involvement in Behçets disease.