I. Ertenli

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.

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, …

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.

Assessment of Atrial Conduction in Patients with Scleroderma by Tissue Doppler Echocardiography and P Wave Dispersion

Background: Atrial conduction abnormalities in patients with scleroderma have not been evaluated in terms of P wave duration, P wave dispersion (Pd) and electromechanical coupling measured by tissue Doppler echocardiography. Methods: Twenty-four patients with scleroderma and 24 control subjects underwent resting electrocardiogram (ECG), M mode and tissue Doppler echocardiography. The P wave duration was calculated in all leads of the surface ECG. The difference between the maximum (Pmax) and minimum P wave duration was calculated and defined as Pd. Interatrial and intraatrial electromechanical delays were measured with tissue Doppler tissue echocardiography. Results: The left ventricular dimensions, fractional shortening, and left atrial diameter did not differ between the patients and the controls. Pd and Pmax were significantly higher in patients with scleroderma compared with controls: 51 ± 17 versus 28 ± 7 ms (p < 0.01) and 109 ± 10 versus 93 ± 6 ms (p < 0.01), respectively. There was a delay between the onset of the P wave on surface ECG and the onset of the late diastolic wave (A wave; PA) obtained by tissue Doppler echocardiography in patients with scleroderma compared with controls measured at lateral septal annulus (lateral PA; 122 ± 8 vs. 105 ± 7 ms, p = 0.001), septal mitral annulus (104 ± 11 vs. 93 ± 10 ms, p = 0.01) and tricuspid annulus (right ventricular PA; 71 ± 9 vs. 64 ± 7 ms, p = 0.05). Interatrial conduction time (lateral PA – right ventricular PA) was delayed in patients with scleroderma compared with controls (88 ± 13 vs. 76 ± 11 ms, p = 0.01). A positive correlation was detected between interatrial electromechanical delay (lateral PA – right ventricular PA) and Pd (r = 0.5, p = 0.03). Conclusion: Atrial conduction abnormalities as estimated with Pd and Pmax are significantly higher in patients with scleroderma compared with controls. There is a delay in both intraatrial and interatrial electromechanical coupling intervals in patients with scleroderma.

The efficacy of oral cyclophosphamide plus prednisolone in early diffuse systemic sclerosis

Pharmacological treatment of diffuse systemic sclerosis (SSc) directed at the tissue fibrosis has generally been ineffective. Many immunosuppressive drugs have been tried as therapy for SSc, regardless of the disease subtype and/or stage. The aim of this study was to show the efficacy and the toxicity of oral cyclophosphamide and prednisolone therapy on the prevention of fibrosis-based tissue damage in the early stages of the diffuse SSc. Twenty-seven patients with early diffuse SSc were treated with oral cyclophosphamide (1–2 mg/kg/day) plus oral prednisolone (40 mg/every other day) between the years 1995 and 1998. The results regarding the efficacy and toxicity of cyclophosphamide were compared with those of 22 early SSc patients who had been treated with oral D-penicillamine between 1992 and 1995. All the patients were evaluated using clinical and laboratory parameters every 6 months for 2 years. There was a significant improvement on the skin score, maximal oral opening, flexion index, predicted forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLCO) in the cyclophosphamide group. The decrease in skin score in the cyclophosphamide group started earlier than in the D-penicillamine group. No life-threatening or irreversible adverse reaction was observed. This open study supports the use of oral cyclophosphamide plus prednisolone therapy to prevent fibrosis and its complications in the early stages of diffuse SSc.

Megakaryocyte-Related Interleukins in Reactive Thrombocytosis versus Autonomous Thrombocythemia

The primary thrombocytosis (thrombocythemia) associated with myeloproliferative disorders is believed to be due to autonomous platelet production. Secondary or reactive thrombocytosis can be observed in a number of clinical circumstances, and may be related to persistent overproduction of some thrombocytopoietic factors acting on megakaryocytes. Several cytokines, including IL-6, IL-1 and IL-4 have been shown to act alone or in concert, to affect various cellular stages of megakaryocytopoiesis in humans. The aim of this study is to assess the serum concentrations of these cytokines in myeloproliferative disorders (MPD) with thrombocythemia and in rheumatoid arthritis (RA) with marked reactive thrombocytosis. Twenty-two patients (14 men, 8 women) with MPD and thrombocythemia (platelet counts > 500 x 10(9)/1; range 507-996 x 10(9)/1), 33 RA patients (28 women, 5 men) with marked thrombocytosis (platelet counts > 500 x 10(9)/1; range 500-745 x 10(9)/ 1), 27 RA patients (24 women, 3 men) with normal platelet counts (range 168-399 x 10(9)/1) and 15 healthy volunteers (8 women, 7 men) with normal platelet counts (range 161-385 x 10(9)/1) enrolled in the study. Serum IL-1 alpha, IL-1 beta, IL-4 and IL-6 concentrations were measured in these four groups. Of the 22 patients with MPD, 10 had chronic myelogenous leukemia, 5 had polycythemia vera, 6 had essential thrombocytosis and 1 had osteomyelofibrosis. Serum interleukin concentrations in patients with MPD and thrombocythemia were either suppressed or similar to those of normal subjects, whereas IL-6, IL-1 beta and IL-4 levels were increased in RA patients with reactive thrombocytosis. We conclude that thrombocythemia associated with MPD is an autonomous phenomenon, and is not regulated by cytokines which affect megakaryocytopoiesis.

Transverse myelitis in a patient with Behcet’s disease: favorable outcome with a combination of interferon-α

We report here on a 24-year-old patient with Behçet’s disease who had been diagnosed with acute transverse myelitis. He was successfully treated with a combination regimen of a steroids, cyclophosphamide, and interferon-α. The treatment strategy with specific emphasis on interferon-α is discussed in the light of the pertinent literature.