Possible association of low dose methotrexate therapy for rheumatoid arthritis with chronic pulmonary fibrosis

Low dose methotrexate [MTX] treatment is used extensively as a second-line therapy in RA. Two forms of interstitial lung diseases are related to low dose MTX therapy, the first is acute methotrexate pneumonitis which is a life-threatening complication that occurs in less than 10% of RA patients treated with MTX. The other interstitial lung affection is chronic pulmonary fibrosis [PF]. To evaluate whether chronic PF can be a significant complication in RA patient treated with low dose methotrexate [MTX]. The study was performed on 40 RA patients who fulfilled the American College of Rheumatology classification criteria for RA, The patients were classified into two separate groups. The first group consisted of 20 RA patients who were being treated with low dose MTX at the time of initial assessment, while the other group comprised another 20 RA patients who were not being treated with MTX, but treated with second-line therapy other than MTX. Pulmonary function tests were performed for all patients at the time of initial assessment using the standard protocol. All patients underwent HRCT chest scanning. Supine views were taken in serial slices 10 mm apart and 1 mm in width. According to the study design, the patients were followed over 18 months from the time of the initial assessment. Clinically, the patients were assessed regularly at time intervals of 3 months particularly for development of any chest illness together with the patient compliance of drug therapy and its effect on disease. Follow up chest radiographs and HRCT were performed at the end point. The age of the patients and disease duration in the MTX group were 52.1+ 2.9 years and 8.9 +/- .2 years respectively while in the other group they were 50.8 +/- 2.1 years and 9.2 +/- 5.1 years respectively. Pulmonary function results at baseline assessment expressed no significant differences between the two groups with p value > 0.05. On initial HRCT chest scanning, 3 patients were found to have PF interstitial lung disease pattern, two of them were being treated with MTX. There was no significant difference in the dose and duration of MTX treatment between the two RA patients treated with MTX and has PF on initial evaluation and those who were being treated with the drug and had no evidence of PF on HRCT on chest scanning at the initial evaluation. Change in pulmonary function tests from the time of initial assessment to the end of the study was not clinically or statistically significant in both groups [p value > 0.05]. Furthermore, there was no clinical or pulmonary function evidence that MTX had any deteriorating effect on PF detected in two patients on initial assessment even when compared with the patients who were not being treated with it. This study showed no clinical, physiological or radiological evidence that low dose MTX treatment used successfully in treatment of RA is associated with chronic fibrotic lung disease

fat deposition in the muscles a significant factor that predisposes women to cardiovascular disease?

To determine if fat deposition within mid-thigh muscles represented by low density lean tissue was associated with age, menopausal status, visceral adiposity, hyperleptinemia, hyperinsulinemia and dyslipidemia in a relatively cohort group of women. Eighty women aged 28-63 years with a body mass index [BMI] < 40 kg/ m[2]. Mid-thigh muscle, mid-thigh fat, low density lean tissue, intra-abdominal adipose tissue [IAAT] and subcutaneous abdominal fat [with Computed Tomography], plasma insulin and leptin [with radioimmunoassay, RIA] and lipoprotein lipid profiles [with enzymatic methods]. IAAT increased with age [r= 0.69, p<0.000] also subcutaneous adipose tissue increase with age [r= 0.58, p<0.001]. Mid-thigh total fat and low density lean tissue increased with age [r= 0.53 and r= 0.59 both p<0.001] in contrast, mid-thigh muscle area decreased with age [r= 0.62, p<0.001]. Premenopausal women had lower plasma leptin and glucose levels than post-menopausal women [p<0.001], while mid-thigh low density lean tissue was significantly associated with higher leptin level [r= 0.44, p<0.001] and insulin level [r= 0.34, p<0.005]. Mid-thigh low density tissue correlated with plasma levels of total cholesterol, LDL-C and triglycerides [r= 0.5, 0.53, 0.41 and all p<0.001]. There was no significant correlation between mid-thigh low density lean tissue and HDL-C. Mid-thigh low density lean tissue is directly related to age and adiposity. Furthermore, it appears that fat accumulation in skeletal muscle adversely influences plasma insulin and lipoprotein metabolism in women, but not independently of total adiposity and age

role of lipoprotein [A] as a risk factor for cardiovascular disorders in rheumatoid arthritis

To determine the serum LP [a] level in rheumatoid arthritis [RA] patients in order to assess its role in their increased prevalence of cardiovascular disease. Thirty-two RA patients in the age group 40-50 years [mean 46.5 +/- 2.9] and 22 healthy subjects in the same age group as control were selected for this study. ESR, CRP, Lipid profile and serum level of LP [a] were measured in RA and control groups. LP [a] levels were significantly higher in RA patients than in control group [p <0.001]. There was no significant difference in LP [a] levels between male and female subjects in both groups. Also, there was no significant correlation between ESR [r = 0.18] or CRP [r = 0.27] as a marker of disease activity and LP [a] concentration in RA patients. There was no significant correlation between LP [a] levels and other lipid profiles in RA patients. LP [a] concentrations in RA patients with atherosclerotic diseases as IHD, Cerebral infarction or TIA tended to be higher in RA patients. LP [a] seems to have a significant role in the increased incidence of cardiovascular disease in RA patients

Significance of elevated interleukin-6 level in juvenile rheumatoid arthritis patients

IL-6 is supposed to be involved in the pathogenesis of anemia of chronic disease [ACD] and juvenile rheumatoid arthritis [JRA]. We investigated IL-6 in the plasma and bone marrow in patients of JRA with and without ACD to study its significance during the course of the disease and its role in the pathogenesis of ACD in JRA. The level of IL-6 was measured with ELISA in the plasma and supernatant of bone marrow [BM] of 25 patients with JRA [10 patients had systemic onset, 15 polyarticular onset], 14 patients with systemic JRA and ACD and 11 patients with JRA without anemia. In addition IL-6 examined in 10 healthy children. We found that IL-6 level was significantly [p<0.001] higher in patients with systemic JRA, but not in patients with polyarticular JRA than those of healthy controls. Also, IL-6 level was significantly higher in patients with persistence of systemic symptoms than patients in remission [p<0.001]. In patients with JRA and anemia the level of IL-6 was significantly higher in the bone marrow supernatant than those without anemia [p<0.001]. There was a negative correlation between bone marrow IL-6 and Hb. Our findings suggested that the use of IL-6 as a predictive parameter for the development of ACD with JRA. We recommend the use of anti -IL-6 antibodies in the therapy of those patients