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Biomedical subjects

F Salaffi

Publications and source records attributed to F Salaffi.

At least 37 records · Page 2Linked to original sources

Accelerated nodulosis during methotrexate therapy for refractory rheumatoid arthritis. A case report.

Accelerated nodulosis (AN) is a potential complication of methotrexate (MTX) therapy for rheumatoid arthritis (RA). We report on a 62-year old man affected by seropositive RA who developed AN after five months of MTX treatment. MTX-dose reduction was followed by rapid regression of the skin nodules. The Authors describe the typical features of AN and discuss on the pathogenetic mechanisms.

Antirheumatic Agents↗

[Pulmonary hypertension in rheumatic diseases].

In rheumatic diseases (RD) pulmonary hypertension (PH) may result by either direct damage of the pulmonary arteries (isolated PH) or pulmonary interstitial fibrosis and other causes. PH is an important cause of morbidity and mortality in systemic sclerosis in which it is more frequently isolated in the limited cutaneous variant and secondary to interstitial fibrosis in the diffuse type. In isolated PH the main histopathological finding is an occlusive arteriopathy. The role of recurrent vasospasm ("lung Raynaud's phenomenon") is still being debated. In systemic lupus erythematosus, although uncommon, PH is being increasingly reported and may recognize multiple etiological factors including vasoconstriction, vasculitis, in-situ pulmonary thrombosis or chronic recurrent thromboembolism. PH may be a severe and often fatal complication of mixed connective tissue disease and dermato/polymyositis. PH may also be diagnosed in patients with rheumatoid arthritis, primary Sjögren's syndrome and primary antiphospholipid syndrome. Doppler echocardiography is the technique of choice for the evaluation of PH because it is nonivasive and allows serial determinations of the arterial pulmonary pressure. The therapy of PH associated with RD includes corticosteroids, immunosuppressive drugs, calcium-antagonists, ACE-inhibitors, anticoagulants, O2, prostacyclin or its stable analogue, iloprost. Carefully selected patients may benefit from single lung or heart-lung transplantation.

Algorithms↗

A longitudinal study of pulmonary involvement in primary Sjögren's syndrome: relationship between alveolitis and subsequent lung changes on high-resolution computed tomography.

Eighteen non-smoking women suffering from primary Sjögren's syndrome (pSS) with previously documented alveolitis were re-examined, clinically and by pulmonary function tests (PFT), bronchoalveolar lavage (BAL), chest X-ray and high-resolution computed tomography (HRCT) after a 2 yr follow-up period. Longitudinal evaluation revealed unchanged PFT. The final BAL study showed a normal differential count in six of 14 patients with initial lymphocyte alveolitis, and a persistent alveolar lymphocytosis in the remaining eight patients, associated with an increased percentage of neutrophils in one of them. In four patients with initial mixed alveolitis, the BAL cell profile was unchanged 2 yr later. Five of 18 patients (28%) had abnormal HRCT, represented by isolated septal/subpleural lines in three patients, ground-glass opacities with irregular pleural margins in one patient, and ground-glass opacities associated with septal/subpleural lines in another. All these patients had abnormal BAL results with an increased proportion of both neutrophils and lymphocytes. The presence of alveolar neutrophils was associated with a significantly (P=0.005) greater mean rate of reduction of carbon monoxide diffusing capacity (DLCO) -- more than four times the normal rate of loss of DLCO. Chest X-ray, repeated at the end of the 2 yr follow-up period, showed parenchymal abnormalities in only one patient who had evidence of fibrosis on HRCT. This study provides evidence that lung involvement is not an uncommon extraglandular manifestation of pSS and that a BAL neutrophilia may play an important role in the pathogenesis of pulmonary disease in this autoimmune disorder.

Adult↗

Circulating levels of interleukin 10 and other cytokines in rheumatoid arthritis treated with cyclosporin A or combination therapy.

OBJECTIVE: To assess longitudinally over a 12 month period circulating serum levels of interleukin 10 (IL-10) and cytokines IL-3, IL-4, IL-6, and IL-12 in a cohort of patients with early onset rheumatoid arthritis (RA) treated with either cyclosporin A (CyA) or with combination therapy of CyA plus hydroxychloroquine as disease modifying antirheumatic drugs. METHODS: We studied 8 patients receiving CyA and 12 patients receiving CyA plus hydroxychloroquine. IL-3, IL-4, IL-6, IL-10, and IL-12 were determined by ELISA at entry, after 2 weeks, after one month, after 6 months, and after 12 months. Rheumatoid factor levels and the possible appearance of monoclonal gammopathies over time were studied by immunofixation and immunoblotting techniques. RESULTS: The pooled data show that at entry only the median baseline levels of IL-10 (3.9 vs 1.6 pg/ml; p < 0.01) and IL-6 (16.9 vs 1.4 pg/ml, p < 0.001) were higher in patients than in controls. IL-4 was not detectable. Some patients at entry (those with the longest disease duration) had detectable levels of IL-3. Only levels of IL-10 decreased significantly between entry and final values, in monotherapy and combination therapy as well. A single transient monoclonal band was observed after 6 months of treatment, which disappeared afterwards. No difference was seen in any of the cytokines between the CyA and the CyA plus hydroxychloroquine treated patients. CONCLUSION: During treatment with either CyA or CyA plus hydroxychloroquine, IL-10 levels decreased significantly. No additive effect of the 2 drugs was detected.

Adolescent↗

Methotrexate-induced pneumonitis in patients with rheumatoid arthritis and psoriatic arthritis: report of five cases and review of the literature.

Pneumonitis is emerging as one of the most unpredictable and potentially serious, adverse effects of treatment with MTX. Its prevalence in rheumatoid arthritis (RA) has been estimated from several retrospective and prospective studies to range from 0.3% to 18%. On the other hand, MTX-induced pneumonitis seems to be very rare in psoriatic arthritis (PsA). Our review of 194 RA patients and 38 PsA patients receiving MTX has identified four RA patients and one PsA patient with MTX-induced pneumonitis, giving a prevalence of 2.1% and 0.03%, respectively. Diagnosis was suggested by clinical history and radiographic findings, but the bronchoalveolar lavage plays an important role both in excluding infectious agents and in providing information for understanding the pathogenesis of lung injury. The presence of a lymphocyte alveolitis with a predominance of CD4+ T cells in 3 RA patients and CD8+ T cells with a concomitant increase in neutrophils in another case suggests that immunologically mediated reactions may be one damage mechanism in MTX-induced pneumonitis. Although risk factors for MTX-induced pulmonary toxicity are poorly understood, the presence in 3 out of 5 of our patients of pre-existing lung disease, represented by diffuse interstitial changes on chest X-ray, and mild bronchial asthma in two RA patients and by pulmonary silicosis in the patient with PsA may account for a predisposition to the development of MTX pneumonitis.

Aged↗

Clinical and subclinical alveolitis in connective tissue diseases assessed by bronchoalveolar lavage.

Subclinical alveolitis, as assessed by bronchoalveolar lavage (BAL) cell analysis, may be present in the lower respiratory tract of a high proportion of symptomless patients with connective tissue diseases (CTDs) with normal chest roentgenograms. The distribution of BAL cell types, mainly macrophages, lymphocytes, and polymorphonuclear neutrophils, varies according to type of CTD and to the presence of associated interstitial lung disease (ILD). Nevertheless, subclinical alveolitis can be classified into two major groups: lymphocyte and neutrophil alveolitis. A mixed, lymphocyte and neutrophil alveolitis may be detected as well. Subclinical alveolitis, particularly in systemic sclerosis, frequently is associated with abnormalities of lung parenchyma as assessed by computed tomography (CT) scan, supporting the hypothesis that it may be associated with the development of overt ILD. Close follow-up of these patients is needed to better determine whether subclinical alveolitis precedes ILD and whether early detection of subclinical alveolitis in CTDs may identify those patients who are at risk for the development of ILD in the future.

Bronchoalveolar Lavage Fluid↗

[Quantitative analysis of radiologic progression in rheumatoid arthritis: controversies and perspectives].

Rheumatoid arthritis (RA) is a chronic inflammatory disease with symmetrical polyarthritis as the major feature. Persistent inflammation leads to largely irreversible joint damage which can be seen radiographically. Radiographs depict the progression of joint damage and alterations, which are one of the major parameters of RA evolution. Delayed radiologic progression is a good indicator of the success/failure of long-term drug treatment, but the quantitative analysis of changes over time and the reliability of scoring systems remain difficult steps. This paper focuses of the main current scoring systems, with an emphasis on the following four: Larsen method and its modification by Kayle, Sharp method and its modification by van der Heijde. The scoring method--be it grading, counting, or weighted counting--did not appear to influence reliability or repeatability, while the radiologist's training and the film reading technique were critical to identify disease progression accurately. Our data consistently suggest the paired reading method as the most suitable for radiologic progression assessment in RA. The radiologic studies of 62 patients with early RA after 7 years' follow-up showed joint damage in 82% of patients. The average annual progression rate of the total radiologic score obtained with Sharp method, summing erosions and joint space abnormalities, was faster in the earlier years of the disease (8.8 units/year) than later on (4.9 units/year) (p < 0.01). From the trialist's point of view, these results imply that disease duration is a critical feature for RA treatment outcome.

Adult↗

Bronchoalveolar lavage in mixed cryoglobulinaemia associated with hepatitis C virus.

In order to evaluate the presence of an inflammatory process of the lower respiratory tract in patients with mixed cryoglobulinaemia (MC) associated with hepatitis C virus (HCV), bronchoalveolar lavage (BAL) was performed in 16 non-smoking females free of clinical pulmonary symptoms and with normal chest roentgenograms. Pulmonary function tests including diffusion capacity for carbon monoxide (DLCO) were also carried out. Thirteen healthy subjects were evaluated as the control group. Patients with MC had a lower percentage of alveolar macrophages (75% vs 92%, P = 0.001) and a higher percentage of lymphocytes (19.7% vs 7%, P = 0.001) than healthy controls. The percentage of CD3+ lymphocytes was higher in MC patients than in controls (86.5% vs 70%, P = 0.004). No significant differences in the percentage of CD4+, CD8+ and CD19+ lymphocytes, neutrophils and eosinophils were found. Pulmonary function tests showed significantly lower values of forced expiratory flow (FEF) 25-75 (P = 0.05) and DLCO (P = 0.05) in MC patients than in healthy controls. No correlations between BAL results and pulmonary function tests were found. The 5 yr follow-up of five patients did not demonstrate deterioration in lung function. Thus, BAL results indicate a subclinical T-lymphocytic alveolitis in MC HCV+ patients that is not associated with a risk of deterioration in lung function.

Adult↗

Combination therapy of cyclosporine A with methotrexate or hydroxychloroquine in refractory rheumatoid arthritis.

We evaluated the efficacy and toxicity of cyclosporine A (CsA) in combination with methotrexate (MTX) or hydroxychloroquine (HCQ) in patients with refractory rheumatoid arthritis (RA). Fourteen patients with active RA who had failed to respond adequately to injectable MTX and 14 who had failed to respond to oral HCQ had CsA added to their regimens for 6 months. Adverse effects were monitored every 2 weeks for 2 months, and monthly thereafter; outcome parameters were assessed at 0, 3, and 6 months. The starting dose of CsA was 2.5 mg/kg/day in both groups. Twenty-four patients (12 in each group) completed the 6-month study. All clinical variables (except grip strength in the HCQ + CsA group) significantly improved with both treatment regimens. Global efficacy was evaluated by means of the composite Chronic Arthritis Systemic Index. Fifteen patients (9 in the MTX + CsA and 6 in the HCQ + CsA group) could be considered responders, and 9 non-responders. The final mean daily dose of CsA was 3.3 +/- 0.8 mg/kg in the HCQ + CsA group and 3.1 +/- 0.9 mg/kg in the MTX + CsA group. Mild adverse events were more frequently observed in the MTX-CsA than in HCQ + CsA-treated patients (33 events in 11 patients as against 20 in nine). In combination with HCQ or MTX, CsA, over a 6 month period, may improve efficacy in patients with refractory RA without any significant increase in toxicity; MTX + CsA seems to be slightly more efficacious and more toxic than HCQ + CsA. Larger prospective controlled trials are necessary to define the efficacy of these combinations.

Adult↗

Methotrexate in polymyalgia rheumatica: preliminary results of an open, randomized study.

OBJECTIVE: Steroids are the only treatment of polymyalgia rheumatica (PMR). We report the effects of methotrexate (MTX) plus prednisone versus prednisone alone in PMR. METHODS: Twenty-four patients with recent onset PMR were studied in a randomized prospective study lasting one year. Patients were given MTX (MTX arm) 10 mg intramuscularly plus prednisone every week, or prednisone alone (Pred arm). After 6 months an attempt was made to stop prednisone, and to use the lowest possible dose over the next 6 months. RESULTS: At the 12th month, all patients were in clinical remission, acute phase reactants were in the normal range in both arms of the study, 6 patients were no longer taking steroids in the MTX arm versus 0/12 in the Pred arm, and the amount of prednisone in the 2 groups was statistically different (1.84 versus 3.2 g; p < 0.0001). In addition, bone mineral density was significantly decreased in the Pred arm, but not in the MTX arm. CONCLUSION: The MTX regimen allowed the use of much less prednisone over one year to obtain full control of PMR with no loss of efficacy. It also allowed sparing of bone in elderly patients at increased risk of osteoporotic fractures.

Aged↗

Serum soluble interleukin-2 receptor levels in rheumatoid arthritis: effect of methotrexate, sulphasalazine and hydroxychloroquine therapy.

The aim of this study was to assess the correlations of the serum soluble interleukin 2 receptor (sIL-2R) concentrations with disease activity parameters and response to treatment with second line drugs in patients with rheumatoid arthritis (RA). Sixty-seven patients with active disease completed a 24-week, open, randomized study of methotrexate (MTX) versus sulphasalazine (SSZ) or hydroxychloroquine (HCQ). Serum sIL-2R levels were evaluated before entry and after 24 weeks by ELISA. Serum sIL-2R were significantly higher in RA patients than in controls (P = 0.0001) and correlated significantly only with erythrocyte sedimentation rate (P = 0.03) and with Chronic Arthritis Systemic Index (P = 0.01) at study entry. No correlation was found between serum sIL-2R and other laboratory and clinical indices of disease activity. After 24 weeks of treatment no differences in serum sIL-2R in comparison with basal levels were found in either responding or in non-responding patients, although the mean reduction of sIL-2R was more marked in the MTX-treated cohort than in the HCQ and SSZ-treated groups. These data suggest that in RA the measurement of sIL-2R should be used with caution as an isolated index of disease activity and that it is not a useful marker of response to treatment with second line drugs.

Adult↗

Soluble interleukin-2 receptor in sera and synovial fluids of rheumatoid patients: correlations with disease activity.

The measurement of serum soluble interleukin-2 receptor (sIL-2R), a sensitive marker of lymphocyte activation, has been proposed as an indicator of disease activity and "outcome" in patients with inflammatory diseases characterized by the activation of immune cells. Serum sIL-2R levels have been reported higher in rheumatoid patients than in controls. Using an enzyme-linked immunoabsorbent assay (ELISA), we evaluated soluble IL-2R levels in the serum of 34 patients with RA and in the synovial fluid of 25 of these patients and we compared it with levels found in the serum of 13 healthy controls. Serum sIL-2R levels were significantly elevated in RA patients compared with the healthy age-matched control group (P < 0.005). The mean level of soluble IL-2R in synovial fluids was significantly higher than the mean sera levels in RA patients (P < 0.0001). Moreover, we examined the correlation between serum and synovial fluid sIL-2R levels and disease activity measures. Serum sIL-2R correlated only with ESR (P < 0.04). The synovial fluid sIL-2R correlated with ESR (P < 0.02) and a visual analogue scale (VAS) pain score (P < 0.04). Both serum and synovial fluid sIL-2R levels correlated with the chronic arthritis systemic index (CASI; P < 0.04 and P < 0.005, respectively). Our data suggested that in RA the measurement of sIL-2R may certainly mirror the degree of chronic inflammation and the continuous activation of the immune cells in the joint, although the role of this molecule in the immune response is still unclear.

Adult↗

Fibromyalgic syndrome: depression and abnormal illness behavior. Multicenter investigation.

This study reports psychological symptoms assessed in 327 patients with fibromyalgia (FS) in a multicenter investigation. Two self-report scales, in their validated Italian translations, were used for screening: the CES-D (the Center of Epidemiologic Studies-Depression) developed at the NIMH for measuring depression and the Illness Behavior Questionnaire (IBQ) developed by Pilowsky and Spence. The cutoff point of 23 in the CES-D scores revealed about 49% of the fibromyalgic patients as depressed. In analyzing patterns of illness behavior patients with FS showed a high score on IBQ scales of disease conviction, psychological versus somatic focusing and denial. CES-D scores showed significant correlations with illness behavior scales. These results and their implications for the treatment of fibromyalgic patients are discussed.

Adult↗

Progression of erosion and joint space narrowing scores in rheumatoid arthritis assessed by nonlinear models.

OBJECTIVE: To determine whether the first order kinetics model or the function proportional to the square root of disease duration better represents the progression of radiographic damage according to the disease duration than a linear model in rheumatoid patients. METHODS: Two hundred twenty-eight patients assessed at a single time point were studied by using 2 nonlinear models of radiographic damage. In 44 patients a second radiographic analysis was taken within a 3-year period. RESULTS: In this data set, both models reveal the highest rate of progression in the first 3 years of the disease. The square root of the disease duration seems to better depict the whole disease course. CONCLUSION: Nonlinear models should be compulsory in the assessment of radiographic damage, especially when slow acting antirheumatic drug effects after 5 years of disease duration are studied.

Adolescent↗

[Pulmonary inflammation in systemic sclerosis. An assessment by bronchoalveolar lavage].

Interstitial pulmonary fibrosis is a common feature of systemic sclerosis (SS). Clinicopathologic observations suggest that interstitial and alveolar inflammation may appear prior to fibrosis. Using the bronchoalveolar lavage (BAL) technique, we have characterized the nature of the inflammatory process in the lower respiratory tract of 15 non-smoking scleroderma patients and compared the results with those found in eight normal subjects. Alveolitis was detected in 11 patients (73%). Abnormalities in the cellular constituent included a significant increase of the proportion of lymphocytes (20.8 +/- 3.2 vs 8.1 +/- 1.2; p = 0.01) and neutrophils (3.3 +/- 0.8 vs 0.8 +/- 0.2; p = 0.04). T cell subsets, evaluated by flow cytometry, showed a significant increase of CD8+ T cells (36.6 +/- 3.2 vs 25, 1 +/- 3.3; p = 0.04) and a decrease of CD4+/CD8+ ratio (1.1 +/- 0.1 vs 2.1 +/- 0.4; p = 0.04). Seven patients with an elevation of proportional BAL (lymphocyte count > 15%) had greater dyspnoea and chest radiographic score than patients without lymphocytic alveolitis (p = 0.02) and they had greater reduction in carbon monoxide diffusing capacity (DLco) (p = 0.04). Furthermore, a statistically significant correlation between the total lymphocyte cell count and the DLco (p = 0.03) was observed. Finally the stepwise multiple regression analysis identified lymphocyte count in lavage fluid as the predictor most strongly associated with an abnormal interstitial radiographic pattern (p = 0.001). Our results report the notion that the lymphocytes, in addition to the macrophages and neutrophils, may play roles in the pathogenesis of lung injury.

Adult↗