Antibodies against oxidized LDL and atherosclerosis in rheumatoid arthritis patients treated with biological agents: a prospective controlled study.

OBJECTIVES: The aim of this study was to investigate the relation among atherosclerosis, antibodies against oxidized LDL (anti-oxLDL), and inflammation in rheumatoid arthritis (RA) patients treated with biological (b) disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Fifty-nine patients who were receiving conventional synthetic DMARDs and were eligible for treatment with a biological agent were included in the study. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and IgG antibodies against oxidized LDL (anti-oxLDL) as well as carotid intima-media thickness (cIMT) were determined before and after 6 months of treatment. Thirty-one healthy individuals were used as a control group. RESULTS: At baseline, RA patients had lower TC and HDL-C levels and increased cIMT compared to controls. After a 6-month follow-up, the re-evaluation of carotids revealed a statistically important decrease of cIMT values. This observation was accompanied by a statistically important elevation of HDL-C levels and a reduction of the titer of anti-oxLDL antibodies regardless of the bDMARD that was administered. No statistically significant association was found between the cIMT and anti-oxLDL, HDL-C, CRP, or DAS28 score neither before nor 6 months after treatment using linear regression analyses adjusted for age and gender. CONCLUSIONS: We provide evidence that atherogenic lipid profile and ongoing atherosclerosis which characterize RA patients appear to improve after biological therapy, and we also suggest a possible atherogenic effect of IgG anti-ox LDL antibodies.

The effects of biologic agents on cardiovascular risk factors and atherosclerosis in rheumatoid arthritis patients: a prospective observational study.

We aimed to evaluate the impact of biologic treatment on subclinical atherosclerosis and risk factors for cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). Forty-nine biologic naïve RA patients, treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), who were eligible for treatment with a biologic agent, were included in the study. The serum levels of lipid parameters, as well as disease activity parameters were determined in RA patients before and after 3 and 6 months of therapy. Carotid artery intima-media thickness (cIMT) was measured before and after treatment. A comparison analysis of change of these parameters was also performed between anti-tumor necrosis factor (anti-TNF) and non-anti-TNF users. Furthermore, 31 non-smoking healthy volunteers, matched for age and gender, were used as a control group. At baseline, RA patients had a decrease in serum total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels compared with controls (209 ± 63 vs 233 ± 44 and 58 ± 15 vs 61 ± 14, p < 0.004), while cIMT was higher versus controls [0.9 (0.8-1) vs 0.6 (0.5-0.7), p < 0.001]. TC, HDL-C and apolipoprotein A1 levels were significantly increased 3 months after treatment (209 ± 63, 58 ± 15, 162 ± 32, vs 227 ± 45, 60 ± 15, 169 ± 29, respectively, p < 0.03) and this observation remained stable at a 6-month follow-up. After 6 months, there was also a statistically significant decrease in the cIMT [0.9 (0.8-1) vs 0.7 (0.6-0.8), p < 0.001]. Anti-TNF and non-anti-TNF users had comparable changes in cardiovascular risk parameters. The atherogenic lipid profile and subclinical atherosclerosis are features of RA, which appeared improved after biologic therapy initiation.

Subclinical atherosclerosis in scleroderma patients.

OBJECTIVE: To investigate subclinical atherosclerosis in patients with systemic sclerosis (SSc). METHODS: Sixty-six patients with SSc who met the American College of Rheumatology criteria for the disease were included. The serum levels of total cholesterol (TC), triglycerides, high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were determined in all patients. Carotid artery intima-media thickness (IMT) and carotid plaques were measured. Patients with a history of atherosclerosis, hypertension, smokers, or patients suffering from conditions that affect the lipid profile, such as diabetes mellitus, hypothyroidism, liver or kidney diseases, Cushing's syndrome, obesity, and a history of familial dyslipidaemia, were excluded. Patients receiving medication affecting lipid metabolism were also excluded from the study. Fifty-one age- and sex-matched non-smoking volunteers were used as controls. RESULTS: Sixty patients were investigated. Six were excluded. Of these, two were smokers, two had diabetes mellitus, one hypothyroidism, and one had hypertension treated with diuretics. Patients with SSc exhibited mild dyslipidaemia expressed mainly by low serum levels of HDL-C and high TC (p < 0.001 and p < 0.021, respectively) compared to controls. In addition, the atherogenic ratio LDL-C/HDL-C was significantly higher among SSc patients (p < 0.0001). Common carotid artery IMTs were higher in SSc compared to controls (0.77 +/- 0.2 vs. 0.59 +/- 0.14, p < 0.0001). No correlation between IMTs and any SSc features were found. Logistic regression analysis showed an independent association of scleroderma with IMTs and TC. CONCLUSION: The scleroderma patients exhibited an atherogenic lipid profile and subclinical atherosclerosis and have an increased risk for cardiovascular events.

Glucocorticoid receptor variants may predispose to rheumatoid arthritis susceptibility.

OBJECTIVES: Deregulation of glucocorticoid (GC) secretion could be associated with rheumatoid arthritis (RA). The GC receptor (GR) has two isoforms. In the present study, we explored the role of GR-alpha polymorphisms rs33388, rs33389, and Bcl I, and the GR-beta variant rs6198 in RA susceptibility. METHODS: One hundred and thirty-six RA patients and 148 ethnic matching controls were studied. Polymorphisms rs33388 and Bcl I were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and variants rs33389 and rs6198 by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) coupled with sequencing. Arlequin and SPSS softwares were used in the statistical analysis. RESULTS: The polymorphisms studied were in Hardy-Weinberg equilibrium in both groups. A marginally statistical significant difference was observed in the distribution of rs33388 genotypes between RA patients and controls (p = 0.053). When the A and T alleles were compared, the statistical significance was p = 0.025. Specific complex genotypes were also differentially distributed: the GR-alpha complex genotypes (a) [homozygote (homo) wild-type (wt) rs33388-homo wt rs33389] (11% RA vs. 21% controls; p = 0.023), (b) [homo wt rs33388-homo wt rs33389-homo non-wt Bcl I] (0.7% RA vs. 4.7% controls; p = 0.042), and (c) the GR-beta complex genotype [homo wt rs33388-homo wt rs33389-homo non-wt Bcl I-homo wt rs6198] (0.7% RA vs. 4.7% controls; p = 0.042). CONCLUSIONS: GR-alpha and GR-beta polymorphisms are potentially associated with RA susceptibility. However, additional studies in larger and other ethnic groups of patients are needed to confirm the results of the present study.

Pulmonary involvement in patients with early rheumatoid arthritis.

OBJECTIVES: To assess the pleuropulmonary changes in patients with early rheumatoid arthritis (RA), using high-resolution computed tomography (HRCT). METHODS: Forty-three non-smoking patients with early RA were included. The disease duration was<1 year, without previous treatment. Disease activity was assessed using the 28-joint indices score (DAS28). Hand and wrist X-rays were evaluated using Larsen's criteria. Pulmonary functional tests (PFTs) were performed in 32 patients. The patients and 18 non-smokers healthy individuals were assessed by plain chest X-ray (CXR) and HRCT of the lungs. RESULTS: HRCT revealed air trapping in 69% (25/36), bronchiectasis in 58% (25/43), bronchial wall thickening in 52% (22/43) and ground glass opacities (GGOs) in 35% (15/43) of the patients. Pleural thickening and effusion were observed in 11% (5/43). CXR was abnormal in one patient revealing a single pulmonary nodule. GGOs were the only HRCT sign observed exclusively in RA patients. All the other abnormalities were depicted in the control group at the same frequency as in the patients. However, the extent (as expressed by the HRCT score) of air trapping, bronchiectasis and bronchial wall thickening was significantly greater in the patients than in the control group (p<0.05). The PFTs were within normal values. DAS28, PFTs, and the Larsen score did not show any significant correlation with either each HRCT sign score separately or the total score. CONCLUSIONS: Lung abnormalities are frequently observed in patients with early RA on HRCT, even when CXR and PFTs are normal. Limited areas of GGOs were the abnormalities depicted exclusively in patients.

Efficacy and safety of switching from infliximab to adalimumab: a comparative controlled study.

OBJECTIVE: To describe the efficacy and safety of adalimumab in patients with rheumatoid arthritis (RA) who had previously discontinued infliximab treatment. METHODS: 24 patients with RA who discontinued treatment with infliximab (switchers) were treated with adalimumab (40 mg every 2 weeks, subcutaneously) for 12 months. The results were compared with those for 25 patients with RA receiving adalimumab who had not previously used an anti-tumour necrosis factor alpha inhibitor (controls). Disease activity was measured with the 28 joint count Disease Activity Score (DAS28), and clinical response with the American College of Rheumatology (ACR) 20% response criteria. RESULTS: At baseline there were no differences in demographic, clinical, and laboratory features between the two groups. After 12 months' adalimumab treatment, clinical improvement was similar in both groups. More specifically, ACR 20% response criteria were achieved by 18/24 (75%) switchers and by 19/25 (76%) subjects in the control group. Four switchers discontinued the study-two because of adverse events and two because of lack of efficacy, while three control patients discontinued the study-one because of lack of efficacy and two owing to side effects. CONCLUSION: Adalimumab is a well tolerated and effective treatment for patients with RA, even when infliximab has been discontinued.

Psychological distress and personality traits in early rheumatoid arthritis: A preliminary survey.

OBJECTIVES: To investigate psychiatric manifestations, personality traits, and ego mechanisms of defense involved in early rheumatoid arthritis (RA). METHODS: Twenty-two unselected early RA outpatients with disease duration less than 1 year participated in the study. The majority of participants were females (72.7%), married (81.8%), aged 51.0+/-14.6 years. Thirty-four subjects matched for age, sex and educational level served as "healthy" controls. General Heath Questionnaire, Symptom Distress Checklist, Defense Style Questionnaire and Hostility and Direction of Hostility Questionnaire were used; disease activity was estimated by disease activity for 28-joint indices score. RESULTS: Seven patients (31.8%) presented psychological distress scores indicative of possible psychiatric caseness, expressing obsessive-compulsive symptoms and depression, as compared to six (17.6%) of controls. Social dysfunction distress and somatization were prominent psychiatric manifestations in early RA group. Early RA patients tend to adopt a less adaptive defense style than controls. Although disease activity was not correlated to psychological distress, a significant association between disease activity and patients' defensive style was observed: as the disease is exacerbated, there was a shift from "non-adaptive" to "immature image distorting or borderline" defense style, suggesting a rather fragile underlying personality structure. CONCLUSION: Psychological distress is a relatively common experience in early RA. Social dysfunction, along with the less adaptive defense style, which under the stress of the disease exacerbation turns to "borderline", underlines the importance of a careful assessment and consultation in early RA patients in order to face the distress shortly after diagnosis and highlights potential risk factors for future adaptation to exacerbations of the disease.

Lymphocytic alveolitis: A surprising index of poor prognosis in patients with primary Sjogren's syndrome.

Twelve years ago we reported that lymphocytic alveolitis [or bronchoalveolar lavage (BAL) lymphocytosis] correlates with clinical pulmonary involvement in primary Sjogren's syndrome (pSS). Our thesis was based on subtle clinical and functional evidence of interstitial lung disease (ILD) in pSS patients with "high lymphocytic alveolitis" (>15% lymphocytes in BAL). This report is a follow-up study of these patients. Basic clinical and functional re-evaluation of the 22 patients with pSS, studied in 1991, emphasized the differences between those with alveolitis and those without alveolitis. There was no significant functional decline. There were, however, two statistically significant differences between the two groups: (1) only patients with BAL lymphocytosis had to be treated with steroids (5/12 vs. 0/10, P < 0.05) and (2) only patients with BAL lymphocytosis had died in the mean time (6/12 vs. 0/10, P < 0.01). The causes of death were various. On only two occasions were they related to respiratory infections while there were no deaths from respiratory failure secondary to ILD. BAL lymphocytosis appears to be a surprisingly serious index of dismal prognosis in patients with pSS. We offer no unifying pathophysiologic mechanism for it and, therefore, all we propose is that BAL is performed early, in as many patients with pSS as possible. These patients should then be followed up systematically, in order to evaluate if BAL lymphocytosis has any pathophysiologic importance in the development of clinically serious pSS, which is serious enough to lead to death.

Sinus histocytosis with massive lymphadenopathy (Rosai-Dorfman disease) in a patient with primary Sjogren's syndrome.

Sinus histocytosis with massive lymphadenopathy is a rare disease that has been described by Rosai and Dorfman. It is characterized by massive, cervical lymphadenopathy, with extranodal manifestations in about 40% of patients. It occurs as a distinct entity, never associated with other diseases, and in most cases the prognosis is good. Lymphadenopathy is also a frequent sign of patients with primary Sjogren's syndrome (SS), usually associated with disease activity or concurrent infection. However, excessive lymphadenopathy in SS patients is a sign of lymphoproliferative disorder development. In this report, we describe a patient with primary SS, and excessive lymphadenopathy and splenomegaly who developed Rosai-Dorfman disease, and we discuss the possible aetiopathophysiological mechanism linking these two entities.

Infliximab therapy in patients with ankylosing spondylitis: an open label 12 month study.

OBJECTIVE: To evaluate the efficacy and safety of long term infliximab therapy in patients with severe refractory ankylosing spondylitis (AS). PATIENTS AND METHODS: Twenty five patients (24 male, 1 female; mean (SD) age 36.0 (10.5); disease duration 13.8 (8.5) years) with AS fulfilling the modified New York criteria for AS were investigated. Twenty two (88%) patients were HLA-B27 positive. All patients had active axial disease (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >/=30/100) and C reactive protein (CRP) >/=10 mg/l, despite adequate treatment. Intravenous infliximab (5 mg/kg) was given at weeks 0, 2, 6, and every eight weeks thereafter for 12 months. The primary end point was the reduction of the patient's global assessment of pain (GAP) by >20% on a 100 mm visual analogue scale. RESULTS: GAP was reduced by >20% in 23 (92%) patients, by 50% in 21 (84%) patients, and by 70% in 13 (52%). The change in BASDAI and CRP from baseline was statistically significant. The treatment was well tolerated with minimal side effects. One patient dropped out owing to inefficacy and one stopped treatment owing to an allergic reaction. CONCLUSION: This longer length study confirms the efficacy of infliximab and the good safety profile in patients with AS.

Seropositive rheumatoid arthritis associated with Crohn's disease.

In the present study we report a patient with long-standing seropositive rheumatoid arthritis, who developed Crohn's disease. We discuss the possible pathophysiologic mechanisms and their associations between these two entities.

Infliximab treatment in combination with cyclosporin A in patients with severe refractory rheumatoid arthritis.

OBJECTIVE: To investigate whether infliximab can be used in combination with cyclosporin A (CsA) in patients with refractory rheumatoid arthritis (RA) who cannot tolerate methotrexate (MTX). MATERIALS AND METHODS: Eighteen patients with refractory RA receiving low dose CsA (2 mg/kg/day) and prednisone (5 mg/day) were treated with intravenous infliximab. The patients were given infliximab (3 mg/kg weight) at 0, two, six, and every eight weeks thereafter for a total period of 12 months. Clinical improvement was evaluated according to the American College of Rheumatology (ACR) 20% response criteria. RESULTS: Eighty per cent of patients receiving the combination treatment with CsA and infliximab achieved the 20% ACR criteria for response to treatment, whereas 39% satisfied the 50% response criteria. In addition, a 76% reduction in swollen and tender joint count was found. Finally, a reduction in C reactive protein and erythrocyte sedimentation rate was maintained throughout the study. In general, treatment was well tolerated, with minimal adverse drug reactions. Two patients dropped out; one because of an immediate hypersensitivity reaction and the other because of the development of pulmonary tuberculosis. CONCLUSION: Multiple infusions of infliximab and low doses of CsA improve patients with refractory RA. It seems that CsA may be an alternative disease modifying drug to be used in combination with infliximab in patients with refractory RA who cannot tolerate MTX.