Yannis Alamanos

Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment – a prospective, controlled study

We investigated lipid profiles and lipoprotein modification after immuno-intervention in patients with early rheumatoid arthritis (ERA). Fifty-eight patients with ERA who met the American College of Rheumatology (ACR) criteria were included in the study. These patients had disease durations of less than one year and had not had prior treatment for it. Smokers or patients suffering from diabetes mellitus, hypothyroidism, liver or kidney disease, Cushings syndrome, obesity, familiar dyslipidemia and those receiving medications affecting lipid metabolism were excluded from the study. Sixty-three healthy volunteers (controls) were also included. Patients were treated with methotrexate and prednisone. Lipid profiles, disease activity for the 28 joint indices score (DAS-28) as well as ACR 50% response criteria were determined for all patients. The mean DAS-28 at disease onset was 5.8 ± 0.9. After a year of therapy, 53 (91.3%) patients achieved the ACR 20% response criteria, while 45 (77.6%) attained the ACR 50% criteria. In addition, a significant decrease in the DAS-28, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were observed. ERA patients exhibited higher serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides, whereas their serum high-density lipoprotein cholesterol (HDL-C) levels were significantly lower compared to controls. As a consequence, the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was significantly higher in ERA patients compared to controls. After treatment, a significant reduction of the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was observed, a phenomenon primarily due to the increase of serum HDL-C levels. These changes were inversely correlated with laboratory changes, especially CRP and ESR. In conclusion, ERA patients are characterized by an atherogenic lipid profile, which improves after therapy. Thus, early immuno-intervention to control disease activity may reduce the risk of the atherosclerotic process and cardiovascular events in ERA patients.

Early Treatment Reduces the Cardiovascular Risk Factors in Newly Diagnosed Rheumatoid Arthritis Patients

OBJECTIVE To investigate subclinical atherosclerosis and the effect of treatment in patients with early rheumatoid arthritis (RA). PATIENTS AND METHODS Forty patients with early RA who met the revised American College of Rheumatology (ACR) criteria and disease duration of <1 year were included in the study. Smokers and patients with classical risk factors for atherosclerosis were excluded. The serum levels of total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were determined in all patients before and after 1 year of therapy. Carotid artery intima-media thickness (IMT) and carotid plaque were measured before and after treatment. RA disease activity was measured using the 28 joint indices score (DAS-28) and clinical improvement was determined by the ACR response criteria. Forty-five age- and sex-matched nonsmoking volunteers were used as controls. All patients were treated with methotrexate and prednisone. RESULTS RA patients had a baseline mild dyslipidemia characterized by a decrease in serum HDL-C levels and a high TC/HDL-C atherogenic ratio compared with controls. Both lipid parameters were significantly improved after treatment (P<0.01). Common carotid artery IMTs at baseline were higher in RA patients compared with controls (P<0.05). After 1 year of therapy there was a significant decrease in the IMTs (P<0.001). Thirty-five patients (88%) achieved the ACR 20%, while 30 (75%) reached the ACR 50% response criteria. A significant decrease of DAS-28 was observed after treatment (P<0.03). CONCLUSIONS The atherogenic lipid profile and subclinical atherosclerosis are features of early RA, which improved after therapy. Early intervention and control of the disease activity may reduce the risk of atherosclerosis and cardiovascular events in patients with RA.

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 Larsens 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.

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.

Prevalence of Raynaud's phenomenon in a healthy Greek population

OBJECTIVE Raynauds phenomenon (RP) is comprised of repeated episodes of colour changes of the skin of digits on cold exposure or emotional stress. The prevalence of RP in the general population is variable fluctuating between 4%–15%, among surveys. The aim of this study was to estimate the prevalence of RP in a healthy working Greek population and to investigate the possible association of RP with various demographic, social and other factors. METHODS A total of 756 employees of the University Hospital of Ioannina was included in the study. They belong to the administrative (120 subjects), nursing and technical (a representative sample of 418 and 218 subjects, respectively) personnel. Five hundred subjects (111 men and 389 women) responded in a face to face interview based on a specially conformed questionnaire. The study began in November 1997 and was completed in March 1998. RESULTS Twenty six subjects with RP (1 man and 25 women) were found. Their mean (SD) age was 32.73 (5.77) years. The prevalence of RP was 5.2% (0.9% in men and 6.4% in women). The sex ratio, male/female, was 1/7.1. An association between RP and migraine was found. However, there were no significant correlations of RP with smoking, alcohol and coffee consumption, dietary habits, occupational history and drug exposure. No social or other demographic parameters associated to RP frequency were found. CONCLUSIONS The prevalence of RP (5.2%) in the population studied is relatively low compared with previous studies. RP focuses on the fourth decade of life and affects mainly women. There was no evidence of any correlation of RP with social, environmental or personal parameters while an association of RP with migraine was found. Geographical or genetic factors, or both, may be responsible for these results.

Prognostic Factors of Radiological Damage in Rheumatoid Arthritis: A 10-year Retrospective Study

Objective. To describe the longterm clinical and radiological outcomes in rheumatoid arthritis (RA) in a cohort in northwestern Greece; and to investigate predictive factors of radiological damage at the 10-year followup in patients with RA. Methods. We studied the disease course and outcome of 144 patients with RA and radiographs of the hands and wrists available at baseline and at 10 years. Baseline measurements and time-averaged measures of swollen joint count (SJC) and inflammatory markers [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)] were tested in univariate analysis, and then those presenting a statistically significant association with either Larsen score at 10 years or annual progression rate were included in 2 logistic regression models in order to determine relevant independent prognostic factors. Results. A significant clinical improvement was noted, associated with a decrease of inflammatory markers along the timepoints. Larsen score and the number of erosive joints were increased. In the univariate analysis, both final Larsen score at 10 years and accelerated annual radiological progression rate were significantly associated with baseline radiographic measurements (Larsen score and number of erosive joints), the presence of autoantibodies [anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor of IgA and IgM isotype], disease duration, and time-averaged measures of ESR, CRP, and SJC. In the logistic regression analysis, the baseline Larsen score, anti-CCP antibodies, and time-averaged CRP presented significant and independent associations with Larsen score at 10 years. An accelerated annual radiological progression rate was also predicted by baseline Larsen score and time-averaged measures of SJC and CRP. Conclusion. Despite clinical improvement, the radiologic progression of RA continues over time, because of the underlying inflammatory process. Baseline radiographic damage, anti-CCP antibodies, and time-averaged CRP constitute the main predictive factors of poor radiologic outcome in the long term.

Sustained Clinical Response in Psoriatic Arthritis Patients Treated with Anti-TNF Agents: A 5-year Open-Label Observational Cohort Study

OBJECTIVE To investigate the efficacy, toxicity, and drug discontinuation in patients with psoriatic arthritis treated with anti-tumor necrosis factor agents. METHODS Sixty-five patients with active disease were included in this open-label study. They had tender or swollen joint count ≥5, Psoriatic Arthritis Severity Index (PASI) score ≥10, and erythrocyte sedimentation rate ≥28 mm Hg/1st hour and/or C-reactive protein ≥10 mg/L. All were refractory to at least 2 disease-modifying antirheumatic drugs. Thirty were treated with infliximab, 25 with etanercept, and 10 with adalimumab. Infliximab (5 mg/kg body weight) was given intravenously at weeks 0, 2, 6, and every 8 weeks thereafter; etanercept was given subcutaneously (25 mg twice a week), while adalimumab was given subcutaneously (40 mg every other week) for a period of 5 years. Data concerning anti-tumor necrosis factor efficacy tolerability, adverse events, and drug discontinuation were recorded. The percentage of patients who achieved the Psoriatic Arthritis Response Criteria (PSARC), the improvement of PASI, the improvement according to the American College of Rheumatology (ACR) criteria, and the disease activity for 28 joint indices score (DAS-28) were recorded. RESULTS After 5 years, PSARC was 60%, PASI 70 was 66.7%, PASI 90 was 63.3%, while ACR 50 was 56.7% for the patients treated with infliximab. Moreover, PsARC was 64%, PASI 70 and PASI 90 were 68%, while ACR 50 was 56% for those treated with etanercept. Furthermore, in the adalimumab group PsARC was 56%, PASI 70 and PASI 90 were 58% and 50%, respectively, while ACR 50 was 50%. Additionally, DAS-28 scores were significantly improved. Thirteen patients treated with infliximab, 6 with etanercept, and 5 patients with adalimumab were withdrawn. At the end of treatment, the survival of infliximab was 56.7%, for etanercept 76%, and for adalimumab 50%. CONCLUSION All drugs were effective, safe, and well-tolerated. The clinical improvement was maintained through the 5 years with satisfying infliximab and adalimumab survival and high etanercept survival.

Outcome in 1,000 head injury hospital admissions: the Athens head trauma registry

BACKGROUND The aim of this study was to establish a head trauma registry to (a) examine demographics, etiology, severity, clinical course, and outcome; (b) compare results with previous published series; (c) identify causes of bad outcomes; and (d) propose methods to improve therapy and prognosis. METHODS The following data were collected on 1,000 consecutive victims with head injury over 14 years of age admitted during a 4-year period: demographic characteristics, cause of injury, clinical variables, neuroimaging, therapy data, and outcome in 6 months. RESULTS Seventy-four percent were men, and mean age was 43 years. Seventy-one percent suffered injuries due to road crashes, 14% due to alcohol, and 2% due to substances. The secondary transfer rate was 49%. For severe injuries, the time intervals from incident to hospital and subsequently to neurosurgical unit were 35 minutes and 4 hours, respectively. In 65% and 72% of cases, there was no record of preresuscitation hypoxia or hypotension, respectively, whereas suspected or definite episodes of hypoxia and hypotension were 27% and 13%, respectively. Most cases were mild trauma (63%), the remaining were severe (26%) and moderate (11%) injuries. Severe systemic trauma coexisted in 18%. Cranial surgery rate was 19% and it increased to 39% in severe trauma. The 6-month overall good outcome was 71%, with lower rates in moderate (58%) and severe (24%) injuries. CONCLUSIONS The organization of Greeces first head injury registry offered an important preliminary core data concerning brain trauma etiology, management, and long-term outcome.

Defense mechanisms in inflammatory bowel disease.

BackgroundAlthough psychiatric disturbances and personality features are possibly involved in inflammatory bowel disease, little attention has been given to the potential role of defense mechanisms in the formation, course, or prognosis of the disease. The purpose of the present study was to determine whether certain defense styles and ego mechanisms of defense are associated with inflammatory bowel disease, including both ulcerative colitis and Crohn’s disease.MethodsSeventy-six consecutive unselected outpatients participated in the study. The sample consisted of 39 patients with Crohn’s disease, 33 with ulcerative colitis, and 4 with an intermediate form of inflammatory bowel disease. The Symptom Distress Checklist (SCL-90-R), Defense Style Questionnaire (DSQ), and Hostility and Direction of Hostility Questionnaire (HDHQ) were used.ResultsCrohn’s disease patients presented a more immature defensive profile than ulcerative colitis patients, using a “maladaptive action” style, as well as “consumption” and “pseudo-altruism” defense mechanisms more often. These differences were statistically significant and they were independent of age, sex, educational level, disease extension, and pharmacologic treatment. A significant positive correlation was also found between disease activity and defensive profiles in both ulcerative colitis and Crohn’s disease patients. In contrast, there was no statistically significant difference between ulcerative colitis and Crohn’s disease patients in terms of psychiatric symptoms.ConclusionsCrohn’s disease patients presented a different and more immature defensive profile than patients with ulcerative colitis. In addition, the more psychologically mature inflammatory bowel disease patients had lower rates of relapses and surgical operations, providing evidence that these aspects of personality are likely to influence the patients’ adaptation to the disease.

Cardiovascular risk profile in patients with spondyloarthritis

OBJECTIVES The spondyloarthritides (SpA) are associated with an increased cardiovascular risk. We studied cardiovascular risk factors in patients with SpA. METHODS The following risk factors were assessed in SpA patients and healthy controls: smoking, family history of premature ischemic heart disease, obesity, serum lipids, apolipoproteins, urate and carotid intima media thickness (IMT). RESULTS Overall 150 patients (73 with ankylosing spondylitis [AS], 71 with psoriatic arthritis [PsA] and six with other SpA types) were included. Generally SpA patients were significantly more often smokers, while PsA patients had greater values of abdominal obesity. AS patients had significantly lower levels of triglyceride, HDL, ApoB, ApoE and Lp(a) and a higher atherogenic index (total cholesterol/HDL). PsA patients had significantly lower levels of HDL, ApoAI and ApoE, an elevated atherogenic index and higher serum urate. In multivariate analysis the atherogenic index was positively associated with SpA across all patient groups independently of smoking and other lipid parameters. Carotid IMT in SpA patients (0.71 mm) was higher than controls (0.63 mm, P=0.017), although after adjusting for smoking this ceased to be significant. Treatment of patients with previously untreated disease resulted in a small but significant decline in ApoB levels at 6 months (P=0.045), which, however, was no longer evident at 12 months. CONCLUSION Spondyloarthritis patients are at a greater cardiovascular risk owing to the higher prevalence of smoking and a higher atherogenic index. PsA patients have more abdominal fat and higher urate levels. Immunosuppressive treatment of SpA produces minor and temporary effects on the lipid profile.