Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the "Euro-Lupus Project".

The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium--the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Lessons from the "Euro-Lupus Cohort".

The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1,000 patients. European Working Party on Systemic Lupus Erythematosus.

In the present study we assessed the frequency and characteristics of the main causes of morbidity and mortality in SLE during a 5-year period and analyzed the prognostic significance for morbidity and mortality of the main immunologic parameters used in clinical practice. We started in 1990 a multicenter study of 1,000 patients from 7 European countries. All had medical histories documented and underwent medical interview and routine general physical examination when entered in the study, and all were followed prospectively by the same physicians during the ensuing 5 years (1990-1995). Four hundred thirteen patients (41.3%) presented 1 or more episodes of arthritis, 264 (26.4%) had malar rash, 222 (22.2%) active nephropathy, 139 (13.9%) fever, 136 (13.6%) neurologic involvement, 132 (13.2%) Raynaud phenomenon, 129 (12.9%) serositis (pleuritis and/or pericarditis), 95 (9.5%) thrombocytopenia, and 72 (7.2%) thrombosis. Two hundred seventy patients (27%) presented infections, 113 (11.3%) hypertension, 75 (7.5%) osteoporosis, and 59 (5.9%) cytopenia due to immunosuppressive agents. Sixteen patients (1.6%) developed malignancies, with the most frequent primary localizations the uterus and the breast. Several immunologic parameters (anti-dsDNA or antiphospholipid antibodies) were found to have a predictive value for the development of SLE manifestations during the period of the study. Forty-five patients (4.5%) died; the most frequent causes of death were divided similarly among active SLE (28.9%), infections (28.9%), and thromboses (26.7%). A survival probability of 95% at 5 years was found. A lower survival probability (92%) was detected in those patients who presented at the beginning of the study with nephropathy.

Seizures and hepatotoxicity following sulphasalazine administration.

Sulphasalazine (SSZ) is a widely used second-line agent for several rheumatic diseases. Most of its side effects are relatively minor and dose dependent. We report a patient with juvenile onset chronic arthritis who developed hepatotoxicity and seizures on the third week of SSZ when the daily dose was increased to 2 g. Clinical and laboratory findings of liver and central nervous system toxicity gradually returned to normal in the month following SSZ withdrawal.

Elevated levels of soluble intercellular adhesion molecule-1 correlate with disease activity in Behçet's disease.

The objective of this study was to measure soluble intercellular adhesion molecule-1 (sICAM-1) in patients with Behçet's disease (BD) and to analyse the relationship of sICAM-1 levels with clinical and some laboratory measures of disease activity. Forty patients with BD fulfilling the International Study Group Criteria for the diagnosis of BD and 20 healthy controls were studied. Twenty patients had active, and 20 patients had inactive disease. Serum sICAM-1 was determined by a sandwich ELISA. The mean (+/- SD) sICAM-1 level was significantly higher in the whole BD group (297.3 +/- 86.6 ng/ml) than in the healthy controls (213 +/- 83.5 ng/ml; P < 0.05). The mean sICAM-1 levels in active and inactive BD patients were 315.7 +/- 76.3 ng/ml and 258.3 +/- 73.3 ng/ml, respectively. The mean sICAM-1 level in active patients was significantly higher than in inactive patients and healthy controls (P < 0.02 and P < 0.001, respectively). No statistically significant difference in mean sICAM-1 levels was found between inactive BD patients and healthy controls (P > 0.05). There was no statistically significant difference between the mean sICAM-1 levels of active patients with (351.3 +/- 77.2 ng/ml) or without vascular lesions (292 +/- 68.8; P > 0.05). In spite of a positive correlation between disease activity and both erythrocyte sedimentation rate and C-reactive protein (CRP; P < 0.01), we found no correlation between sICAM-1 and either of them (P > 0.05). The elevated levels of sICAM-1 may be due to endothelial cell activation and/or damage or may be the result of inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies to endothelial cells in patients with Behçet's disease.

Autoantibodies that bind to endothelial cells have been identified in patients with several forms of vasculitis. Behçet's disease--a multisystem inflammatory disorder of unknown etiology--is associated with thrombosis in addition to systemic manifestations resulting from small and large vessel vasculitis. We studied 72 Turkish patients (33 female, 39 male) with Behçet's disease in order to investigate the prevalence of antiendothelial cell antibodies (AECA) and to examine their possible relationship with clinical and laboratory features of the illness. Sera from 30 healthy Turkish people were used as controls. Human umbilical vein endothelial cells were cultured and used unfixed in a cellular ELISA to detect AECA. IgG and/or IgM AECA were found in 13 (18.1%) patients but not in healthy controls. Antiendothelial cell antibodies did not induce complement-mediated cytotoxicity as assessed by 51Cr release assay and the binding was not due to immune complexes. The prevalences of acute thrombotic events and retinal vasculitis at the time of the AECA assay among patients with AECA were significantly higher than those in patients without AECA. Laboratory parameters of active disease were higher in patients with AECA. There was no correlation between other clinical and laboratory features of Behçet's disease and AECA. Anticardiolipin and antineutrophil cytoplasmic antibodies were negative in our series, excluding a possibility of cross-reaction with AECA. Our results suggest a possible role of AECA in association with thrombosis and vasculitis in patients with Behçet's disease.

Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on Systemic Lupus Erythematosus.

In the present study we have analyzed the prevalence and characteristics of the most relevant clinical and immunologic features in 1,000 patients with SLE. Several differences in the expression of the disease have been observed in relation to the patients' age at onset, sex, and autoantibody serology. The childhood-onset patients more often had malar rashes (55% vs 39%) and nephropathy (28% vs 15%) as presenting manifestations. During the evolution of the disease, these patients had an increased prevalence only of malar rash (79% vs 56%) and a lower prevalence of rheumatoid factor (6% vs 19%). The older-onset patients (age 50 or older) less often showed malar rash (21% vs 42%), arthritis (52% vs 71%), and nephropathy (3% vs 17%) as the first symptom. During the evolution of their disease, these patients had a decreased prevalence of malar rash (33% vs 60%), photosensitivity (29% vs 47%), arthritis (73% vs 85%), nephropathy (22% vs 41%), thrombosis (4% vs 15%), and anti-La antibodies (6% vs 20%), but an increased prevalence of sicca syndrome (33% vs 15%). Males more often had serositis (28% vs 16%) as a first symptom, but they presented with a lower prevalence of arthritis (74% vs 85%) during the evolution of the disease. The presence of ANA, a high titer of anti-dsDNA, rheumatoid factor, anti-ENA, and antiphospholipid antibodies also distinguished additional homogeneous SLE subsets of clinical significance.

Systemic lupus erythematosus in males: analysis of clinical and laboratory features.

We analysed the clinical and laboratory features of 16 males in comparison with 231 females from a series of 247 unselected patients with systemic lupus erythematosus (SLE). There was no significant difference between male and female patients with regard to age at onset and age at diagnosis. Apart from serositis, which was found to occur at a significantly higher frequency in male patients, the incidence of clinical features at disease onset was similar in both sexes. Analysis of clinical findings during the evolution of the disease showed no significant difference between male and female patients. Similarly, no significant immunological difference was found between the two groups. Thus, except for a higher frequency of serositis as the presenting symptom in males, we could not find any notable differences in clinical and serological parameters of male and female patients with SLE.

Low dose methotrexate treatment in adult Still's disease.

Six patients with adult Still's disease who had either failed to respond to or had adverse effects from previous therapy were given weekly low dose methotrexate (MTX) therapy. They were followed for 4-28 months (mean 14 +/- 9 months). At 12 months of therapy 3 patients were evaluated as having a complete response. One patient had a partial response to MTX after 7 months. Therapy was discontinued in 1 patient at 4 months due to flares of rash and arthralgias after each MTX administration. One patient failed to respond to therapy despite maximum dosage, but was able to reduce his corticosteroid dose. MTX may be a useful therapy to consider in patients with adult Still's disease who are resistant to conventional therapy and may allow a reduction in the concomitant dose of corticosteroids.

Polymyositis complicating D-penicillamine treatment.

Although there is good evidence that D-penicillamine can induce polymyositis, the exact pathogenic mechanism remains unclear. We report two patients with psoriatic arthritis and primary biliary cirrhosis respectively, who developed polymyositis while receiving D-penicillamine treatment for their primary diseases. Whether D-penicillamine treatment was the sole cause of polymyositis or acted as a trigger for the development of a secondary autoimmune disease is discussed.