Psychological stress in rheumatoid arthritis patients: a comparative Polish-German study: summary of the current conceptualization of the role of stress in rheumatoid arthritis.

Cultural differences in experiencing individual stress in rheumatoid arthritis (RA) patients might be observed. The aim of the study was to assess quality of life and psychological stress (distress) in RA patients, and to evaluate socio-demographic and disease specific variables predicting stress of patients. The study covered 300 Polish and 137 German RA patients. SF-36v2 scale was used to evaluate the patients' health. Psychological stress was defined as the feeling of "social isolation" and "being a burden" as demanding help in everyday activities. In both countries, the mental and physical health of patients deteriorated and about 50% of patients required support in everyday activities. 95% of Polish and 62% of German patients felt rejected from social activities. For the psychological stress perceived, functional capacity class 3 and male gender were shown to be predictive in Polish patients and living in a small town - in German patients. In the Polish group, the tertiary/bachelor level of education was linked with lower distress level. RA has a serious impact on the mental health owing to a great disease burden. Awareness of impact of the disease on quality of life and psychological stress of patients should be considered in routine clinical practice.

Risk factors for atherosclerosis in healthy employees-a multidisciplinary approach.

BACKGROUND: The aim of the study was to investigate the prevalence of early atherosclerosis in healthy workers and the relationship between classical, psychological, and immunological risk factors and atherosclerosis, as well as their predictive value. METHODS: One hundred healthy managers and 50 office workers aged 35-65 were studied. In all subjects, individual, family, and occupational stress/coping risk factors were evaluated, including plasma levels of biochemical (total cholesterol, LDL, HDL, TG, glucose) and inflammatory-immunological (aCL, anti-beta(2) GPI, oxLDL, HSP, HSCRP) parameters. Carotid artery intima-media thickness (IMT) and atherosclerotic plaques in carotid arteries were assessed with computer analysis of B-mode ultrasound images. RESULTS: In 107 persons (71%) no changes were found in ultrasound images and in 43 individuals (29%) the presence of plaque was shown. The mean IMT value was 0.0618+/-0.013 mm. Cross-domain analysis showed that core predictors for IMT were age, LDL level, smoking, and occupation (being a manager) (beta=0.33, 0.30, 0.23, and 0.20, respectively); the core predictors for plaque were age, total cholesterol level, and an occupational stressor home-work balance (Wald=7, 6.7, and 5.6, respectively). Immunological factors were not independent predictors. CONCLUSIONS: In atherosclerosis, not only traditional risk factors (age, lipid disorders, and lifestyle) but also occupational stress factors may play a role. Immunological factors do not seem to play a role in the development of atherosclerosis in a population of healthy workers. The interplay between occupational stress and atherosclerotic changes requires further investigation.

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.

[Neurological and psychiatric symptoms in patients with systemic lupus erythematosus]. / Zaburzenia neurologiczne i psychiczne u chorych z toczniem rumieniowatym ukladowym.

Sixty patients (51 women/9 men) with diagnosis of SLE were studied for finding out the frequency of nervous system involvement in SLE, the time of of appearance of neurological involvement after diagnosis establishing, the coexistence of the antiphospholipid syndrome, and the character of changes in MR, CT and CSF. Nervous system involvement was found in 40 cases (67%), with 34 cases (56%) had involvement of the CNS, 6 patients (10%) had symptoms of peripheral nervous system dysfunction, and 3 (5%) had involvement of both systems. In 4 cases polineuropathy and transverse spinal cord lesion, and in 3 cases psychiatric symptoms were the first manifestations of SLE. Changes due to involvement of cerebral vessels (TIA, stroke) were observed in 20 patients (33%), and psychiatric symptoms in 16 cases (26.6%). No difference was found in the occurrence of stroke or TIA between SLE patients with and without antiphospholipid syndrome, and no correlations were noted between the presence of neurological or psychiatric symptoms and other SLE symptoms. CT scans demonstrated corticosubcortical atrophy in 28.3% of cases, while in MRI in T2 images small hyperintense lesions were situated mainly in the white matter (33.9%). In 5 cases oligoclonal band was found in the CSF, but without any correlation with specific neurological symptoms.

Evaluation of cerebrospinal fluid for the presense of anticardiolipin antibodies (aCL) in NP-SLE patients.

Many neurological or psychiatric manifestations of SLE (NP-SLE) are related to the presence of anticardiolipin antibodies (aCL) in the patient's sera. The aim of this study was to evaluate the presence of aCL in cerebrospinal fluid (CSF) in SLE patients with NP features. Fifteen SLE patients were studied, all with NP features. CSF was evaluated for intrathecal IgG synthesis, oligoclonal IgG, and blood-brain barrier impairment. Sera and CSF were tested by ELISA for the presence of aCL-IgG and aCL-IgM with and without beta2 glycoprotein (beta2 GPI) cofactor. CSF and sera of 50 low back pain patients served as controls. Six patients were aCL(+) and nine aCL(-). In all patients the general CSF examination was normal. In all patients the value of indices of intrathecal IgG synthesis were normal but oligoclonal protein was present in the CSF of three patients. In none of the patients was the blood-brain barrier impaired. Neither aCL-IgG nor aCL-IgM was detected in the CSF of any NP-SLE patient. Mean levels of aCL in patients without cofactor beta2 GPI and with cofactor were as follows: for IgG class 0.005 and 0.057 OD (negative); for IgM class 0.004 and 0.024 OD (negative). We could not detect aCL in the CSF of patients with NP-SLE, even if sera were positive for aCL.

HLA class II alleles associations of anticardiolipin and anti-beta2GPI antibodies in a large series of European patients with systemic lupus erythematosus.

The objective of this study was to determine the HLA class II associations of the anticardiolipin (aCL) and anti-beta2GPI (abeta2GPI) antibodies in a large series of European patients with systemic lupus erythematosus (SLE). A cohort of 577 European SLE patients was enrolled. aCL and abeta2GPI were measured by ELISA methods. Molecular typing of HLA-DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1 loci was performed by the polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method. aCL of IgG, IgM and IgA isotypes were detected in 22.8%, 14% and 13.9% of patients, respectively. IgG and IgM abeta2GPI were detected in 20% of patients. aCL showed positive association with HLA DRB1*04, DRB1*0402, DRB1*0403, DRB1*07, DRB3*0301, DQA1*0201, DQA1*0301, DQB1*0302, and negative association with DQA1*0501, DRB3*0202. abeta2GPI showed positive association with DRB1*0402, DRB1*0403, DQB1*0302. DRB1*0402 carried the highest relative risk for the presence of both aCL (RR=8. 1) and abeta2GPI (RR=4.6). Our results confirm the already described associations of aCL with HLA DR4 and DR7, but also demonstrate that, among the alleles at the DRB1*04 locus, the *0402 was most represented both in aCL and in abeta2GPI positive patients. In addition, HLA class II associations of abeta2GPI are for the first time extensively examined in a large cohort of European SLE patients.

Anti-ganglioside antibodies in a large cohort of European patients with systemic lupus erythematosus: clinical, serological, and HLA class II gene associations. European Concerted Action on the Immunogenetics of SLE.

OBJECTIVE: To assay anti-ganglioside antibodies (aGM1) in sera of a large cohort of European patients with systemic lupus erythematosus (SLE) to define the prevalence of these autoantibodies in SLE; to evaluate the association of aGM1 with clinical manifestations and other autoantibodies found in SLE; and to search for aGM1 association with HLA class II alleles. METHODS: Four hundred forty-eight patients with SLE were consecutively enrolled in 8 centers from 6 European countries. All sera were tested for antinuclear antibodies by immunofluorescence on HEp-2 cells as substrate, anti-dsDNA, aGM1, aCL, abeta2-glycoprotein I (abeta2-GPI) antibodies by ELISA, and antineutrophil cytoplasmic antibodies (ANCA) by immunofluorescence and by ELISA. Genomic typing for HLA class II loci was performed by polymerase chain reaction-sequence specific oligonucleotide probe method. Clinical assessment was done at the time of enrolment. RESULTS: We found 41.9% of patients with clinical signs of neuropsychiatric involvement; 15.5% of patients were positive for aGM1, 8% of the IgG isotype and 8.6% of the IgM isotype; aGM1-IgG were associated with neuropsychiatric manifestations (NPM) (RR = 3.7), with migraine (RR = 2.4), with OBS (RR = 7.3), and with peripheral neuropathy (RR = 8.5). aGM1-IgM were associated with NPM (RR = 4) and with depression (RR = 3.4). Furthermore, the genetic study showed that aGM1-IgG were associated with HLA-DQB1*0404 (RR = 7.2) while aGM1-IgM were associated with HLA-DQB1*0605 (RR = 33.3). No associations were found between aGM1 and anti-dsDNA, aCL, abeta2GP1, or ANCA. CONCLUSION: Our results show aGM1 can be found in patients with SLE. aGM1 may play a pathogenetic role for some NPM in this condition.

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.

Anticardiolipin and anti-beta2GPI antibodies in a large series of European patients with systemic lupus erythematosus. Prevalence and clinical associations. European Concerted Action on the Immunogenetics of SLE.

OBJECTIVE: To test the prevalences and the clinical associations of anticardiolipin (aCL) and anti-beta2GPI (abeta2GPI) antibodies in a large series of European patients with systemic lupus erythematosus (SLE). METHODS: 574 SLE patients from 7 European countries were tested for aCL and abeta2GPI by ELISA methods. RESULTS: aCL of IgG, IgM, and IgA isotypes were detected in 22.8%, 14%, and 13.9% of the patients, respectively. IgG and IgM abeta2GPI were detected in 20% of the patients. The presence of aCL was highly associated with the presence of abeta2GPI. Medium-high titer IgG aCL and abeta2GPI were associated with thrombosis, with similar sensitivity, specificity, and positive predictive value. When present at medium-high titer, IgG aCL were associated with thrombocytopenia, IgM aCL with hemolytic anemia, and cerebrovascular accidents. IgA aCL with livedo reticularis and Raynaud's phenomenon. CONCLUSIONS: aCL, when present at medium-high titer, are as important as abeta2GPI, as a risk factor for thrombosis. Medium-high titer aCL, but not abeta2GPI, are associated with other clinical features of the antiphospholipid syndrome.

Anti-neutrophil cytoplasmic antibodies in 566 European patients with systemic lupus erythematosus: prevalence, clinical associations and correlation with other autoantibodies. European Concerted Action on the Immunogenetics of SLE.

OBJECTIVES: To evaluate, in a cohort of 566 patients with systemic lupus erythematosus (SLE) drawn from 11 European centres: (i) the prevalence of ANCAs and their subspecificities in a large series of European SLE patients; (ii) the possible associations of ANCA with the most common clinical manifestations of the disease; and (iii) whether ANCAs correlate with some of the autoantibodies commonly found in SLE. METHODS: ANCA detection was performed by indirect immunofluorescence (IIF), and by ELISA for lactoferrin (LF), myeloperoxydase (MPO), proteinase3 (PR3) and lysozyme (LZ) subspecificities. RESULTS: The prevalence of ANCA was 16.4% (IIF). The prevalence of LF was 14.3%, LZ 4.6%, MPO 9.3%, and PR3 1.7%. Our results show that ANCA is associated with certain clinical manifestations of SLE. In particular, positive correlations were found between IIF ANCA and serositis (p = 0.026), livedo reticularis (p = 0.01), venous thrombosis (p = 0.03) and arthritis (p = 0.04), while anti-LF antibodies were associated with serositis (p = 0.05) and livedo reticularis (p < 10(-3). Nevertheless, multivariate analysis demonstrated that other autoantibodies, such as aCL and SSA/Ro, are more closely correlated than ANCA with some of the aforementioned clinical features. CONCLUSION: Our results demonstrate that ANCA are detectable in SLE sera and that some of them are associated with particular clinical manifestations. Whether ANCA plays a direct pathogenetic role in the vascular damage of SLE or only represents an epiphenomenon or a marker of disease activity remains to be elucidated.

[Coexistence of severe aortic insufficiency and systemic lupus erythematosis with antiphospholipid syndrome--case report]. / Wspólistnienie duzej niedomykalnosci aortalnej i tocznia rumieniowatego ukladowego z zespolem antyfosfolipidowym--opis przypadku.

We presented the coexistence of the severe aortic insufficiency and the systemic lupus erythematosus with antiphospholipid syndrome in 33-years old woman. She was qualified for the operation of the prosthesis aortic valve replacement after she was treated with steroids. During the operation, the heart infarct of the inferior wall had been observed, but finally in the postoperation period the heart efficiency improvement was observed. We have discussed same theories and clinical experiences of lupus erythematosus with antiphospholipid syndrome and clinical sequels.

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.

Isotype profile and clinical relevance of anticardiolipin antibodies in Sjögren's syndrome.

The purpose of this study was to determine the occurrence and clinical value of anticardiolipin antibodies in patients with Sjögren's syndrome. Thirty one patients with primary Sjögren's syndrome (all women, mean (SD) age 48.3 (11.2) years) and 32 patients with secondary Sjögren's syndrome with rheumatoid arthritis (all women, mean (SD) age 54.9 (11) years) were studied. IgG, IgM, and IgA anticardiolipin antibodies were determined by a standard enzyme linked immunosorbent assay (ELISA) technique. Anticardiolipin antibodies were found in five patients (16%) with primary Sjögren's syndrome and in seven patients (22%) with secondary Sjögren's syndrome. There was no correlation between anticardiolipin antibodies and the clinical features of the antiphospholipid syndrome (thrombotic events, fetal loss, thrombocytopenia) or extraglandular manifestations of Sjögren's syndrome (arthritis, skin lesions, myositis, polyneuropathy, central nervous system disease, pulmonary and renal disease) in either group. Among the various serological features studied, anticardiolipin antibodies correlated with antinuclear antibodies and antibodies to RNP only in patients with primary Sjögren's syndrome. These results indicate that although anticardiolipin antibodies are often found in serum samples from patients with Sjögren's syndrome, their clinical significance remains unclear.

Systemic lupus erythematosus in 50 year olds.

We compared the clinical and serological characteristics of 15 patients with onset of systemic lupus erythematosus after the age of 50 with those of 232 younger patients. The sex distribution was similar in both groups. All 15 patients were Caucasian. Autoimmune thyroiditis was found in 20% of the elderly patients. Initial manifestations, which presented more frequently in the older group, included thrombocytopenia (P < 0.05), sicca syndrome (P < 0.01) and cardiomyopathy (P < 0.005), whereas butterfly rash (P < 0.05) presented more frequently in the younger group. Analysis of cumulative clinical symptoms showed that butterfly rash (P < 0.05) and livedo reticularis (P < 0.05) were less frequent in the elderly. However, this group presented a significantly increased incidence of sicca syndrome (P < 0.005) and cardiomyopathy (P < 0.005). Antibodies to double-stranded DNA tended to occur less frequently in older patients (P < 0.05).

Extrapulmonary location of sarcoidosis.

Two cases of sarcoidosis located outside the lungs are reported. In both cases the symptoms of the sicca syndrome were in the foreground. In the first case other clinical manifestations included mediastinal and retroperitoneal lymphadenopathy, and lacrimal gland impairment. In the other case the symptoms of the sicca syndrome were associated with polyneuropathy and maculopapular skin rash. The diagnosis of sarcoidosis was confirmed by histological examination of a biopsy specimen of lower lip mucosa in the first case, and biopsy of skin lesion in the second case. Abnormal results of laboratory tests included only raised erythrocyte sedimentation rate, in both cases and presence of circulating immune complexes in one case. Serological tests failed to demonstrate the presence of rheumatoid factor, antinuclear and anti-ds DNA antibodies. No decrease was observed also in the haemolytic activity of the complement, and cryoglobulins were absent. Regression of clinical signs was obtained in both cases after treatment with glucocorticosteroids.