Clinical characteristics of Polish patients with ANCA-associated vasculitides-retrospective analysis of POLVAS registry.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers-members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). METHODS: We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population). RESULTS: Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3-12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06-9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05-6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3-25.5), skin involvement (OR = 4.4; 95% CI = 1.02-19.6), and age > 65 (OR = 6.3; 95% CI = 1.18-33.7). CONCLUSIONS: In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease.

Serum leptin in systemic lupus erythematosus.

Leptin, a peptide hormone, plays an essential role in the regulation of body weight, the endocrine function, reproduction, the immune response and inflammation. The immune system, in turn, modifies leptin's production. Systemic lupus erythematosus (SLE) is an autoimmunological disease characterized by widespread inflammation with possible involvement of each body organ and system. In this study, we assessed serum leptin levels in SLE patients and the control group in search for correlations between leptin concentrations and other markers' level, the activity of the disease, its duration, the age of the patients and their bone mineral density. Blood samples were collected from 30 SLE and 30 control group women. Each SLE patient was matched with one from the control for age (+/-1 year) and the body mass index (BMI; +/-1). Serum leptin levels were determined using the DRG Leptin ELISA Kit. Serum leptin levels in SLE patients ranged from 1.8 to 66.3 ng/ml (median value 7.5), and in control group it was 8.8 ng/ml (0.7-39.2) (NS). In SLE, serum leptin levels (after the logarithmic transformation) correlated with BMI (r = 0.89, P < 0.0001), the age (r = 0.34, P < 0.01) and the patients' disease duration (r = 0.59, P < 0.0005). Serum leptin levels in SLE patients with arthritis (P < 0.05) and central nervous system (CNS) involvement (P = 0.05) were significantly lower in comparison with serum leptin levels in SLE patients without arthritis and CNS involvement. No correlation was found between serum leptin levels and the T-score. In the control group, the logarithmic transformation of serum leptin levels positively correlated with BMI (r = 0.52, P < 0.05). No differences in serum leptin levels were shown between SLE patients and the control group. However, we found correlation between BMI and serum leptin levels in both groups. Furthermore, serum leptin levels in SLE patients with arthritis and CNS involvement were significantly lower in comparison with SLE patients without arthritis and CNS involvement, which suggests that active chronic inflammation may lower plasma leptin concentrations.

Diastolic heart function in RA patients.

The results of some epidemiological studies point to the presence of an increased risk of cardiovascular disease (CVD), particularly atherosclerosis and congestive heart failure (CHF) in rheumatoid arthritis (RA). At least 50% of abnormalities remained asymptomatic. Pathological conditions contributing to myocardial dysfunction such as high serum levels of IL-6, C-reactive protein (CRP) and TNF alpha are present both in RA and CHF patients. The most common pathological mechanism leading to the development of heart failure is left ventricular (LV) diastolic dysfunction, which remains clinically asymptomatic for a long time. The aim of this study was to assess the systolic and diastolic functions of the LV in RA patients without clinically evident cardiovascular disease, using pulsed Doppler echocardiography. Our purpose was also to estimate whether there is a correlation between the duration and severity of RA and the degree of LV diastolic dysfunction. A comparison of the average values of echocardiographic measurements was made between the RA group and control group, which constituted healthy volunteers. Left ventricular mass index in RA group was significantly greater than in the control group (105.2 +/- 32.6 vs. 87.9 +/- 16.8; p < 0.05) so were the interventricular septum end-diastolic thickness (1.01 +/- 0.33 vs. 0.86 +/- 0.12; p < 0.05), the LV posterior wall end-diastolic thickness (0.94 +/- 0.08 vs. 0.83 +/- 0.11; p < 0.0001) and the aortic root diameter (3.18 +/- 0.31 vs. 3.10 +/- 0.63, p < 0.001). The ejection fraction in RA group was significantly lower than in the control group (64.4 +/- 1.3 vs. 66.3 +/- 1.3; p < 0.0001). The assessment of diastolic function parameters revealed significantly longer isovolumetrc relaxation time (IVRT) and shorter deceleration time (DT) in RA patients compared to the control group. Patients in stage II or III revealed significantly lower LV mass index (99 +/- 17 vs. 131 +/- 42; p < 0.05) and the interventricular septum end-diastolic thickness (0.94 +/- 0.10 vs. 1.28 +/- 0.5; p < 0.05) than those in stage IV. Mean aortic diameter was significantly greater in individuals in stages III and IV (3.73 +/- 0.28) than in the stage II of the disease (2.77 +/- 0.21), p < 0.05. No differences in echocardiographic parameters' values were observed between seropositive, seronegative, nodule-present and nodule-absent persons. Echocardiographic examination revealed valvular heart disease in 24 (80%) RA and 6 (20%) control patients (p < 0.0001).

Serum cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis and knee osteoarthritis.

The cartilage oligometrix matrix protein (COMP) is a noncollagenous protein, a glycoprotein, the function of which is to bind to type II collagen fibres and stabilise the collagen fibre network in the articular cartilage. In the serum of the normal population the COMP level is 5 mug/ml. An increased level of COMP in the synovial fluid was described in the early stage of rheumatoid arthritis (RA), whereas in advanced stages of RA, the level of COMP decreased. In this study we assessed the serum COMP level in patients with RA and knee osteoarthritis (OA) and found a correlation between the serum COMP level and other markers as well as bone mass density (BMD) changes, activity of disease, disease duration and the age of the patients. The blood was collected from 30 RA patients and 30 OA patients who constituted the control group. The serum COMP level was determined using an inhibition enzyme-linked immunosorbent assay (ELISA). The average value of the serum COMP level in RA patients was 10.4+/-3.6 U/l. There was a correlation between the serum COMP level and the age of RA patients (p<0.005) and disease activity score (DAS) value (p<0.01). According to correlation coefficients, the serum COMP level was independent of stage of disease, number of painful and swollen joints, duration of morning stiffness, disease duration and titre of the Waaler-Rose test. The influence of rheumatoid nodule presence on the serum COMP level was shown (p<0.05). In RA patients with erythrocyte sedimentation rate (ESR) values below 20 mm/h compared with patients with ESR values over 60 mm/h, the serum COMP level was observed to be significantly lower (p<0.05). The average value of COMP in OA patients was 10.4+/-2.7 U/l. No correlation was found between the serum COMP level and patients' age and disease duration. There was a correlation between the serum COMP level and Western Ontario and McMaster Universities (WOMAC) index pain scale for the lower limbs (p<0.005) and T-score value of densitometry examinations (p<0.036) in OA patients. No statistical differences were found between the average serum COMP level in RA and OA patients.

Cartilage oligomeric matrix protein in serum in systemic lupus erythematosus and knee osteoarthritis. Preliminary communication.

The cartilage oligomeric matrix protein (COMP) is a glycoprotein, which occurs mainly in an articular cartilage. The amount of this protein increases under the influence of cytokines and growth factors. As a result of various diseases that cause damage to cartilage, fragments of matrix protein are released into synovial fluid and then into blood. The assessment of matrix protein level in serum, for example COMP, permits the establishment of the degree of cartilage damage in inflammatory joint diseases, and permits observation of the effectiveness of the treatment. Blood was collected from 30 systemic lupus erythematosus (SLE) patients, and from 30 patients with knee osteoarthritis (OA) who constituted the control group. Serum COMP level was determined using an inhibition enzyme-linked immunosorbent assay (ELISA). The average value of the serum COMP level in SLE patients was 11.3+/-3.7 U/l. According to correlation coefficients, serum COMP level is independent of patients' age, disease duration and the clinical picture of SLE. No correlation was found between serum COMP level and bone mass density (BMD) changes. In SLE patients with decreased haemoglobin levels (<11.0 g/dl) values compared with patients with normal haemoglobin level, the serum COMP level was observed to be significantly higher (P<0.05). Both in SLE patients with erythrocyte sedimentation rate (ESR) values over 60 mm/h and in patients with ESR values below 60 mm/h, the serum COMP level was observed to be significantly higher (P<0.05). A significant positive correlation was found between serum COMP level and ESR value, as well as a number of thrombocytes. Negative correlation occurred between the serum COMP level and the value of haemoglobin. The average value of COMP in OA patients was 10.4+/-2.7 U/l. No correlation was found between serum COMP level and patients' age and disease duration. There was correlation between the serum COMP level and the T-score value of densitometry examinations in OA patients. No statistical differences were found between the average serum COMP levels for SLE and OA patients.

Echocardiographic findings and 24-h electrocardiographic Holter monitoring in patients with nodular and non-nodular rheumatoid arthritis.

Echocardiographic examination and 24-h electrocardiographic Holter monitoring were carried out on 35 patients with nodular rheumatoid arthritis (RA) and 35 with non-nodular RA, who were matched with the nodular RA group regarding age, sex and BSA. A further 35 patients with osteoarthrosis and spondyloarthrosis matched, with both RA groups, constituted a control group. Patients with a history of myocardial infarction, hypertension, rheumatic fever and diabetes were excluded from the study. Cardiac involvement, evaluated using echo-Doppler cardiography, 24-h electrocardiographic Holter monitoring and ECG at rest, occurred in 25 (71.9%) patients with nodular RA and in 15 (42.9%) with non-nodular RA in comparison to 8 (22.9%) control group patients (P < 0.0002). Holter electrocardiographic monitoring over 24 h did not present any essential differences in frequency of rhythm disorders between the examined groups and the control group. However, it revealed more patients with 1-mm ST depression in the nodular RA group than in the non-nodular and control groups. Echocardiographic examination revealed more cases of valvular heart abnormalities, especially those of mitral insufficiency, in nodular RA patients than in non-nodular and control patients. Both a mitral valve prolapse and a pericardial effusion were noted in 8.6% of nodular RA patients. Patients with nodular RA were noted to have a bigger aortic root diameter, but smaller ejection fraction, mean velocity of circumferential fibre shortening and fractional shortening in comparison to non-nodular and to control group patients.

Echocardiographic findings, 24-hour electrocardiographic Holter monitoring in patients with rheumatoid arthritis according to Steinbrocker's criteria, functional index, value of Waaler-Rose titre and duration of disease.

Electrocardiographic (ECG) and echocardiographic examinations and 24-h ECG Holter monitoring were carried out in 100 patients (age < 65 years) with rheumatoid arthritis (RA) of stages II-IV according to Steinbrocker's criteria. One hundred patients with osteoarthrosis, spondyloarthrosis and painful shoulder matched for age, sex and body surface area constituted the control group. All patients with myocardial infarction, hypertension, rheumatic fever or a history of diabetes were excluded. Cardiac involvement, evaluated by echo-Doppler cardiography, 24-h ECG Holter monitoring and an ECG at rest, occurred in 52 (52%) patients with RA and in 23 (23%) control group patients (p < 0.0005). In the RA group ECG examination, 1 mm ST depression in at least two consecutive leads was observed more frequently, and occurred statistically more frequently for the highest stage of RA according to Steinbrocker's criteria, highest level of functional index and longer duration of disease. The 24-h Holter ECG monitoring did not show any differences in frequency of rhythm disorders between the RA group and the control group. However, silent myocardial ischaemia episodes appeared more often in the RA group. An ECG examination revealed more cases of valvular heart disease, especially mitral insufficiency, in RA patients than in the control group. A mitral valve prolapse was noted in 6% of patients and a pericardial effusion in 4% of patients. Patients with RA were noted to have a larger diastolic left ventricular diameter and aortic root diameter, and smaller ejection fraction, mean velocity of circumferential fibre shortening and fractional shortening. The results of the examinations show that RA is associated with cardiac involvement in a significant proportion of cases.

[Etiopathogenesis of rheumatoid arthritis]. / Etiopatogeneza reumatoidalnego zapalenia stawów.

Rheumatoid arthritis is a disease, which etiopathogenesis depends on genetic and environment factors. Little is the progress of knowledge the environment factors but the strong is association with HLA DR4/DR1. The hypothesis being proposed is that RA is a chronic immune-mediated disease whose initiation and perpetuation is dependent on T-cell CD4 helper is connected by activation monocyte/macrophage cells which per production proteolytic enzymes and prostaglandins way to local inflammation and destruction articular cartilage and bone. Lymphocytes B proliferate to plasmocytes, which produce rheumatoid factor and other antibodies. Production of antibodies leads to production immune complexes, activation complement and migration and activation granulocytes. In the end of the process of RA occurs destruction articular cartilage and osteoclasts activated to erode bone together with mastocytes and growing pannus leads to synostosis. Like self perpetuation inflammation never disappears.

[Polymyositis in pulmonary tuberculosis]. / Polymyositis w przebiegu gruzlicy pluc.

A case in reported of the clinical syndrome of polymyositis in a young man. The syndrome masked pulmonary tuberculosis. Sudden appearance of pains and weakness of the muscles of the shoulder and abdominal muscles was accompanied by fever up to 40 degrees C, and macular rash on the trunk and extremities. During the disease right-sided pneumonia developed and regressed after treatment with antibiotics (tetracyclines, penicillin). Laboratory investigations showed high ESR, high leucocyte count, high levels of transaminases, CPK and LDH, and in cutaneo-muscular++ biopsy specimen scan subepidermal infiltrations were present. The patient was treated with corticosteroids with a striking improvement of the general condition. During this treatment left-sided pleural effusion developed. Bacteriological examination of the pleural fluid, including tests for acid-fast bacilli, was negative in direct examination, but these bacilli were cultured from fluid. No malignant cells were found. After antituberculous treatment the condition of the patient and the biochemical parameters became normal.