Elevated prolactin levels in patients with rheumatoid arthritis: association with disease activity and structural damage.

OBJECTIVES: Prolactin (PRL) is a hormone with cytokine-like activities that has been demonstrated to be involved in immune responses. However, there are inconsistent results related to the role of PRL in rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the levels of PRL in serum and synovial fluid in patients with RA and osteoarthritis (OA) and examine whether PRL might be associated with laboratory and clinical disease activity of RA. METHODS: A total of 29 patients with RA and 26 patients with OA were included in the study. The concentration of PRL in the serum and synovial fluid was measured by immunoradiometric assays, and the levels of serum anti-citrullinated protein/peptide autoantibodies (ACPA) and IgM rheumatoid factor (IgM-RF) were analysed by ELISA. Disease activity score (DAS 28) and radiological (Larsen) score were assessed. RESULTS: The levels of PRL in serum (299.55±27.28 vs. 230.59±16.61 mIU/l, p=0.041) as well as in synovial fluid (338.85±33.49 vs. 245.97±21.88 mIU/l, p=0.024) were significantly higher in patients with RA than in patients with OA. A moderate correlation was found between disease activity of RA and levels of PRL in synovial fluid (r=0.485, p=0.010) and the serum PRL levels correlated significantly with the total Larsen score (r=0.484, p=0.014). CONCLUSIONS: The findings of increased prolactin levels in patients with RA lead to the assumption that prolactin may play a role in disease severity and the process of joint damage in RA.

Radiographic progression of rheumatoid arthritis in patients from the Czech National Registry receiving infliximab treatment.

OBJECTIVE: To evaluate the clinical status and radiographic progression in patients with rheumatoid arthritis (RA) being followed by the Czech National Registry of biological treatments. METHODS: Patients who failed at least two disease-modifying antirheumatic drugs and had high disease activity (DAS28 > 5.1) were treated with infliximab. Radiographic progression was measured with a modified version of the Sharp score (TSS) after 54 weeks of treatment. RESULTS: Ninety-nine patients with an average disease duration of 13.7 years were enrolled. The DAS28 dropped from 6.66 to 4.07 (p < 0.001). Before treatment the mean TSS was 90.1 and the mean estimated yearly disease progression was 8.56. After 54 weeks of infliximab, radiographic progression was 4.15 times slower than the estimated rate before treatment and 63 patients did not show any radiographic progression at all. In the remaining 36 patients, the progression rate slowed to 3.8 +/- 0.9 from the estimated TSS of 10.9 +/- 6.9 before the initiation of treatment (p = 0.011). CONCLUSION: Data derived from the Czech National Registry, which reflect general clinical practice, show a significant retardation of radiographic progression in patients treated with anti-TNF and the magnitude of the improvement seen is similar to results from clinical trials.

The role of MRI in the assessment of polymyositis and dermatomyositis.

OBJECTIVES: Acute inflammation in idiopathic inflammatory myopathies (IIM) causes oedema that can be visualized by magnetic resonance imaging (MRI). The inflammatory infiltrate in IIM is thought to be frequently in a focal distribution. The aim of this study is to better evaluate the relationship of MR image of thigh muscles to clinical and histological parameters in patients with IIM. METHODS: MRI-short tau inversion recovery (STIR) technique was used to distinguish between affected and non-affected muscles. Computer tomography (CT)-controlled targeted needle biopsy was used for sampling. The intensity of muscle oedema, its extent and total assessment on MRI were evaluated with 10 cm visual analogue scale. The intensity of inflammatory infiltrate was assessed using 5-point grading system. The second MRI and muscle biopsy were performed after the time interval of treatment. RESULTS: MR scans, muscle biopsy and clinical examination were performed in 29 patients with polymyositis (PM) and dermatomyositis (DM). Paired MRI-affected and MRI-non-affected biopsy samples were obtained from 17 cases. In six cases, the biopsy was available for comparison before and after period of treatment. At the initial examination, it was the intensity of oedema on MRI that was associated with clinical status. Mean intensity of MRI findings significantly decreased in 10 patients where the MRI was available also after treatment. The mean intensity of inflammatory infiltrate in PM/DM patients was 2.5 +/- 0.7 for MRI-affected and 1.7 +/- 0.6 for MRI-non-affected muscles (P < 0.001). Mean intensity of inflammatory infiltrate in the MRI-affected muscles in the first examination (n = 6) was 2.2 +/- 0.8 and did not significantly decrease in the second examination in samples taken after the treatment (2.0 +/- 0.9). CONCLUSION: It is mainly the signal intensity in MR scan, which is associated with disease activity in the acute presentation of PM/DM. Muscle biopsy guided by positive MRI finding contains significantly more inflammatory cells than the biopsy taken from MRI non-affected sites. However, even in parts of muscles, which look unaffected on MR scan, the inflammatory cells can be found. The intensity on MR scans decreases significantly after the treatment, but the histologically detected inflammation does not change substantially.

The expression of cyclooxygenase-1, cyclooxygenase-2 and 5-lipoxygenase in inflammatory muscle tissue of patients with polymyositis and dermatomyositis.

OBJECTIVE: To describe cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) expression in muscle tissue in patients with idiopathic inflammatory myopathies (IIM) - dermatomyositis (DM) and polymyositis (PM) and to find out if any differences between affected and non-affected muscles detected by MRI exist. METHODS: Samples of muscle tissue from 7 patients with dermatomyositis (DM) and from 4 with polymyositis (PM) were obtained by needle biopsy from affected and non-affected sites distinguished by magnetic resonance imaging. In situ hybridization with antisense mRNA probes was employed to detect COX-1, COX-2 and 5-LOX mRNA. RESULTS: Expression of COX-1, COX-2, and 5-LOX mRNA was found in all samples - in the muscle cells, inflammatory cells and in vessels. COX-1 mRNA expression predominated in the inflammatory cells and vessels and was higher in affected than in non-affected sites detected by MRI (mean intensity 3.22+/-0.67 vs. 2.0+/-0.87; p = 0.0006). The expression of COX-2 mRNA was high mainly in inflammatory cells and/or vessels and was increased in MRI-detected affected tissues (3.5+/-0.88; 1.9+/-1.1; p = 0.003), as was the expression of COX-2 mRNA in muscle cells (2.1+/-1.0 vs. 1.3+/-1.0; p = 0.021). 5-LOX mRNA was largely expressed in muscle cells from MRI-detected affected sites and the signal intensity was higher in comparison with samples taken from non-affected tissues detected by MRI (3.22+/-0.7 vs. 1.67+/-0.7; p = 0.0007). CONCLUSION: Expression of COX-1, COX-2 and 5-LOX mRNA was observed for the first time in muscle tissues from IIM patients. This expression was increased in affected tissues detected by MRI, which may suggest a role of COX-1, COX-2, and 5-LOX in the pathogenesis of IIM.

[Specific inhibitors of cyclooxygenase type 2] ]. / Specifické inhibitory cyklooxygenázy typu 2.

In the submitted review the author analyzes the ratio, function and role of two different forms of cyclooxygenases--cyclooxygenase type 1 and cyclooxygenase type 2--in the human organism. Special attention is devoted to specific inhibitors of cyclooxygenase type 2. Specific inhibition of COX-2 is associated with a lower incidence of undesirable reactions while the antiinflammatory and analgetic effect is preserved. Celecoxib and rofecoxib--the oldest representatives of drugs from this group were used in a number of clinical studies. The results of some of these studies are presented and commented.

Cyclosporine A versus methotrexate in the treatment of polymyositis and dermatomyositis.

OBJECTIVE: To determine the effectiveness and tolerance of treatment with cyclosporine A (CyA) or methotrexate (MTX) added to corticosteroids in patients with severe, active polymyositis (PM) and dermatomyositis (DM). PATIENTS AND METHODS: Thirty-six patients (20 with DM, 16 with PM) were enrolled into the study and randomized in MTX (n = 17) and CyA (n = 19) groups. Muscle endurance and functional test (MEFT), clinical assessment (CA), global patient's assessment (GPA), muscle MRI, serum CK, myoglobin, IL-1Ra, and autoantibody status were used to assess the response to therapy after 1, 3, and 6 months. RESULTS: Significant improvement in MEFT, CA, GPA, and muscle MRI was found in both groups. Patients treated with MTX showed insignificantly better response than patients with CyA. CK levels in the MTX group decreased significantly after 1, 3, and 6 months, whereas a significant reduction in the CyA group was first observed after 6 months. IL-1Ra serum levels significantly dropped in the CyA group after two weeks, whereas in the MTX group the significant decrease was first seen after 3 months of treatment. Good correlation was found between each of the clinical parameters (MEFT, CA, and GPA), none of them showed any correlation with CK or IL-1Ra levels. CONCLUSIONS: Administration of MTX or CyA added to corticosteroids was associated with clinical and laboratory improvement. Changes in CK and IL-1Ra levels were not associated with parameters of clinical disease severity measured in this study.