Recommendations for the Management of Uveitis Associated With Juvenile Idiopathic Arthritis: The Czech and Slovak adaptation of SHARE Initiative.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is its most important extra-articular manifestation. Evidence-based recommendations are available only to a limited extent and therefore JIA associated uveitis management is mostly based on physicians experience. Consequently, treatment practices differ widely, both nationally and internationally. Therefore, an effort to optimize and publish recommendations for the care of children and young adults with rheumatic diseases was launched in 2012 as part of the international project SHARE (Single Hub and Access Point for Pediatric Rheumatology in Europe) to facilitate clinical practice for paediatricians and (paediatric) rheumatologists. The aim of this work was to translate published international SHARE recommendations for the diagnosis and treatment of JIA associated uveitis and to adapt them for use in the Czech and Slovak Republics. International recommendations were developed according to the standard methodology of the European League against Rheumatism (EULAR) by a group of nine experienced paediatric rheumatologists and three experts in ophthalmology. It was based on a systematic literature review and evaluated in the form of an online survey and subsequently discussed using a nominal group technique. Recommendations were accepted if > 80% agreement was reached (including all three ophthalmologists). A total of 22 SHARE recommendations were accepted: 3 on diagnosis, 5 on disease activity assessment, 12 on treatment and 2 on future recommendations. Translation of the original text was updated and modified with data specific to the czech and slovak health care systems and supplemented with a proposal for a protocol of ophthalmological dispensarization of paediatric JIA patients and a treatment algorithm for JIA associated uveitis. Conclusion: The aim of the SHARE initiative is to improve and standardize care for paediatric patients with rheumatic diseases across Europe. Therefore, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated based on the evidence and agreement of leading European experts in this field.

Increasing the infliximab dose in rheumatoid arthritis patients: a randomised, double blind study failed to confirm its efficacy.

OBJECTIVE: To evaluate the effect of infliximab dose escalation in incomplete responders in a randomised controlled trial. METHODS: 141 rheumatoid arthritis (RA) patients treated with infliximab for 12 months (3 mg/kg; intervals 0, 2, 6 and then 8 weeks) who responded to the drug (disease activity score in 28 joints (DAS28) decrease >1.2) but who were not in remission (DAS28 >2.6) were enrolled into the study. Patients were randomly assigned into arm A, 3 mg/kg, and arm B, 5 mg/kg infliximab every 8 weeks. Outcome measures included the DAS28, its components and C-reactive protein (CRP). RESULTS: There were no significant differences in changes in the DAS28, its components, or CRP in patients in arms A and B during the 12 months of treatment. All patients showed a DAS28 decrease greater than 0.6 after 28 weeks. Eleven patients interrupted therapy in arm A and 14 in arm B. Infusion reactions and non-serious adverse events were observed in 4.2% and 28.2% of arm A patients and in 7.2% and 47.8% of arm B patients. The frequency of serious adverse events was comparable between arms A and B (16.9% and 15.9%, respectively), and the frequency of serious infections was not significantly greater in the higher dose group (5.8%) than in the lower dose group (5.6%). CONCLUSIONS: In this setting, increasing the infliximab dose from 3 mg/kg to 5 mg/kg in RA patients with residual disease activity did not improve efficacy but moderately increased toxicity. These data indicate that a switch to another biological treatment would be a more appropriate strategy in incomplete responders.

Polyarticular Form of Pigmented Villonodular Synovitis. Radiation and Surgical Therapy: Long Term Follow-up.

We describe a case of 30-year old male followed-up since the age of 6 for severe type of rare combination of polyarticular form of pigmented villonodular synovitis with hereditary malformation constellation consistent with Noonan-like syndrome. Within 20 years, the patient underwent repeated synovectomies of large joints with temporary effect only. Radiation therapy with the dose of 30 Gy in 15 sessions has been applied for active aggressive synovitis of both knees associated with pain and progressive joint destruction. Favorable effect lasted for 3 years. Progressive destruction with range-of-motion limitation required successive total joint replacement of both knee joints. Left knee prosthesis has been revised for aseptic loosening after 3.5 years. It is now 5 years since the right knee primoimplantation and 3 years since the left knee reimplantation without signs of component loosening or recurrence, with satisfactory clinical and functional outcome.

SAPHO syndrome - rare case of joint damage treated by knee synovectomy and total hip joint replacement.

This report describes the case of a young male who had been followed-up between the ages of 14-21 years at different health facilities for symptoms initially considered to be caused by tumor, then by chronic osteomyelitis or ankylosing spondylitis and finally diagnosed as the SAPHO syndrome. Musculoskeletal symptoms of the SAPHO syndrome include focal, probably aseptic chronic osteomyelitis, synovitis and formation of hyperostoses. Therapy of the SAPHO syndrome is predominantly conservative. However, in this case we had to employ arthroscopic synovectomy first, for severe synovitis resistant to any conservative therapy approach. Later, left total hip replacement has been performed for advanced hip joint damage accompanied by intense pain and significant range of motion reduction. At the present time, the patient is 51/2 years after synovectomy of the knee and 5 years after the hip joint replacement. The knee joint is without effusion or functional limitations, with intermittent pains only. The hip prosthesis in the risk area is fully integrated without signs of component loosening, with very good functional outcome. While synovectomy can be obviously fully recommended in cases like this, the total joint replacement should be considered unique and indicated only rarely after careful consideration of all circumstances.We consider this approach absolutely exceptional also because we have not found reference to similar case in any national or international professional literature available.

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.

[Mutations in the HFE gene in patients with rheumatic diseases]. / Mutace v genu HFE u osob s revmatickým postizením.

BACKGROUND: Hereditary hemochromatosis is one of the most common autosomal recessive diseases. Aim of the study. 1. To establish frequency of C282Y and H63D mutations in the HFE gene (the hemochromatosis gene) in general population of the Czech Republic and in patients with hemochromatosis. 2. To find out whether hemochromatosis in homo- or heterozygous state plays a role in the pathogenesis of rheumatic diseases. METHODS AND RESULTS: In 32 patients with hereditary hemochromatosis, in 84 patients with polymyositis or dermatomyositis, in 246 patients with juvenile idiopathic arthritis and in 481 persons of the control group the presence of HFE gene mutations was etablished. The HFE gene mutations were screened for by restriction enzyme analysis performed on PCR amplified products. In the control group, 6.86% carriers of the C282Y mutation and 26.61% those of H63D were found. Homozygous C282Y or H63D mutation was found in 90.6% (p<0.001) of patients with hemochromatosis. Heterozygous C282Y mutation was found in 12.2% (p<0.05) of patients with juvenile idiopathic arthritis. We didn't detected higher prevalence of HFE gene mutations in patients with polymyositis and dermatomyositis. CONCLUSIONS: Results of this study show that heterozygosity for C282Y mutation may be a risk factor for juvenile idiopathic arthritis but not for polymyositis and dermatomyositis.

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.

Tumour necrosis factor alpha G-->A -238 and G-->A -308 polymorphisms in juvenile idiopathic arthritis.

OBJECTIVES: To study G-->A -238 and G-->A -308 polymorphisms in the promoter region of the tumour necrosis factor (TNF) alpha gene in patients with juvenile idiopathic arthritis (JIA). We analysed whether there were any associations between these polymorphisms and the type of JIA and/or the clinical course of the disease in two populations. METHODS: The first group consisted of 51 Turkish JIA patients and the second consisted of 159 JIA patients from the Czech Republic. Healthy individuals (93 and 100) from each country served as controls. Subgroups of JIA were defined according to the Durban criteria. The course of the disease was defined on the basis of the physician's global evaluation of disease activity, the swollen and tender joint count and the erythrocyte sedimentation rate. RESULTS: In both JIA cohorts, the distribution of genotypes was not significantly different among the types of JIA. The G-->A -238 polymorphism did not have an effect on the patients' outcome in either group. The G-->A -308 polymorphism was significantly associated with a poor outcome in the Turkish group (P=0.005) but there was no association in the Czech patients. Some features of JIA in Turkish patients differed from those in Czech patients. CONCLUSIONS: Genetic differences may accompany the phenotypic differences found in the Turkish group. Although larger numbers of patients are clearly needed to verify this, we suggest that the G-->A -308 polymorphism may be operative in defining disease outcome in selected groups.

Higher frequency of allele 2 of the interleukin-1 receptor antagonist gene in patients with juvenile idiopathic arthritis.

OBJECTIVE: An increased incidence of allele 2 of the interleukin-1 receptor antagonist gene (IL1RN*2) in several inflammatory diseases has recently been reported. The aim of this study was to examine a variable number tandem repeat (VNTR) polymorphism of the IL1RN gene in patients with juvenile idiopathic arthritis (JIA). METHODS: Findings in 185 Czech patients with JIA were compared with those in 168 Czech controls, 50 JIA patients and 52 controls of Turkish origin, and 79 controls from central England. VNTR polymorphism analysis of IL1RN was performed by polymerase chain reaction using 2 flanking primers to amplify an 86-bp tandem repeat region in intron 2. RESULTS: The frequency and carriage rate of IL1RN*2 were significantly increased in Czech JIA patients compared with the Czech controls (frequency 27.6% versus 15.8%; carriage rate 44.3% versus 26.2%). Increased frequency and carriage rate of IL1RN*2 were found in 23.3% and 40.0% of Turkish JIA patients and in 17.3% and 34.6% of ethnically matched controls. The high representation of IL1RN*2 in 52.3% of the 22 patients with extended oligoarthritis, 31.3% of the 56 patients with enthesitis-related arthritis, and 42.9% of the 14 patients with other arthritis was particularly responsible for the increased frequency of IL1RN*2 in the Czech JIA patients. We found no association of IL1RN*2 with disease activity or severity parameters. CONCLUSION: Inheritance of IL1RN*2 may contribute to genetic susceptibility in several forms of autoimmune diseases, including JIA. The IL1RN*2 allele may be useful as a prognostic indicator of the evolution of an extended oligoarticular course of JIA.

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.