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.

Methotrexate efficacy, but not its intolerance, is associated with the dose and route of administration.

BACKGROUND: There is a lack of published evidence on the importance of methotrexate (MTX) dose and route of administration on both its efficacy and adverse events in children with Juvenile Idiopathic Arthritis (JIA). We aimed to document our clinical practice based on the treat-to-target approach in order to support the concept that better therapeutic effect achieved with an optimal dose of parenteral MTX is associated with clinically acceptable adverse effects comparable to those reported for oral treatment. METHODS: Study inclusion criteria were indication of new MTX therapy for active arthritis in confirmed JIA patients younger than 18 years. Eligible patients were evaluated prospectively every 3 months for 1 year using standardized instruments for treatment response (American College of Rheumatology Pediatric (ACRPedi) response, Juvenile Arthritis Disease Activity Score (JADAS) 71, Clinically Inactive Disease (CID)) and adverse events (laboratory monitoring, Methotrexate Intolerance Severity Score (MISS)). MTX responders had to achieve at least ACRPedi 70 response. MTX intolerance was defined by MISS ≥ 6. RESULTS: In 45/55 patients (81.8 %) MTX was started as subcutaneous injection. The initial median weekly dose was 14.4 mg/m(2) in parenteral and 11.7 mg/m(2) in oral administration. MTX therapy was effective in the level of ACRpedi70 and CID in 50.9 % and 30.9 % of patients at month 6 and in 70.9 % and 56.4 % after 12 months of the treatment, respectively. MTX intolerance at 6 and 12 months was noted in 25.5 % and 30.6 %, respectively. Management of intolerance included change in the dose and/or route of administration, education and councelling. Adverse events led to MTX withdrawal in 5 patients (9 %) due to toxicity (n = 3) and intolerance (n = 2). We did not find any significant predictive factors for either MTX therapeutic response or intolerance. CONCLUSION: Subcutaneous MTX weekly dose around 15 mg/m(2) is associated not only with a high response rate within the first 12 months of treatment, but also with a relatively low rate of significant adverse effects that would lead to the treatment termination. It allows early recognition of MTX non-responders and addition of biologic therapy. Sustainability of therapeutic effect and longer-term evolution of adverse events will be addressed by an ongoing extension of the study.

Factors affecting survival in juvenile systemic sclerosis.

OBJECTIVES: To determine whether demographic, clinical and immunological features may predict the outcome in juvenile SSc (JSSc). METHODS: Clinical and laboratory characteristics of patients with JSSc collected from paediatric rheumatology centres worldwide were analysed. First, univariate tests identified those features significantly related with fatal outcome, and then multivariate logistic regression analysis was applied to determine the predictors of mortality. RESULTS: One hundred and thirty-four patients from 40 centres were eligible for the analysis. Sixteen patients died and a rapidly fatal course was observed in most of them: 4/16 died within 1 yr after diagnosis and 10/16 within 5 yrs. At the moment of diagnosis, patients with poor outcome showed a significantly higher frequency of internal organ involvement, particularly cardiac, respiratory and gastrointestinal systems. No significant difference emerged for entity of skin, vascular and musculo-skeletal involvement, nor for auto-antibodies profile and laboratory tests. Multivariate analysis showed the following factors to be significant predictors of mortality: fibrosis on chest X-rays [odds ratio (OR) 11.2], raised creatinine levels (OR 22.7) and pericarditis (OR 41.3), while a short disease duration at diagnosis conferred protection (OR 0.3). CONCLUSIONS: All patients with JSSc and fatal outcome were affected by the diffuse form of the disease, and most of them showed a very rapid progression and early signs of internal organ involvement. This suggests that, in children, SSc may have two possible courses: a rapid development of internal organ failure leading to severe disability and eventually to death, or a slow course of the disease with lower mortality.

Methotrexate bioavailability after oral and subcutaneous dministration in children with juvenile idiopathic arthritis.

OBJECTIVE: To compare the bioavailability of oral and subcutaneous methotrexate (MTX) in children with juvenile idiopathic arthritis (JIA). METHODS: Seventeen JIA patients were administered oral (6.1-22.5 mg/m(2)) or subcutaneous (8.8-28.6 mg/m(2)) MTX. Blood samples were drawn pre-dose, and at 1, 2, and 4 hours after administration. Plasma MTX was determined by high-performance liquid chromatography. Non-compartmental pharmacokinetic analysis included the maximum concentration of plasma MTX (C(max)) and the area under the plasma concentration-time curve in the interval of 0-4h (AUC(0-4h)). RESULTS: The slopes of the regression lines of the dose-corrected parameters Cmax and AUC(0-4h) plotted against the dose were negative for oral administration indicating non-linearity in pharmacokinetics, while they did not differ from zero for subcutaneous MTX. In two groups dosed orally with < or = 10 or >10 mg/m(2) (the average doses: 7.8 vs. 13.8 mg/m(2), p<0.002), the C(max) and AUC(0-4h) were comparable (p > or = 0.32). In four patients switched from oral to subcutaneous administration of the same dose, the bioavailability of oral MTX tended to be 11-15% lower when compared to subcutaneous route. CONCLUSION: The differences in the pharmacokinetic measures of early systemic exposure between oral and subcutaneous routes support the view that lower and saturable intestinal absorption of oral MTX limits its bioavailability and efficacy within the range of standard doses used to treat children with JIA. In light of this evidence it can be recommended to use parenteral route of administration when MTX dose around and above 10-15 mg/m(2) is needed to achieve sufficient response.

The incidence of infectious diseases after renal transplantation: a single-centre experience.

This single-centre study was designed to investigate the incidence of infections and their causative pathogens during the first three months after renal transplantation (RTx) in patients who had undergone the procedure in 2005 (n=174). We compared this group of patients with a previous one (1998-2000, n=437). In 2005, infection was diagnosed in 82 patients (47%). Symptomatic lower urinary tract infection (UTI) was present in 43 patients (25%), pyelonephritis in 15 (8.6%), and urosepsis in 7 (4%). Wound infection developed in 21 patients (12%), cytomegalovirus (CMV) disease in 15 (8.6%), and pneumonia in 5 (3%). The most frequent pathogens in UTI were Klebsiella pneumoniae and Enterococcus faecalis. Pathogens of wound infection included Staphylococcus coagulase negative and K. pneumoniae. Pneumonia was frequently caused by Mycoplasma pneumophila. Compared with the previous group, we noted decreases in the total number of infections (77.7 vs. 47%, P<0.001), pneumonia (8.5 vs. 3%, P<0.02) and UTI (33.3 vs. 24.7%, P<0.05). We observed an increased incidence of multiresistant Klebsiella. Based on these results, we have changed our scheme of antibiotic prophylaxis and the algorithms of antibiotic treatment. We reduced the use of antibiotics with an adverse epidemiological effect (quinolones, third-generation cephalosporins) and increased the use of relatively safe antibiotics (penicillins, aminopenicillins, with and without beta-lactam inhibitors).

Quantitative ultrasonometry of the calcaneus in children with juvenile idiopathic arthritis.

OBJECTIVES: To evaluate bone quality by means of quantitative ultrasonometry (QUS) in children with juvenile idiopathic arthritis (JIA). METHODS: Seventy children [37 with oligoarticular JIA, mean age (+/-s.d.) 10.54 +/- 3.42 yr; and 33 with polyarticular rheumatoid factor negative JIA, mean age (+/- s.d.) 11.33 +/- 2.88 yr] were enrolled. Quantitative ultrasonometry was measured on both heels with a Cuba Clinical portable device. Body height, weight and body mass index were recorded together with disease duration and cumulative dose of prednisone. RESULTS: The lowest QUS parameters were observed in children with polyarticular JIA (P< 0.001 and 0.01 when compared with reference data and oligoarticular JIA, respectively). In children with oligoarticular JIA, the QUS values were also significantly lower in comparison with the reference data (P< 0.002). The QUS parameters were strongly influenced by body height, and to a lesser degree by body weight. In children with polyarticular JIA, there were significant inverse correlations between QUS parameters and disease duration [r=-0.57, P< 0.01 for broadband ultrasound attenuation (BUA) and r = - 0.67, P< 0.01 for velocity of sound (VOS)]. Similarly, there were inverse correlations between QUS and cumulative dose of prednisone (r = - 0.48, P< 0.05 for BUA and r =- 0.50, P < 0.01 for VOS, respectively). Similar results were obtained when BUA and VOS were adjusted for height. CONCLUSIONS: Disease duration and cumulative dose of prednisone in children with polyarticular JIA are risk factors of stunted growth and decreased QUS values of bone quality.

Adenosine and methotrexate polyglutamate concentrations in patients with juvenile arthritis.

OBJECTIVE: In contrast to the anti-proliferative properties of high-dose methotrexate (MTX) its anti-inflammatory mechanism of action in rheumatic diseases has been attributed to increased adenosine accumulation, most likely caused by long-lived intracellular MTX polyglutamates. The aim of this study was to assess adenosine concentrations in MTX-treated and untreated children and to relate it to MTX polyglutamate concentration measured in erythrocytes and to the therapeutic efficacy. METHODS: Adenosine and MTX-polyglutamate concentrations in erythrocytes (EMTX) were assessed in venous blood samples taken before the next MTX dose in 30 patients treated long-term for juvenile idiopathic arthritis (JIA) and in 16 untreated matched controls. The blood concentration of adenosine was measured by the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method and EMTX by an enzymatic assay. Therapeutic efficacy was assessed using the preliminary definition of improvement in JIA patients. RESULTS: Mean blood adenosine concentration in MTX-treated patients was 48.05 nmol/l (s.d. 10.1) vs 49.6 nmol/l (s.d. 12.5) in untreated controls (P=0.55). Mean EMTX was 215.56 nmol/l (s.d. 212.9). No significant correlation was found between adenosine concentrations and MTX dose or EMTX (P=0.8 and 0.6, respectively). Adenosine concentration did not differ in clinical responders when compared with non-responders (P=0.9). CONCLUSIONS: We have shown that there is no impact of effective MTX dose represented by EMTX on blood adenosine concentration in JIA patients. If MTX anti-inflammatory action is mediated by adenosine it is likely that local release of adenosine at inflamed tissues is responsible for its action which may not be reflected by sustained increase of its blood concentration.

[Laboratory indicators of endothelial involvement in rheumatic diseases associated with vasculitis in children]. / Laboratorní ukazatele postizení endotelu u revmatických onemocnení provázených vaskulitidou u detí.

BACKGROUND: Endothelial activation is an important etiopathogenetic factor in a group of disorders characterised by primary or secondary vasculitis. The aim of our study was to determine blood concentrations of von Willebrand factor (vWF), vypusteno soluble intercellular adhesion molecule-1 (ICAM-1) and E-selectin (E-sel) in children with various rheumatic diseases and in paediatric controls and to correlate them with clinical and laboratory variables. METHODS AND RESULTS: Total of 28 healthy children (ZD) and 48 patients were evaluated: 6 with systemic lupus erythematosus (SLE), 7 with other diffuse connective tissue diseases (SSD), 11 with Henoch-Schönlein purpura (HSP), 14 with oligoarticular juvenile idiopathic arthritis (JIA) and 10 febrile controls (FC). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and full blood count were recorded. ICAM-1, E-sel and vWF concentrations were measured by sandwich ELISA kits. In SLE patients' concentrations of vWF and ICAM-1 were significantly higher than in healthy (p < 0.05), but not febrile controls. ICAM-1 was significantly increased also in SSD group when compared to healthy children (p < 0.01). Differences in other groups did not reach statistical significance. Significant negative correlation with age was observed for the group as a whole, E-sel correlated with leukocyte and thrombocyte counts (p < 0.01), both molecules with CRP (p < 0.05) and with each other (p < 0.01). CONCLUSIONS: Combined measurement of vWF, ICAM-1 and E-sel as possible markers of endothelial activation in such vypusteno wide spectrum of paediatric patients and controls is unique vypusteno. Our finding of increased concentrations of vWF and/or ICAM-1 in children with systemic autoimmune diseases underlines the importance of endothelial involvement in these disorders, but their predictive value in the disease monitoring needs to be further studied.

[Metformin has a positive effect on disorders of carbohydrate metabolism in long-term care with low doses of prednisone]. / Metformin príznive ovlivnuje poruchy glycidového metabolizmu pri dlouhodobé lécbe nízkými dávkami prednisonu.

BACKGROUND: The influence of long-term, low doses of prednison administration (< 0.3 mg/kg/day) on glucoregulation and glucose tolerance was studied in 20 female patients (15-20 yrs), including verification of possibility to correct the impairment of glucose tolerance (IGT) by metformin (M). METHODS AND RESULTS: During prednison treatment, we found typical signs of insulin resistance manifestation: HOMAIR 3.55 (5.13), blood insulin/glucose ratio 3.8 (5.84), QUICKI 0.61 (0.124). These were associated with higher Langerhans (L.) islets hormone secretion detected under basal conditions as well as after bolus of 5 g arginine chloride. However, detailed analysis of hormone secretion ratios revealed distinct signs of L. islets function impairment and subcompensation. Specifically, low ratio C peptide/proinsulin and C peptide/glucagon were characteristicaly observed. Six months of M. administration (1000 mg/day) had a beneficial effect on glucose metabolisms deviations as indicated by the following: insulin resistance decreased (HOMAIR 1.96 (1.60), insulin/glucose ratio 2.34 (1.52), QUICKI increased at 0.699 (0.238)). At the same time we found a decrease in the basal levels of insulin, proinsulin, glucagon, C peptide and amyline, and AUC proinsulin and glucagon as well. HOMAsecretion decreased from an initial value of 389 (376) to 207 (119). CONCLUSIONS: Judging by the new hormonal secretion ratios, the L. islets' function following M. treatment substantially improved. From the clinical point of view, it is important to note that M. was tolerated very well. No patient interrupted the follow up because of M. intolerance. IGT in the whole group normalised, in spite of the fact that no accent was put on the regime, diet including. The 90% of lactate values did not exceed 1.7 mmol/l. Based on the results, we may conclude that M. has a beneficial effect on long-term, low doses of glucocorticoid-related (induced) glucose metabolism impairment, and therefore, M. administration could be recommended, particularly in the situations with higher levels of glycosylated hemoglobin.

Soluble adhesion molecules ICAM-1 and E-selectin in juvenile arthritis: clinical and laboratory correlations.

OBJECTIVE: To determine serum and synovial fluid (SF) concentrations of soluble intercellular adhesion molecule-1 (ICAM-1) and E-selectin (E-sel) in patients with active juvenile idiopathic arthritis (JIA) and in paediatric controls and correlate them with clinical and laboratory variables. METHODS: Total of'30 JIA patients were evaluated: 15 with polyarticular disease course (JIA-poly) and 15 with oligoarthritis (JIA-oligo). Paediatric age-matched control groups consisted of 11 Henoch-Schönlein purpura (HSP) and 10 febrile patients (FC) and 28 healthy children (HC). Current medication, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and full blood count (FBC) were recorded. Soluble ICAM-1 and E-sel in serum and SF were measured by a sandwich ELISA kit. RESULTS: In the JIA-poly group the concentration of ICAM-1 was significantly higher than in healthy (p < 0.01), but notfebrile controls. Both ICAM-1 and E-selectin correlated with the active joint count (p < 0.01). In 13 JIA patients no correlanon was found between SF ICAM-1 and E-sel levels and the SF leucocyte counts. No significant differences were seen in the disease control and JIA-oligo groups compared to HC. A significant negative correlation with age was observed for the group as a whole (ICAM-1: p < 0.05, E-sel: p < 0.01); E-sel correlated with the leucocyte and thrombocyte counts (p < 0.01), and both molecules with CRP (p < 0.05) and with each other (p < 0.01). CONCLUSION: A high concentration of soluble ICAM-1 in JIA patients with polyarthritis is reported here for the first time. None of the patients showed signs of injection or vasculitis, where generalised endothelial activation could be its main source. Our finding of correlations between both ICAM-1 and E-sel levels and joint counts supports the hypothesis of their synovial origin. ICAM- I and E-sel could serve as a marker of aggressive disease, but their predictive value needs to be further studied.

[Role of the steroids, SHBG, IGF-1, IGF BP-3 and growth hormone in glucose metabolism disorders during long-term treatment with low doses of glucocorticoids]. / Vztah nekterých steroidu, SHBG, IGF-1, IGF BP-3 a rustového hormonu k poruchám glycidového metabolizmu pri dlouhodobé lécbe nízkými dávkami glukokortikoidu.

BACKGROUND: The relationships between selected steroids, SHBG, growth hormone, IGF-1, IGF BP-3 and indicators of glucose metabolism were studied in the group of 20 female patients (15-20 yrs) on long-term treatment with low prednisone doses (< 0.3 mg/kg/day) (baseline phase) and after adding 1000 mg of metformin per day for following 6 months to improve impaired glucose metabolism (control phase). METHODS AND RESULTS: Lower basal DHEAS and DHEA (DHEA/S) levels were found as compared with reference values. Only DHEAS level returned into the reference range after the treatment with metformin. Decrease of DHEA/S depended on the doses (DHEAS -0.7621, DHEA -0.7685). Positive correlations between DHEA/S and of the results insulin tolerance were found as at the baseline (+0.4452, resp. +0.4455) as well as in the control period after the metformin administration (+0.7549, resp. +0.6073). Testosterone (T) and dihydrotestosterone(DHT) values were within the reference range during the whole study. Due to very low SHBG levels higher free androgen index (FAI) was recorded in more than half of the patients. Significant relationships were revealed between former gonadal androgens and indicators of glucose metabolism deterioration at the control phase: T correlated: with fasting insulin (+0.6005), with HOMAIR (+0.5380), with insulin/glucose (+0.5261), with fasting glucose (+0.9268), with AUC glucose (+0.6792), FAI: with fasting insulin (+0.5560), with HOMAIR (+0.5269), with fasting glucose (+0.9025), with AUC glucose (+0.7143), DHT: with fasting C peptide (+0.7921), with AUC C peptide (+0.7143). SHBG correlated: with fasting glucose (-0.6519), and with AUC glucose (-0.5868). The tendency of GH to lower, and IGF-1, IGF BP-3 to higher values at the baseline changed at the control phase: fasting and AUC value of GH increased (signif.), while were IGF-1 (nonsignif.) and IGF BP-3 (signif.) levels decreased. Surprisingly, no correlation was observed between GH and parameters of glucose metabolism. Contrary to GH, baseline IGFBP-3 values correlated: with HOMAIR (+0.5002), with insulin/glucose (+0.4860). The same relationships were found between AUC IGF BP-3 (+0.5676, +0.5559), IGF-1 (HOMAIR only +0.5412), IGF-1/IGF BP-3 (+0.5059, +0.5716) and parameters of insulin sensitivity (HOMAIR, insulin/glucose) in the control period. For the first time negative correlations between IGF-1, IGF-1 AUC, IGF BP-3, IGF-1/IGF BP-3 and somatostatin blood levels were discovered at the control phase. CONCLUSIONS: The study brought a number of new information about the importance of the "non-classical" glucoregulatory hormones in impairment of glucose metabolism, during long-term administration of low prednisone doses. The results suggest, that without normalisation of low DHEA/S, SHBG and high FAI levels it would not be possible to correct glucose metabolism properly in patients with long-term glucocorticoid therapy.

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.

The Czech version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Czech language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Czech CHAQ-CHQ were fully validated with 3 forward and 3 backward translations. A total of 150 subjects were enrolled: 81 patients with JIA (14% systemic onset, 44% polyarticular onset, 10% extended oligoarticular subtype, and 32% persistent oligoarticular subtype) and 69 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Czech version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Immunological investigation in children with juvenile chronic arthritis.

BACKGROUND: Immunological investigation is a part of the complex view on a child with juvenile chronic arthritis (JCA). We analyzed the data of a cohort of children with JCA in order to determine the real contribution of this investigation to their diagnosis and therapy. MATERIAL AND METHODS: We included the investigation of humoral immunity and autoantibodies of 78 children with JCA. 18 children completed investigation of both humoral and cellular immunity of paired peripheral blood (PB) and synovial fluid (SF). Humoral immunity consisted from immunoglobulins, complement, circulating immune complexes, rheumatoid factors, soluble HLA I. molecules and antinuclear and antineutrophil cytoplasmic antibodies. Cellular immunity included cytometric studies of CD3, CD4, CD8, CD16/CD56, CD19, CD20, 23, CD3 HLA DR+, CD45 RA, CD45 RO, alpha/beta and gamma/delta T cells. To observe the status of Th1/Th2 balance in children with JCA, the cytokines IL-4, IFN gamma, TNF alpha and IL-6 were measured in the tissue culture of the synovial cells. RESULTS: The parameters of humoral immunity in serum showed wide variability. We could not confirm particular changes specific for the forms or stage of the disease. ANCA were positive in 21 out of 78 children with JCA, 3 times both in PB and SF. More typical pattern could be followed in the comparison of PB and SF, with immunoglobulins and complement always found lower in SF than in PB. The cellular immunity was represented by the activation of lymphocytes mainly in SF, reverse ratio of CD45 RA and RO cells in PB and SF with marked predominance of memory T cells in the joint. High levels of sHLA in SF are the nonspecific marker of activation, the same is true for high levels of TNF alpha and IL 6 in SF cell culture supernatant. CONCLUSION: The described changes in immunological parameters of humoral and cellular immunity are not specific for JCA. In the individual cases they can contribute to the diagnosis and monitoring of the disease. The investigation of sHLA molecules and cytokine profile should be restricted only for research.

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.

Eosinophilic fasciitis in an adolescent girl with lymphadenopathy and vitiligo-like and linear scleroderma-like changes. A case report.

The patient, a 14-year-old girl, suffered from arthralgias which occurred after tonsillitis. Two months later she developed edema of the left lower extremity, finger flexion contractures and induration of the skin of the left leg, associated with hypergammaglobulinemia, peripheral hypereosinophilia, elevated ESR and a positivity of ANA and anti ds-DNA antibodies. A biopsy of the inguinal lymph node, performed because of left inguinal and retroperitoneal lymphadenopathy, showed only slight inflammatory activation and a granulomatous reaction after lymphography. A few days after the lymphography linear erythema evolving later into hyperpigmentation and corresponding to the superficial lymphatics developed on the left side of the body, very probably as a reaction to the patent-blue dye. Deep en-block skin biopsy confirmed the diagnosis of eosinophilic fasciitis (EF). After two years of therapy with prednisone and d-penicillamine the patient felt well, and her flexion contractures resolved, ANA were positive, while anti ds-DNA were negative. Linear hyperpigmentation persisted, and linear scleroderma-like changes developed on the left lower limb. A vitiligo-like lesion on the right foot which occurred after one year of therapy persisted. The possible risk of developing systemic connective tissue disease necessitates the long term follow up of this patient.

The effect of long-term glucocorticoid therapy on glucocorticoid receptor content and on steroid response to ACTH.

The effect of long-term glucocorticoid therapy for systemic diseases on glucocorticoid receptor (GR) content and on basal and ACTH-stimulated levels of plasma and salivary cortisol 17 alpha-hydroxy-progesterone, androstenedione, 11 beta-hydroxyandrostenedione, DHEA, its sulfate and sex hormone-binding globulin (SHBG), as well as on basal levels of aldosterone, was investigated in a group of 24 children treated with prednisone for at least 8 months. The therapy was interrupted 24 h before the ACTH test and before plasma and saliva sampling. The control group consisted of 21 healthy children of corresponding age and sex. The patients were divided into two subgroups with normal and subnormal basal cortisolemia, they also differed in their response to ACTH. The GR levels in patient groups were indistinguishable from those found in controls. No correlation was found between GR content and basal levels of the above steroids or their response to ACTH. The best markers, apart from basal cortisolemia, for evaluation of the degree of suppression of adrenal function appeared to be the response of salivary (but not of plasma) cortisol and 17 alpha-hydroxy-progesterone to ACTH. Surprisingly, significantly lower levels of SHBG levels, which rose markedly after ACTH, were found in all the patients.

Juvenile chronic arthritis--bone mineral density in relation to corticosteroid therapy.

Bone demineralization often accompanies juvenile chronic arthritis (JCA). Fourteen patients with confirmed diagnosis of JCA had their bone mineral density (BMD) measured with the use of dual photon X-ray absorptiometry. The results obtained were compared to the Lunar BMD DPXA standards. Seven patients received Prednisone in doses of more than 0.16 mg/kg/day for more than 6 months and 7 patients (sex and age matched) never received any steroids at all. In the first group BMD was decreased in 7 patients (100%), in the second group BMD was mildly decreased in 2 patients (28%). Due to the difference in BMD in both groups, it is obvious that corticosteroids have substantial influence on bone demineralization in JCA.

Calciuria in children with juvenile chronic arthritis.

Demineralization of bone is a frequent finding in children with juvenile chronic arthritis (JCA). Recently there have been reports about hypercalciuria accompanying JCA. This is believed to be associated with increased bone resorption due to cytokines and immobility of the patients and steroid treatment. In 12 patients with confirmed diagnosis of JCA basic biochemical indices of bone metabolism, were performed (S-Ca, P, ALP, U-Ca/U-creatinine, U-P). Bone mineral density (BMD) was measured using DPXA method and results obtained were compared to the Lunar BMD DPXA standards. In spite of decreased BMD, no significant hypercalciuria was found and other mentioned biochemical indices of bone and mineral metabolism were normal as well.