Prophylactic low-dose paracetamol for ductal closure and neurodevelopmental outcome in very preterm infants.

AIM: To investigate the direct effect of prophylactic low-dose paracetamol administration for ductal closure on neurodevelopmental outcome in very preterm infants who did not receive ibuprofen or surgical ligation for treatment of a patent ductus arteriosus. METHODS: Infants < 32 gestational weeks born 10/2014-12/2018 received prophylactic paracetamol (paracetamol group, n = 216); infants born 02/2011-09/2014 did not receive prophylactic paracetamol (control group, n = 129). Psychomotor (PDI) and mental (MDI) outcome were assessed using Bayley Scales of Infant Development at 12 and 24 months corrected age. RESULTS: Our analyses showed significant differences in PDI and MDI at age 12 months (B = 7.8 (95% CI 3.90-11.63), p < 0.001 and B = 4.2 (95% CI 0.81-7.63), p = 0.016). At age 12 months, the rate of psychomotor delay was lower in the paracetamol group (OR 2.22, 95% CI 1.28-3.94, p = 0.004). There was no significant difference between the rates of mental delay at any time-point. All group differences remained significant after adjustment for potential confounders (PDI 12 months B = 7.8 (95% CI 3.77-11.34), p < 0.001, MDI 12 months B = 4.3 (95% CI 0.79-7.45), p = 0.013, PDI < 85 12 months OR 2.65 (95% CI 1.44-4.87), p = 0.002). CONCLUSION: We found no impairment of psychomotor and mental outcome at age 12 and 24 months in very preterm infants after prophylactic low-dose paracetamol administration.

The various clinical spectra of juvenile xanthogranuloma: imaging for two case reports and review of the literature.

BACKGROUND: Juvenile xanthogranuloma (JXG) belongs to the heterogeneous group of non-Langerhans cell histiocytosis and is caused by an accumulation and proliferation of macrophages. In the majority of cases JXG is a disorder of early childhood presenting during the first 2 years of life. The typical presentation is a solitary reddish or yellowish skin papule or nodule with spontaneous regression and no need for treatment. CASE PRESENTATION: Two infants with an atypical presentation of JXG, one with multiple blueberry muffin rash-like skin lesions and the other with severe multi-systemic involvement, are reported. Diagnosis was established by skin biopsy including histological work-up and immunostaining, where markers for macrophages (CD68 and CD163) exhibited significant reactivity. CONCLUSION: JXG is the most common of the non-Langerhans cell histiocytosis. The typical presentation is a solitary skin lesion. The purpose of this report is to familiarize paediatricians with an unusual variant of this entity in order to facilitate early diagnosis and raise awareness for possible visceral complications and associated medical conditions.

Cardiac biomarkers and left ventricular systolic function in former very preterm infants and term controls at preschool age.

Introduction: Due to improvements in perinatal care, survival rates of preterm infants have improved during the last decades. However, these infants remain at risk of developing cardiovascular sequelae later in life. This study aimed to investigate the cardiac biomarkers and left ventricular systolic function in former preterm infants in comparison with term controls at preschool age. Methods: The study included children aged 5-7 years old born below 32 weeks of gestational age. The control group consisted of same-age children born at term. Basic data of study participants were collected using questionnaires and follow-up databases. During the study visit, we recorded anthropometric data and blood pressure readings, determined high-sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) concentrations, and calculated fractional shortening (FS) and left ventricular mass (LVM). Results: Term-born (n = 25; median gestational age, 40.1 weeks) compared with preterm-born infants (n = 80; median gestational age 29.6 weeks) showed no significant differences in the median concentration of hs-cTnT [median, 3.5 (IQR 3.5; 3.5) vs. 3.5 (3.5; 3.5) ng/L, p = 0.328] and the median concentration of NT-pro-BNP [median, 91.0 (IQR 40.8; 150.3) vs. 87.5 (50.1; 189.5) ng/L, p = 0.087]. FS and LVM/LVMI were not significantly different between the two groups. Conclusion: At preschool age, we observed no significant differences in cardiac biomarkers and left ventricular systolic function in preterm infants. Further studies are warranted to explore the potential of cardiac biomarkers as a prognostic tool for subclinical cardiac alterations after preterm birth.

Prophylactic Low-Dose Paracetamol Administration for Ductal Closure and Amplitude-Integrated Electroencephalography in Preterm Infants.

Introduction: Prophylactic low-dose paracetamol administration is used to induce closure of the ductus arteriosus in preterm infants. In our recent study we found no impairment on microstructural maturation processes in the brain of preterm infants at term-equivalent age following prophylactic low-dose paracetamol administration. We now assessed amplitude-integrated electroencephalography (aEEG) signals in preterm infants with and without exposure to prophylactic low-dose paracetamol administration. Methods: Infants <32 gestational weeks born between 10/2014 and 12/2018 received prophylactic paracetamol (10 mg/kg intravenously every 8 h until echocardiography after at least 72 h) and form the paracetamol group; infants born between 02/2011 and 09/2014 formed the control group. Four single parameters (continuity, cyclicity, amplitude of lower border, bandwidth span) together with their sum (Burdjalov total score) and presence of sleep-wake cycles were compared between the groups. Results: Included in the study were 338 infants. Two-hundred and seventeen infants received prophylactic paracetamol and 121 formed the control group. The paracetamol group showed a significantly higher number of sleep-wake cycles per hour and a significantly higher total scores compared to the control group (p < 0.05). Conclusion: Paracetamol exposure has been regarded critically with respect to safety in preterm infants in recent years. We found no impairment on amplitude-integrated electroencephalography signals in preterm infants receiving low-dose prophylactic paracetamol compared to controls. Growing awareness and greater availability of data may encourage the clinicians to administer prophylactic paracetamol for ductal closure in preterm infants. The clinical relevance of our findings has to be evaluated in long-term follow up studies on neurodevelopmental outcome.

Prophylactic Low-Dose Paracetamol Administration for Ductal Closure and Microstructural Brain Development in Preterm Infants.

INTRODUCTION: Prophylactic low-dose paracetamol administration is used to induce closure of the ductus arteriosus. Effects on the neurological outcome in preterm infants remain unknown. We compared microstructural brain development in very preterm infants with and without exposure to prophylactic paracetamol by using MR-based diffusion tensor imaging. MATERIALS AND METHODS: Infants aged <32 gestational weeks born between October 2014 and December 2018 received prophylactic paracetamol (10 mg/kg intravenously every 8 h until echocardiography after at least 72 h) and form the paracetamol group; infants born between February 2011 and September 2014 form the control group. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) at term-equivalent age were measured in 14 defined cerebral regions and compared between the groups. RESULTS: Included in the study were 340 infants, of whom 217 received prophylactic paracetamol, and 123 formed the control group. The paracetamol group showed significantly higher FA values and lower ADC values in the splenium of the corpus callosum, as well as higher FA values in the pons bilaterally, the left middle cerebellar peduncle, the right occipital white matter, and the right posterior limb of the internal capsule (p ≤ 0.02). CONCLUSION: The perceived safety of prenatal paracetamol exposure has been questioned in recent years. We found no impairment on microstructural maturation processes in the brain of preterm infants at term-equivalent age following early paracetamol administration. The clinical relevance of these imaging findings has to be determined in long-term follow-up studies on neurodevelopmental outcome.

Less invasive surfactant administration is associated with a higher need for nonpharmacological pain-relieving interventions compared to the intubation-surfactant extubation technique in preterm infants.

Aim: LISA is a promising method in improving preterm outcome. The aim of this study was to assess whether the INSURE (intubation-surfactant extubation) technique or LISA (less invasive surfactant administration) procedure for surfactant administration is associated with more pain-relieving interventions after the intervention in preterm infants. Methods: Preterm infants born at <32 weeks gestational age admitted to the Neonatal Intensive Care Unit of Innsbruck University hospital between Jan 2012 and June 2017 subjected to INSURE or LISA were included in the study, which was performed as a retrospective analysis of routinely collected data. Pain assessments were made bedside using the Bernese Pain Scale for Neonates. Results: During the study period 15 preterm infants (median gestational age 30.7 weeks; range: 25.9-32.0 weeks) were subjected to INSURE technique and 59 (median gestational age 29.4 weeks; range: 25.1-31.4 weeks) to LISA. Infants subjected to LISA showed a higher need for nonpharmacological pain-relieving interventions in the first three days of life. Conclusion: LISA procedure compared to INSURE technique was associated with a higher need for pain-relieving interventions in the first three days of life. Prospective randomized controlled trials are needed to optimize this less invasive method for surfactant application with special focus on pain in neonates.

Dietary treatment of congenital chylothorax with skimmed breast milk.

BACKGROUND: Congenital chylothorax (CC) is a rare but potentially life-threatening condition in newborns. It is defined as an accumulation of chyle in the pleural cavity. The few publications regarding medical management and therapeutic dietary intervention motivated us to share our experience. METHODS: Neonates diagnosed with congenital chylothorax and treated at Innsbruck Medical University Hospital between 2013 and 2020 (n = 6, gestational age: 36 3/7, 32 5/7, 36 4/7, 35 0/7, 35 4/7, 37 3/7 weeks) were eligible for this report. The cornerstones of treatment for chylothorax conventionally consist of chest tube drainage (CTD), respiratory support, dietary restriction of long-chain triglycerides (LCT) or total parenteral nutrition (TPN). In further course the introduction of a medium-chain triglyceride (MCT)-based formula followed by an overlapping switch to a formula with low LCT and high MCT, containing the essential long-chain fatty acids (LCFA), is attempted. In three patients we used fat-modified (skimmed) breast milk to provide a high protein and low fat diet and to avoid the discontinuation of breast milk. RESULTS: The outcome of an early introduction of LCFA in the form of skimmed breast milk after resolution of chylothorax diverse. One patient had a favourable outcome, meaning no recurrence of pleural effusion, adequate weight gain and a content mother, while another patient had a relapse of pleural effusion after the administration of skimmed milk and was therefore transitioned back to Basic F® . The CC of patient 5 was difficult due to Noonan syndrome. Two weeks after the introduction of skimmed breast milk the mother wanted to stop to express breast milk, so nutrition was changed to Basic F®. CONCLUSION: The first-line therapy of chylothorax is a combination of respiratory stabilization and dietary modification. The use of skimmed breast milk is advisable in CC and feasible by means of a simple milk defatting procedure. It offers benefits to mothers who wish to resume breast feeding after resolution of chylothorax and has proven positive effects, above all in preterm infants as optimal nutrition with protective components superior to formula feeding. However, the nutritional analysis of the skimmed milk and the correlation to a re-accumulation of pleural fluid remains a question to be answered.

Prophylactic low-dose paracetamol administration associated with lowered rate of patent ductus arteriosus in preterm infants - Impact on outcome and pain perception.

BACKGROUND: To determine the rate of patent ductus arteriosus after prophylactic low-dose paracetamol administration, the impact on outcome parameters, possible treatment side-effects and the influence on pain perception. METHODS: We report retrospective single-centre outcome data of premature infants ≤ 32 weeks of gestation (n = 476). The intervention group received intravenous paracetamol, the control group obtained no preventive therapy. Ductal closure rate and outcome parameters were compared between the two groups. Adverse effects were determined by laboratory parameters. For the assessment of pain the Bernese Pain Scale for Neonates was used. RESULTS: The rate of patent ductus arteriosus was significantly lower in the paracetamol-treated group compared to the control group (13.6% vs. 38.2%, p < 0.001). With regard to secondary outcome parameters, severe and moderate bronchopulmonary dysplasia (2.7% vs. 7.4%, p = 0.023), severe retinopathy of prematurity (0% vs. 4.4%, p = 0.002) and late onset sepsis (2.7% vs. 8.3%, p = 0.009) were significantly less frequent in the paracetamol group. Except for a 1.5-fold increased risk for hyperbilirubinemia (86.0% vs. 77.6%, p = 0.035) in the paracetamol group following treatment, no significant differences in laboratory parameters were found. Relating to pain, the administration of Glucose 33% was significantly more often necessary in the control group compared to the paracetamol-treated group (mean 13.48 vs. 8.71, p < 0.001), just as the need for additional treatment with systemic analgesics, which was more frequent in the control group (mean 0.72 vs. 0.57, p = 0.361). CONCLUSION: In our study we were able to show a significantly lower rate of patent ductus arteriosus after prophylactic paracetamol administration without serious adverse effect, but a beneficial influence of this regime on the patient's pain perception.

Protocols on classification, monitoring and therapy in children's rheumatology (PRO-KIND): results of the working group Polyarticular juvenile idiopathic arthritis.

OBJECTIVE: Several effective pharmacologic treatment options for polyarticual juvenile idiopathic arthritis (JIA) have emerged but initial treatment is heterogeneous in Germany. Therefore, the German Society of Pediatric Rheumatolgy has established a commission to develop consensus "Protocols on classification, monitoring and therapy in children's rheumatology (PRO-KIND)" to harmonize diagnostic and treatment approaches for new-onset JIA in Germany. METHODS: A set of definitions for in- and exclusion, diagnostic workup, parameters for the evaluation of disease activity criteria, therapeutic options, medication dosing, monitoring recommendations, targets, definitions of a therapy failure and four therapeutic algorithms developed by a working group were agreed by web based survey to which all members of the GKJR have been invited. A final protocol with 4 consensus treatment plans (CTP) was agreed in a face-to-face consensus conferences employing modified nominal group technique. RESULTS: The initial 17 definitions and recommendations for new-onset polyarticular JIA agreed by the working group reached >80% agreement in a web survey in 68 German paediatric rheumatologist. Four CTPs were developed based on treatment strategies for the first 12 months of therapy, as well as definitions for clinical and laboratory monitoring. The CTPs include a step-up plan (nonbiologic Disease-modifying antirheumatic drug [DMARD] followed by a biologic), a combination plan (combination of nonbiologic and biologic after failure of initial DMARD), an intensive pulse corticosteroid scheme in parallel with a DMARD followed by combination therapy and a multiple corticosteroids joint injections strategy in a treat to target approach. Step up will be guided by a treat to target strategy to reach a JADAS-improvement at month 3, acceptable disease at month 6 or 9 and JADAS remission or at least JADAS minimal disease activity at month 12. CONCLUSION: Standardized baseline work-up, disease activity evaluation and a definition of a treat to target approach will result in better health outcomes for polyarticular JIA patients. Four CTPs were developed for new-onset polyarticular JIA, which coupled with data collection at defined intervals will be evaluated and improved to optimize management of polyarticular JIA. Harmonization of treatment will be the basis for future comparative effectiveness research.

Secretoneurin Serum Levels in Healthy Term Neonates and Neonates with Hypoxic-Ischaemic Encephalopathy.

BACKGROUND: Hypoxic-ischaemic encephalopathy is a major cause of neurologic impairment and mortality in neonates. Early knowledge of brain injury is important to guide therapeutic decisions and reliably inform the parents. Increased secretoneurin levels have been detected in adult patients suffering from brain injury and it has also been shown to be a promising early serum biomarker of unfavourable neurological outcome. However, no data are available in neonates. OBJECTIVE: The aim of this study was to obtain reference values for secretoneurin in healthy term neonates and then to assess the potential of this neuropeptide as a biomarker in the context of hypoxic-ischaemic encephalopathy in asphyxiated term neonates. METHODS: A total number of 139 term neonates, of which 7 were asphyxiated and 132 were healthy, were prospectively enrolled. Secretoneurin serum concentrations were assessed by radioimmunoassay. RESULTS: In healthy controls, secretoneurin serum concentrations were influenced by the mode of delivery (highest in infants born per vacuum extraction and lowest in infants born per caesarean section) and abnormal cardiotocography. In asphyxiated term neonates, secretoneurin concentrations were higher in umbilical cord blood and significantly lower 48 h after birth in comparison to healthy controls. CONCLUSION: Secretoneurin levels are elevated in cord blood in infants suffering from hypoxic-ischaemic encephalopathy following perinatal asphyxia. The potential of secretoneurin as a marker of neonatal hypoxic-ischaemic brain injury should be further evaluated in larger trials.

ALG8-CDG: novel patients and review of the literature.

BACKGROUND: Since 1980, about 100 types of congenital disorders of glycosylation (CDG) have been reported representing an expanding group of inherited disorders. ALG8-CDG (= CDG-Ih) is one of the less frequently reported types of CDG, maybe due to its severe multi-organ involvement with coagulation disturbances, edema, massive gastrointestinal protein loosing enteropathy, cataracts, and often early death. We report three additional patients, provide an update on two previously reported, and summarize features of ten patients reported in literature. RESULTS: Of 15 ALG8-CDG patients, three were homozygous and 12 compound heterozygous. There were multiple prenatal abnormalities in 6/12 patients. In 13/15, there were symptoms at birth, 9/15 died within 12 months. Birth weight was appropriate in 11/12, only one was small for gestational age. Prematurity was reported in 7/12. Hydrops fetalis was noticed in 3, edemas in 11/13; gastrointestinal symptoms in 9/14; structural brain pathology, psychomental retardation, seizures, ataxia in 12/13, muscle hypotonia in 13/14. Common dysmorphic signs were: low set ears, macroglossia, hypertelorism, pes equinovarus, campto- and brachydactyly (13/15). In 10/11, there was coagulopathy, in 8/11 elevated transaminases; thrombocytopenia was present in 9/9. Eye involvement was reported in 9/14. CDG typical skin involvement was reported in 8/13. CONCLUSION: In ALG8-CDG, isoelectric focusing of transferrin in serum or plasma shows an abnormal sialotransferrin pattern. The diagnosis is confirmed by mutation analysis in ALG8; all patients reported so far had point mutations or small deletions. The prognosis is generally poor. Thus, a timely and correct diagnosis is important for counselling.

Kawasaki disease in children and adolescents: clinical data of Kawasaki patients in a western region (Tyrol) of Austria from 2003-2012.

BACKGROUND: Kawasaki disease (KD) is a rare vasculitis seen predominantly in children. In developing countries, it is the leading cause of childhood-acquired heart disease. Besides a case report from 1981 there have been no data published dealing with the epidemiology and clinical aspects of KD in Austria. METHODS: The purpose of the present study was to investigate the clinical spectrum of KD in a geographically determined cohort of infants, children, and adolescents that were diagnosed and treated at the University Hospital of Innsbruck from 2003-2012. RESULTS: Thirty-two patients were included in the study with a median age of 32.96 months (2-192). 59.4% of the patients were aged between six months and four years. The male-to-female ratio was 1:1.13. Clinical examination revealed non-purulent conjunctivitis and exanthema as the most common symptoms (84.4%). 75% showed oropharyngeal changes, 21.9% had gastrointestinal complaints such as diarrhoe, stomachache or vomiting prior to diagnosis. One third of the patients were admitted with a preliminary diagnosis, whereas 78.1% were pre-treated with antibiotics. The median fever duration at the time of presentation was estimated with 4.96 days (1-14), at time of diagnosis 6.76 days (3-15).75% were diagnosed with complete KD, and 25% with an incomplete form of the disease. There was no significant difference in the duration of fever neither between complete and incomplete KD, nor between the different age groups. Typical laboratory findings included increased C-reactive protein (CRP) (80.6%) and erythrocyte sedimentation rate (ESR) (96%),leukocytosis (48.4%) and thrombocytosis (40.6%) without any significant quantitative difference between complete and incomplete KD. Coronary complications could be observed in six patients: one with a coronary aneurysm and five with tubular dilatation of the coronary arteries. Our patient cohort represents the age distribution as described in literature and emphasizes that KD could affect persons of any age. The frequency of occurrence of the clinical symptoms differs from previous reports - in our study, we predominantly observed non-purulent conjunctivitis and exanthema. CONCLUSION: KD should always be considered as a differential diagnosis in a child with fever of unknown origin, as treatment can significantly decrease the frequency of coronary complications.

Quantitative alterations of CD8+ T cells in juvenile idiopathic arthritis patients in remission.

The study was aimed to investigate whether quantities of CD8(+) T cell subsets are normal in juvenile idiopathic arthritis (JIA) patients with disease remission compared to age-matched healthy donors (HD) and whether chronological age may have an impact on proportions of naive CD8(+) T cells. CD8(+) T cell subsets were analyzed in 17 JIA patients and 32 age-matched HD by flow cytometry. JIA patients showed lower CD3(+)CD8(+) T cells compared to HD. Total counts of CD8(+)CD28(+) and CD8(+)CD28(+)CD45RA(+) T cells were inversely correlated to chronological age in JIA patients and HD. In JIA patients, percentages of CD8(+)CD28(+)CD45RA(+) T cells and of CD62L-expressing CD8(+)CD28(+)CD45RA(+) T cells showed a negative correlation with age. The trend to lower CD28(+)CD45RA(+) T cell proportions in aged JIA patients in remission may reflect a disturbed T cell homeostasis independently of disease activity and may be due to an intrinsic effect in reconstitution of the peripheral T cells.

Feasibility of second-generation ultrasound contrast media in the detection of active sacroiliitis.

OBJECTIVE: To determine whether a recently available contrast-enhanced ultrasound (CEUS) technique using second-generation microbubbles allows for the detection of active sacroiliitis, and to measure CEUS enhancement depth at the dorsocaudal part of the sacroiliac (SI) joints in healthy volunteers compared with patients with sacroiliitis. METHODS: Forty-two consecutive patients (84 SI joints) presenting with a clinical diagnosis of sacroiliitis in 50 SI joints and 21 controls (42 SI joints) were investigated by CEUS using a standardized low mechanical index ultrasound protocol. Detected vascularity was used to retrospectively measure the enhancement depth in the dorsocaudal part of the SI joints. RESULTS: CEUS detected enhancement in all clinically active SI joints, showing an enhancement depth into the dorsal SI joint cleft of 18.5 mm (range 16-22.1), which was significantly higher compared with both inactive joints of patients (3.6 mm, range 0-12; P < 0.001) and healthy controls (3.1 mm, range 0-7.8; P < 0.001). All inactive joints were correctly classified based on a lack of deep enhancement in patients with sacroiliitis and controls (42 of 42, 100% sensitivity, 100% specificity; Cohen's kappa = 1). CONCLUSION: CEUS allowed the differentiation of active sacroiliitis from inactive SI joints, and proved to be a feasible method for the detection of vascularity in clinically active sacroiliitis by showing deep contrast enhancement into the SI joints not detectable in inactive joints of patients or controls. If this technique might add information to the earlier detection of sacroiliitis, it should be addressed in further studies.

US guided injections in arthritis.

US guided procedures for diagnosis or treatment of different forms of arthritis are becoming more and more important. This review describes general considerations for fluid aspiration, articular or periarticular injections and biopsies by US guidance according to the recent literature. Guidelines regarding instrumentation, different techniques, pre- and postprocedural care as well as complications are outlined and in the second part a more detailed overview of different interventions in joints, tendons and other periarticular regions (nerves, bursae, etc.) is included. Furthermore, some newer, more sophisticated techniques are briefly discussed.

Premature aging of the immune system in children with juvenile idiopathic arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is an autoimmune disease of the young. The pathogenesis is not completely understood. Premature aging, associated thymic involution, and compensatory autoproliferation could play important roles in the pathogenesis of autoimmunity. We undertook this study to determine whether patients with JIA demonstrate premature immunosenescence. METHODS: To test this hypothesis, we measured 3 indicators of aging: the percentages and total counts of peripheral blood naive T cells, the frequency of T cell receptor excision circles (TRECs) in naive T cells, and telomeric erosion and Ki-67 expression as estimates of the replicative history of homeostatic proliferation. RESULTS: JIA patients showed an accelerated loss of CD4+,CD45RA+,CD62L+ naive T cells with advancing age and a compensatory increase in the number of CD4+,CD45RO+ memory T cells. JIA patients demonstrated a significantly decreased frequency of TRECs in CD4+,CD45RA+ naive T cells compared with age-matched healthy donors (P = 0.002). TREC numbers correlated with age only in healthy donors (P = 0.0001). Telomeric erosion in CD4+,CD45RA+ naive T cells was increased in JIA patients (P = 0.01). The percentages of Ki-67-positive CD4+,CD45RA+ naive T cells were increased in JIA patients (P = 0.001) and correlated with disease duration (P = 0.003), which was also an independent factor contributing to telomeric erosion (P = 0.04). CONCLUSION: Our findings suggest that age-inappropriate T cell senescence and disturbed T cell homeostasis may contribute to the development of JIA. In patients with JIA, dysfunction in the ability to reconstitute the T cell compartment should be considered when exploring new therapeutic strategies.

Evidence-based use of methotrexate in children with rheumatic diseases: a consensus statement of the Working Groups Pediatric Rheumatology Germany (AGKJR) and Pediatric Rheumatology Austria.

Juvenile idiopathic arthritis (JIA) is the most common diagnosis in children and adolescents with rheumatic disorders. In many children and adolescents, JIA is successfully treated with non-steroidal anti-inflammatory drugs (NSAID) and physiotherapy. However, in a significant number of cases the disease is resistant to this therapy, and treatment with "second line" disease-modifying antirheumatic drugs (DMARDs) is required. Methotrexate (MTX) is frequently referred to as "first-choice second-line agent" for the treatment of JIA. To increase drug safety, the Working Groups for Children and Adolescents with Rheumatic Diseases in Germany (AGKJR) and Pediatric Rheumatology Austria have initiated the formulation of evidence-based recommendations. Evidence is based on consensus expert meetings, a MEDLINE search with the key words "Methotrexate" and "juvenile arthritis" limited to age 0-18 years, standard textbooks and review articles, data from the central registry of the German Research Center for Rheumatic Diseases (Deutsches Rheumaforschungszentrum Berlin DRFZ), experience with MTX in adults with rheumatoid arthritis (RA), and recommendations of the German Society of Rheumatology (DGRh). Based on these data, evidence and recommendations are graded, and evidence-based recommendations for the use of MTX in children and adolescents with rheumatic disease are presented.

No evidence for hyperhomocysteinemia or increased prevalence of genetic polymorphisms in the homocysteine pathway in patients with moderate juvenile idiopathic arthritis.

OBJECTIVE: Elevated plasma total homocysteine (tHcy) concentrations are associated with premature cardiovascular disease. We assessed tHcy, folate, vitamin B12 (Vit B12), vitamin B6 (Vit B6), and genetic polymorphisms potentially enhancing tHcy in patients with juvenile idiopathic arthritis (JIA) and healthy controls. METHODS: Open study of 56 consecutive patients with JIA and 62 controls. RESULTS: tHcy concentrations were normal in JIA patients (mean 6.5 +/- 2 micromol/l) and controls (mean 7.5 +/- 2.2 micromol/l). Folate concentrations were significantly higher in JIA patients (40.2 +/- 67.9 ng/ml) compared to controls (13.6 +/- 8.2 ng/ml). The prevalence of genetic polymorphisms coding for key enzymes in the homocysteine pathway did not differ between patients and controls. Erythrocyte sedimentation rate (ESR) showed significant inverse correlations with circulating Vit B6 and tHcy concentrations. CONCLUSION: No evidence for hyperhomocysteinemia or evidence for a specific genetic predisposition for hyperhomocysteinemia was present in patients with JIA. Elevated ESR is not associated with hyperhomocysteinemia.

Reduced aortic elastic properties in a child with Takayasu arteritis: case report and literature review.

UNLABELLED: Takayasu arteritis (TA) is a chronic inflammatory vasculitis of the aorta and its major branches with a very low incidence in Europe and North America. Our objective was to determine the elastic properties of the affected ascending and descending aortic walls non-invasively in a 14-year-old Iraqi girl with a 3-year history of fever, fatigue, malaise and diffuse pain. Ultrasound and magnetic resonance angiography showed marked thickening of the aortic wall, dilatation of the aortic arch, and decreased luminal diameters of the abdominal aorta and both subclavian arteries, consistent with TA. Ascending and descending aortic elastic properties such as distensibility and stiffness index were markedly reduced compared to a group of healthy controls (n=39): ascending aortic distensibility was 20 kPa(-1) x 10(-3) versus 63+/-23 kPa(-1) x 10(-3) in controls, and the ascending aortic stiffness index 9.6 versus 3.5+/-1.3 in controls. Although the patient's general condition improved rapidly on oral prednisolone and azathioprine and inflammatory parameters normalised within 3 weeks, the aortic elastic parameters did not change during the first 2 weeks of anti-inflammatory treatment. Unfortunately, no further follow-up was possible. CONCLUSION: In patients with Takayasu arteritis, non-invasive quantification of reduced aortic elastic properties can help to assess aortic involvement, and possibly to follow disease activity and vascular response to therapy.