Update of the evidence based, interdisciplinary guideline for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis.

BACKGROUND: Uveitis in juvenile idiopathic arthritis (JIAU) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first line therapy, and disease modifying anti-rheumatic drugs (DMARDs) are commonly used. However, treatment has not been standardized. METHODS: Interdisciplinary guideline were developed with representatives from the German Ophthalmological Society, Society for Paediatric Rheumatology, Professional Association of Ophthalmologists, German Society for Rheumatology, parents' group, moderated by the Association of the Scientific Medical Societies in Germany. A systematic literature analysis in MEDLINE was performed, evidence and recommendations were graded, an algorithm for anti-inflammatory treatment and final statements were discussed in a consensus meeting (Nominal Group Technique), a preliminary draft was fine-tuned and discussed thereafter by all participants (Delphi procedure). RESULTS: Consensus was reached on recommendations, including a standardized treatment strategy according to uveitis severity in the individual patient. Thus, methotrexate shall be introduced for uveitis not responding to low-dose (≤ 2 applications/day) topical corticosteroids, and a TNFalpha antibody (preferably adalimumab) used, if uveitis inactivity is not achieved. In very severe active uveitis with uveitis-related deterioration of vision, systemic corticosteroids should be considered for bridging until DMARDs take effect. If TNFalpha antibodies fail to take effect or lose effect, another biological should be selected (tocilizumab, abatacept or rituximab). De-escalation of DMARDs should be preceded by a period of  ≥ 2 years of uveitis inactivity. CONCLUSIONS: An interdisciplinary, evidence-based treatment guideline for JIAU is presented.

[The child presenting with arthralgia or arthritis - what do we need to consider?]. / Das Kind mit Gelenksproblemen - was ist zu bedenken?

Musculoskeletal symptoms in children are among the most frequent presenting symptoms. Besides traumatic etiology - which accounts for most of the symptoms- more than 100 differential diagnoses need to be considered in the pediatric patients. Therefore children with limp pain or gait abnormalities always require thorough assessment for early exclusion of potentially threatening diseases e.g. leukemia, chronic metabolic or inflammatory diseases. Pediatric patients with arthralgia or arthritis therefore represent a population of risk which should always require referral to the experienced pediatrician whenever the diagnosis or condition of the child remains uncertain.

Successful treatment of severe juvenile microscopic polyangiitis with rituximab.

Microscopic polyangiitis (MPA) previously called hypersensitivity angiitis is a systemic necrotizing vasculitis affecting predominantly small vessels. MPA involves multiple organ systems including the lung, the kidneys, the joints, and the skin. MPA mostly affects adults in their fourth and fifth decade of life. MPA and Wegener;s granulomatosis are grouped together as ANCA-associated vasculitis. MPA is associated with high titre of myeloperoxidase antineutrophil cytoplasmic antibodies (MPO)-ANCA. We present a 14-year-old female patient presented with MPA. She was treated with steroids and cyclophosphamide. After the complication of severe lung involvement, rituximab was administered as immune-modulating treatment. The MPA came to remission. This is the first report of a pediatric patient with MPA treated with rituximab. Rituximab might be a potential therapeutic option for relapsing ANCA associated vasculitis in childhood.

Growth and body composition in children with classical phenylketonuria: results in 34 patients and review of the literature.

Treatment of phenylketonuria (PKU, OMIM 261600) means a diet restricted in natural protein and supplemented with phenylalanine (Phe)-free L-amino acid mixtures. Growth impairment has been described even in patients with a total protein intake at or above the recommended dietary allowance (RDA). In the present study, growth and body composition (fat-free mass (FFM) and fat) were recorded over 12 months in 34 treated PKU patients (mean age 8.7 years at baseline). Measurements were compared with those of healthy peers and with general population standard (Z-) scores calculated using the LMS method. In 28 PKU patients, data on birth weight and birth length were available and related to measurements at baseline of the study. Mean total protein intake in PKU patients was 124% (range 77-193%) of the RDA (DACH 2000). No significant differences in growth and body composition were present between PKU patients and healthy populations either at birth or during the study period. The significant correlation of FFM (representing muscle mass) with intake of natural protein--rather than total protein--indicates that the enhancement of tolerance to natural protein may be of value in PKU patients.

Health-related quality of life of patients with juvenile idiopathic arthritis coming from 3 different geographic areas. The PRINTO multinational quality of life cohort study.

OBJECTIVES: To compare health-related quality of life (HRQL) and to identify clinical determinants for poor HRQL of patients with juvenile idiopathic arthritis (JIA) coming from three geographic areas. METHODS: The HRQL was assessed through the Child Health Questionnaire (CHQ). A total of 30 countries were included grouped in three geographic areas: 16 countries in Western Europe; 10 in Eastern Europe; and four in Latin America. Potential determinants of poor HRQL included demographic data, physician's and parent's global assessments, measures of joint inflammation, disability as measured by Childhood Health Assessment Questionnaire (CHAQ) and erythrocyte sedimentation rate. Poor HRQL was defined as a CHQ physical summary score (PhS) or psychosocial summary score (PsS) <2 S.D. from that of healthy children. RESULTS: A total of 3167 patients with JIA, younger than 18 yrs, were included in this study. The most affected health concepts (<2 S.D. from healthy children) that differentiate the three geographic areas include physical functioning, bodily pain/discomfort, global health, general health perception, change in health with respect to the previous year, self-esteem and family cohesion. Determinants for poor HRQL were similar across geographic areas with physical well-being mostly affected by the level of disability while the psychosocial well-being by the intensity of pain. CONCLUSION: We found that patients with JIA have a significant impairment of their HRQL compared with healthy peers, particularly in the physical domain. Disability and pain are the most important determinants of physical and psychosocial well-being irrespective of the geographic area of origin.

[Periodic fever syndromes]. / Genetische Fiebersyndrome.

Periodic fever syndromes comprise a group of disorders characterized by attacks of seemingly unprovoked inflammation. The genetic causes of five hereditary autoinflammatory syndromes have been identified in the last few years: familial Mediterranean fever, the cryopyrinopathies [Muckle-Wells, chronic infantile neurological, cutaneous, articular syndrome (CINCA) and familial autoinflammatory syndromes], TNF-receptor associated periodic syndrome, cyclic neutropenia syndrome and periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. The study of periodic fever syndromes has progressed from clinical characterization to genetic analysis and to the definition of the functional defects linking genes or domains to apoptotic proteins and signal transduction pathways. This new research opens the way for more specific treatment options with a further improvement in prognosis and outcome.

Hyperhomocysteinemia in children with juvenile idiopathic arthritis is not influenced by methotrexate treatment and folic acid supplementation: a pilot study.

OBJECTIVE: Our first objective was to compare plasma total homocysteine (tHcy) concentrations in juvenile idiopathic arthritis (JIA) patients requiring methotrexate (MTX) treatment and healthy children. Our second aim was to evaluate the influence of low-dose (10-15 mg/m2/week) MTX treatment combined with folic acid supplementation (1 mg/d) or placebo on tHcy concentrations in JIA patients. METHODS: In 17 JIA patients and 17 age- and sex-matched healthy children, baseline tHcy concentrations were measured. When MTX treatment was initiated, JIA patients were randomly assigned to folic acid 1 mg/d/p.o. followed by placebo (8 weeks each) or vice versa. Blood samples for measurement of tHcy, vitamin B6, B12 and folate were taken after 4 weeks, 12 weeks and 20 weeks of treatment. RESULTS: 1) In the healthy children the mean tHcy concentration was 6.3 +/- 1.68 mumol/l as compared to 9.99 +/- 5.17 mumol/l in JIA patients (p < 0.04). At baseline, 5/17 JIA patients had tHcy concentrations > 10.5 mumol/l, the 99th percentile for teenagers. 3/5 patients even exceeded the upper normal level for adults (tHcy > or = 15 mumol/l). MTX treatment did not result in a significant increase of tHcy and folic acid supplementation had no significant impact on tHcy levels. CONCLUSION: This pilot study shows that patients with JIA requiring MTX treatment have significantly elevated baseline plasma tHcy concentrations compared to age- and sex-matched healthy controls. No significant impact of MTX and folate supplementation on tHcy concentration was found.

Incidence of pediatric rheumatic diseases in a regional population in Austria.

OBJECTIVE: To establish a population based disease registry for pediatric rheumatology in a defined population of Austria; to describe the demographic and diagnostic classification of children referred to pediatric rheumatology clinics; and to estimate the incidence of pediatric rheumatic diseases in Eastern Austria. METHODS: For 2 years (1997-98) all pediatric rheumatology centers in the area contributed data on all new cases to a prospective multicenter patient registry. Diagnostic criteria defined the rheumatic disease cases, determined by a pediatric rheumatologist, and record linkage was carried out to avoid duplication of subjects. RESULTS: Rheumatic conditions were diagnosed in 107 subjects. Juvenile rheumatoid arthritis (JRA) was the most frequently encountered rheumatic condition (49.5%), followed by spondyloarthropathy (SpA, 33.6%) and systemic lupus erythematosus (SLE, 5.6%). The mean annual incidence of JRA, SpA, and SLE among children referred to pediatric rheumatology centers was 4.28, 2.9, and 0.48 per 100,000 children at risk, respectively. CONCLUSION: Establishment of a population based disease registry led to collection of descriptive epidemiologic data on a defined regional cohort of children with rare disorders. Our registry will provide data on pediatric rheumatic diseases in a European population and will allow more accurate comparisons between populations for future research. Our data also indicate that more resources should be designated for the care of pediatric rheumatic diseases in view of the relatively high incidences of these diseases.

The Austrian 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 Austrian language of the parentís 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 Austrian CHAQ CHQ were adapted from the German version of the CHAQ-CHQ, and revalidated in this study. A total of 134 subjects were enrolled: 74 patients with JIA (9.5% systemic onset, 42% polyarticular onset, 9.5% extended oligoarticular subtype, and 39% persistent oligoarticular subtype) and 60 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 Austrian version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Does the BMI reflect body fat in obese children and adolescents? A study using the TOBEC method.

OBJECTIVE: Due to the fact that obesity is defined as excess of body fat mass, we tested the hypothesis whether the body mass index (BMI) can be used as a valid measure for the detection of the degree of obesity in individual obese children and adolescents. METHODS: A total of 204 obese children and adolescents (105 boys, 99 girls) aged 6-17 y, using total body electrical conductivity (TOBEC) for fat measurement, were included into this study. A multiple regression analysis was performed with percentage body fat (PBF) as dependent variable and BMI, age and sex as independent variables. First- and second-order interaction terms were also included. Since all interaction terms showed a significant influence on PBF, regression analysis was performed separately for boys and girls, dividing each group into two age subgroups (subjects younger than 10 y, and subjects 10 y or older). RESULTS: BMI and PBF were observed to be positively correlated (overall: r=0,65; P=0.0001; boys r=0.63 and girls: r=0.68). Through a multiple regression analysis 57% of the variance of PBF could be explained by the independent variables. In boys younger than 10 y 73% and in girls younger than 10 y 63% of the variance of PBF was explained by the BMI. In subjects 10 y or older the association was poor (boys: 27%; girls: 38%). It should be emphasized that there is a wide range in the relationship between PBF and BMI in the obese subjects. CONCLUSION: From these results we conclude that BMI might be a useful parameter for epidemiological studies: however in the individual pediatric patient, especially from 10 y onwards, it gives only a limited insight to the degree of obesity based on the definition.

Lipodystrophy in patients with juvenile dermatomyositis--evaluation of clinical and metabolic abnormalities.

OBJECTIVE: Lipodystrophy and associated metabolic abnormalities are being increasingly recognized as complications of juvenile dermatomyositis (JDM). We investigated the prevalence of lipodystrophy and the extent of metabolic abnormalities related to lipoatrophic diabetes mellitus in patients with JDM. METHODS: Twenty patients with JDM were evaluated for evidence of lipodystrophy and associated lipoatrophic diabetes mellitus. All patients underwent clinical assessment, laboratory investigations, and metabolic studies (oral glucose tolerance test, lipid studies, insulin antibodies). RESULTS: We found clinical evidence of lipodystrophy and lipoatrophic diabetes mellitus in 4 of 20 patients with JDM and metabolic abnormalities known to be associated with lipodystrophy in another 8 patients. The 20 patients with JDM were categorized as follows: Group 1 (Patients 1-4) consisted of patients with lipodystrophy and either diabetes mellitus (2 patients) or impaired glucose tolerance (2 patients); Group 2 (Patients 5-12): no lipodystrophy but abnormal glucose and/or lipid studies; Group 3 (Patients 13-20): no lipodystrophy and no abnormalities of glucose and lipid studies. CONCLUSION: We found 25% of patients with JDM have lipodystrophy, and 50% present with hypertriglyceridemia and insulin resistance. Screening for metabolic abnormalities in JDM should be included in routine followup because of the effect of lipodystrophy on longterm prognosis.

Scleroderma-like syndrome in a child: eosinophilic fasciitis or scleredema adultorum?

UNLABELLED: A 6-year-old female patient presented with a rapidly progressive scleroderma-like syndrome involving almost the entire integument. Initially clinical patterns and histopathological data of both eosinophilic fasciitis and scleredema adultorum were present. The course of the disease remained unusual for both conditions but finally argued in favour of the diagnosis of eosinophilic fasciitis. CONCLUSION: Eosinophilic fasciitis and scleredema adultorum might be subtypes of one disease entity.

Elevation of plasma leptin concentrations in obese hyperinsulinaemic hypothyroidism before and after treatment.

BACKGROUND: Plasma leptin is considered to play a role in maintenance of energy balance and body weight by neuroendocrine mechanisms. Thyroid hormones are permissive for adrenergic activation, which in turn has been shown to decrease leptin expression. This study was therefore designed to test the hypothesis that hyperthyroidism results in lower leptin concentrations, whereas hypothyroidism leads to higher plasma leptin concentrations. In addition, the effects of normalization of thyroid function on plasma leptin were investigated. MATERIALS AND METHODS: Fasting plasma leptin concentrations and body fat mass (total body electrical conductivity) were measured in patients with overt hypothyroidism and hyperthyroidism before and after successful treatment. Plasma leptin, glucose, insulin and free fatty acid concentrations were monitored during an oral glucose tolerance test (OGTT 75 g). RESULTS: Fasting plasma leptin concentrations were similar in lean patients, independently of their thyroid function (hyperthyroid 12.5 +/- 2 ng mL-1, hypothyroid 10.2 +/- ng mL-1, euthyroid 12.7 +/- 3 ng mL-1). In obese hypothyroid patients, plasma leptin was threefold higher (P < 0.0005) than in lean hypothyroid patients, twofold higher (P < 0.005) than in obese hyperthyroid patients matched for fat mass and 30% increased (P < 0.01) compared with obese euthyroid subjects. There were no differences between fasting and post-prandial (OGTT) leptin concentrations in any group. Normalization of thyroid function did not affect plasma leptin, which remained elevated (P < 0.005) in formerly obese hypothyroid patients. Plasma leptin was not associated with serum thyroid hormones but highly correlated with body mass index and body fat mass in all patients (r = 0.85, P < 0.001). Plasma leptin correlated with plasma insulin concentration only in hyperthyroid patients (P < 0.01, r = 0.64), who presented with blunted stimulation of insulin release and higher plasma glucose (P < 0.05) than hypothyroid subjects. CONCLUSION: The results indicate that (a) the correlation of leptin with body fat mass is preserved in thyroid dysfunction, (b) plasma leptin is markedly increased in obese hypothyroid hyperinsulinaemic patients and (c) plasma leptin is not affected by oral glucose loading.

Respiratory compliance assessed from chest expansion and inflation pressure in ventilated neonates.

We evaluated a bedside method of assessing respiratory compliance from chest expansion, which is judged by eye and classified into three tidal volume categories, and from the inflation pressure read on the respirator's manometer. Compliance assessed by this method was compared with the compliance measured by the injection technique in 45 randomly chosen newborns ventilated for various diseases. The compliance assessed from chest expansion and inflation pressure correlated significantly with the measured compliance (r = 0.86, p < 0.001). Interobserver reliability was acceptable for clinical practice and improved within 6 months of training (weighted kappa = 0.67 versus 0.86). Within ten individuals, changes of compliance assessed by this method were also significantly correlated with those of measured compliance (r = 0.85, p < 0.01). This method, termed "optical compliance," is instantaneously and always available for all patients on ventilators without any additional apparatus and thus might improve the assessment of respiratory function in routine care and emergency situations.

Iron nutrition and growth of breast- and formula-fed infants during the first 9 months of life.

Feeding of iron (Fe)-fortified (12-15 mg/L) infant formulas is an effective and convenient means to protect infants from Fe deficiency. To study lower levels of Fe fortification of infant formulas (3 or 6 mg/L) compared with those currently in use, we compared Fe intake and Fe nutritional status of three groups of healthy, term infants between 90 and 274 days of age. One group received an Fe-fortified whey-predominant formula (3 mg/L) and the second group received the same formula with a higher Fe level (6 mg/L). A comparison group was breast-fed at least until 274 days of age. All infants received infant foods and cereals according to European Community recommendations. Mean Fe intake of infants fed formula fortified with 3 mg/L was significantly lower at 183 and 274 days of age (p < 0.05) than that of infants fed formula fortified with 6 mg/L. None of the infants fed the formula fortified with 3 mg/L met the recommended daily allowance value (10 mg) for infants between 6 and 12 months of age. Hemoglobin, hematocrit, mean corpuscular volume, free erythrocyte protoporphyrin, and serum ferritin levels were similar in the formula-fed groups; none of the infants had depleted Fe stores (ferritin < 10 micrograms/L) at 183 and 274 days of age. Thirteen percent of breast-fed infants had depleted Fe stores at 183 days of age, but only 3% were depleted at 273 days of age, when Fe-fortified beikost was already part of the diet. No influence of Fe nutritional status was found on zinc and copper nutritional status or on growth.(ABSTRACT TRUNCATED AT 250 WORDS)

[Acute diarrheal diseases. Treatment with carrot-rice viscous solution is more effective than ORS solution]. / Akute Durchfallerkrankungen. Behandlung mit Karotten-Reisschleim ist effektiver als ORS-Lösung.

In infants and children, the treatment of acute diarrhoea with glucose-based electrolyte solutions results in rehydration but does not reduce the severity and duration of diarrhoea. In german-speaking countries, rice- and carrot-based solutions have a long tradition in the treatment of diarrhoea and may also reduce stool output and the duration of diarrhoea. Therefore, we evaluated the efficacy and safety of a carrot-rice-based rehydration solution (Na 57 mmol/L, n = 70) and two conventional glucose-based solutions with high or low sodium concentrations (Na 90 mmol/L, n = 48 or Na 55 mmol/L, n = 60) in a prospective study. The study subjects were Pakistani boys and girls between 3 and 48 months of age with mild or moderate dehydration. We measured duration of diarrhoea, fecal and urine output, fluid intake and serum electrolytes. The duration of diarrhoea was significantly lower (p less than 0.05) in the group receiving the carrot-rice based rehydration solution (59.5 +/- 30.9 h) than in the groups receiving the high-Na (75.5 +/- 30.5) and low-Na (74.8 +/- 32.5) glucose-electrolyte solutions. The mean fecal output (p less than 0.01) and fluid intake (p less than 0.001) were also significantly lower in the infants and children receiving the carrot-rice-based rehydration solution. No major electrolyte imbalances were observed in the three groups. We conclude that the carrot-rice-based rehydration solution was safe and more effective than two conventional glucose-electrolyte solutions in the rehydration of infants and children with acute diarrhoea.

Interactions between infections, malnutrition and iron nutritional status in Pakistani infants. A longitudinal study.

The interactions between infections, malnutrition and poor iron nutritional status in infants at weaning ages are poorly defined. Therefore, four groups of infants from an area with a high incidence of malnutrition (Lahore, Pakistan) were enrolled in a prospective, randomized nutritional intervention study. Between 122 and 365 days of age, the infants from one community received either a milk cereal without iron fortification (n = 29), a milk cereal fortified with ferrous fumarate (7.5 mg/100 g; n = 30), or a milk cereal fortified with ferric-pyrophosphate (7.5 mg/100 g; n = 27). Forty-four infants from a neighbouring community did not receive a nutritional supplement and served as the control group. Calculated mean daily energy- and protein intake with the cereals was between 259-287 kcal, and 9.6-10.6 g at 12 months of age, respectively. Mean daily iron intake with the fortified cereals was between 4.1-5.1 mg at corresponding age. Nutritional supplementation resulted in significantly lower incidence of malnutrition and higher weight gain. Incidence of acute diarrhoea was significantly (p less than 0.05) lower in the supplemented groups. The infants fed the iron-fortified milk cereals had significantly higher hemoglobin (mean 10.4 vs. 9.8 g.dl-1) and serum ferritin (mean 13.3 vs. 8.5 ng.ml-1) values than the infants fed the non-fortified milk cereals. However, no differences in the incidence of infections were found between the supplemented groups. It is concluded that poor nutritional intake between 122 and 365 days of age substantially contributed to the high incidence of diarrhoea and malnutrition in Pakistani infants.

[Therapeutic drugs, illicit poisons and environmental chemicals in breast milk--assessing the risk]. / Medikamente, Suchtgifte und Umweltchemikalien in der Muttermilch--Risikobeurteilung.

Our knowledge about the transfer of drugs and environmental chemicals into breast milk has increased in the last years. This review is mainly based on recently published literature and focuses on all drugs and environmental substances with documented effects on lactation and the nursing infant. Our aim is to provide brief information for physicians who are counseling breastfeeding mothers.

[Does breast feeding protect from atopic diseases?]. / Schützt Stillen vor atopischen Erkrankungen?

It is well established that food antigens can pass from mothers to infants via the breast milk. Bovine-beta-lactoglobulin has been detected in several breast milk samples from mothers with regular intake of cow's milk. Healthy breastfed infants can produce IgG antibodies against cow's milk protein and in infants at risk for atopic disease specific IgE antibodies were found before cow's milk based infant formula was introduced into the diet. However, several clinical studies in infants at risk for atopic disease indicate that exclusive breastfeeding decreases the incidence of atopic disease. The protective effect of breastfeeding is only relative and it is uncertain, how long protection lasts. Sensitization to food antigens may occur already in utero, because infants whose mothers avoid common allergenic foods during the whole pregnancy and then during the lactation period have a lower incidence of atopic eczema than infants whose mothers are on an unrestricted diet. Avoidance of common allergenic foods only during the last trimester of pregnancy had no effect, because the fetus is capable of forming IgE immune response.