Anti-inflammatory effect of exclusive enteral nutrition in patients with juvenile idiopathic arthritis.

OBJECTIVES: There is extensive evidence for an influence of gut microbiota on the immune system, which has consequences for inflammatory diseases. Exclusive enteral nutrition (EEN), which may change the gut microbiota, is an effective anti-inflammatory treatment for Crohn's disease in children. We wanted to explore the immediate anti-inflammatory effect of EEN in children with juvenile idiopathic arthritis (JIA). METHODS: Thirteen patients with JIA (7-17 years of age), in a disease flare-up, were included in the study. Six children dropped out within 1.5-2.0 weeks of treatment, and seven patients continued, constituting the study cohort. EEN was given for three to eight weeks, with clinical and laboratory status assessed before and after treatment periods. In addition to conventional laboratory tests, 92 inflammatory proteins were analysed with a multiplex system (Proseek Multiplex Inflammation I, Olink Bioscience). RESULTS: EEN had a significant anti-inflammatory effect on active joints (p=0.031), JADAS27 (p=0.016) and morning stiffness (p=0.031). In the multiplex analysis of inflammatory proteins, MMP-1 (matrix metalloproteinase), involved in the degradation of collagens in chondrocytes, decreased significantly (p=0.047), as did MCP-4 (p=0.031) and 4E-BP1 (p=0.031). CONCLUSIONS: Exclusive enteral nutrition for three to eight weeks had anti-inflammatory effect in all children with JIA that continued with EEN for more than two weeks. The study is only exploratory but the result supports an immunologically important role for the intestinal canal in these patients.

Childhood idiopathic thrombocytopenic purpura in the Nordic countries: epidemiology and predictors of chronic disease.

AIM: To describe the epidemiology of idiopathic thrombocytopenic purpura (ITP) in the Nordic countries, to define clinical subgroups and to investigate factors predicting chronic disease. METHODS: A prospective registration was done from 1998 to 2000, including all children with newly diagnosed ITP aged 0-14 y and at least one platelet count <30 x 10(9)/l. RESULTS: 506 children were registered and 423 followed for 6 mo. The incidence was 4.8/10(5) per year. Most children were aged 0-7 y (78%), with a predominance of boys, while patients aged 8-14 y had equal representation of the two sexes. There were seasonal variations determined by variations in postinfectious cases with sudden onset. The platelet count was <10 x 10(9)/l in 58%, but bleeding manifestations were mild or moderate in 97%. The insidious form (symptoms for more than 2 wk) was more frequent in older children and girls, showed little seasonal variation, had milder manifestations and ran a chronic course in more than half the cases. Intracranial haemorrhages did not occur in the first 6 mo after diagnosis. Chronic ITP developed in 25%. The strongest predictor of chronic disease was insidious onset of symptoms (OR 5.97). CONCLUSION: In the Nordic countries, ITP mainly affects children aged 0-7 y, with a winter bulk of postinfectious cases superimposed on a steady occurrence of non-infectious cases. Clinically, it may be useful to distinguish between children with sudden versus insidious onset of symptoms rather than between different age groups.

Randomized study of IVIg and high-dose dexamethasone therapy for children with chronic idiopathic thrombocytopenic purpura.

PURPOSE: To investigate whether pulsed high-dose dexamethasone is more efficacious than intravenous immunoglobulin (IVIg) as treatment of symptomatic chronic idiopathic thrombocytopenic purpura (ITP) in childhood. METHODS: In a 2:1-randomized study, 23 children with chronic ITP received dexamethasone (0.6 mg/kg per day for 4 consecutive days once monthly for 6 months, n = 15) or IVIg (800 mg/kg intravenously once monthly for 6 months, n = 8). After four courses of treatment a crossover was offered to nonresponders. A total of 20 children received dexamethasone and 11 received IVIg. RESULTS: One of the 8 IVIg patients and 2 of the 15 dexamethasone patients achieved complete response, defined as a platelet count of at least 150 x 10(9)/L for more than 3 months without treatment. Two of the 15 dexamethasone patients achieved partial response, defined as a platelet count of at least 30 x 10(9)/L for more than 3 months without treatment. One of the 8 IVIg patients and 5 of the 15 dexamethasone patients discontinued treatment. Five patients crossed over from IVIg to dexamethasone (one complete response) and three from dexamethasone to IVIg (none responded). In summary, 5 of the 20 dexamethasone patients achieved a complete or partial response and 1 of the 11 IVIg patients achieved a complete response. Platelet counts of at least 30 x 10(9)/L by day 3 were reached in 9 of the 12 (75%) dexamethasone patients and all 8 (100%) IVIg children using available data. Five years after study completion, two of the three children who achieved a complete response and one of the two with a partial response to dexamethasone were in remission, as was the child with a complete response to IVIg. CONCLUSIONS: Treatment with pulsed high-dose dexamethasone is not always effective in children with chronic ITP, but it is worth trying in severe symptomatic chronic childhood ITP.

Reliability and reproducibility of classification of children as "bleeders" versus "non-bleeders" using a questionnaire for significant mucocutaneous bleeding.

The diagnosis of type 1 von Willebrand disease (VWD), the most common inherited bleeding disorder in humans, is greatly dependent on an accurate diagnosis of significant mucocutaneous bleeding. In a previous study, the authors modified the criteria of the International Society on Thrombosis and Haemostasis for significant mucocutaneous bleeding to a format, the Hospital for Sick Children (HSC) criteria, that was more applicable to diagnose significant mucocutaneous bleeding in children. To assess the reliability and reproducibility of classification of subjects as "bleeders" versus "non-bleeders" using a questionnaire for significant mucocutaneous bleeding targeted to children, 39 subjects interviewed for a previous HSC VWD study were reinterviewed for the current study. The original bleeding classification was confirmed in 80% of subjects interviewed for a second time, indicating that this method of classification is reproducible (kappa = 0.65), with a "substantial" agreement among the investigators who reviewed the questionnaire responses (kappa = 0.71). The validity and utility of the HSC questionnaire for primary screening of children with suspected mucocutaneous bleeding disorders merits assessment in further clinical studies.

Duration and morbidity of newly diagnosed idiopathic thrombocytopenic purpura in children: A prospective Nordic study of an unselected cohort.

OBJECTIVE: To determine the duration of the risk period with platelet counts <20 x 10(9)/L and the frequency of bleeding episodes in unselected children with idiopathic thrombocytopenic purpura (ITP). STUDY DESIGN: We established a registry for patients with newly diagnosed ITP in the five Nordic countries, enrolling children aged 0 to 14 years with platelet counts <30 x 10(9)/L. Treatment centers prospectively reported presenting features, management details, and disease-related events during the first six months after diagnosis. RESULTS: At presentation (n=501), more than half of the children had a platelet count <10 x 10(9)/L, but only 15 (3.0%) had a hemorrhage requiring blood transfusion. During follow-up of 409 patients, thrombocytopenia resolved uneventfully in 277. A risk period was present in 376 cases. Among 283 with self-limiting ITP, 26 were at risk >1 month and 25 had 30 events. Among 93 patients with chronic ITP, 73 were at risk >1 month and 44 had 111 events. Events occurred with an average frequency of 0.39 per month at risk. Life-threatening hemorrhages did not occur in the first six months after diagnosis. CONCLUSION: Most children with ITP are at risk for serious bleeding for less than one month. Continuing severe thrombocytopenia is associated with little morbidity, bleeding episodes being infrequent and very rarely serious.