A composite of exhaled LTB4 , LXA4 , FeNO, and FEV1 as an "asthma classification ratio" characterizes childhood asthma.

BACKGROUND: Aberrant generation of eicosanoids is associated with asthma, but the evidence remains incomplete and its potential utility as biomarkers is unclear. Major eicosanoids in exhaled breath condensates (EBCs) were assessed as candidate markers for childhood asthma. METHODS: Ten exhaled eicosanoid species was evaluated using ELISA in the discovery phase, followed by prediction model-building and validation phases. RESULTS: Exhaled LTB4 , LTE4 , PGE2, and LXA4 showed significant difference between asthmatics (N = 60) and controls (N = 20). For validation, an expanded study population consisting of 626 subjects with asthma and 161 healthy controls was partitioned into a training subset to establish a prediction model and a test sample subset for validation. Receiver operating characteristic (ROC) analyses of the training subset revealed the level of exhaled LTB4 to be the most discriminative among all parameters, including FeNO, and a composite of exhaled LTB4 , LXA4 , together with FeNO and FEV1 , distinguishing asthma with high sensitivity and specificity. Further, the Youden index (J) indicated the cut point value of 0.598 for this composite of markers as having the strongest discriminatory ability (sensitivity = 85.2% and specificity = 83.6%). The predictive algorithm as "asthma classification ratio" was further validated in an independent test sample with sensitivity and specificity being 84.4% and 84.8%, respectively. CONCLUSIONS: In a pediatric study population in Taiwan, the levels of exhaled LTB4 , LTE4 , LXA4, and PGE2 in asthmatic children were significantly different from those of healthy controls, and the combination of exhaled LTB4 and LXA4 , together with FeNO and FEV1 , best characterized childhood asthma.

Tobacco smoke exposure and multiplexed immunoglobulin E sensitization in children: a population-based study.

BACKGROUND: Although there is evidence that exposure to tobacco smoke is harmful to children's respiratory health, the effects of tobacco smoke exposure on the regulation of immunoglobulin E (IgE)-mediated immune responses to specific allergens remain unclear. This study aimed to investigate the relationship between objectively assessed tobacco smoke exposure and specific IgE profiles for a broad spectrum of allergens in a population setting. METHODS: Children aged 5-18 years (N = 1315) were assessed using serum cotinine measurement and microarray-based multiplexed detection of specific IgE against 40 allergens. RESULTS: Serum cotinine levels were positively associated with sensitization to foods (adjusted odds ratio [AOR] = 4.95; 95% CI: 1.59-15.34), cockroaches (AOR = 3.77; 95% CI: 1.49-9.51), and pollen (AOR = 2.84; 95% CI: 1.20-6.73) while the association was borderline significant for animals (AOR = 2.53; 95% CI: 0.92-6.93). No associations were found for sensitization against mites, mold, and latex. When considering the degree of allergic sensitization, serum cotinine levels were positively correlated to the number of sensitization to cockroaches (P = 0.004), pollen (P = 0.006), and foods (P < 0.001), with statistically significant positive dose-response relationships (all P < 0.01). Similar results were observed when summing up specific IgE concentrations for the aforementioned allergen categories. CONCLUSIONS: The association between tobacco smoke exposure and IgE sensitization to environmental allergens varies for different allergens among children. This study demonstrates that elevated serum cotinine levels are significantly associated with IgE sensitization to cockroaches, grass pollen, and certain foods, with potential dose-dependent relationships.

Multiplexed immunoglobulin E sensitization in relation to exhaled nitric oxide in a population sample of children.

This study investigated the relationship between the specific immunoglobulin E (IgE) profile for 40 allergens using a novel microarray technique (BioIC) and fraction of exhaled nitric oxide (FeNO) in a population sample of 1321 children. Significant positive associations were found between FeNO and sensitization to mites (P < 0.001), animals (P = 0.001), cockroaches (P < 0.001), and foods (P = 0.042), and furthermore, between FeNO and the number of sensitizations (all P < 0.05) or the sum of specific IgE (all P ≤ 0.01) against the aforementioned allergen categories. Specifically, sensitization to the following allergens was significantly related to higher FeNO: Dermatophagoides pteronyssinus, Dermatophagoides farina, Blomia tropicalis, cat, German cockroach, Oriental cockroach, codfish, crab, shrimp, and cheese (all P ≤ 0.01). In conclusion, IgE sensitization to mites, pets, cockroaches, seafood, and cheese, respectively, is significantly associated with elevated FeNO levels in a dose-dependent fashion in children. Our results provide new evidence that sensitization to certain food allergens may contribute to prompt inflammation in the airways.

Impaired phagocytosis and susceptibility to infection in pediatric-onset systemic lupus erythematosus.

OBJECTIVES: Impaired function of polymorphonuclear cells (PMNs) in systemic lupus erythematosus (SLE) leads to severe gram-positive and gram-negative bacterial infection, and to major morbidity and mortality. Few studies have focused on the association of impaired function of PMNs and SLE patients' susceptibility to infection. This study aimed to analyze function of PMNs in peroxidase production, chemotaxis, and phagocytosis in pediatric-onset SLE with severe infection. METHODS: This study compared function of PMNs among pediatric-onset SLE patients with and without histories of severe infection and in normal control subjects. Human peripheral blood PMNs were isolated from patients and controls. Function of PMNs was measured by analyzing peroxidase, chemotaxis, and phagocytic activities. Different disease activity and severity, and drug use in newly diagnosed SLE patients were also compared. RESULTS: In total, 34 SLE patients (12 patients with severe infection, 22 patients without infection) and 25 healthy controls were analyzed. There were no differences in function of PMNs between SLE patients with or without severe infection. Regardless of infection status, medication, and disease activity, SLE patients had impaired phagocytic ability against Salmonella-specific lipopolysaccharides (LPS) compared with normal controls (p < 0.01). The use of immunosuppressants did not influence phagocytic ability against Salmonella-derived LPS. CONCLUSIONS: Immunosuppressant agents do not influence phagocytic ability against Salmonella in SLE subjects. Impaired phagocytosis against Salmonella is prominent in pediatric-onset SLE subjects, which may result in the high prevalence of Salmonella infection. There is no deficiency of peroxidase production and chemotaxis activity among SLE subjects.

The outcome of patients with renal involvement in pediatric-onset systemic lupus erythematosus--a 20-year experience in Asia.

Systemic lupus erythematosus (SLE) predominantly affects women of childbearing age, but 15-20% of cases are diagnosed during childhood. It is important for physicians to understand the epidemiology and clinical presentation for early detection and diagnosis of this disease in difference races. The aim of this retrospective review was to provide a 20-year experience for initial clinical and laboratory manifestations and outcomes in pediatric-onset SLE (pSLE) in a medical center in Asia. We reviewed medical records between April 1990 and June 2012 of patients with a diagnosis of International Classification of Diseases, Ninth Revision (ICD-9) code 710.0 (SLE), who admitted or received follow-up in the Department of Pediatrics at Chang Chung Memorial Hospital. Patients with a diagnosis of SLE prior to their 18th birthday and followed up at our hospital were eligible for inclusion in this study. Medical records regarding age, gender, date of birth and diagnosis, clinical manifestations at diagnosis, laboratory results, image studies and the classification criteria were reviewed. Patients received regular outpatient department follow-up and laboratory survey every 1-6 months. The study cohort consisted of 189 patients; 164 females (86.87%) and 25 males (13.23%). The overall mean age at pSLE diagnosis was 12.62 ± 2.77 years. The most common clinical symptom was malar rash, followed by arthritis and oral ulcers. There was no significant difference in clinical and laboratory manifestations between females and males. More than half of the patients presented with renal involvement initially. The most common histological finding was Class IV lupus nephritis (LN), especially in males (p = 0.034) and young age. Even with severe LN, the rate of end-stage renal disease (ESRD) was low if adequate treatment was initiated. The 5, 10 and 15-year ESRD-free survival rates were 95.4%, 94.0% and 89.9% in patients with biopsy-proven LN. However, infection was the leading cause of mortality. Therefore, aggressive treatment for major organ involvement is important, but physicians must also be aware of fatal infection. The overall survival rates were 5 years: 93.4% and 10-20 years: 89.6%.

Reference values of exhaled nitric oxide in healthy Asian children aged 5 to 18 years.

This study was undertaken to establish reference values of exhaled nitric oxide fraction (F(eNO)) and its determinants in healthy Asian children. 693 healthy Asian children aged 5-18 yrs were assessed using a single-breath online F(eNO) measurement (exhaled flow 50 mL·s(-1)), questionnaires, anthropometric measurements, spirometry and total and specific immunoglobulin (Ig) E. Geometric mean F(eNO) and the upper 95% CI were 13.7 ppb and 49.7 ppb, respectively, for healthy children, and 11.2 ppb and 30.2 ppb, respectively, for those without allergic sensitisation. F(eNO) was positively associated with age, allergic sensitisation, total IgE, ambient nitric oxide, measurement in the afternoon, and drinking water within 1 h before testing, and was negatively associated with weight. In healthy children without allergic sensitisation, age was the single best explanatory variable. The F(eNO) predicted values were 1-2 ppb higher in Asian than in Caucasian children in earlier studies, while the upper 95% CI were 9-10 ppb higher. In conclusion, the upper limits of normal F(eNO) in Asian children depend on age, from 21 ppb in young children to 39 ppb in adolescents. Ethnicity, age, allergic sensitisation, total IgE, ambient nitric oxide, time of testing, drinking water and weight are important determinants.

Exhaled nitric oxide discriminates children with and without allergic sensitization in a population-based study.

BACKGROUND: Fraction of exhaled nitric oxide (FeNO) as a biomarker of airway inflammation in children warrants better clarification. OBJECTIVE: To identify the determinants of FeNO in children and assess the validity of FeNO as a discriminative tool for asthma, rhinitis or allergic sensitization in a population setting. METHODS: Children aged 5-18 years (N=1717) were evaluated using online FeNO measurements, questionnaires, anthropometric measurements, pulmonary function tests and total and specific serum IgE. RESULTS: FeNO levels were age-dependent, with an average increase of 7.4% per year of age. It decreased with increasing body mass index (BMI), estimated at 1.5% decrease per kg/m(2) . Children with allergic sensitization had elevated FeNO independent of allergic symptoms. In the combined analyses of asthma, rhinitis and allergic sensitization, elevated FeNO levels were confined mainly to children having allergic sensitization. After adjusting for allergic sensitization, a significant association between rhinitis and FeNO remained, but no such association was seen with asthma. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of FeNO at the optimum cut-off of 28 p.p.b. for diagnosing asthma were 64.3%, 69.9%, 8.8%, and 97.7%, respectively (area under the ROC curve [AUC] 0.67), and were slightly better for diagnosing allergic asthma: 70.0%, 70.4%, 9.0%, 98.3%, respectively (AUC 0.71). FeNO had modest accuracy in discriminating rhinitis with an AUC value of 0.70, and performed better in discriminating allergic rhinitis (AUC 0.78). FeNO was a robust discriminator of allergic sensitization independent of symptoms at a cut-off of 15.4 p.p.b. (AUC 0.80; sensitivity 72.2%; specificity 71.2%; PPV 76.9%; NPV 65.8%). CONCLUSION AND CLINICAL RELEVANCE: FeNO measurement discriminates children with and without allergic sensitization independent of allergic symptoms. On the other hand, low FeNO levels in children may help exclude allergic asthma but high levels may be caused by allergic sensitization, older age, rhinitis, and lower BMI, in addition to asthma.

Acute pancreatitis in pediatric and adult-onset systemic lupus erythematosus: a comparison and review of the literature.

This study aimed to compare differences of acute pancreatitis between adult- and pediatric-onset systemic lupus erythematosus (SLE) patients and to clarify the risk factors for mortality. Medical records that carried the dual diagnosis of SLE and acute pancreatitis between 1991 and 2005 were reviewed. Forty-eight episodes of acute pancreatitis were identified in 13 pediatric-onset SLE (pSLE) and 27 adult-onset SLE (aSLE) patients. The prevalence was 1.34% overall, with higher prevalence in pSLE (5.22%) compared with aSLE (0.99%) (p < 0.001). The SLEDAI score on presentation of acute pancreatitis was higher in pSLE (mean ± SD: 21.77 ± 13.09) than in aSLE patients (13.37 ± 8.32) (p = 0.05). Eleven patients died during episodes of acute pancreatitis and mortality rate was significantly higher in pSLE than in the aSLE group (53.8% and 14.8%, respectively, p = 0.015). Mortality was associated with concurrent SLE symptoms (p = 0.049), higher SLEDAI score at presentation of acute pancreatitis (p = 0.011), severe acute pancreatitis (p < 0.001), and the presence of complications (p < 0.001). The multivariate logistic regression analysis showed that severity of acute pancreatitis was the most powerful risk factor for mortality in SLE patients with this disease. In summary, our results indicate that acute pancreatitis occurs more frequently, tends to be more severe, and is associated with higher mortality in pSLE patients when compared with aSLE patient.

Pediatric lupus in Asia.

Of all patients with systemic lupus erythematosus (SLE), 15-20% are diagnosed during childhood, with disease onset prior to the age of 16 years. Because disease expression in SLE is influenced by environment factors and differs between racial and ethnic groups. The aims of this review were to describe prevalence, clinical manifestations, common infectious complications, and outcome of pediatric-onset SLE in Asia. The prevalence of pediatric-onset SLE was 6.3-19.3 per 100,000 in Asia. The ratio of female to male was 4.7-6.2. The mean age at diagnosis of pediatric-onset SLE was 8.6-13.5 years. The most common clinical features of pediatric-onset SLE in Asia were cutaneous rashes, arthritis, hematological involvement and nephritis. The occurrence of nephritis varies from 29% to 81%. The most common histopathology of lupus nephritis was diffuse proliferative glomerulonephritis (WHO Class-IV) which occurred in 39.4-54% of case of lupus nephritis. Pediatric-onset SLE patients with infections have poor outcomes than uninfected patients. Gram-negative bacilli are the most common microorganisms responsible for bacteremia in Asian patients with SLE. Recurrent major infections predict poorer disease outcome and associated organ damage in pediatric-onset SLE. Improving the survival of SLE patients was reported in Asia in recent decades. The survival was 92% at the age of 5 years, 86% at 10 years and 79% at 15 years in children with SLE in Taiwan in 2008.

Longitudinal investigation of nasopharyngeal methicillin-resistant Staphylococcus aureus colonization in early infancy: The PATCH birth cohort study.

OBJECTIVES: The study aimed to determine the long-term Staphylococcus aureus colonization patterns and strain relatedness, and the association between maternal and infant colonization in infancy. METHODS: A birth cohort study was conducted from January 2012 to November 2014. Nasopharyngeal swabs for S. aureus detection were collected from infants at the age of 1, 2, 4, 6 and 12 months and from mothers when their children were 1-month-old. RESULTS: In total, 254 samples were collected at each planned visit during the first 12-month study. The prevalence of S. aureus colonization decreased in the first year of life, ranging from 61.0% (155/254) at the age of 1 month to 12.2% (31/254) at 12 months. Persistent colonization, defined as a positive culture on four or five occasions, was detected in only 13.8% (35/254) of carriers. Most of the persistent carriers were colonized with methicillin-resistant S. aureus (MRSA) only, and among persistent MRSA carriers, 61.1% (11/18) had indistinguishable genotypes. Of the mothers with MRSA colonization, 77.1% (27/35) had infants who were concomitantly colonized at the age of 1 month; 70.4% (19/27) of the infant-mother paired isolates belonged to indistinguishable or related subtypes, which suggests that surrounding carriers, probably their mothers, may be the possible source for MRSA acquisition in early infancy. CONCLUSIONS: Staphylococcus aureus colonization including MRSA was commonly observed in our cohort. Strains of persistent MRSA among infant-mother pairs were usually of indistinguishable genotypes. Therefore, horizontal spread within households is possibly an important factor related to infant MRSA colonization.

Prevalence of pediatric systemic lupus erythematosus and juvenile chronic arthritis in a Chinese population: a nation-wide prospective population-based study in Taiwan.

OBJECTIVE: To estimate the national prevalence of systemic lupus erythematosus (SLE) and juvenile chronic arthritis (JCA) in Chinese children in Taiwan. METHODS: A nationwide prospective population based epidemiologic study for the prevalence of pediatric SLE and JCA was undertaken in Taiwan (23 million inhabitants). The population at risk was identified as children under the age of 16 living in Taiwan (5.78 million). All citizens have been obligated to participate in Taiwan's National Health Insurance program since 1995. This gave us access to nationwide case data from the Major Illness/Injury registry and enabled us to calculate population prevalence. The population data were derived from the 1999 Taiwan census. RESULTS: Three hundred sixty-five and 218 prevalent cases of pediatric SLE and JCA were identified, respectively. The prevalence of pediatric SLE was 6.3 per 100,000 (95% CI: 5.7-7.0). The prevalence in girls (11.2 per 100,000, 95% CI: 10.0-12.5) was 6.2 times higher than that in boys (1.8 per 100,000, 95% CI: 1.4-2.4). The prevalence of SLE substantially increased in children over the age of seven, especially in girls. The prevalence of JCA was 3.8 per 100,000 (95% CI: 3.3-4.3). The figures were similar for boys (3.5 per 100,000, 95% CI: 2.9-4.2) and girls (4.1 per 100,000, 95% CI: 3.3-4.9). CONCLUSION: In this first population based epidemiologic survey of pediatric SLE and JCA in Taiwan, we provided a good starting point in our understanding of the epidemiology of these serious conditions in the Chinese population. The discrepancies between our prevalence figures and those reported from Western countries are possibly the results from true differences pertaining to ethnicity, geography or both. Future studies are necessary to elucidate the implications suggested by these data.

Advances in the diagnosis and treatment of neonatal hyperbilirubinemia.

Many controversies remain regarding the role of bilirubin in the developing human. Although kernicterus and cognitive impairment have been linked to hyperbilirubinemia, more recent studies have suggested that there might actually be beneficial effects of bilirubin at a cellular level; thus, the need to better understand the molecular and cellular physiology of this molecule is important. The attempted management of serum or tissue levels of bilirubin may either have implications for long-term neurologic development or interfere with normal body stress responses. Production of CO via heme catabolism also warrants further investigation regarding its role in cell to cell communication or in other important cellular reactions. New methods are being developed to better detect CO under a variety of experimental conditions, as well as to estimate total bilirubin production by measuring the COHb level of pulmonary excretion of CO. The development of new drugs to modulate bilirubin production is the subject of ongoing research. Although some metalloporphyrins already have been used clinically, the advantages and disadvantages of each drug still require further study. These new drugs are not only raising fascinating research questions about heme and bilirubin metabolism, but they may soon revolutionize the way we approach the diagnosis and management of neonatal jaundice, and provide new pharmacologic tools for exploring other aspects of metabolism.

Lack of association of mannose-binding lectin gene polymorphisms with development and clinical manifestations of systemic lupus erythematosus in Chinese children.

Mannose-binding lectin (MBL) gene polymorphisms may be associated with adult-onset systemic lupus erythematosus (SLE), but studies in children with SLE are rare. This study tested the genetic association between MBL polymorphisms and paediatric-onset SLE in a cohort of Chinese children in Taiwan. In all 150 children with SLE and 100 healthy controls of comparable age were genotyped for codon 52, 54 and 57 mutations of the MBL gene using a polymerase chain reaction-based assay. Clinical manifestations, organ involvement, disease activity, laboratory characteristics and outcome were recorded and compared between patients with different MBL genotypes. Codon 54 mutation was fairly common in both SLE patients and controls, whereas codon 52 and codon 57 mutations were not detected in our study subjects. No statistically significant differences were found in allele frequencies of the codon 54 mutation between SLE and control groups. Moreover, no association was found between this MBL polymorphism and clinical manifestations, organ involvement, disease activity, laboratory characteristics or outcome of SLE. These results suggest that MBL polymorphisms do not influence susceptibility to paediatric-onset SLE and do not influence clinical manifestations of SLE in Chinese children.

Endogenous endophthalmitis and necrotising pneumonia caused by Klebsiella pneumoniae in a child with beta-thalassaemia major.

A case beta-thalassaemia major complicated with Klebsiella pneumoniae endogenous endophthalmitis is presented to increase physician awareness of the association of the two clinical conditions. Severe morbidity including subretinal abscess and retinal detachment may develop despite aggressive intravenous and intravitreal ceftriaxone therapy, along with vitrectomy and external drainage.

Pitfalls in the diagnosis of idiopathic pulmonary haemosiderosis.

Idiopathic pulmonary haemosiderosis is a very rare but devastating disorder. Diagnosis is sometimes difficult and the clinical course exceedingly variable, as illustrated by this report of a girl, aged 2 years 4 months, with severe iron deficiency anaemia. There was no response to iron therapy and transfusions. Sustained and striking reticulocytosis associated with low haptoglobin mimicked haemolytic anaemia. Positive faecal blood test was documented after repeated testing. There were no pulmonary symptoms. A chest radiograph showed bilateral diffuse alveolar infiltrates. Bronchoalveolar lavage fluid showed numerous siderophages. High resolution computed tomography of the thorax revealed early pulmonary fibrotic changes. Recurrent reticulocytosis appeared to be a very useful sign of recurrent bleeding episodes.

Idiopathic pulmonary haemosiderosis: an Oriental experience.

OBJECTIVES: Idiopathic pulmonary haemosiderosis (IPH) is a rare but potentially lethal disorder. A retrospective analysis of documented cases of IPH in our hospital was conducted in order to study the clinical spectrum and radiographic features, and to explore therapeutic strategies. METHODS: A retrospective chart review was carried out, collecting medical records of patients with pulmonary haemo-siderosis at Chang Gung Children's Hospital (CGCH), a tertiary children's hospital in northern Taiwan. Secondary causes of pulmonary haemosiderosis were excluded. RESULTS: Five patients were diagnosed as having IPH over a 25-year period. The classical triad of IPH was found at initial presentation in only 2/5 patients. One patient had well-established pulmonary fibrosis, but no pulmonary symptoms. The clinical course of IPH was exceedingly variable, with a mean delay of 9 months before diagnosis was made. Bronchoalveolar lavage (BAL) confirmed IPH in 3/5 patients. Immunological abnormalities were noted in two patients, without progression to immune disorders during follow up. While using corticosteroids alone, 4/5 patients continued to have recurrent bleeding episodes. All five patients required immunosuppressive therapy for maintenance of a symptom-free period, but survived to a mean follow up of 2 years. CONCLUSIONS: Early definitive diagnosis and aggressive immunosuppressive therapy of IPH are imperative in order to avoid pulmonary fibrosis and mortality in IPH. A chest radiograph should be included in a serial work-up of unexplained anaemia in children. An examination using BAL can confirm IPH and high-resolution thoracic computed tomography scans are useful for early detection of pulmonary fibrosis.

MCP-1 gene regulatory region polymorphism in Chinese children with mild, moderate and near-fatal asthma.

BACKGROUND: A polymorphism in the monocyte chemoattractant protein 1 (MCP-1) gene regulatory region has been associated with asthma in Caucasians. This polymorphism is possibly endemic to the Asian region, but its impact on Asian populations is unclear. In addition, the relationship of this marker with life-threatening asthma has not been clarified. The aim of this study was to test the genetic association between the MCP-1 -2518A/G polymorphism and asthma/atopy in a cohort of Chinese children, with particular emphasis on those patients who had experienced life-threatening asthma attacks. METHODS: Forty-eight children with near-fatal asthma, 134 mild-to-moderate asthmatics, 69 allergic-disorder cases without asthma, and 107 nonasthmatic, nonatopic control children were genotyped by a polymerase chain reaction-based assay. RESULTS: Comparison of the four groups of children (n = 358) revealed no detectable differences in genotype or allele frequencies of the MCP-1 -2518A/G polymorphism. There was no evidence of association between the polymorphism and any of the outcomes of interest including clinical severity, blood eosinophil count, atopy, total serum IgE levels, and degree of bronchial hyper-responsiveness. CONCLUSION: These results suggest that the MCP-1 -2518A/G polymorphism is not a risk factor for near-fatal asthma. Furthermore, this polymorphism seems to play no role in the development of asthma or atopy in Chinese subjects, possibly as a result of the genetic heterogeneity between Asian and Caucasian populations with respect to regulation of MCP-1 expression. Our results underscore the necessity of accounting for ethnic background in the investigation of asthma-predisposition genes.

HLA-DRB1 genotyping in patients with juvenile idiopathic arthritis in Taiwan.

The object of this study was to investigate whether there is an association between HLA-DRB1 alleles and the development of juvenile idiopathic arthritis (JIA) in Taiwan. HLA-DRB1 alleles were studied in 60 patients with JIA and 200 healthy controls using polymerase chain reaction (PCR)/sequence-specific oligonucleotide probes (SSO). The frequency of HLA-DRB1*0405 in patients with JIA was found to be significantly higher than that in healthy controls [odds ratio (OR) 2.64, 95% confidence interval (CI) 1.01-6.91]. The DRB1*0405 allele was significantly associated with the development of both polyarthritis (OR 4.30, 95% CI 1.34-13.80) and oligoarthritis (OR 3.27, 95% CI 1.01-10.58). The frequency of HLA-DRB1*1502 was higher in Taiwanese JIA patients with systemic arthritis than in controls (OR 18.09, 95% CI 2.25-145.73). We conclude that, in Taiwan, HLA-DRB1*0405 is associated with the development of polyarthritis and oligoarthritis in children, and HLA-DRB1*1502 is associated with the development of systemic arthritis.