Newly Proposed Classification for Juvenile Idiopathic Arthritis

No abstract available.

Clinical Characteristics of Macrolide-Resistant Mycoplasma pneumoniae from Children in Jeju

Mycoplasma pneumoniae is the major pathogen of community-acquired pneumonia in children. The prevalence of macrolide-resistant M. pneumoniae (MRMP) is important owing to the limited alternative therapies for children. We analyzed 111 M. pneumoniae obtained from 107 children admitted for lower respiratory tract infection at Jeju National University Hospital between 2010 and 2015. Macrolide resistance of M. pneumoniae was searched for using polymerase chain reaction (PCR) and sequencing. Of 107 clinical M. pneumoniae, 11 (10.3%) carried macrolide resistance mutations in the 23S rRNA gene. All macrolide resistance mutations were A2063G transitions. We found an acquired A2063G mutation of M. pneumoniae from a patient during macrolide treatment. Patients' characteristics and clinical severity did not differ between those with MRMP and macrolide-sensitive M. pneumoniae, with the exception of frequent pleural effusion in the MRMP group. The prevalence of MRMP (10.3%) in Jeju Island was relatively lower than those of surrounding countries in East Asia. Previous antimicrobial usage and timing of diagnostic test should be considered when determining of macrolide resistance of M. pneumoniae.

Sonographic Growth Charts for Kidney Length in Normal Korean Children: a Prospective Observational Study

Kidney length is the most useful parameter for clinical measurement of kidney size, and is useful to distinguish acute kidney injury from chronic kidney disease. In this prospective observational study of 437 normal children aged between 0 and < 13 years, kidney length was measured using sonography. There were good correlations between kidney length and somatic values, including age, weight, height, and body surface area. The rapid growth of height during the first 2 years of life was intimately associated with a similar increase in kidney length, suggesting that height should be considered an important factor correlating with kidney length. Based on our findings, the following regression equation for the reference values of bilateral kidney length for Korean children was obtained: kidney length of the right kidney (cm) = 0.051 × height (cm) + 2.102; kidney length of the left kidney (cm) = 0.051 × height (cm) + 2.280. This equation may aid in the diagnosis of various kidney disorders.

Concomitant use of corticosteroid and antimicrobials for liver abscesses in patients with chronic granulomatous disease / 소아과

Chronic granulomatous disease (CGD) is a rare inherited disorder caused by defective nicotinamide adenine dinucleotide phosphate oxidase enzyme and characterized by recurrent bacterial and fungal infections. Although liver abscess is a common manifestation of CGD, its management in CGD patients is not well-defined. In addition, the generalized guidelines for treating liver abscesses do not necessarily apply to CGD patients. Corticosteroids are commonly used to control granulomatous complications, such as inflammatory gastrointestinal and genitourinary lesions, in patients with CGD, Corticosteroids have also been used in combination with antimicrobials to treat refractory infections in patients with CGD. Because corticosteroids are capable of suppressing symptomatic inflammation, all potential infections must be adequately controlled prior to corticosteroid initiation. We report 3 typical CGD cases with liver abscesses refractory to conventional treatments that were successfully treated with the concomitant use of corticosteroid and antimicrobials. It remains unclear whether corticosteroid therapy is required for liver abscesses in CGD refractory to conventional treatments. However, based on our observations, use of corticosteroids in combination with optimal antimicrobials should be considered for refractory liver abscesses in CGD.

Long-term outcome of patients with p22phox-deficient chronic granulomatous disease on Jeju Island, Korea / 소아과

PURPOSE: This study investigated the long-term clinical outcomes of patients with p22(phox)-deficient chronic granulomatous disease (CGD) on Jeju Island and retrospectively evaluated the effects of interferon-gamma (IFN-gamma) prophylaxis. METHODS: The medical records of 15 patients with CGD were retrospectively reviewed. The efficacy of IFN-gamma prophylaxis was evaluated by comparing the frequency of severe infections before and after starting continuous prophylaxis with IFN-gamma. RESULTS: At the time of the analysis, 14 patients were alive, with a median age of 14.3 years. The diagnosis of CGD was made at a median age of 2.4 years, and the median age at onset of severe infection was 0.3 years. Thirteen of the 15 patients had their first severe infection within the first year of life. The overall incidence of severe infection was 1.36 infections per patient-year; pneumonia, suppurative lymphadenitis, and skin and subcutaneous abscesses were the most common infections. Aspergillus species were the most frequently isolated microorganisms, present in 15.8% of isolates. IFN-gamma did not significantly change the rate of severe infection. The survival rate for patients after 2 years of age was 93%; there was a prolonged survival plateau beyond the age of 2. CONCLUSION: Compared with cases of X-linked CGD reported in other studies, patients with CGD on Jeju Island did not show obviously different clinical manifestations, but they had a significantly higher survival rate. Further studies with a substantially longer period of observation, and with more patients under intensive surveillance are necessary to elucidate the prophylactic efficiency of IFN-gamma.

Systemic Classification for a New Diagnostic Approach to Acute Abdominal Pain in Children / 대한소아소화기영양학회지

PURPOSE: With previous methods based on only age and location, there are many difficulties in identifying the etiology of acute abdominal pain in children. We sought to develop a new systematic classification of acute abdominal pain and to give some helps to physicians encountering difficulties in diagnoses. METHODS: From March 2005 to May 2010, clinical data were collected retrospectively from 442 children hospitalized due to acute abdominal pain with no apparent underlying disease. According to the final diagnoses, diseases that caused acute abdominal pain were classified into nine groups. RESULTS: The nine groups were group I "catastrophic surgical abdomen" (7 patients, 1.6%), group II "acute appendicitis and mesenteric lymphadenitis" (56 patients, 12.7%), group III "intestinal obstruction" (57 patients, 12.9%), group IV "viral and bacterial acute gastroenteritis" (90 patients, 20.4%), group V "peptic ulcer and gastroduodenitis" (66 patients, 14.9%), group VI "hepatobiliary and pancreatic disease" (14 patients, 3.2%), group VII "febrile viral illness and extraintestinal infection" (69 patients, 15.6%), group VIII "functional gastrointestinal disorder (acute manifestation)" (20 patients, 4.5%), and group IX "unclassified acute abdominal pain" (63 patients, 14.3%). Four patients were enrolled in two disease groups each. CONCLUSION: Patients were distributed unevenly across the nine groups of acute abdominal pain. In particular, the "unclassified abdominal pain" only group was not uncommon. Considering a systemic classification for acute abdominal pain may be helpful in the diagnostic approach in children.

Chronic Granulomatous Disease on Jeju Island, Korea

Chronic granulomatous disease (CGD) is a rare inherited disorder of a defective NADPH oxidase enzyme, resulting in very low or no production of superoxide and subsequent reactive oxygen species. Consequently, patients with CGD are highly susceptible to severe bacterial and fungal infections. CGD is a genetically heterogeneous disease caused by defects in any one of the genes encoding the NADPH oxidase components. CGD generally affects about 3-4 per 1,000,000 individuals; thus, it is surprising that the prevalence of CGD on Jeju Island is 34.3 per 1,000,000 individuals. At present, 20 patients with CGD from 14 unrelated families on Jeju Island have been identified; nine males and 11 females. All patients with CGD tested on Jeju Island had an identical and homozygous mutation (c.7C>T in CYBA, p.Q3X in p22phox). Therefore, all patients were autosomal recessive form of CGD. This strongly suggests that the unique and identical mutation in CYBA may be inherited from a common proband. Using mutation-specific primers to detect the mutated allele in CYBA, the frequency of subjects carrying a mutated allele was 1.3% of enrolled subjects from Seogwipo City. Further studies are necessary to elucidate how frequently this mutant allele occurs in the population on Jeju Island. Additionally, it is important to construct a national registry system to understand the pathophysiology of CGD and develop a strategy for long-term therapy.

Potential Role of Epstein-Barr Virus in Juvenile Rheumatoid Arthritis

No abstract available.

Prevalence of Primary Immunodeficiency in Korea

This study represents the first epidemiological study based on the national registry of primary immunodeficiencies (PID) in Korea. Patient data were collected from 23 major hospitals. A total of 152 patients with PID (under 19 yr of age), who were observed from 2001 to 2005, have been entered in this registry. The period prevalence of PID in Korea in 2005 is 11.25 per million children. The following frequencies were found: antibody deficiencies, 53.3% (n = 81), phagocytic disorders, 28.9% (n = 44); combined immunodeficiencies, 13.2% (n = 20); and T cell deficiencies, 4.6% (n = 7). Congenital agammaglobulinemia (n = 21) and selective IgA deficiency (n = 21) were the most frequently reported antibody deficiency. Other reported deficiencies were common variable immunodeficiencies (n = 16), X-linked agammaglobulinemia (n = 15), IgG subclass deficiency (n = 4). Phagocytic disorder was mostly chronic granulomatous disease. A small number of patients with Wiskott-Aldrich syndrome, hyper-IgE syndrome, and severe combined immunodeficiency were also registered. Overall, the most common first manifestation was pneumonia. This study provides data that permit a more accurate estimation PID patients in Korea.

The Influence of the Residential Environment on the Sensitization Rates to Aeroallergens and the Prevalence of Allergic Disorders in the School Children in Jeju / 소아알레르기및호흡기학회지

PURPOSE: This study is to investigate the influence of the residential environment on the sensitization rates to aeroallergens and the prevalences of atopic disorders in the school children. METHODS: Two elementary schools in Jeju, Korea were selected according to their distinctive residential environment, one located in the area surrounded by the tangerine farms and Japanese cedar forests (tangerine farming community) and the other rarely with them (non-tangerine farming community). All the school children (1,550 students) from the two school were enrolled in this study. Under their parents' informed consent, surveys based on International Study of Asthma and Allergies in Childhood questionnaire were answered by the parents and skin prick tests with 16 common aeroallergens were performed. RESULTS: The questionnaire is responded from 1,290 parents (83.2%) and the skin test was done in 1,284 students (82.8%). The sensitization rates to more than one aeroallergen was 41.9%, increasing by age. The children residing in the tangerine farming community showed significantly higher sensitization rates than those from non-farming one (47.5% vs. 38.4%, P=0.004). The former were sensitized more frequently to house dust mite, citrus red mite and Japanese cedar pollen, while the others to outdoor moulds. However, the prevalence of atopic disorders had no difference between the two groups. CONCLUSION: The residential environment might influence the sensitization rates to prevalent aeroallergens in the environment among school children, but there is no difference in the prevalence of the atopic disorders.

Distribution of Disease Severity and Group A Rotavirus Genotypes (VP7 & VP4) in Children with Acute Rotavirus Gastroenteritis / 대한소아소화기영양학회지

PURPOSE: We aimed to study the distribution of rotavirus genotypes (VP7 and VP4) and disease severity of rotavirus gastroenteritis prevalent in our community. METHODS: Stool samples were collected from 156 children who were hospitalized with rotavirus gastroenteritis from December 2007 to June 2008. The disease severity of all patients was scored using the Vesikari scale. After extraction of ds-RNA of the rotavirus, cDNA synthesis using reverse transcription and polymerase chain reaction (RT-PCR) and multiplex PCR was performed. Following this, the final identification of genotypes was performed. RESULTS: Of the 156 samples, VP7(G) and VP4(P) genotypes were identified in 147 (94.2%) and 140 (89.7%) samples, respectively. G1 (116 of 147 samples; 78.9%) and P[8] (137 of 140 samples; 97.9%) were the most prevalent, respectively. Of the 138 samples identified of combination types of VP7 and VP4, G1P[8] (111 samples; 80.4%) was the most prevalent. Other combination types varied with very low distribution rates. 9.4% of genotypes were not included in the new vaccines. The disease severity score was 11.8+/-3.3 (mean+/-2SD). The distribution of disease severity was mild or moderate in 37.8% and severe in 62.2% of patients. CONCLUSION: The most prevalent genotype combination of rotavirus was G1P[8] and genotypes not included in the vaccines represented 9.4% in our community. Disease severity distribution of hospitalized children with rotavirus gastroenteritis was higher in the severe than in the mild and moderate categories.

Toll-like receptor 2 expression on monocytes from patients with BCG vaccine-associated suppurative lymphadenitis / 소아과

PURPOSE: Toll-like receptor 2 (TLR2) is critical in the immune response to mycobacterial infections. The purpose of this study was to analyze TLR2 surface expressions and TLR2-mediated tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production in patients with BCG vaccine-associated suppurative lymphadenitis. METHODS: Peripheral monocytes were separated from 16 patients with BCG vaccine-associated suppurative lymphadenitis and 10 healthy controls using a magnet cell isolation kit. Monocytes (1x10(6) cells/well) were incubated with a constant amount of Pam(3)CSK(4) (100 microgram/mL) for 24 hours. TLR2 surface expression on monocytes was analyzed by FACS analysis and TLR-2 mRNA expression was determined by RT-PCR. TLR2-mediated TNF-alpha and IL-6 production were measured by ELISA. RESULTS: In patients with BCG vaccine-associated suppurative lymphadenitis, low TLR2 expression on monocytes (3.39+/-1.2% versus 4.64+/-2.6%) together with significantly lower TLR2 mRNA expression than in the healthy controls was seen after Pam(3)CSK(4) stimulation. TLR2-mediated TNF-alpha and IL-6 production in patients with BCG vaccine-associated suppurative lymphadenitis (TNF-alpha, 775.5+/-60.8 pg/mL; IL-6, 4,645.8+/-583.9 pg/mL) were also lesser than that in healthy controls (TNF-alpha, 1,098.5+/-94.3 pg/mL; IL-6, 6,696.3+/-544.3 pg/mL). CONCLUSION: These findings suggest that low TLR2 expression on monocytes might be associated with increased susceptibility to BCG vaccine-associated suppurative lymphadenitis.

Estimating the Prevalence of Atopic Dermatitis in School Students of Jejudo, Korea / 예방의학회지

OBJECTIVES: The frequency of visiting clinics in Jejudo for treating atopic dermatitis (AD) has been reported to be higher than that for other counties of Korea. The aim of this work was to estimate the prevalence of AD for the students of the primary, middle and high schools in Jejudo, Korea. METHODS: We planned to evaluate about 5,000 students, so classes were randomly selected by random systematic sampling methods. The parents of all the students in the selected classes were asked to respond to a structured questionnaire concerned with the prevalence of AD. RESULTS: The prevalence of AD based on ever being diagnosed by a doctor, on currently being diagnosed by a doctor, on ever being treated for AD by a doctor, on currently being treated for AD by a doctor was 25.57% (95% CI=25.3-25.8), 14.67% (95% CI=14.5-14.9), 21.90% (95% CI=21.6-22.2) and 14.41% (95% CI=14.2-14.6), respectively. CONCLUSIONS: On comparing the prevalence of AD, the students in Jejudo had a higher number of recurrence events in spite of their lower number of cases. Further studies are needed to evaluate these aspects of AD.

Genetic Analysis of 10 Unrelated Korean Families with p22-phox-deficient Chronic Granulomatous Disease: An Unusually Identical Mutation of the CYBA Gene on Jeju Island, Korea

Chronic granulomatous disease (CGD) is a rare hereditary disorder characterized by recurrent life-threatening bacterial and fungal infections. The underlying defect in CGD is an inability of phagocytes to produce reactive oxygen species as a result of defects in NADPH oxidase. Considering that CGD generally affects about 3-4 in 1,000,000 individuals, it is surprising that the prevalence of CGD on Jeju Island is 20.7 in 1,000,000 individuals. We performed genetic analysis on 12 patients from 10 unrelated families and found that all patients had an identical homozygous single-base substitution of C to T in exon 1 (c.7C>T) of the CYBA gene, which was expected to result in a nonsense mutation (p.Q3X). Because Jeju Island has long been a geologically isolated region, the high prevalence of CGD on Jeju Island is presumably associated with an identical mutation inherited from a common ancestor or proband.

Familial systemic lupus erythematosus in two Korean male siblings / 소아과

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterized by the production of a wide range of autoantibodies, resulting in tissue damage. Although the susceptibility to SLE has been attributed to complex interactions between genetic and environmental factors, the influence of a genetic predisposition to SLE is supported by observations of familial aggregations. Family studies have found that siblings with an SLE-affected relative have a 20-fold higher risk of developing SLE compared with the general population. Here, we present a rare case of two male siblings with SLE. The clinical, laboratory, and histopathological findings of these individuals showed the characteristic features of SLE. Human leukocyte antigen (HLA) typing revealed that the brothers and their mother shared the common HLA haplotype of DRB1*1501 and DQB1*0602, which is significantly associated with disease susceptibility in both family-based and casecontrol studies. This report provides an opportunity to reveal the role of genetic factors in the development of SLE.

TNF-alpha stimulated IL-8 and IL-10 expression in monocytes from patients with chronic granulomatous disease / 소아과

PURPOSE: Patients with chronic granulomatous disease (CGD) have genetic mutations in a component of the NADPH oxidase enzyme that is necessary for the generation of the superoxide anion. The profound defect in innate immunity is reflected by the patients susceptibility to catalase-positive bacteria and fungi. In addition, CGD patients display signs of persistent inflammation, which is not associated only with deficient superoxide anion production. The aim of this study was to elucidate the cytokine responses in CGD patients after TNF-alpha stimulation. METHODS: Heparinized blood samples were collected from 8 CGD patients and 10 healthy volunteers. Monocytes (1x10(6) cell/well) isolated by the magnet cell isolation system were incubated with a constant amount of TNF-alpha (10 ng/mL) at 37degrees C for 6 h. Incubated cells were harvested at 60-min intervals for IL-8 and IL-10 mRNA analysis, and the supernatant was collected at the same intervals to determine IL-8 and IL-10 expression. Monocytes from healthy volunteers were also incubated with antioxidants followed by TNF-alpha stimulation for IL-8 and IL-10 expression. RESULTS: In CGD patients, a high expression of IL-8 together with a significantly higher IL-10 expression than in the healthy controls was seen after TNF-alpha stimulation. Moreover, normal monocytes treated with antioxidants exhibited increased IL-8 responses. CONCLUSION: The absence of phagocyte-derived reactive oxidants in CGD might be associated with a dysregulated production of pro- and antiinflammatory cytokines. Additional research related to reactive oxidants is needed to clarify the role of cytokines in CGD patients.

VP7 Genotypes of Group A Rotavirus Isolated from Infants and Toddlers with Rotavirus Gastroenteritis in Jeju / 대한소아소화기영양학회지

PURPOSE: Efficacy of the new rotavirus vaccines (Rotarix(R), RotaTeq(R)) recently developed can be affected by the rotavirus genotypes prevalent in communities. We performed this study to identify the recent distribution of rotavirus genotypes prevalent in Jeju. METHODS: Genotyping of human rotaviruses was performed using 81 samples collected from 154 inpatients and outpatients with rotavirus gastroenteritis at Cheju National University Hospital between July 2005 and June 2006. All six (1, 2, 3, 4, 8, 9) G serotypes were identified by amplification of segments of the gene for VP7 using the reverse transcription-polymerase reaction (RT- PCR). RESULTS: The results of RT-PCR for 81 samples were all positive. G typing of the VP7 protein showed that G1 was the most dominant circulating genotype (65.5%) followed by G2 (14.8%), G3 (13.6%), G8 (1.2%), G9 (1.2%), G4 (0%), and a combination of G1/G3 (3.7%). CONCLUSION: This distribution of rotavirus VP7 genotypes in Jeju is different from that in other domestic areas; the most dominant circulating genotype was G1.

Polymorphism of Matrix Metalloproteinase-3 Promoter Gene as a Risk Factor for Coronary Artery Lesions in Kawasaki Disease

Kawasaki disease (KD) is a major cause of acquired coronary artery diseases in childhood. The serum levels of matrix metalloproteinase (MMP)-3 and MMP-9 in KD have been reported to be significantly higher than other diseases. Several studies have demonstrated that MMP-3 5A/6A polymorphism and MMP-9 C-1562T polymorphism modify each transcriptional activity in allele specific manner. We hypothesized that these polymorphisms may play a role as a risk factor for development of coronary artery lesions (CAL) in KD. Eighty-three patients, diagnosed with KD in Cheju National University Hospital from January 2000 to February 2004, were divided into two groups according to the presence of CAL. Genotyping of MMP-3 and MMP-9 gene polymorphisms were determined by restriction fragment length polymorphism. With regard to MMP-3 gene polymorphism, the KD with CAL group had a higher frequency of 6A/6A genotype than control group (p=0.0127) and the KD without CAL group (p=0.0036). However, no significant differences in the allele and genotype distributions of the MMP-9 polymorphism were observed. These findings suggest that MMP-3 6A/6A genotype may be an independent risk factor for CAL formation in KD.

Association of Leukotriene C4 Synthase Gene Polymorphism with Clinical Response to Montelukast in Childhood Asthma / 소아과

PURPOSE: Cysteinyl leukotrienes are important inflammatory mediators in the pathogenesis of asthma; therefore interruption of cysteinyl leukotrienes by leukotriene receptor antagonists improves clinical symptoms in the management of patients with mild to moderate asthma. We evaluated whether clinical response to montelukast, a leukotriene receptor antagonist, in childhood asthma was predicted by genotypes of leukotriene C4 synthase (LTC4S) promoter gene polymorphism. METHODS: An 8-week prospective, open trial of montelukast was carried out in 161 children with mild to moderate asthma. Genotyping of LTC4S gene polymorphism was determined by restriction fragment length polymorphism. RESULTS: The distribution of the LTC4S genotypes AA, AC, and CC was 70.8 percent, 23.6 percent, and 5.6 percent, respectively in asthma group and 74.0 percent, 22.6 percent, and 3.4 percent, respectively in control group. A statistically significant difference in the distribution of LTC4S genotype was not observed between the asthma and the control groups, and there was no significant difference between the LTC4S genotype and asthma severity. The responders to montelukast were significantly prevalent in the mild asthma group (P< 0.05). There was no significant difference in the distribution of the responders compared to non-responders within genotype in the total asthma group or the moderate asthma group. However, the responsiveness for montelukast was significant difference within genotype for both AA and AC/CC in the mild asthma group: The AA genotype was more included in the responder group (P< 0.05). CONCLUSION: In the mild persistent asthma group, the A allele of LTC4S polymorphism may be regarded as a predictable factor for clinical response to montelukast. However, LTC4S polymorphism was not significantly associated with the clinical response to montelukast in asthmatic children.

Congenital Heart Disease in Jeju: Postnatal Incidence and Clinical Features / 소아과

PURPOSE: This is a retrospective descriptive study to determine the incidence of congenital heart disease(CHD) in Jeju and to estimate the suitability of the Jeju population as the subject for a regional birth cohort study. METHODS: All patients with CHD diagnosed by two dimensional echocardiography in Cheju National University Hospital and Halla General Hospital from January 1999 to March 2003 were included in this study. RESULTS: From April 1999 to March 2002, the crude incidence rate was 10.06 per 1,000 live births (236 cases/23,464 live births). Among the 236 cases, the proportion of each type was as follows: Ventricular septal defect(44.9%), atrial septal defect(21.2%), pulmonary stenosis(11.0%), patent ductus arterios us(9.3%), tetralogy of Fallot(3.4%), transposition of great arteries(2.1%), aortic stenosis(1.3%), hypoplastic left heart syndrome(1.3%), coarctation of aorta(0.8%), total anormalous pulmonary venous return(0.8%), tricuspid atresia(0.8%), heterotaxia(0.4%), single ventricle(0.4%), atrioventricular septal defect(0.4%), Ebstein anomaly(0.4%). The male to female ratio was 1:1.380(P=0.011). For unknown reasons, females showed significantly higher incidence in VSD(P=0.005) and PDA(P=0.019). Mortality rate was 0.34 per 1,000 live births. The types of VSD were 72.1% of perimembranous, 16.4% of trabecular muscular, 5.7% of subarterial, and 5.7% of unknown. CONCLUSION: This is the first regional study on the incidence of CHD in Korea. The incidence of CHD in Jeju was 10.06 per 1,000 live births. Most of our cases were VSDs and ASDs. Jeju would be a good subject for a regional cohort study in the future.