Blood Pressure Reference Values for Normal Weight Korean Children and Adolescents: Data from The Korea National Health and Nutrition Examination Survey 1998–2016: The Korean Working Group of Pediatric Hypertension

BACKGROUND AND OBJECTIVES: Hypertension is becoming one of the most common health conditions in children and adolescents due to increasing childhood obesity. We aimed to provide the auscultatory blood pressure (BP) normative reference values for Korean non-overweight children and adolescents. METHODS: BP measurements in children and adolescents aged 10 to 18 years were performed in the Korean National Health and Nutrition Examination Survey (KNHANES) from 1998 to 2016. BP was measured using a mercury sphygmomanometer. Sex-, age- and height-specific systolic BP (SBP) and diastolic BP (DBP) percentiles were calculated in the non-overweight children (n=10,442). We used the General Additive Model for Location Scale and Shape method to calculate BP percentiles. RESULTS: The 50th, 90th, 95th, and 99th percentiles of SBP and DBP tables and graphs of non-overweight children and adolescents aged 10 to 18 years were presented by age and height percentiles. We found that the SBP and DBP at the 95th percentile were well correlated with height. The BP tables presented by height contained BP values from 124 cm to 190 cm for boys and from 120 cm to 178 cm for girls. Boys had higher SBP and DBP. CONCLUSIONS: We provided the sex-, age- and height-specific auscultatory BP values using the KNHANES big data. These may be useful in diagnosis and treatment of hypertension in Korean children and adolescents.

Blood Pressure Reference Values for Normal Weight Korean Children and Adolescents: Data from The Korea National Health and Nutrition Examination Survey 1998–2016: The Korean Working Group of Pediatric Hypertension

BACKGROUND AND OBJECTIVES@#Hypertension is becoming one of the most common health conditions in children and adolescents due to increasing childhood obesity. We aimed to provide the auscultatory blood pressure (BP) normative reference values for Korean non-overweight children and adolescents.@*METHODS@#BP measurements in children and adolescents aged 10 to 18 years were performed in the Korean National Health and Nutrition Examination Survey (KNHANES) from 1998 to 2016. BP was measured using a mercury sphygmomanometer. Sex-, age- and height-specific systolic BP (SBP) and diastolic BP (DBP) percentiles were calculated in the non-overweight children (n=10,442). We used the General Additive Model for Location Scale and Shape method to calculate BP percentiles.@*RESULTS@#The 50th, 90th, 95th, and 99th percentiles of SBP and DBP tables and graphs of non-overweight children and adolescents aged 10 to 18 years were presented by age and height percentiles. We found that the SBP and DBP at the 95th percentile were well correlated with height. The BP tables presented by height contained BP values from 124 cm to 190 cm for boys and from 120 cm to 178 cm for girls. Boys had higher SBP and DBP.@*CONCLUSIONS@#We provided the sex-, age- and height-specific auscultatory BP values using the KNHANES big data. These may be useful in diagnosis and treatment of hypertension in Korean children and adolescents.

Multicenter, Single-Arm, Phase IV Study of Combined Aspirin and High-Dose “IVIG-SN” Therapy for Pediatric Patients with Kawasaki Disease

BACKGROUND AND OBJECTIVES: Intravenous immunoglobulin-SN (IVIG-SN) is a new human immunoglobulin product. Its safety is ensured by pathogen-elimination steps comprising solvent/detergent treatment and a nanofiltration process. This multicenter clinical study was designed to evaluate the efficacy and safety of combined aspirin and high-dose IVIG-SN therapy in pediatric patients with Kawasaki disease (KD). SUBJECTS AND METHODS: We evaluated coronary artery lesions (CALs) at 2 and 7 weeks after administering IVIG-SN; total fever duration; and variations in erythrocyte sedimentation rate, N-terminal pro B-type natriuretic peptide or B-type natriuretic peptide, and creatine kinase-myocardial band level before and after treatment with IVIG-SN (2 g/kg). Adverse events were monitored. RESULTS: Forty-five patients were enrolled, three of whom were excluded according to the exclusion criteria; the other 42 completed the study. The male:female ratio was 0.91:1, and the mean age was 29.11±17.23 months. The mean fever duration before IVIG-SN treatment was 6.45±1.30 days. Although most patients had complete KD (40 patients, 90.91%), four had atypical KD (9.09%). After IVIG-SN treatment, one patient (2.38%) had CALs, which was significantly lower than the incidence reported previously (15%) (p=0.022), but not significantly different from recent data (5%). There were no serious adverse events, though 28 patients (63.64%) had mild adverse events. Three adverse drug reactions occurred in 2 patients (eczema, anemia, and increased eosinophil count), all of which were transient. CONCLUSION: IVIG-SN treatment in patients with KD was safe and effective.

Interleukin-21 Receptor Gene Polymorphisms in Kawasaki Disease

BACKGROUND AND OBJECTIVES: Interleukin-21 receptor (IL-21R) gene polymorphism is related with the development of systemic vasculitis. In this study, we investigated the polymorphisms of IL-21R gene in patients with Kawasaki disease (KD). SUBJECTS AND METHODS: We genotyped the promoter region of IL-21R gene (-2500 bp to +1 bp) in 100 patients with KD and 100 healthy controls. All study subjects were Korean. We designed five pairs of primers and performed polymerase chain reaction (PCR) and direct sequencing. We analyzed whole promoter sequences of 200 individuals with comparison to reference sequences of IL-21R gene (NG_012222.1/NC_000016.9). RESULTS: We found five single nucleotide polymorphisms (SNPs) of which minor allele frequency (MAF) >0.01 in the promoter region of IL-21R gene. Those are -1681 G>T (chromosome site 27411802), -379 G>A (27413104), -332 G>C (27413151, rs2214537), -237 A>T (27413246), and -53 G>A (27413430). There is no significant difference in MAF of each SNP between patients with KD and healthy controls except -237 A>T. Twenty five patients with KD had more than 1 SNP in contrast to only seven healthy controls had. The patients with KD have significantly more IL-21R gene polymorphisms than controls (odds ratio: 3.0, 95% confidence interval: 1.6-5.6, p=0.0005). There was no significant correlation between IL-21R gene polymorphisms and the serum level of IL-21. The serum level of total IgE was not significantly correlated with the presence of IL-21R gene polymorphisms. CONCLUSION: Our data suggest that the genetic susceptibility profile for KD may include IL-21R gene.

Hereditary Hemorrhagic Telangiectasia with Pulmonary and Splenic Arteriovenous Malformation / 소아알레르기및호흡기학회지

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is a rare autosomal dominant vascular disorder involving arteriovenous malformation (AVM) due to angiodysplasia. HHT is characterized by mucocutaneous hemorrhagic telangiectasia and AVM of various different organs. The mutated genes in HHT encode proteins that mediate signaling by the transforming growth factor-beta superfamily, leading to migration and proliferation of endothelial cells to finally result in AVMs of various organs. Amongst various affected organs, pulmonary AVM is the most common. This 11-year-old female patient with a past and familial history of frequent epistaxis visited the hospital for abdominal pain and vomiting which developed on the same day. Nodular opacity was found in chest X-ray. Subsequently, AVMs in the lungs and the spleen were recognized in chest computed tomography along with detection of ENG gene mutation. Here we report a case of hereditary hemorrhagic telangiectasia diagnosed by incidental chest X-ray findings followed by genetic and radiologic studies.

Elevated Serum Levels of IL-21 in Kawasaki Disease

PURPOSE: The serum level of immunoglobulin (Ig)E has been reported to be elevated in patients with Kawasaki disease (KD). We investigated whether interleukin (IL)-21, rather than IL-4, could be related to elevated serum levels of IgE in KD. METHODS: Sera from 48 patients with KD and 12 controls with high fever were collected to determine the level of IgE using an immunoassay system and the levels of IL-4 and IL-21 were determined using enzyme-linked immunosorbent assay kits. RESULTS: The median IL-21 level of KD patients was significantly elevated, at 499.5 pg/mL (range: <62.5-1,544 pg/mL), whereas that of controls was <62.5 pg/mL (<62.5-825 pg/mL; P<0.001). The median IL-4 level of KD patients was not elevated (4.0 pg/mL; 2.1-7.6 pg/mL). The median level of total IgE in KD patients was 58.0 IU/mL (5-1,109 IU/mL). No statistically significant correlation was found between IL-21 and total IgE levels (Spearman's R=0.2; P=0.19). CONCLUSIONS: Patients with KD have elevated levels of IL-21 in the serum. IL-21 may play a role in the pathogenesis of KD.

Predicting Factors for Refractory Kawasaki Disease

BACKGROUND AND OBJECTIVES: About 10-15% of Kawasaki disease (KD) is refractory to intravenous immunoglobulin (IVIG) therapy. This study was designed to investigate the predicting factors for refractory KD. SUBJECTS AND METHODS: We reviewed retrospectively the clinical records of 77 patients with typical KD admitted at Wonju Christian Hospital from January, 2005, to December, 2008. The variance of laboratory and demographic parameters between the IVIG-responsive group and IVIG-resistant group were analyzed. Thirteen patients with urinary tract infections were randomly collected as a febrile control group. RESULTS: Among 77 patients diagnosed with complete KD, 13 patients (16.9%) were IVIG-resistant. The febrile period and hospital days were significantly longer in the IVIG-resistant group than IVIG-responsive group (p<0.001, p=0.002). Serum levels of albumin and sodium were significantly lower in the IVIG-resistant group (p=0.025). The Kobayashi score could differentiate these two groups (p=0.015). Fewer lymphocytes was observed during the subacute phase in the IVIG-resistant group (p=0.032). Coronary arterial dilatations (CADs) were observed in 10.9% (7/64) of IVIG-responders and 38.5% (5/13) of IVIG-resistant patients (p=0.038). CONCLUSION: The percentage of neutrophils and lymphocytes in patients with KD, in addition to known risk factors for refractory KD, may help predict IVIG-resistance in patients with KD.

Relationship Between Gallbladder Distension and Lipid Profiles in Kawasaki Disease

BACKGROUND AND OBJECTIVES: Kawasaki disease (KD) is an acute systemic vasculitis in children which causes coronary arterial dilatation (CAD) and gallbladder distension (GBD). There is a dearth of investigating the relationship between the severity of KD and GBD with lipid profiles. SUBJECTS AND METHODS: A total of 80 patients with 'complete KD' who were diagnosed from January 2005 to May 2009 was enrolled in this study. Serum cholesterol {total, high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C)}, triglyceride (TG), complete blood count, inflammation markers {erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)} were measured at the time of admission during febrile period. Echocardiography and abdominal sonogram were performed in all patients to determine CAD and gallbladder size. According to GBD, patients with KD were classified as patients with GBD and patients without GBD. Between two groups, demographic and clinical data were analyzed. RESULTS: The serum level of LDL-C was significantly lower in patients with GBD (p=0.03) compared with patients without GBD or febrile control. There was no significant difference in inflammatory indices between patients with GBD and patients without GBD. GBD was not significant risk factor of CAD in this study (odds ratio=2.0, 95% confidence interval=0.82-5.3, p=0.16). CONCLUSION: This is the first study that highlights the relationship between the GBD and lipid metabolism in patients with KD. This study provides clinical insights about potential mechanism underpinning the relationship between the GBD and lipid metabolism.

Group A beta-hemolytic Streptococcal Meningoencephalitis with Unilateral Hemiparesis / 소아감염

Group A streptococcus (GAS) rarely causes meningoencephalitis in children without risk factors. A previously healthy 8 year-old child presented with lethargy, high fever, and vomiting. The clinical course was unusual including intractable seizures, disseminated intravascular coagulation (DIC), and left hemiparesis in spite of the appropriate and timely administration of antibiotics and corticosteroids. The microbiologic studies revealed that the pathogen was susceptible to penicillin and GAS M18 strains. This case showed the importance of the GAS vaccine in addition to appropriate antibiotics.

Febrile Seizures and Benign Convulsion with Mild Gastroenteritis in Children / 대한소아신경학회지

PURPOSE: Febrile Seizures and Benign convulsion with mild gastroenteritis(BCwMG) are common neurological disorders in children. We would like to know the clinical characteristics and prognosis of febrile seizure associated with acute gastroenteritis(A), BCwMG(B) and febrile seizure associated with a febrile illness not caused by acute gastroenteritis(C) in children. METHODS: We reviewed the medical records of 569 pediatric patients aged from 3 months to 5 years that admitted to the Wonju Christian Hospital from 2004 to 2007 for febrile seizures or BCwMG. RESULTS: The mean ages were A; 1.51+/-1.10 years, B; 1.14+/-0.44 years, C; 1.84+/-1.33 years. The most common seizure type was generalized seizure(95.4%). The average frequency of seizure was higher in B than A and C(A; 1.53+/-0.88, B; 2.12+/-1.35, C; 1.23+/-1.11 times/day, P<0.001). The incidence of positive parents history for febrile seizures was higher in A and C compared to B(A; 14.5%, B; 4.3%, C; 17.8%, P<0.05). The mean WBC count in peripheral blood was higher in C than A and B(A; 10,532+/-5,151, B; 8,686+/-3,053, C; 12,932+/-5,866 mmol/L, P<0.001). The positive rate of stool rotavirus antigen test was higher in A and B compared to C(A: 45.7%, B: 42.6%, C: 14.5%, P<0.05). But there were no statistically significant differences of sex ratio, duration of seizures, serum sodium level, abnormal neurodevelopmental status, rate of EEG and neuroimaging abnormalities among three groups. The recurrence rate of febrile seizure after the 1st seizure was A; 9.1%, B; 5.8%, C; 11.9% and unprovoked seizure was A; 5.4%, B; 1.4%, C; 1.6%. CONCLUSION: We consider prophylactic short term management of recurrent episodes of seizures within 24 hours, especially in febrile seizure associated with acute gastroenteritis and BCwMG. Also, It will be necessary to educate parents about the possibility of recurrence of febrile seizures or unprovoked seizures, although the risk is low.

Association between Coronary Artery Abnormality and Serum Amyloid A in Kawasaki Disease

PURPOSE: Kawasaki disease can cause cardiovascular complications if not properly treated from the beginning. Recently, serum amyloid A(SAA) was reported to be a predictive factor of cardiovascular diseases. Therefore, it was examined whether the existence of coronary artery abnormality in Kawasaki disease can be predicted in acute stage. METHODS: Forty nine patients who were diagnosed with Kawasaki disease between October, 2006 and May, 2007 at Yonsei University, Wonju College of Medicine were selected for this study. We reviewed results of CBC, AST, ALT, CK, LDH, total bilirubin, albumin, CRP, CK-MB, troponin-I, LDL, HDL, SAA, ESR. We divided the patients into two groups: Group A consisting of patients with coronary artery lesions, and group B consisting of patients without coronary artery lesions. RESULTS: CRP was significantly higher in group A (group A 11.0+/-7.0 mg/dL vs group B 5.3+/-5.3 mg/dL, P=0.030). SAA was slightly higher in group A but did not show any statistical significance (group A 283.8+/-357.3 microgram/mL vs group B 133.2+/-293.4 microgram/mL, P=0.128). Binary regression analysis was used to identify the significance of SAA as a predictor of coronary artery abnormality but did not find any significance (SAA OR=1.000, 95% CI=0.998-1.002, P=0.950). CONCLUSION: SAA are not significant predictors of coronary artery abnormality in Kawasaki disease but are non specific factors which increase in the acute stage.

Rheumatic Fever with IgA Nephropathy: a Case Report

Rheumatic fever with renal involvement is rarely seen. The prevalence is found to be low although it may differ by reporters. We report a case of rheumatic fever with IgA nephropathy. The patient was a 14-year-old male. The patient's chief complaint were fatigue and gross hematuria. On the physical examination, the pansystolic murmur (grade II) on the left lower sternal border was noted. Cardiomegaly was seen on chest X-ray and pulmonary vasculatures were increased. Prolonged PR intervals were found on EKG. Echocardiogram showed rheumatic carditis with grade mild to moderate MR, regurgitant shunt from LV to LA through anterior leaflet. On the laboratory findings, ESR, CRP and ASO were increased, C3, C4 and IgA were normal. On the urine analysis, gross hematuria was noted as RBC over 30/HPF and RBC dysmorphism 90%. On the immunofluoroscent microscope of renal biopsy, IgA deposit on mesangial matrix was noted.

A Case of Partial Trisomy 9p Syndrome with 3-Ketothiolase Deficiency / 대한소아신경학회지

Trisomy 9p syndrome was first described by Rethore et al in 1970 and about 150 cases have been reported. The characteristic features of the partial trisomy 9p syndrome is clearly recognizable faces, which include microcephaly, facial deformities, skeletal and dermatoglyphic anomalies with variable degrees of mental retardation. The 3-ketothiolase deficiency was first described in 1971 and about 30 cases have been reported. The 3-ketothiolase deficeiency is an inborn error of isoleucine and ketone body catabolism that shows autosomal recessive traits, caused by a deficiency of mitochondrial acetoacetyl-coenzyme A thiolase(T2). We report a case of partial trisomy 9p syndrome with 3-ketothiolase deficeiency in a 4-years-old female. The karyotype of the patient was confirmed as 46,XY, add(9)(p23) mat. In the urine organic acid test, 3-ketothiolase deficiency was reported.

Bronchiolitis Obliterans Associated with Stevens-Johnson Syndrome / 소아과

Bronchiolitis Obliterans(BO) is one of the rare inflammatory lung disease that primarily affects bronchi and bronchioles, followed by partial or complete obstruction. In children, the etiology of BO has been under consideration, but infections and toxic inhalation, connective tissue diseases, lung transplantation, congestive pulmonary edema, etc., may be causes of BO. Even though steroid therapy was reported as an effective treatment, there are few data regarding the epidemiology, pathophysiology, long term prognosis and therapy. Here we describe a 5-year-old boy who presented with intractable wheezing associated with Stevens-Johnson syndrome after Varicella-Zoster virus infection and was diagnosed as BO through chest high-resolution computed tomography.

Coronary Risk Factors in Kawasaki Disease

PURPOSE: Kawasaki disease is an acute febrile vasculitis that may cause coronary artery dilatation after the acute phase. We assessed the risk factors of coronary artery dilatation in patients diagnosed with Kawasaki disease. METHODS: From January 1995 through April 2003, a total of 362 patients with Kawasaki disease were enrolled. After dividing these patients into two groups by presence of coronary artery dilatation, we analyzed and compared the early symptoms and laboratory findings. RESULTS: A total of 362 patients were divided into two groups: Group 1 consisted of 65 patients(18.0%) with coronary artery dilatation, while Group 2 consisted of 297 patients(82.0%) with normal coronary arteries. Group 1 exhibited longer duration of fever during the early symptoms and showed elevated levels of CRP and cardiac Troponin-I(cTnI). WBC count, hemoglobin, hematocrit, platelet count, erythrocyte sedimentation rate, hepatic enzymes, serum albumin, CK-MB, total eosinophil count, age and sex were not significantly different between the two groups. CONCLUSION: As the severity of early inflammatory reaction increased, the risk of coronary artery dilatation increased accordingly. Therefore it is essential to establish a treatment to reduce the early inflammatory reaction in order to decrease coronary artery complications.

The Relationship between Human Neutrophil Elastase and Coronary Arterial Dilatation in Kawasaki Disease

PURPOSE: Kawasaki disease is notorious for coronary arterial complication which is usually developed as a febrile disease in early childhood. Increased polymorphonucleus(PMN) cell levels in acute phases may be associated with the pathophysiology of Kawasaki disease. We studied the relationship between coronary arterial dilatation and elastase activity which was excreted from PMN cell and roles as an important factor for vasculitis. METHODS: Ten patients diagnosed with Kawasaki disease in Yonsei University Medical Center were examined between November, 2001 and January, 2002. In addition, 15 patients with other febrile diseases were also examined. Echocardiography was done in patients with Kawasaki disease on the first day of admission and four weeks after the onset of the disease. At each time, venous samples were drawn and separated into plasma and leukocytes. In patients with other febrile disease, samples were drawn on admission. Elastase activities in plasma and neutrophil extracts were measured. RESULTS: The significant increased plasma elastase activity, 6.19+/-0.74 U/mL, found in Kawasaki disease patients compared with the other febrile disease patients, 4.86+/-1.17 U/mL(P<0.05). And there was no significance between the above two diseases in terms of the elastase activity in neutrophil extracts. The relationship between initial elastase activity and the coronary arterial complication which was shown in subacute phase wasn't significant. CONCLUSION: Plasma elastase activity was increased in Kawasaki disease significantly, but the initial plasma elastase activity in the acute phase could not reflect the range of coronary arterial complication.

Assessment of Left Ventricular Function with Echocardiography in Patients Treated with Adriamycin: A Load-Independent Index of Myocardial Contractility and Comparisons between Rest and Exercise

PURPOSE: The aim of this study was to evaluate myocardial injury in children treated with adriamycin by echocardiography, which is non-invasive and safe measurement for children. METHODS: Left ventricular dimensions, wall stress, and contractile function were determined by echocardiographic methods in 17 patient recepients with adriamycin chemotherapy at rest(group 1) and during stress(group 2). Twenty age-matched normal subjects were established as control group. RESULTS: End-diastolic dimension was decreased in both groups(group 1; 92+/-7% of normal, group 2; 87+/-8% of normal, P<0.05). Left ventricular end diastolic volume and wall mass were also decreased in both groups(group 1; 96+/-12 mL/m2 and 145+/-18 g/m2, group 2; 87+/-8 mL/m2 and 137+/-16 g/m2, respectively, P<0.05 and P<0.05) and group 2 showed lower values than group 1. Meridional end systolic stress(ESSm) was increased in both groups but there was no significant difference between the two groups(group 1; 52.6+/-6.2 g/cm2, group 2; 63.5+/-8.5 g/cm2, P<0.05, normal value 45.7+/-3.5 g/cm2). The load-independent relation of rate-corrected circumferential fiber shortening velocity(Vcfc) to ESSm has a significant abnormal change in 7 out of 17(41%) in group 1 and 12 out of 17(71%) in group 2. CONCLUSION: The load-dependent systolic index, such as fractional shortening, may fail to show abnormality because of the compensatory changes in preload and afterload which can mask the impaired contractility. Therefore, systolic performance also should be monitored by a load-indepedent contractility index such as slope value of the end-systolic pressure-dimension relation and the position of the left ventricular stress-fiber shortening velocity after exercise.

A Case of Vibrio cholerae Non-O1/O139 Gastroenteritis / 대한임상병리학회지

Vibrio cholerae non-O1/O139 strains are widely distributed in the environment such as sewage, estuarine waters, seafood, seawater, animals and contaminated foods in Europe, Asia, and the United States. V. Cholerae non-O1/O139 is the etiologic agent of gastroenteritis and extraintestinal infections such as bacteremia and wound infection. Gastroenteritis by Vibrio cholerae non-O1/O139, a prevalent disease in western countries and Asia, is considered rare in Korea. The authors isolated V. cholerae non-O1/O139 from a stool of a 2 year-old male with diarrhea and mild fever. To our knowledge, this is the first documented case of V. cholerae non-O1/O139 gastroenteritis in Korea.

A Case of Early Onset Cerebellar Ataxia with Retained Tendon Reflexes

Early onset cerebellar ataxia with retained tendon reflexes is clinical syndrome characterized by progressive cerebelar ataxia of unknown etiology with an onset within the first two decades. This disorder was distinguished from Friedreich's ataxia by the preservation of the tendon reflexes. We have experienced a case of early onset cerebellar ataxia with retained tendon reflexes which was diagnosed by clinical features, eletrophysiologic studies, and MRI scan. This 8 year-old male patient had suffered from gait ataxia with delayed growth and development since 3 years of age. A brief review of the related literatures was also made.

A Case of Early Onset Cerebellar Ataxia with Retained Tendon Reflexes

Early onset cerebellar ataxia with retained tendon reflexes is clinical syndrome characterized by progressive cerebelar ataxia of unknown etiology with an onset within the first two decades. This disorder was distinguished from Friedreich's ataxia by the preservation of the tendon reflexes. We have experienced a case of early onset cerebellar ataxia with retained tendon reflexes which was diagnosed by clinical features, eletrophysiologic studies, and MRI scan. This 8 year-old male patient had suffered from gait ataxia with delayed growth and development since 3 years of age. A brief review of the related literatures was also made.