Change in Severity and Clinical Manifestation of MIS-C Over SARSCoV-2 Variant Outbreaks in Korea

Background@#There is difference in the incidence of multi-system inflammatory syndrome in children (MIS-C) in patients with different variants of severe acute respiratory syndrome coronavirus 2, however, little is known about the epidemiology in Asian countries. We investigated and compared the epidemiology of the MIS-C during omicron-dominant period with that of previous periods in South Korea. @*Methods@#We obtained clinical, epidemiological and laboratory data on MIS-C cases from national MIS-C surveillance in South Korea. We defined pre-delta period as January 2020–May 2021; delta period as June 2021–December 2021; and omicron period as January 2022–April 2022. We describe the clinical characteristics and outcomes of MIS-C patients by period. @*Results@#A total of 91 cases were assessed to be MIS-C cases. Number of MIS-C cases have increased from six cases during pre-delta period to 66 cases during omicron period, while the incidence rate (the number of MIS-C cases per 100,000 cases of reported coronavirus disease 2019) has decreased from 38.5 cases per 100,000 (95% confidence interval [CI], 14.1–83.9) during pre-delta period to 1.6 cases per 100,000 (95% CI, 1.2–2.0) during omicron periods. During pre-delta period, 66.7% and 100% had hypotension and gastrointestinal involvement, respectively; while during omicron period, 12.1% and 6.1% had such clinical manifestations. Fifty percent of pre-delta MIS-C patients were taken intensive care unit (ICU) cares, while 10.6% of patients during omicron periods were in ICUs. @*Conclusion@#Omicron period were associated with less severe clinical manifestation compared to pre-delta and delta periods. Although incidence rate of MIS-C was lower for the omicron period than pre-delta and delta periods, number of patients reported with MIS-C may pose a substantial clinical burden.

Trends of Sensitization to Inhalant Allergens in Korean Children Over the Last 10 Years

Purpose@#Climate and lifestyle changes increase an individual’s susceptibility to various allergens and also the incidence of allergic diseases. We aimed to examine the changes in sensitization rate for aeroallergens over a 10-year period in Korean children. @*Materials and Methods@#We retrospectively reviewed the medical records of 4493 children who visited the allergy clinic at a tertiary hospital in Korea for allergic rhinitis or asthma from January 2009 to December 2018. The serum specific immunoglobulin E (IgE) levels were measured to confirm the sensitization against Dermatophagoides farinae (D. farinae), Alternaria, weed and tree pollen mixtures, as well as cat and dog dander through ImmunoCAP test. @*Results@#D. farinae was the most common sensitizing aeroallergen (45.9%) during the 10-year span. The sensitization rate for tree pollen mixture (p for trend <0.001), weed pollen mixtures (p for trend <0.001), dog dander (p for trend=0.025), and cat dander (p for trend=0.003) showed ascending trends during the 10-year study period. Furthermore, the sensitization rate for multiple allergens (≥2) in 2018 increased significantly compared to that in 2009 (p for trend=0.013).Compared with children without sensitization to D. farinae, those with sensitization to D. farinae showed higher sensitization rates to other aeroallergens (p for interaction <0.001). @*Conclusion@#Children’s sensitization rate to cat and dog dander and weed and tree pollen mixtures significantly increased during the 10-year period in Korea. Children with sensitization to D. farinae are likely to be sensitized to other aeroallergens as well.

A Case of Von Hippel-Lindau Disease Presented with Multiple Pancreatic Cysts and Medullary Hemangioblastoma / 임상소아혈액종양

Von Hippel-Lindau (VHL) disease is a rare inherited cancer predisposition syndrome characterized by benign and malignant tumors in multiple organs, especially cerebellar hemangioblastomas, retinal angiomas, renal-cell carcinoma, and pheochromocytomas. Clinically, VHL disease also presents an increased risk for developing multiple visceral cysts in the pancreas, liver, and kidneys. Regular surveillance for VHL disease-associated tumors after early diagnosis is necessary for better outcomes in VHL disease. An 11-year-old girl was admitted with prolonged fever lasting for more than 10 days and cervical lymphadenopathy. She did not have a family history of cysts or malignancy. Initial blood tests showed mild leukopenia and moderate elevation in aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, but with normal amylase and lipase. Hepatobiliary ultrasonography and magnetic resonance cholangiopancreatography were done and revealed multiple cysts involving the whole pancreas with cyst sizes up to 1.6 cm, indicating VHL disease. Direct sequencing of the VHL gene showed a heterozygous duplication at codon 384 (c.384dup), which is predicted to cause a frameshift of the reading frame (p.Leu129Serfs*3). This was a novel pathogenic variant VHL gene. We carried out the surveillance protocol for VHL disease-associated tumors, and found a hemangioblastoma in the medulla of the brainstem. We are reporting an 11-year-old female patient of VHL disease with brainstem hemangioblastoma who could be suspected and diagnosed of VHL disease in asymptomatic state due to incidentally found multiple pancreatic cysts.

Multisystem Inflammatory Syndrome in Children Related to COVID-19: the First Case in Korea

Since mid-April 2020, cases of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 that mimics Kawasaki disease (KD) have been reported in Europe and North America. However, no cases have been reported in Korea.We describe an 11-year old boy with fever, abdominal pain, and diarrhea who developed hypotension requiring inotropes in intensive care unit. His blood test revealed elevated inflammatory markers, thrombocytopenia, hypoalbuminemia, and coagulopathy. Afterward, he developed signs of KD such as conjunctival injection, strawberry tongue, cracked lip, and coronary artery dilatation, and parenchymal consolidation without respiratory symptoms. Microbiological tests were all negative including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction.However, serum immunoglobulin G against SARS-CoV-2 was positive in repeated tests using enzyme-linked immunosorbent assay and fluorescent immunoassay. He was recovered well after intravenous immunoglobulin administration and discharged without complication on hospital day 13. We report the first Korean child who met all the criteria of MIS-C with features of incomplete KD or KD shock syndrome.

Significance of Differential Characteristics in Infantile Kawasaki Disease

BACKGROUND AND OBJECTIVES: Immunological variability in Kawasaki disease (KD) shows age-specific differences; however, specific differences in laboratory values have not been compared between infants and non-infants with KD. We compared age-adjusted Z-values (Z) of white and red blood cells in infants with KD with those in non-infants with KD. METHODS: This study retrospectively investigated 192 infants and 667 non-infants recruited between 2003 and 2015 at the Korea University Hospital. Laboratory values for infants with KD and non-infants with KD were analyzed and age-unadjusted raw values (R) and age-adjusted Z for blood cells counts were determined. RESULTS: Z in infants with KD during pre-intravenous immunoglobulin (IVIG), post-IVIG, and chronic phases showed increased lymphopenia and eosinophilia, low neutrophil:lymphocyte and neutrophil:eosinophil ratios, worse anemia, increased thrombocytosis, and reduced erythrocyte sedimentation rates compared with those in non-infants with KD. The optimal cut-off value for pre-IVIG Z-hemoglobin for prediction of KD in all patients was 40 mg/L (AUC, 0.811; sensitivity/specificity, 0.712/0.700; p=0.04). CONCLUSIONS: Laboratory characteristics enable differentiation between infants and non-infants with KD and contribute to a better understanding of changes in blood cell counts. Infants with incomplete KD can be more easily differentiated from infants with simple febrile illness using pre-IVIG Z-hemoglobin and pre-IVIG CRP values.

Significance of Differential Characteristics in Infantile Kawasaki Disease

BACKGROUND AND OBJECTIVES@#Immunological variability in Kawasaki disease (KD) shows age-specific differences; however, specific differences in laboratory values have not been compared between infants and non-infants with KD. We compared age-adjusted Z-values (Z) of white and red blood cells in infants with KD with those in non-infants with KD.@*METHODS@#This study retrospectively investigated 192 infants and 667 non-infants recruited between 2003 and 2015 at the Korea University Hospital. Laboratory values for infants with KD and non-infants with KD were analyzed and age-unadjusted raw values (R) and age-adjusted Z for blood cells counts were determined.@*RESULTS@#Z in infants with KD during pre-intravenous immunoglobulin (IVIG), post-IVIG, and chronic phases showed increased lymphopenia and eosinophilia, low neutrophil:lymphocyte and neutrophil:eosinophil ratios, worse anemia, increased thrombocytosis, and reduced erythrocyte sedimentation rates compared with those in non-infants with KD. The optimal cut-off value for pre-IVIG Z-hemoglobin for prediction of KD in all patients was 40 mg/L (AUC, 0.811; sensitivity/specificity, 0.712/0.700; p=0.04).@*CONCLUSIONS@#Laboratory characteristics enable differentiation between infants and non-infants with KD and contribute to a better understanding of changes in blood cell counts. Infants with incomplete KD can be more easily differentiated from infants with simple febrile illness using pre-IVIG Z-hemoglobin and pre-IVIG CRP values.

Increased procalcitonin level is a risk factor for prolonged fever in children with Mycoplasma pneumonia / 소아과

PURPOSE: Macrolide-resistant Mycoplasma pneumoniae pneumonia (MPP) is characterized by prolonged fever and radiological progression despite macrolide treatment. Few studies have examined serum procalcitonin (PCT) level in children with MPP. We aimed to investigate the association of acute inflammation markers including PCT with clinical parameters in children with MPP. METHODS: A total of 147 children were recruited. The diagnosis of MPP relied on serial measurement of IgM antibody against mycoplasma and/or polymerase chain reaction. We evaluated the relationships between C-reactive protein (CRP), PCT, and lactate dehydrogenase (LDH) levels and white blood cell (WBC) counts, and clinical severity of the disease. We used multivariate logistic regression analysis to estimate the odds ratio for prolonged fever (>3 days after admission) and hospital stay (> 6 days), comparing quintiles 2–5 of the PCT levels with the lowest quintile. RESULTS: The serum PCT and CRP levels were higher in children with fever and hospital stay than in those with fever lasting ≤ 3 days after admission and hospital stay ≤ 6 days. CRP level was higher in segmental/lobar pneumonia than in bronchopneumonia. The LDH level and WBC counts were higher in children with fever lasting for >3 days before compared to those with fever lasting for ≤ 3 days. The highest quintile of PCT levels was associated with a significantly higher risk of prolonged fever and/or hospital stay than the lowest quintile. CONCLUSION: Serum PCT and CRP levels on admission day were associated with persistent fever and longer hospitalization in children with MPP.

A 75-Year-Old Natural Survivor with Uncorrected Tetralogy of Fallot Presenting with Hypoxic Spell / 이화의대지

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Only a few patients reach adulthood without surgical correction. Unrepaired TOF patients with mild to moderate right ventricular outflow tract (RVOT) obstruction may be clinically silent until adulthood. TOF with hypoxic spells present as periods of profound cyanosis that occur because of almost total RVOT obstruction. So, hypoxic spell typically occurs in a crying infant but is rare in an adult. In this report, we presented a case of a 75-year-old patient with uncorrected TOF presenting with hypoxic spell, consequent pulmonary hypertension and chronic heart failure. This is the oldest case of natural survivor with uncorrected TOF in Korea and the oldest patient presenting hypoxic spell worldwide.

Prediction of Resistance to Standard Intravenous Immunoglobulin Therapy in Kawasaki Disease

BACKGROUND AND OBJECTIVES: Ten to twenty percent of children with Kawasaki disease (KD) do not respond to initial intravenous immunoglobulin (IVIG) treatment. If untreated, approximately 15% to 25% of KD patients have complications. The aim of this study was to find useful predictors of responsiveness to initial IVIG treatment in KD. SUBJECTS AND METHODS: We retrospectively reviewed medical records of 91 children diagnosed with KD at Myong Ji Hospital from March 2012 to April 2014. Before and after (24 hours to 36 hours) IVIG treatment, the following laboratory data were obtained: hemoglobin (Hb) level, white blood cell count, proportion of neutrophil, lymphocyte and eosinophil, platelet count, erythrocyte sedimentation rate (ERS), C-reactive protein (CRP), creatine kinase (CK), creatine kinase MB (CK-MB), and N-terminal pro-brain natriuretic peptide (NT-proBNP). Subjects were then divided into two groups: IVIG-responsive or IVIG-resistant. RESULTS: Of 91 patients, 11 (12%) required retreatment. By univariate analysis, before-IVIG laboratory parameters of white blood cell count, % neutrophil, ERS, CRP, sodium, CK, CK-MB, and NT-proBNP were significantly different between IVIG-responsive and IVIG-resistant patient groups. In the after-IVIG laboratory parameters, Hb level, white blood cell count, % neutrophil, % lymphocyte, CRP, CK, CK-MB, and NT-pro-BNP were significantly different between the two groups. While the mean-differences were not statistically significant, fractional change (FC)-CRP and FC-% neutrophil showed significant difference. By multivariate analysis, FC-CRP was confirmed to be an independent predictor for initial IVIG resistance. CONCLUSION: Fractional change-C-reactive protein might be a useful and important value for predicting initial IVIG resistance in KD patients.

Changes in Coronary Perfusion after Occlusion of Coronary Arteries in Kawasaki Disease

PURPOSE: Myocardial infarction in children with total occlusion of a coronary artery after Kawasaki disease is rare due to multiple collateral vessels. We aimed to investigate the changes in coronary perfusion associated with coronary artery occlusion after Kawasaki disease. MATERIALS AND METHODS: Eleven patients with coronary artery occlusion after Kawasaki disease were investigated. Serial coronary angiographies after total occlusion of a coronary artery were reviewed and the changes were described in all patients with additive information collected. RESULTS: The median age at the occlusion was 5.9 years old. The interval to occlusion was 6.2+/-6.9 years. Four left anterior descending coronary artery total occlusions and 10 right coronary artery total occlusions were detected. Immediate coronary artery bypass graft for left anterior descending coronary artery total occlusion made right coronary total occlusion occurred in all except one patient and the intervals thereof were 1 year, 1.8 years, and 4 years. Collaterals to the left coronary artery regressed after recanalization, while new collaterals to the right coronary artery developed. In three, collaterals to the right coronary artery decreased without recanalization without clinical signs. CONCLUSION: The right coronary artery should be followed up carefully because of possible occlusion of new onset or changes in collaterals.

Clinical features of acute noroviral gastroenteritis in children : comparison with rotaviral gastroenteritis / 소아과

PURPOSE: Our aim was to describe the clinical features of noroviral gastroenteritis in children. METHODS: This study included 22 children with noroviral gastroenteritis, as confirmed by stool RT-PCR, who were admitted to Bundang CHA Hospital between July 2006 and June 2008. Their medical records were reviewed and compared with those of 45 children with rotaviral gastroenteritis. RESULTS: In the norovirus group, 19 (86.4%) children showed vomiting and 21 (95.5%) children showed diarrhea, while all children in the rotaviral group showed both vomiting and diarrhea. The duration of vomiting was not different in the two groups, but mean episodes of vomiting/24 h were higher in the norovirus group than in the rotavirus group. The duration of diarrhea was longer and mean episodes of diarrhea/24 h were higher in the rotavirus group. The Vesikari Scale was not different in the two groups. Frequency and duration of fever did not show a significant difference. Most children in both groups were below 2 years of age. CONCLUSION: Clinical features of noroviral gastroenteritis were largely similar to those of rotaviral gastroenteritis, but vomiting was more severe in noroviral infection, and diarrhea was more severe and prolonged in rotaviral infection. With regard to noroviral infection, further epidemiologic investigations and preventive efforts are essential.

A comparison between impulse oscillometry system and spirometry for spirometry for detecting airway obstruction in children / 소아과

PURPOSE: Measurement of forced expiratory volume in 1 second (FEV1) is usually difficult to obtain in children under six years of age because it requires active cooperation. This study evaluates the sensitivity of impulse oscillometry system (IOS) parameters for detecting airway obstruction in comparison with FEV1. METHODS: We studied 174 children who performed the lung function and methacholine challenge tests to diagnose asthma by IOS and spirometry. Children were divided into two subgroups according to their PC20, which is a parameter for bronchial sensitivity. We compared IOS parameters with FEV1 at the baseline, post-methacholine challenge, and evaluated their correlation. RESULTS: At the baseline, reactance at 5 Hz (X5) and resistance at 5 Hz (R5) significantly differed between the PC20 positive (PC2016 mg/mL) group; however, FEV1, FEV1% predicted, FEV1_Zs (Z score) did not differ. FEV1 is correlated with X5 (r=0.45, P<0.01) and R5 (r=-0.69, P<0.01). FEV1_Zs is also correlated with X5_Zs (r=-0.26, P<0.01) and R5_Zs (r=-0.31, P<0.01). After the methacholine challenge test, dose-response slopes in FEV1 and X5 significantly differed between the two subgroups (P<0.05). CONCLUSION: IOS parameters were more discriminative than FEV1 for detecting decreased baseline lung function between two subgroups and have a good correlation with FEV1.

Safety and efficacy of the ultra-rush immunotherapy with extracts of Dermatophagoides pteronyssinus in children / 소아과

PURPOSE: Immunotherapy is accepted as the only treatment of allergic disease that can modify the natural course of the disease and ameliorate symptoms. This study aimed to evaluate the safety and efficacy of ultra-rush therapy using Dermatophagoides extracts in children. METHODS: Of children older than four years who had visited Bundang CHA Pediatric Allergy Clinic, those showing positive reactions only to Dermatophagoides in the skin prick test and to the nasal provocation test were included. In all, 11 and 12 patients respectively preferred conventional and ultra-rush immunotherapy. We elevated allergen concentrations diluted to 1,000:1 of the end strength by 2-3 times with 30-minute intervals and checked oxygen saturation, pulse rate, blood pressure, and systemic reactions every 15 minutes. Immunotherapy effectiveness was valued by changes in nasal provocation test scores before and after immunotherapy. RESULTS: The average ages of patients in the conventional and ultra-rush immunotherapy groups were 8.3+/-2.3 and 9.2+/-2.8 years, respectively. Systemic reactions were observed in six in the ultra-rush group (50%) without anaphylaxis and one (9%) in the conventional group. The average scores in the nasal provocation test before and after treatment in the conventional group were 8.2+/-1.5 and 4.6+/-2.1, respectively (P=0.043). In the ultra-rush immunotherapy group, the scores changed from 6.2+/-2.2 to 3.7+/2.5 (P=0.017). CONCLUSION: Ultra-rush immunotherapy using Dermatophagoides in children is effective for treating allergic disease but can induce systemic effects rather than conventional immunotherapy.