Antibiotic-induced Severe Neutropenia with Multidrug-Dependent Antineutrophil Antibodies Developed in A Child with Streptococcus pneumoniae Infection

Drug-induced neutropenia (DIN), particularly that in which antibiotic-dependent antineutrophil antibodies have been detected, is a rare disorder. We report the case of a child with pneumococcal pneumonia, who experienced severe neutropenia during various antibiotic treatments. We detected 4 kinds (cefotaxim, augmentin, vancomycin, and tobramycin) of antibiotic-dependent antineutrophil antibodies by using the mixed passive hemagglutination assay (MPHA) technique with this child.

New Patterns of Childhood Asthma Pevalence in Six Asian Countries: Comparison of ISAAC Phases I and III / 소아알레르기및호흡기학회지

PURPOSE: Over the past few decades, prevalence of childhood asthma has increased worldwide. However, in some countries, it remains stable or even decreased. Nationwide cross-sectional surveys were performed to obtain comparable data of the prevalence in Korea and other Asian countries (China, Hong Kong, Singapore, Taiwan, Thailand and Philippines). METHODS: The collaborative international phase III studies were carried out in 1995 and 2000 using a Korean versions of the International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire (WQ) and a video questionnaire (VQ). In 1995, 15,894 children aged 12-15 years were enrolled in this study, and in 2000, 15,481 children from the same 34 selected schools were investigated. Prevalence of asthma or ever-wheeze had steadily increased until 1995. RESULTS: Both lifetime and past 12-month prevalence of wheeze decreased or reached the plateau from 1995 to 2000; 17.0% vs. 13.0% and 13.4% vs. 12.8% for 6-7 years old children, and 9.5% vs. 4.9% and 8.5% vs. 8.5% for 13-14 years old children, respectively. Prevalences of asthma in China, Hong Kong and Singapore have generally decreased, whereas it remained stable or slightly increased in Taiwan, Thailand and the Philippines. CONCLUSION: Prevalence of asthma symptoms decreased or reached the plateau in Korean children during a period of 1995 to 2000 and was generally stable in the other Asian countries. This was attributed to greater awareness of symptoms, diagnosis and proper management by patients and physicians together with a successful 'National Asthma Campaign' in Korea and other countries.

Detection of SNP of Phospholipase D1 in Children with Atopic Dermatitis / 소아알레르기및호흡기학회지

BACKGROUND: Phospholipase D (PLD) is a widely distributed enzyme that hydrolyzes phosphatidylcholine, a major phospholipids in the cell membrane, to form phosphatidic acid (PA) which acts by itself as a cellular messenger. PLD can also be transformed by PA phosphohydrolase into diacylglycerol (DAG), which is essential for the activation of protein kinase C (PKC). PLD has been shown to induce the proliferation of T cells and to activate by Der p 1 in peripheral blood mononuclear cells from atopic dermatitis. Single nucleotide polymorphism (SNP) has recently served as a key marker to discover the genetic mechanism of special chronic diseases. METHODS: One hundred eighteen children with atopic dermatitis were recruited, and graded as 23 mild (50) by measuring SCORAD index. Genomic DNA were purified from blood and made into PCR primers attaching GC-Clamp, and 26 exons of PLD were amplified by PCR-DGGE (denaturing gradient gel electrophoresis). RESULTS: Polymorphism was found in four subjects. Of them, three PLD1 cSNP (Exon23: G2658A, T2664A, G2684A) were detected in exon 23 of 26 exons of PLD1. Four cases among 118 subjects had cSNP of G2658A (3.4%), two T2664A cases (1.7%), one G2684A case (0.8%). There were no significant correlations between IgE and detected cSNP. CONCLUSION: Three PLD1 gene cSNPs (G2658A, T2664A, G2684A) were detected in the blood of children with atopic dermatitis. Among them, G2658A polymorphism seems to be correlated to the serum IgE level, but PLD1 cSNP does not appear to contribute to the pathogenic processing of atopic dermatitis.

Ultrastructure of nasal cilia in children with recurrent or persistent respiratory diseases / 소아과

PURPOSE: Ciliary abnormalities of the respiratory system usually accompany recurrent or persistent respiratory diseases such as paranasal sinusitis, bronchiectasis, rhinitis, and/or otitis media, since they cause certain derangements in ciliary cleaning activities. This disease is usually inherited by autosomal recessive trait, but may also be found to be acquired or transient in rare cases after heavy exposure to pollutants, cigarette smoking or severe infection. We performed this study in children with frequently recurrent or persistent respiratory diseases to clarify if the ciliary abnormalities are preceding factors. METHODS: We enrolled 17 children with suspected respiratory ciliary abnormalities. The indications for evaluation of ciliary ultrastructure were recurrent or persistent respiratory infections. Children with immunologic abnormalities were excluded. From August 2000 to July 2003, we performed a biopsy on nasal mucosa and examined the structure of ciliary status by using an electron microscope. RESULTS: Of the subjects, there were seven males and 10 females, aged 2 to 10 years. Out of the 17 subjects, 12 cases of chronic paranasal sinusitis, nine chronic coughs, nine frequent upper respiratory infections, seven cases of recurrent otitis media, four cases of recurrent pneumonia, and four cases of bronchial asthma were found. Out of the 17 cases on which histologic examinations were conducted, four cases showed pathologic findings, including one case of inner dynein arm defect, one of microtubular transposition, one of supernumerous tubules, and one singlet, respectively. CONCLUSION: It is essential for differential diagnosis and effective treatment to identify the abnormalities of ultrastructure of nasal cilia in children with symptoms of frequently recurrent or persistent respiratory diseases, if immunodeficiency or respiratory allergy could be excluded.

DNA Methylation Change of IL-4 Gene from T Cell in Allergic Children / 소아과

PURPOSE: An understanding of the immunological process is required if primary prevention of atopic diseases is to be developed in early childhood. But, it is too hard to distinguish atopy from nonatopy under the age of two clinically, because the expression of phenotype and cytokines is vague in early childhood. We evaluated DNA methylation changes at Th2 interleukin-4 gene in peripheral blood from atopic children. METHODS: We selected 15 allergic children (mild: eight, moderate to severe: seven) and seven normal controls by using family allergy scores and clinical histories. We measured Total IgE and Der f II specific IgE levels and cultured peripheral blood mononuclear cells with Der f II stimulation and extracted DNA from Der f II specific T cells. We examined the change of CpG methylation in DNA from atopic and nonatopic children. RESULTS: In T cells from normal children, IL-4 DNA were predominantly methylated; otherwise, CpG demethylation occurred in Der f II specific T cells from allergic children. CONCLUSION: IL-4 DNA methylation changes occurred in T genes from allergic children and DNA methylation assay in early childhood.

Crucial Factors for Bronchial Hyperresponsiveness in Children with Mild Asthma / 소아알레르기및호흡기학회지

PURPOSE: Bronchial hyperresponsiveness (BHR) is one of the key components of childhood asthma phenotype. Patients with mild asthma may have coexisting severe BHR, although the reasons for this are uncertain. The factors of any relationship between BHR has been identified as a central issue in our understanding of asthma. METHODS: To investigate the factors that determine the presence of BHR in mild childhood asthmatics, 62 children (49 boys and 13 girls) with mild asthma were studied. Patients were characterized by skin prick tests, spirometry and bronchial challenge with methacholine. BHR to methacholine was expressed as the provocative methacholine concentration causing a 20 percent fall in FEV1 (PC20), PC20 value of 8 mg/mL was used as a cut-off for defining a BHR to methacholine. RESULTS: This cohort of 62 children with mild asthma was classified into two groups according to the results of methacholine challenge test (MCT). A positive MCT group was obtained for 33 subjects (53.2 percent). The proportion of children sensitized to house-dust mites (HDM) was significantly higher in the MCT-positive group than the negative one. Results showed a, a positive rate of skin prick test: 47% vs. 23% (P< 0.05) and HDM-specific IgE: 68% vs. 43% (P< 0.05). CONCLUSION: Asthmatics with positive MCT were clearly accompanied by increased sensitization to house-dust mites and reduced small airway calibers. Therefore, sensitization to common aeroallergens and changed small airway calibers might be crucial factors in the successful management of asthma.

A Case of Cold Urticaria Induced by Ice Cream in a 5-Year-Old Boy with Family History / 소아알레르기및호흡기학회지

Cold urticaria is characterized by the development of urticaria and/or angioedema after cold exposure. It is an uncommon form of physical urticaria and thought to be rare in children. There is a higher rate of family history of atopy and cold urticaria. We report a case of cold urticaria in a 5-years-old boy who showed perioral swelling, wheal and flare associated with ice cream. He had a relevant family history on his grandmother's side with cold urticaria, and on his father's side with dermographism, respectively. In this patient, cold urticaria was confirmed by ice cube test and a brief review followed.

Elevated Circulating ICAM-1 and Eosinophil Cationic Protein in Children with Chronic Urticaria / 소아과

PURPOSE: Chronic urticaria is characterized by recurrent, itchy, and evanescent wheals over a period of six weeks. The mechanisms of chronic urticaria in children have not been fully elucidated. However, urticaria lesions represent a dynamic inflammatory process involving a complex interplay of various inflammatory mediators, chemokines, adhesion molecules and cellular interaction. The aim of this investigation was to elucidate the possible role of intercellular adhesion molecule-1 (ICAM-1) in the promotion of eosinophil trafficking and the interaction of soluble ICAM-1 (sICAM-1) with eosinophil cationic protein (ECP) in chronic urticaria. METHODS: Twenty-three children with chronic urticaria and five healthy children were recruited into the study. Total IgE, sICAM-1 and ECP concentrations were measured in all the serum samples from the study subjects, and both skin prick tests and dermographisms were performed after counting peripheral blood eosinophil in each subject. RESULTS: Mean concentration of serum sICAM-1 was higher in the urticaria patient group than in the control (P<0.05), however, serum ECP levels were variable. In the urticaria group, there were statistically significant correlations between the levels of serum ICAM-1 and ECP (r=0.24, P<0.001), and between the levels of serum ICAM-1 and the grade of dermographism (r=0.313, P<0.001). On the other hand, serum ICAM-1 level was not significantly related to the number of peripheral blood eosinophil. CONCLUSION: These data suggest that ICAM-1 and ECP might play a certain important role in the cellular interactions of inflammation involved in chronic urticaria, and the role should be verified by further studies.

A Case of Anaphylactic Response to Factor lX Replacement Therapy in Hemophilia B Patient / 대한혈액학회지

We report a first korean case of anaphylactic response to factor lX replacement therapy in 22-month-old male hemophilia B patient. He was admitted to our hospital via emergency room due to anaphylactic response after factor lX infusion. Immediately after the infusion, he became dyspneic and cyanotic. The symptoms completely resolved after sleep. He represented same symptoms after next factor lX infusion, which completely resolved by the administration of oxygen. At the time of anaphylaxis, inhibitors of factor lX was demonstrated(8.8 Bethesda Unit). We planned him to treat with recombinant factor Vll or diluted factor lX at bleeding episode.

Comparative Study for the Diagnostic Usefulness of Brain MRI and CT in Children with Seizure / 대한소아신경학회지

PURPOSE: This study was performed to know and compare the diagnostic usefulness of Magnetic Resonance Imaging(MRI) and Computed Tomography(CT) for the evaluation of patients with seizure. METHODS: We studied retrospectively 96 children who visited Hanyang University Hospital due to seizure and took a brain CT between January 1996 and June 1999, and 60 children who visited Hanyang University Hospital due to seizure and took a brain MRI between June 1999 and March 2002. All children who were enrolled in this study divided into few groups according to seizure type and EEG findings. RESULTS: Among 96 children who took a brain CT, 12 patients had brain abnormalities on CT, and among 60 children took a brain MRI, 13 patients had brain abnormalities on MRI. Abnormalities on CT were more frequently seen in children with focal seizure and/or focal abnormalities on EEG, but contrarily in MRI, abnormalities were more frequently seen in children with generalized seizure. CONCLUSION: Even the MRI is more expensive to be taken than the CT, MRI isrecommended when there is a need to evaluate the causes of seizures even for thepatients with generalized seizure as a result of our study.

Comparative Study for the Diagnostic Usefulness of Brain MRI and CT in Children with Seizure / 대한소아신경학회지

PURPOSE: This study was performed to know and compare the diagnostic usefulness of Magnetic Resonance Imaging(MRI) and Computed Tomography(CT) for the evaluation of patients with seizure. METHODS: We studied retrospectively 96 children who visited Hanyang University Hospital due to seizure and took a brain CT between January 1996 and June 1999, and 60 children who visited Hanyang University Hospital due to seizure and took a brain MRI between June 1999 and March 2002. All children who were enrolled in this study divided into few groups according to seizure type and EEG findings. RESULTS: Among 96 children who took a brain CT, 12 patients had brain abnormalities on CT, and among 60 children took a brain MRI, 13 patients had brain abnormalities on MRI. Abnormalities on CT were more frequently seen in children with focal seizure and/or focal abnormalities on EEG, but contrarily in MRI, abnormalities were more frequently seen in children with generalized seizure. CONCLUSION: Even the MRI is more expensive to be taken than the CT, MRI isrecommended when there is a need to evaluate the causes of seizures even for thepatients with generalized seizure as a result of our study.

Differential Excretion of Urinary Eosinophil Protein X after Methacholine Challenge Test in Children with Asthma

PURPOSE: Eosinophil is one of the important inflammatory cell involved in the airway inflammation in childhood asthma. It has been demonstrated that markers of eosinophil activation, including eosinophil cationic protein or eosinophil protein X(EPX), are increased in childhood asthma. Furthermore, they are related to disease activity and are assumed to be helpful in monitoring the treatment effect as urinary EPX(U-EPX) can be obtained easily and in a noninvasive way in children of all ages. METHODS: Twenty-five children(22 male and three female) aged 11.87+/-3.82 years with stable asthma were challenged with methacholine and urine was collected from each child during the following periods; before methacholine challenge test(MCT); 0-3 hr after the end of MCT; 4-7 hr after the end of MCT; and 8-24 hr after the end of MCT. Bronchial reactivity was determined by using Dosimeter(Jeager, Germany) with serially diluted methacholine from 0.05 to 25.0 mg. The FEV1 less than 80% of baseline value were classified into positive MCT. U-EPX was measured with a sensitive and specific radioimmunoassay(Pharmacia & Upjohn AB, Uppsala, Sweden). Results were expressed as microgramEPX/mmol creatinine. RESULTS: An early airway response after MCT was associated with an increase of U-EPX excretion for 0-3 hr after methacholine inhalation in comparison with beseline values. Most subjects showed a small increase in U-EPX excretion during late asthmatic response for 4-7 hr, which then decreased to normal level in 8-24 hr. Also, a tendency for a higher increase of U-EPX was associated with a lower threshold of methacholine challenge and a longer duration of asthma. CONCLUSION: Measurement of EPX in urine is a noninvasive and easy method to assess the severity of airway inflammation in asthmatic children. It may be a helpful index of the events underlying the airway inflammatory responses during nonspecific bronchial challenge, and in monitoring asthma management.

Clinical Evaluation and Diagnosis of Children with Chest Pain

PURPOSE: Chest pain in the pediatric population is not rare and mostly benign. Causes of chest pain are diverse, and differential diagnosis is not easy. Chest pain in children is less likely to be cardiac in origin. Furthermore, chest pain in the pediatric population is rarely associated with life-threatening disease. This study was designed to evaluate children with chest pain and the usefulness of several diagnostic examinations. METHODS: Between March 2001 and August 2002, 33 patients(15 boys and 18 girls, aged four to 15 years) presented with chronic chest pain. The records of these patients were reviewed. Chest radiography and electrocardiogram were performed in all patients. Cardiologic and gastrointestinal evaluations were carried out when considered necessary. RESULTS: Chest pain was most common in the age group of 10 to 12 years old, and the four to six years old group. The most common diagnostic findings of chest pain were idiopathic(15 cases, 45.5 %), heart disease(9 cases, 27.3%), upper gastrointestinal disease(6 cases, 18.2%), respiratory disease (2 cases, 6%) and trauma(1 case, 3%). In children with abnormal results of cardiologic evaluation, these findings are not major etiologic categories of chest pain. Through history taking and physical examinations, six cases were evaluated concerning gastrointestinal disease and all of them showed gastrointestinal diseases(esophagitis, gastroesophageal reflux disease, nodular gastritis and chronic superficial gastritis). CONCLUSIONS: Chest pain is usually benign in children but the possibility of cardiovascular or gastrointestinal disease is considered. Careful history taking, physical examination and proper clinical examinations are usually required to find out the rare life-threatening causes of chest pain.

Relationship between airway hyperresponsiveness and duration of asthma in children / 천식및알레르기

BACKGROUND: Asthma is a chronic inflammatory disease. Clinical symptoms of asthmatics are triggered by various factors associated with allergic inflammation, airway remodeling and bronchial hyperreactivity, which were frequently related to the duration of asthma history. OBJECTIVES: To investigate the relationships between bronchial hyper-responsiveness and asthma duration thirty-five mild-to-moderate stable asthmatic children (28 boys and 7 girls), aged 6 to 18 years participated in this study. METHODS: By using cross-sectional analysis of data on variables as asthma duration, spiro-metry, results of bronchial responsiveness, symptomatology, and markers of atopy, univarate regression models were used to evaluate whether asthma duration was associated with asthma severity. Bronchial hyperresponsiveness to methacholine was expressed as provocative concentration of methacholine causing a 20% fall in FEV(1)[PC(20)mg/ml]. Exercise challenge consists of free outdoor running for 6 to 8 min at 80% of maximal predicted heart rate for age and a fall of 20% in FEV(1) associated with wheezing or cough was considered as positive. RESULTS: In all subjects methacholine and exercise challenge tests were performed, twenty-five children had atopic asthma(71.4%). Positive challenge tests were observed in 24 patients(68.6%) for methachol, 18(51.4%) for exercise, and 18(51.4%) for both, exercise in 18(51.4%) and both in 18(51.4%) of the 35 asthmatic children, respectively. In this cohort, the decrease of %FEV(1)/FVC was well correlated with the duration of asthma history. There was a significant relationship between %FEV(1)/FVC and %PEFR, %FEV(1), %FEF(25), %FEF(50), %FEF(75) or %MMEF(75/25). CONCLUSION: These data demonstrate that asthma duration is relevantly associated with lower lung function and greater responsiveness to both methacholine and exercise. Consequently, early intervention in childhood asthma management is definitely required.