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THE JOURNAL OF THE JAPAN PEDIATRIC SOCIETY

Vol.124, No.10, October 2020


Original Article
1. Influence of Revisions in the Japanese Diagnostic Guidelines (6th Revised Edition) on the Diagnosis of Kawasaki Disease
2. Survey on the Current Choice of Status Epilepticus in Childhood since the Publication of Treatment Guidelines 2017 for Pediatric Status Epilepticus and Requests for Revision
3. Safety and Efficacy of Pitavastatin for the Treatment of Familial Hypercholesterolemia in Childhood
Case Report
1. Congenital Central Hypoventilation Syndrome with Mild Phenotype, Based on Respiratory Physiological Test Results, Caused by Non-polyalanine Repeat Expansion Mutation
2. Plasma Exchange Therapy for Kawasaki Disease with Clinically Mild Encephalitis/Encephalopathy with a Reversible Splenial Lesion
3. A Case of Moyamoya Disease in an Infant with a Homozygous Variant in the RNF213 p.R4810K〜Suggestions for Subsequent Siblings〜
4. Streptococcal Toxic Shock Syndrome Arising from a Site of Intramuscular Vascular Malformation: Two Case Reports
5. Successful Use of Daptomycin for Acute Pediatric Osteomyelitis Caused by Methicillin-resistant Staphylococcus aureus
6. Intussusception with Idiopathic Pneumatosis Cystoides Intestinalis


Original Article
Title
Influence of Revisions in the Japanese Diagnostic Guidelines (6th Revised Edition) on the Diagnosis of Kawasaki Disease
Author
Sayaka Fukuda1) Hiroaki Konno1) Shun Matsumoto1) Taishi Nada1) Mari Iwamoto1) and Shuichi Ito2)
1)Department of Pediatrics, Saiseikai Yokohamashi Tobu Hospital
2)Department of Pediatrics, Graduate School of Medicine, Yokohama City University
Abstract
In the Japanese diagnostic guidelines for Kawasaki disease (KD) revised in May 2019, redness of the BCG site was introduced in skin symptoms and the duration of fever longer than 5 days was abolished. We assumed this revision to be influential. In total, 176 patients with KD diagnosed under the 5th edition guidelines in our hospital were re-evaluated. According to the 5th edition, complete and incomplete KD was present in 128 and 48 patients, respectively. In the 6th edition, the number of positive diagnostic criteria increased in 20 patients (11.4%), and 8 patients (4.5%) were converted from incomplete to complete KD. Regarding 75 infants between the ages of 6 months to 2 years, the most frequent age of onset, 13 patients (17.3%) had increased positive symptoms while 6 incomplete-KD patients (8.0%) were reclassified as complete KD. BCG-site redness preceded polymorphous exanthema in 25 patients (14.2%), but 38 (21.6%) developed these two symptoms simultaneously. Three patients were newly given a diagnosis of coronary artery lesion (CAL) according to new criteria for CAL using Z score (≥2.5). This revision will influence the diagnosis of KD, especially in small infants. The additional criterion of BCG-site redness as a principal symptom could be especially meaningful for diagnosis.




Original Article
Title
Survey on the Current Choice of Status Epilepticus in Childhood since the Publication of Treatment Guidelines 2017 for Pediatric Status Epilepticus and Requests for Revision
Author
Kenjiro Kikuchi Shin-ichiro Hamano Ryuki Matsuura Hazuki Nonoyama Atsuro Daida Yuko Hirata and Reiko Koichihara
Division of Neurology, Saitama Children's Medical Center
Abstract
Purpose: We surveyed the current choice of status epilepticus (SE) since the publication of Treatment Guidelines 2017 for Pediatric SE in addition to requests for revision.
Methods: We conducted a questionnaire survey among doctors who had participated in lectures about SE. The questions were as follows: 1) the first to fourth choice of intravenous antiepileptic drugs (AEDs) for SE, 2) choice of non-intravenous AEDs, 3) choice of intravenous AEDs against benzodiazepine resistant SE, 4) requests for revision of Treatment Guidelines 2017.
Results: We analyzed 209 responses. As the first choice of AEDs, 49% chose diazepam and midazolam; 38% chose Midazolam and phenytoin/fosphenytoin as the second choice, respectively. As the third choice, 36% chose phenobarbital, and 35% chose phenytoin/fosphenytoin; and; 27% chose barbiturate and 23% chose phenytoin/fosphenytoin as the fourth-choice, respectively. Midazolam® and Dormicum® were chosen as non-intravenous AEDs by 59% of respondents. Against benzodiazepine resistant SE, phenytoin/fosphenytoin was chosen by 46% and phenobarbital by 28% of respondents. Regarding items for revision, treatment flowchart, criteria of the first and second choice of AEDs, and documentation of off-label use of AEDs were requested.
Conclusion: The current choice of AEDs for pediatric SE was almost the same as that of the 2017 Guidelines. Convenient figures illustrating treatment for SE and explanation of off-label use of AEDs are expected for revision.




Original Article
Title
Safety and Efficacy of Pitavastatin for the Treatment of Familial Hypercholesterolemia in Childhood
Author
Akira Ohtake1) Takashi Kanno2) Yuji Kurihara2) Shoko Fujii2) Wataru Shingaki2) and Ryoji Gunji2)
1)Department of Pediatrics, Saitama Medical University
2)Post Marketing Surveillance Department, Kowa Company, Ltd.
Abstract
Background: Pitavastatin is the first statin to be approved for the treatment of children with familial hypercholesterolemia (FH) in Japan. Although the latest guideline recommends statin drugs as first-line treatment for pediatric FH, the long-term safety and efficacy of pitavastatin in real-world clinical practice remains unclear.
Methods: We conducted an all-case, post-marketing surveillance study of children with FH aged 10-14 years who started treatment with pitavastatin within 2 years of its approval. During the observation period of up to 3 years, safety and efficacy data, including drug-related adverse events, changes in physical growth parameters and laboratory values, and changes in low density lipoprotein-cholesterol (LDL-C) values, were collected.
Results: In the 99 patients included in the safety analysis set, male to female ratio was 1 to 1 (mean age 11.8 years) and mean LDL-C level was 215.0 mg/dL. During the observation period (687 days in average), 7 (7.1%) patients exhibited drug-related adverse events, such as headache, liver disorder, and increase in blood creatine kinase. Neither serious drug-related adverse events (e.g., rhabdomyolysis) nor concerns regarding physical growth/pubertal development were identified. The mean LDL-C level at the time of the last observation was 157.9 mg/dL, and a significant decrease in LDL-C level (23.2% in average) from baseline was observed. The proportion of patients who achieved the target LDL-C level (<140 mg/dL) was 30.6%.
Conclusion: We concluded that there are no significant issues requiring attention in the long-term safety and efficacy of pitavastatin in Japanese children with FH.




Case Report
Title
Congenital Central Hypoventilation Syndrome with Mild Phenotype, Based on Respiratory Physiological Test Results, Caused by Non-polyalanine Repeat Expansion Mutation
Author
Megumi Yamada1) Sayu Oomori1) Yosuke Yamada2) Hisaya Hasegawa2) Ayako Sasaki3) Kiyoshi Hayasaka3) and Seiji Sato4)
1)Department of Neonatology, Saitama City Hospital
2)Department of Neonatology, Tokyo Women's Medical University Medical Center East
3)Department of Pediatrics, Yamagata University School of Medicine
4)Department of Pediatrics, Saitama City Hospital
Abstract
We report a case of congenital central hypoventilation syndrome (CCHS). The patient was a female neonate born at 35 weeks and 2 days of gestation with a birth weight of 2,070 g. At birth, she was found to have periodic respiration, apnea, and hypercapnia. Premature birth was initially suspected to be the cause of hypoventilation. However, her prolonged hypercapnia led to a suspicion of CCHS. Genetic testing revealed a partial deletion of PHOX2B gene (c.663_711del), confirming the diagnosis of CCHS. A majority (90%) of mutations found in CCHS are polyalanine repeat expansion mutations (PARMs) and the remaining 10% are non-PARMs (NPARMs). It is widely recognized that patients with NPARMs tend to have a severe phenotype. However, in the present case of CCHS, the patient had an NPARM and exhibited mild clinical and physiological symptoms. This atypical case of CCHS caused by an NPARM should serve as an important reference when exploring the genotype-phenotype correlation.




Case Report
Title
Plasma Exchange Therapy for Kawasaki Disease with Clinically Mild Encephalitis/Encephalopathy with a Reversible Splenial Lesion
Author
Hidehiro Mori1) Mariko Sawada1) Kazuhisa Sato1) Kayo Ogino1) Tomohiro Hayashi1) Aya Kodera2) Kenji Waki1) and Yoshio Aragaki1)
1)Department of Pediatics, Kurashiki Central Hospital
2)Department of Pediatics, National Hospital Organization Fukuyama Medical Center
Abstract
Kawasaki disease (KD) presents with various symptoms, and herein, we report our encounter with a case of KD with encephalitis and encephalopathy.
The patient was a 2-year-old boy who developed fever and was given a diagnosis of KD on Day 6 of his illness. Intravenous immunoglobulin (IVIG) had been administered at the previous hospital. However, on Day 7 of his illness, he became uneasy and drowsy, and clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) was diagnosed based on his symptoms and head magnetic resonance imaging (MRI) findings. His fever and disturbance of consciousness did not improve despite the use of steroid pulse therapy as second-line therapy, and dilated coronary arteries were present. He was transferred to our hospital on Day 10 of his illness and initiated plasma exchange (PE). PE was implemented every day for 5 days. On Day 19 of his illness, his fever resolved and coronary artery diameter normalized. On Day 27 of his illness, his consciousness was clear, no abnormal neurological findings were observed, and no abnormal head MRI findings were noted.
Patients with KD with MERS might have a high risk of developing coronary artery lesions (CALs). In this case, PE was performed for KD with MERS, and treatment was possible without retaining CALs or neurological abnormalities. It was suggested that PE may be effective in IVIG-refractory KD cases with encephalitis and encephalopathy.




Case Report
Title
A Case of Moyamoya Disease in an Infant with a Homozygous Variant in the RNF213 p.R4810K〜Suggestions for Subsequent Siblings〜
Author
Yuta Sakai1) Yasuhiro Ikawa1) Keigo Nishida1) Naohisa Fujita1) Asumi Jinkawa1) Natsumi Inoue1) Mondo Kuroda1) Akihiro Yachie1) Iku Nanbu2) Koichi Misaki2) Masanao Mori2) Mitsutoshi Nakada2) and Taizo Wada1)
1)Department of Pediatrics, Kanazawa University Hospital
2)Department of Neurosurgery, Kanazawa University Hospital
Abstract
Moyamoya disease (MD) is a progressive cerebrovascular obstruction. A homozygous variant in the ring finger protein 213 (RNF213) p.R4810K is a major variant in the RNF213 gene which is involved in the development of MD onset in infancy. Therefore, genetic testing might be effective for the early diagnosis of MD. We encountered a case of MD in an infant boy. At the time of diagnosis, his mother was pregnant. If the RNF213p.R4810K variant was involved with his disease, his subsequent sibling could develop MD. Therefore, the child and his parents underwent genetic testing. The results revealed the presence of homozygous and heterozygous variant in the child and his parents, respectively. If a homozygous variant was confirmed in the subsequent sibling, the advantage of performing regular imaging tests and receiving a revascularization operation at the optimal time point would be apparent. Therefore, we performed genetic testing on the subsequent sibling immediately after birth. The results showed a heterozygous variant, therefore no active intervention was performed. Here, we report a case of MD with onset in infancy. The confirmation of a homozygous variant in the RNF213 p.R4810K may be suggested as an effective tool for subsequent siblings.




Case Report
Title
Streptococcal Toxic Shock Syndrome Arising from a Site of Intramuscular Vascular Malformation: Two Case Reports
Author
Akiko Ando Yuki Ueda Sho Kato Osamu Kawano Takashi Suganuma Makoto Mikawa and Tomonobu Sato
Department of Pediatrics, Kitami Red Cross Hospital
Abstract
Here, we present the cases of two children with congenital intramuscular vascular malformations who developed swelling and pain at the same sites following group A β-hemolytic Streptococcus infection, which subsequently progressed to Streptococcal toxic shock syndrome (STSS). Case 1 was a 6-year-old girl who presented with disseminated intravascular coagulation, septic encephalopathy, and necrotizing fasciitis requiring left-upper-limb amputation. Case 2 was a 6-year-old girl who suffered from septic encephalopathy and soft-tissue necrosis; we were able to save her life by performing debridement involving the sites of vascular malformation. Both cases exhibited central nervous system symptoms such as convulsions and disturbance of consciousness within approximately 40-50 hours of onset of local symptoms. In patients with congenital intramuscular vascular malformations who complain of fever and local soft-tissue inflammation, STSS should be considered, and early treatment including debridement should be actively performed to improve the prognosis.




Case Report
Title
Successful Use of Daptomycin for Acute Pediatric Osteomyelitis Caused by Methicillin-resistant Staphylococcus aureus
Author
Akira Oshima1) Yuko Tatsuno1) Makiko Kitao1) Mayu Yamamoto1) Akiko Hayashi1) Yasuhiro Ichikawa1) Miho Sato1) Rui Kato2) Hiroyuki Shimizu3) and Hiroyuki Machida1)
1)Yokosuka Kyosai Hospital, Department of Pediatrics
2)Yokosuka Kyosai Hospital, Department of Orthopedics
3)Fujisawa City Hospital, Department of Clinical Laboratory Medicine
Abstract
There are few reports regarding the efficacy of daptomycin (DAP) for the treatment of acute pediatric osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA). We report such a case treated with DAP due to adverse reaction to vancomycin (VCM). An 8-year-old boy was admitted due to fever >38Cº, pain in the left knee, gait disorder, and gram-positive cocci detected in two blood cultures. Body temperature was 39.6Cº. Redness and pain were observed on the caudal side of the left knee. Based on simple MRI findings of the lower extremities, we diagnosed acute tibial osteomyelitis. After hospitalization, MRSA was detected in blood cultures, and VCM and clindamycin were administered. Nevertheless, MRSA bacteremia persisted, and bone curettage was performed. Thereafter, he became afebrile and blood cultures were negative. However, erythema worsened following each administration of VCM. Adverse reaction to VCM was suspected and treatment was switched to DAP. Examination showed positivity for the drug lymphocyte stimulation test. DAP was administered for 5 weeks without adverse events. He recovered without relapse or recurrence and was discharged. DAP may be an option for the treatment of MRSA osteomyelitis when other anti-MRSA drugs cannot be administered.




Case Report
Title
Intussusception with Idiopathic Pneumatosis Cystoides Intestinalis
Author
Hiroaki Sammori Akiko Kinumaki and Hiroshi Hataya
Department of General Pediatrics, Tokyo Metropolitan Children's Medical Center
Abstract
Right lower quadrant abdominal pain, a common symptom in pediatric medicine, is rarely due to intussusception associated with pneumatosis cystoides intestinalis (PCI). Intussusception associated with PCI was diagnosed by X-ray and computed tomography (CT) in two patients at our hospital. The X-ray showed multiple, air-filled cysts along the ascending colon, and CT revealed the presence of cysts and intussusception in the intestinal wall. However, detecting intussusception with ultrasonography was difficult due to the presence of air in the cysts. Both cases were treated with hydrostatic reduction, and the PCI was treated with high flow oxygen therapy, after which the cysts resolved almost completely. In both instances, however, the PCI recurred and both developed intussusception again after one year. Each intussusception was treated with normal saline hydrostatic reduction. Intussusception associated with PCI is rare, and surgery is the treatment of choice in most cases. The clinical course of the present two cases suggests that nonsurgical reduction is indicated as the primary intervention and that unnecessary surgery should be avoided. The effectiveness of oxygen therapy for PCI requires further research for verification.




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