Survey of diversity awareness and environment among members of the Pediatric Rheumatology Association of Japan.

BACKGROUND: Diversity management has gained traction in Japan. The Pediatric Rheumatology Association of Japan (PRAJ) has an Advisory Committee for Diversity Promotion with a broader focus on promoting diversity. The objectives of this study were to better understand the problems faced by PRAJ members regarding the work environment, childcare and nursing care, and work-life balance. METHODS: A web-based questionnaire was administered to members of the PRAJ and 79 responses were evaluated. RESULTS: Of the respondents, 73% were male and 27% were female. A total of 14% worked for more than 12 h on weekdays, and 22% worked for more than 60 h per week and 38% had fewer than 4 days off per month. Regarding childcare, 54% of the respondents were raising preschool children and 83% had taken parental leave for less than 1 year. A total of 17% of participants had family members in need of care. For both childcare and caregiving, the burden was greater for women. Only 18% of the respondents reported a well-balanced work-life balance, and the most common reasons for a lack of balance were not having enough time, heavy workload, and heavy housework load. CONCLUSIONS: The working hours of the respondents were long, and female members had a greater burden of childcare and caregiving, which was considered a barrier to the career development of women. In the future, there will be a need to promote a sense of equality in diverse human resources, develop support for family life, and shorten working hours.

Inappropriate secretion of fibroblast growth factor 23 despite hypophosphataemia with changes in bone turnover markers in a girl with systemic lupus erythematosus: Case report and review of the literature.

We report an 11-year-old girl with systemic lupus erythematosus (SLE) who showed hypophosphataemia (1.7 mg/dl, normal range: 3.9-5.8 mg/dl), a decrease in the tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (0.77 mg/dl, normal range: 3.4-5.6 mg/dl), and an elevated serum fibroblast growth factor 23 (FGF23) (circulating phosphate-regulatory hormone) concentration (FGF23: 282 pg/ml, normal range: <52 pg/ml) at the onset. The patient was treated with intravenous pulse methylprednisolone, oral prednisolone, mycophenolate mofetil, hydroxychloroquine, and phosphorus supplement. Serum FGF23 concentrations decreased to near the reference value at 5 months after the onset of SLE, and the TmP/GFR (4.61 mg/dl) simultaneously improved. The urinary deoxypyridinoline (bone resorption marker) concentration on admission (18.9 nmol/mmol creatinine, normal range: 75.4 ± 6.8 nmol/mmol creatinine) was greatly reduced, and the bone-type alkaline phosphatase (bone formation marker) concentration (30.6 µg/l, normal range: 58.6 ± 15.3 µg/l) was also reduced during the increase in FGF23 concentrations before steroid therapy was initiated. The reason for the inappropriate secretion of FGF23, despite hypophosphataemia, remains unknown. The findings in our case suggest that changes in bone turnover markers can occur in patients with SLE and excess inappropriate secretion of FGF23, despite severe and persistent hypophosphataemia.

The Difficulty of Diagnosing Kikuchi-Fujimoto Disease in Infants and Children Under Six Years Old: Case Report and Literature Review.

We came across a 20-month-old boy with Kikuchi-Fujimoto disease (KFD) who showed atypical symptoms that were difficult to diagnose. His symptoms were different from those experienced in common clinical KFD cases. Hence, we report his case presentation and review the literature on the difference in KFD symptoms between infants and young children (under six years of age), and school-age children (6 to 20 years). A 20-month-old boy was admitted to our hospital because of prolonged fever and an enlarged right axillary lymph node with pain. He developed erythema, which was like rubella, on the face, trunk, and upper and lower extremities. The rash soon disappeared after two days. The cervical lymph nodes were not palpable. Hepatomegaly and splenomegaly were palpable. Leukopenia and a decrease in platelets were seen in the blood count. Curiously, leukocytosis developed after leukopenia was first observed. Serology titers for several pathogens were negative. A CT scan of the lungs showed swelling of the mediastinal lymph nodes and interstitial pneumonia. The examination of a specimen of the axillary lymph node obtained by biopsy was compatible with KFD. English language reports on KFD were reviewed. Fourteen (14/335: 4.2%) cases in children under six years in addition to the current case and 321 (321/335: 95.8%) cases of school-age children (6-20 years) were found in the literature. Children of school age tend to more commonly be afflicted with KFD, which is characterized by pyrexia, leukopenia, and cervical lymphadenopathy with tenderness. Inversely, major symptoms of KFD patients under six years old were lesions of the lungs in three cases, leukocytosis in six cases, and generalized lymphadenopathy in eight cases, in contrast with symptoms of school-age children. It is concluded that leukocytosis, generalized lymphadenopathy in sites other than the cervical lymph nodes, and lesions of the lungs are characteristic symptoms of severe KFD in patients under six years old, for whom the occurrence is very rare.

Increases in Acute Phase Reactants in a Patient with Scurvy Despite No Inflammation: Review of Literature.

So far, little attention has been paid to the increase in acute phase reactants (APRs) in patients with scurvy. We report that elevated levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and serum amyloid A were shown in a pediatric patient with scurvy despite the absence of inflammation. These peculiar findings are important to discriminate scurvy from other rheumatic diseases.

Primary carnitine deficiency with severe acute hepatitis following rotavirus gastroenteritis.

Rotavirus infection is a major cause of gastroenteritis, which occurs mainly in children. Liver dysfunction due to rotavirus gastroenteritis has been reported; however, acute hepatitis due to this disease is very rare. We present a rare case in which rotavirus gastroenteritis led to sequential diagnosis of acute hepatitis and systemic primary carnitine deficiency (CDSP) in a 1-year-old girl. The patient's symptoms (hypoglycemia, hepatomegaly, and elevated levels of serum transaminases and creatinine kinase) suggested a steatosis causing liver dysfunction. She was initially considered to have a beta oxygenation defect or secondary carnitine deficiency caused by pivalic acid-containing antibiotics; however, repetitive carnitine analysis and free carnitine clearance measurement confirmed primary carnitine deficiency (carnitine transporter deficiency). Children with severe liver dysfunction due to rotavirus infection and presenting with liver steatosis should undergo blood acyl carnitine analysis to detect potential carnitine or other beta oxidation deficiencies, especially if newborn screening for these diseases is not available.

Low serum alkaline phosphatase activity in Kikuchi-Fujimoto disease.

Various laboratory findings are helpful in making a diagnosis of Kikuchi-Fujimoto disease (KFD); however, they are not specific. We found decreased serum alkaline phosphatase (SAP) activity in children with KFD. The levels of SAP fell in the acute phase and recovered during convalescence. We conclude that low SAP activity is a characteristic of KFD and may be an auxiliary diagnostic marker for the disease.

Invasive Community-Acquired Methicillin-Resistant Staphylococcus aureus in a Japanese Girl with Disseminating Multiple Organ Infection: A Case Report and Review of Japanese Pediatric Cases.

Pediatric invasive community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection is very serious and occasionally fatal. This infectious disease is still a relatively rare and unfamiliar infectious disease in Japan. We report a positive outcome in a 23-month-old Japanese girl with meningitis, osteomyelitis, fasciitis, necrotizing pneumonia, urinary tract infection, and bacteremia due to CA-MRSA treated with linezolid. PCR testing of the CA-MRSA strain was positive for PVL and staphylococcal enterotoxin b and negative for ACME. SCC mec was type IVa. This case underscores the selection of effective combinations of antimicrobial agents for its treatment. We need to be aware of invasive CA-MRSA infection, which rapidly progresses with a serious clinical course, because the incidence of the disease may be increasing in Japan.

Effect of dalteparin, a low-molecular-weight heparin, as adjunctive therapy in patients with Kawasaki disease: a retrospective study.

BACKGROUND: Dalteparin, a low-molecular-weight heparin, has anticoagulant and anti-angiogenic activity. This study investigated whether dalteparin reduced coronary artery lesion (CAL) prevalence, and resistance to intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD). METHODS: This retrospective study comprised two parts. In the first cohort, 126 patients with KD (68 male, 58 female; median age: 22 months, range: 1-67 months) admitted to Nihon University Nerima-Hikarigaoka Hospital from January 2004 to June 2008, received either dalteparin 75 IU/kg/day, IVIG 400 mg/kg/day for 5 consecutive days, and aspirin 30 mg/kg/day, or dalteparin 75 IU/kg/day and aspirin 30 mg/kg/day, until clinical improvement. Control data came from the 2005-6 Nationwide KD survey. In the second cohort, 112 patients with KD (59 male, 53 female; median age: 19 months, range: 1-66 months) admitted from June 2010 to February 2012, received either dalteparin 75 IU/kg/day, IVIG 2.0 g/kg over 12 h, and aspirin 30 mg/kg/day, or dalteparin 75 IU/kg/day and aspirin 30 mg/kg/day. Control data came from the 2009-10 Nationwide KD survey. No patients enrolled in the nationwide surveys received dalteparin. All patients at our institution were given dalteparin in their combination therapy. RESULTS: A comparison of the first cohort with controls in the nationwide survey showed that the prevalence of initial administration of IVIG was 80.2% versus 86.0%; the rate of additional IVIG administration was 7.1% versus 14.0% (p = 0.03); CAL prevalence in the acute period was 4.8% versus 11.9% (p < 0.01); and the prevalence of cardiovascular sequelae was 0% versus 3.8% (p < 0.05). A comparison of the second cohort with controls in the nationwide survey showed that the rate of initial administration of IVIG was 92.9% versus 89.5%; the rate of additional IVIG administration was 8.9% versus 17.1% (p = 0.02); the prevalence of resistance to IVIG was 3.6% versus 14.9% (p < 0.001); and CAL prevalence in the acute period was 2.7% versus 8.6% (p = 0.03). CONCLUSIONS: This study found that adjunctive dalteparin was associated with a lower prevalence of IVIG resistance and CAL in young children with KD. TRIAL REGISTRATION UMIN-CTR: UMIN000010349.

Compound heterozygous mutations in SLC30A2/ZnT2 results in low milk zinc concentrations: a novel mechanism for zinc deficiency in a breast-fed infant.

Zinc concentrations in breast milk are considerably higher than those of the maternal serum, to meet the infant's requirements for normal growth and development. Thus, effective mechanisms ensuring secretion of large amounts of zinc into the milk operate in mammary epithelial cells during lactation. ZnT2 was recently found to play an essential role in the secretion of zinc into milk. Heterozygous mutations of human ZnT2 (hZnT2), including H54R and G87R, in mothers result in low (>75% reduction) secretion of zinc into the breast milk, and infants fed on the milk develop transient neonatal zinc deficiency. We identified two novel missense mutations in the SLC30A2/ZnT2 gene in a Japanese mother with low milk zinc concentrations (>90% reduction) whose infant developed severe zinc deficiency; a T to C transition (c.454T>C) at exon 4, which substitutes a tryptophan residue with an arginine residue (W152R), and a C to T transition (c.887C>T) at exon 7, which substitutes a serine residue with a leucine residue (S296L). Biochemical characterization using zinc-sensitive DT40 cells indicated that the W152R mutation abolished the abilities to transport zinc and to form a dimer complex, indicating a loss-of-function mutation. The S296L mutation retained both abilities but was extremely destabilized. The two mutations were found on different alleles, indicating that the genotype of the mother with low milk zinc was compound heterozygous. These results show novel compound heterozygous mutations in the SLC30A2/ZnT2 gene causing zinc deficiency in a breast-fed infant.

Successful combination treatment of a patient with progressive juvenile localized scleroderma (morphea) using imatinib, corticosteroids, and methotrexate.

We report a case of progressive juvenile localized scleroderma (JLS or morphea) treated with a combination of imatinib, corticosteroids, and methotrexate. This therapy halted the progressive skin thickening and the hand and finger joint deformity in the early stages of the disease. We conclude that imatinib used in addition to standard treatment with systemic corticosteroids and methotrexate may be of therapeutic benefit for individuals with JLS.

A 4-year-old girl with clinically mild encephalopathy with a reversible splenial lesion associated with rotavirus infection.

Rotavirus is a common cause of severe gastroenteritis in children. It is known that rotavirus gastroenteritis may be accompanied by neurological manifestations, including encephalitis/encephalopathy and seizures. We report a case of a 4-year-old girl with clinically mild encephalopathy with a reversible splenial lesion associated with rotavirus infection. She was admitted to our hospital because of reduced level of consciousness, seizures, diarrhea, and vomiting. Fecal rotavirus antigen testing was positive. Cell counts in the cerebrospinal fluid (CSF) were normal. She had a normal serum sodium level on admission. Brain computed tomography showed no cerebral edema. However, electroencephalography showed generalized high-voltage slow waves, and diffusion-weighted magnetic resonance imaging demonstrated a transient abnormality in the splenium of the corpus callosum. We diagnosed clinically mild encephalopathy with a reversible splenial lesion associated with rotavirus infection. She recovered well and exhibited no neurological sequelae. Rotavirus RNA and antigen were not detected in the CSF, suggesting that the reversible splenial change was caused by indirect effects on the central nervous system subsequent to viral infection. Her normal serum sodium level indicates that this change can occur without hyponatremia.

Acute encephalopathy with pandemic (H1N1) 2009 virus infection.

OBJECTIVES: In April 2009, a novel influenza A (H1N1) pdm virus was identified in Mexico and spread quickly around the world. However, the clinical features of acute encephalopathy associated with 2009 pandemic influenza have not yet been elucidated. METHODS: We treated 8 patients (3 boys and 5 girls) aged 4 to 11 years (average age, 8 y 3 months) with influenza virus-associated encephalopathy, who presented at our 2 hospitals between July 2009 and March 2010. We investigated the clinical characteristics, treatments, and outcomes in the patients. RESULTS: In all patients, brain computed tomography showed mild to severe diffuse cerebral edema, and electroencephalography revealed diffuse high-voltage slow waves. They were all treated with oseltamivir and methylprednisolone pulse therapy. Six patients recovered without any sequelae; however, the remaining 2 had residual neurological sequelae. These 2 patients presented with severe disturbance of consciousness, and their central nervous system symptoms appeared within 12 hours after the onset of fever. One patient had periventricular leukomalacia and symptomatic epilepsy by perinatal brain hypoxia, and the other patient had 1 complex febrile and 2 febrile seizures. CONCLUSIONS: This study showed that patients with influenza-associated encephalopathy caused by influenza A (H1N1) pdm infection were all older than those with seasonal influenza. Underlying neurological disease or history may be associated with poor prognosis.

Posterior reversible encephalopathy syndrome in childhood: report of four cases and review of the literature.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a recently described disorder with typical radiological findings of bilateral gray and white matter abnormalities in the posterior regions of the cerebral hemispheres and cerebellum. Its clinical symptoms include headache, decreased alertness, mental abnormalities such as confusion, diminished spontaneity of speech, and changed behavior ranging from drowsiness to stupor, seizures, vomiting, and abnormalities of visual perception such as cortical blindness. In this study, the clinical and radiological findings of 4 children with this syndrome due to a variety of conditions are reported. METHODS: The records of 4 children with a diagnosis of PRES were retrospectively analyzed. RESULTS: PRES is associated with a disorder of cerebrovascular autoregulation of multiple etiologies. Four patients with PRES who had primary diagnoses of severe aplastic anemia, nephritic syndrome, Henoch-Schönlein purpura, and acute poststreptococcal glomerulonephritis are presented. This syndrome has been described in numerous medical conditions, including hypertensive encephalopathy, eclampsia, and with the use of immunosuppressive drugs. CONCLUSIONS: Early recognition of PRES as a complication during different diseases and therapies in childhood may facilitate precise diagnosis and appropriate treatment.

Child-onset systemic sclerosis positive for anticentromere antibodies: two Japanese cases.

Systemic sclerosis (SSc) is an uncommon connective tissue disease of childhood. Moreover, pediatric SSc positive for anticentromere antibodies (ACA) is extremely rare. We describe two cases of ACA-positive SSc in Japanese girls with clinical findings. Case 1 is a 15-year-old female. From disease onset at 7 years, she developed limited cutaneous (no internal involvement) SSc positive for ACA and anti-U1RNP antibodies, but negative for antitopoisomerase I antibodies (ATA). She also showed calcinosis, sclerodactyly, and telangiectasia, but not Raynaud's phenomenon. Case 2 is also a 15-year-old female with onset at the same age. Her diagnosis was limited cutaneous SSc positive for ACA, anti-SSA/Ro antibodies, and anti-thyroid antibodies, but not ATA. She showed sclerodactyly, telangiectasia, and Raynaud phenomenon, as well as complicated Sjögren's syndrome and chronic thyroiditis with euthyroidism. We reported that two Japanese girls with SSc were positive for ACA and other antibodies with the exception of ATA.

A 7-year-old girl with subcutaneous emphysema, pneumomediastinum, pneumothorax, and pneumoretroperitoneum caused by Mycoplasma pneumoniae pneumonia.

A 7-year-old girl presented with subcutaneous emphysema, pneumomediastinum (PM), pneumoretroperitoneum, and pneumothorax caused by Mycoplasma pneumoniae (MP). The patient had been treated with clarithromycin for pneumonia at another hospital; however, her condition deteriorated and complications developed. Soon after admission to our hospital, we started the patient on minocycline and prednisolone, and the complications improved promptly. Laboratory data showed serum ferritin and urinary beta-2-microglobulin levels were greatly elevated. We therefore speculated that the patient might have underlying hypercytokinemia. Prednisolone is an effective treatment for hypercytokinemia. We therefore recommend prednisolone treatment for cases of severe M. pneumoniae pneumonia that do not respond to antimicrobial agents.

A 5-year-old boy with atrophic autoimmune thyroiditis caused by thyroid-stimulation blocking antibodies.

A 5-year-old boy was presented for a growth disturbance, which was initially noted at 3 years of age. Endocrinological testing identified severe hypothyroidism, defined by the following levels: TSH 990.5 microU/mL, F-T3 0.26 pg/mL, and F-T4 0.09 ng/dL. Serum anti-thyroid peroxidase (TPO) antibodies were 158 IU/mL and serum thyroid-stimulation blocking antibodies (TSBab) levels were 82.1 IU/mL (normal range < 45.6). Thyroid scintigraphy with 99mTc showed markedly decreased uptake, and magnetic resonance imaging (MRI) revealed pituitary hyperplasia. He was diagnosed with atrophic autoimmune thyroiditis. His thyroid function and pituitary size normalized following thyroid hormone replacement therapy. We report a rare case of a young boy with atrophic thyroiditis caused by TSBab.

Serum vitamin D concentrations and associated severity of acute lower respiratory tract infections in Japanese hospitalized children.

BACKGROUND: Vitamin D is an immunomodulatory molecule related to innate immunity that may contribute to the increased occurrence of acute lower respiratory infection (ALRI) in children, one of the most common reasons for hospitalization and intensive care unit admission. In the present study, the association between vitamin D deficiency and the severity of respiratory infection was evaluated by determining serum concentrations of 25-hydroxyvitamin D (25(OH)D) in a group of hospitalized children with ALRI. METHODS: Of the 28 children admitted to Nihon University Nerima-Hikarigaoka Hospital with ALRI over the period November 2008­May 2009, 26 were diagnosed as having bronchiolitis and two were found to have pneumonia. A competitive protein binding radioimmunoassay was used to determine serum 25(OH)D concentrations. RESULTS: Mean 25(OH)D concentrations in breast-fed children with ALRI (n = 7) were significantly lower than those in children with ALRI who were bottle fed/weaned (n = 6) or on a regular diet (n = 15; 14.6 ± 9.7, 28.9 ± 6.9 and 24.6 ± 8.8 ng/mL, respectively). There was a significant correlation between vitamin D deficiency (<15 ng/mL) and the need for supplementary oxygen and ventilator management. CONCLUSION: Significantly more children with ALRI who needed supplementary oxygen and ventilator management were vitamin D deficient. These findings suggest that the immunomodulatory properties of vitamin D may influence the severity of ALRI.