Aya Inaba

Acute encephalopathy of Bacillus cereus mimicking Reye syndrome

We present an 11-year-old boy diagnosed as having acute encephalopathy and liver failure with the underlying condition of a metabolic dysfunction. He developed convulsions and severe consciousness disturbance following gastroenteritis after the ingestion of some fried rice. He showed excessive elevation of transaminases, non-ketotic hypoglycemia and hyperammonemia, which were presumed to reflect a metabolic dysfunction of the mitochondrial beta-oxidation, and he exhibited severe brain edema throughout the 5th hospital day. He was subjected to mild hypothermia therapy for encephalopathy, and treated with high-dose methylprednisolone, cyclosporine and continuous hemodiafiltration for liver failure, systemic organ damage and hyperammonemia. The patient recovered with the sequela of just mild intelligence impairment. In this case, Bacillus cereus, producing emetic toxin cereulide, was detected in a gastric fluid specimen, a stool specimen and the fried rice. It was suggested that the cereulide had toxicity to mitochondria and induced a dysfunction of the beta-oxidation process. The patient was considered as having an acute encephalopathy mimicking Reye syndrome due to food poisoning caused by cereulide produced by B. cereus.

A Report of Two Cases of Kawasaki Disease Treated With Plasma Exchange

Abstract:  Kawasaki disease is a generalized vasculitis of unknown etiology that occurs predominantly in infants and young children. It is very important to prevent its cardiovascular manifestations, especially coronary artery lesions. Early treatment with intravenous immunoglobulin reduces cardiovascular sequelae, but some patients do not respond to this treatment, and they have a high incidence of coronary artery lesions. On the other hand, acute heart failure is rare in Kawasaki disease. We report on the cases of two patients with persistent fever and shock even after intravenous immunoglobulin therapy. In both cases, plasma exchange may have reduced the risk of coronary artery lesions and proved effective against acute heart failure with catecholamine‐refractory shock; yet the mechanism of this improvement remains unclear.

Molecular genetic analysis of 30 families with Joubert syndrome

Joubert syndrome (JS) is rare recessive disorders characterized by the combination of hypoplasia/aplasia of the cerebellar vermis, thickened and elongated superior cerebellar peduncles, and a deep interpeduncular fossa which is defined by neuroimaging and is termed the ‘molar tooth sign’. JS is genetically highly heterogeneous, with at least 29 disease genes being involved. To further understand the genetic causes of JS, we performed whole‐exome sequencing in 24 newly recruited JS families. Together with six previously reported families, we identified causative mutations in 25 out of 30 (24 + 6) families (83.3%). We identified eight mutated genes in 27 (21 + 6) Japanese families, TMEM67 (7/27, 25.9%) and CEP290 (6/27, 22.2%) were the most commonly mutated. Interestingly, 9 of 12 CEP290 disease alleles were c.6012‐12T>A (75.0%), an allele that has not been reported in non‐Japanese populations. Therefore c.6012‐12T>A is a common allele in the Japanese population. Importantly, one Japanese and one Omani families carried compound biallelic mutations in two distinct genes (TMEM67/RPGRIP1L and TMEM138/BBS1, respectively). BBS1 is the causative gene in Bardet–Biedl syndrome. These concomitant mutations led to severe and/or complex clinical features in the patients, suggesting combined effects of different mutant genes.

Toxic shock syndrome toxin‐1‐mediated exanthematous disease in a burned infant

Toxic exanthem is a common problem in the pediatric practice setting. Some cases can be attributed to viral infection and others to drug allergy, but several cases are of unknown etiology. Recently, we had a case in which a scalded infant presented with toxic exanthem mediated by toxic shock syndrome toxin-1 (TSST-1). TSST-1, secreted by Staphylococcus aureus , acts as a super antigen and activates polyclonal V 2 + T cells, causing toxic shock syndrome (TSS). 1 Several cases of TSS in burned children have been reported, 2 – 4 but no studies, except one in a non-burned infant, 5 have reported only toxic exanthem. In the present report we propose a possible etiology of toxic exanthem and describe the usefulness of fl ow cytometry analysis as a diagnostic modality.

Elevated d-Dimer Level is a Risk Factor for Coronary Artery Lesions Accompanying Intravenous Immunoglobulin-Unresponsive Kawasaki Disease

Although there are many reports on the resistance of Kawasaki disease (KD) to initial intravenous immunoglobulin (IVIg) therapy, risk factors for coronary artery lesions in such cases remain to be established. The objective of this study was to explore when additional therapies should be administered and to identify factors helpful for selecting a therapeutic option. Based on their written clinical records, we performed a retrospective review of KD patients who did not respond to initial IVIg therapy and who therefore then underwent plasma exchange (PE) therapy. This was a case‐control study to compare the presence or absence of acute coronary lesions in patients treated by PE for IVIg‐unresponsive KD at Yokohama City University Hospital or at Yokohama City University Medical Center. Fifteen of 44 patients had acute coronary artery lesions (CAL) correlating with high levels of white blood cells (WBC) (P = 0.045), d‐dimer (P = 0.008), and fibrin/fibrinogen degradation products (P = 0.009) and lower levels of fibrinogen (P = 0.013) prior to PE therapy. There was a strong correlation between pre‐PE levels of albumin and d‐dimer (Pearsons correlation coefficient of 0.610). Multivariate analyses revealed that the odds ratio for CAL when d‐dimer was ≥ 4.5 μg/mL was 25.06 (95% CI, 2.56–244.91, P = 0.006). d‐dimer elevation and albumin decline in IVIg‐unresponsive KD patients could be risk factors for acute CAL, suggesting the possibility that angitis has spread throughout the arterial system, as far as the coronary artery.

Efficacy of mycophenolate mofetil for steroid and cyclosporine resistant membranoproliferative glomerulonephritis type I

Sirs, We read with great interest the article entitled “Remission of resistant MPGN type I with mycophenolate mofetil and steroids” by De et al. [1]. We encountered a similar case and would like to comment on the efficacy of mycophenolate mofetil (MMF) for refractory membranoproliferative glomerulonephritis (MPGN) type I. A 13-year-old boy was transferred to our hospital because of steroid-resistant nephrotic syndrome with hypocomplementemia. He had been treated with 2 mg/kg of prednisolone (PSL) for 4 weeks, but systemic edema, massive proteinuria and hypertension had not improved. When he was admitted to our hospital, the results of urinalysis were: protein 2,498 mg/dl, creatinine 399 mg/dl, β2 microglobulin 5,691 μg/dl (normal <250 μg/dl), and red blood cell (RBC) count over 50 per high-power field (HPF). Those of blood biochemistry were: 4.4 g/dl of total protein, albumin 2.0 g/dl, serum creatinine 0.83 mg/dl, blood urea nitrogen 33 mg/dl, uric acid 7.3 mg/dl, total cholesterol 404 mg/dl, triglycerides 296 mg/dl, complement (C)3 21 mg/dl (86~160 mg/dl), C4 21 mg/dl (17~45 mg/dl), CH50 20 U/ml (30~40 U/ml), anti-nuclear antibody (negative), and anti-double stranded DNA antibody (negative). Renal biopsy showed diffuse and severe MPGN type I. All the glomeruli showed marked lobulation, intracapillary hypercellularity, thickening of the capillary walls and double contour. Immunofluorescence showed intense staining of all capillary walls and mesangial cells with C3 and immunoglobulin (Ig)G. An electron micrograph showed electron-dense deposits only in the subendothelial space. The patient was initially treated with three courses of methyl prednisolone pulse therapy (MPT, one course; 1 g of methyl prednisolone for 3 days) followed by PSL orally. Lisinopril and losartan were used for hypertension and proteinuria. Proteinuria was dramatically reduced after three courses of MPT, but it was still in the nephrotic range (Fig. 1). Additional cyclosporin was also insufficient to induce remission of proteinuria. In the end, he was started on MMF 3 months from the initiation of treatment. Proteinuria decreased promptly soon after he had started on MMF. Two months later the proteinuria had completely resolved, even though PSL had been withdrawn. Under treatment with PSL, cyclosporin A (CsA) and MMF, he has not had proteinuria for 8 months. Hematuria has also Pediatr Nephrol (2009) 24:1593–1594 DOI 10.1007/s00467-009-1141-x

Long-term outcome of idiopathic steroid-resistant nephrotic syndrome in children: response to comments

Dear Editor, We would like to respond to the letter from Dr. Fujinaga and colleagues in which they report on the clinical outcomes of children with idiopathic steroid-resistant nephrotic syndrome (SRNS) due to mesangial hypercellularity (MH) [1]. In our recent study [2], we analyzed the long-term outcome of 69 children with SRNS. Patients were divided based on initial histopathological patterns, and those with minimal change (MC) and those with diffuse mesangial proliferation (DMP) were assigned to the same group. Some previous studies reported that patients with DMP showed poorer outcome than those with MC [3, 4]. However, Ostalska-Nowicka et al. reported the outcomes of 33 children with DMP (25 patients) or focal segmental glomerulosclerosis (FSGS) (eight patients) and suggested that mimicry between the immunohistochemical pattern of DMP with glomerular immaturity and FSGS might explain the severe initial course of NS, while the transient clinical character of severity of DMP may also indicate that it is not a variant of FSGS [5]. In accordance with OstalskaNowicka’s suggestion, we considered that the character of DMP was closer to that of MC than of FSGS. On the other hand, Fujinaga et al. reported the clinical outcomes of 18 children with initial SRNS due to MC or MH, in which MH showed favorable outcome [1], and Silverstein et al. also reported favorable outcomes of 66 children with MH [6]. However, in our study, we had stronger interest in the character of poorer outcome of patients with SRNS, particularly that of patients with FSGS, and whether the choice of initial immunosuppressant (cyclosporine or cyclophosphamide) would have an impact on the outcome or not, and therefore if patients with DMP had shown better outcomes, the difference between the outcome of MC and that of DMP would not have been an essential matter in our study. In our study, we analyzed the remission rate of the initial SRNS episode and the renal survival rate. We divided patients into four groups based on initial histopathological patterns (FSGS or MC/DMP) and initial immunosuppressant used for SRNS (cyclosporine or cyclophosphamide), and showed that the groups treated with cyclosporine as initial immunosuppressant showed better outcomes regardless of their initial histopathological patterns [the renal survival rates at 10 years in the groups FSGS (cyclosporine), FSGS (cyclophosphamide), MC/DMP (cyclosporine), and MC/DMP (cyclophosphamide) were 100 %, 54.6 %, 96.6 % and 90.9 %, respectively, as calculated using Kaplan–Meier analysis (p=0.013)]. We also analyzed these rates while excluding the patients with initial histopathological findings of DMP, revealing that the difference in renal survival rate between MC group and FSGS group was more significant after exclusion of the patients with DMP [the renal survival rates at 10 years in the groups MC (cyclosporine) and MC (cyclophosphamide) were both 100 %], but the remission rate of the initial SRNS episode * Yuko Hamasaki yuhamasaki@med.toho-u.ac.jp