Infliximab treatment for refractory COVID-19-associated multisystem inflammatory syndrome in a Japanese child.

Patients with multisystem inflammatory syndrome in children (MIS-C) can develop clinical features resembling Kawasaki disease (KD). A full picture of MIS-C in East Asia which has higher incidence of KD than other regions remains unclear. We report on a 15-year-old Japanese boy with refractory MIS-C who was successfully treated with infliximab. A Japanese boy who was diagnosed with coronavirus disease 2019 (COVID-19) before a month developed MIS-C with fulfilling six principal symptoms of KD. Laboratory data showed extreme hyperferritinemia (11,404 ng/mL), besides lymphopenia and thrombocytopenia. The patient was refractory to initial therapy with intravenous immunoglobulin (IVIG; 2 g/kg), aspirin, and prednisolone. He was therefore administered a second IVIG (2 g/kg) and infliximab (5 mg/kg) on days 7 and 8 from the onset of fever, respectively, which resulted in an improvement of clinical symptoms. Only four Japanese cases with MIS-C were reported and all of them were responsive to IVIG. The hyperferritinemia in this case was distinctive from previously reported MIS-C cases in Japan and other cohorts and may be associated with refractoriness to IVIG therapy. Marked elevation of circulating ferritin levels is known to be induced by tumor necrosis factor-α, which plays a key role in the pathogenesis of both KD and MIS-C. Thus, for MIS-C patients with hyperferritinemia, early intervention with adjunctive infliximab may induce a more rapid resolution of inflammation and improve outcome. Because MIS-C may be heterogeneous with respect to immunopathology, genetic background, clinical phenotypes and response to therapies, optimized treatment strategies according to immunopathogenesis are required.

Unilateral nephrectomy for young infants with congenital nephrotic syndrome of the Finnish type.

BACKGROUND: The management of congenital nephrotic syndrome of the Finnish type (CNF) is challenging. It is difficult to withdraw intravenous albumin infusions, resulting in long-term hospitalization. In addition, fatal hypotension after bilateral nephrectomy has been reported. In our center, we have performed unilateral nephrectomy during early infancy. METHODS: Infants diagnosed with CNF between 2011 and 2020 in our institution were enrolled. We examined the clinical course before and after unilateral nephrectomy and evaluated the effectiveness of this strategy. RESULTS: Seven patients (all showing NPHS1 mutations) were enrolled. All required daily intravenous albumin infusion via central venous catheter (CVC). Unilateral nephrectomy was performed at a median of 76 days of age (59-208 days). Surgical complications did not occur in any of patients. The mean albumin dose was decreased after unilateral nephrectomy (2.0 vs 0.4 g/kg/day; p = 0.02). Intravenous albumin infusion could be withdrawn at a median of 17 days, the CVC removed at a median of 21 days, and they discharged at a median of 82 days after unilateral nephrectomy. Although bacterial infections were noted seven times before unilateral nephrectomy, only one episode occurred after surgery. Four patients initiated peritoneal dialysis at two to three years of age and all of them underwent kidney transplantation thereafter. CONCLUSIONS: Unilateral nephrectomy during early infancy may be an effective treatment allowing for withdrawal from albumin infusion, prevention of complications, withdrawal from CVCs and shortening hospital stay for patients with CNF.

Eosinophilic peritonitis in children on chronic peritoneal dialysis.

BACKGROUND: Eosinophilic peritonitis (EP) is sometimes difficult to distinguish from bacterial peritonitis (BP) at onset, as they are often overlapping. Previous reports show EP occurs more frequently in infants, although the reason is unknown. METHODS: The study population was 77 pediatric patients receiving chronic peritoneal dialysis (PD) in our center. We compared clinical and laboratory data at onset of EP with those of BP. We also investigated age distribution at onset of EP and PD-related surgery. RESULTS: Eleven patients developed EP (18 episodes) and 19 patients developed BP (38 episodes). EP patients showed lower rate of cloudy dialysate (44.4% vs. 74.4%; p = 0.04), lower rate of fever (38.9% vs. 56.4%), lower frequency of abdominal pain (16.7% vs. 38.5%), higher peripheral blood eosinophil counts (/µL) (514 vs. 160; p < 0.001), and lower serum C-reactive protein level (mg/dL) (0.4 vs. 4.7; p < 0.001) than BP patients. Thirteen EP events were observed after 169 surgical interventions. Age at surgery-related EP was similar to age at surgery without EP (2.6 vs. 2.1; p = 0.65). There was no significant difference in postoperative EP occurrence between groups <2 years and ≥ 2 years (6.2% vs. 9.1%; p = 0.48). However, infants received more operations than older children. CONCLUSION: Clinical symptoms in children and laboratory data of EP in children were less severe than those of BP. As incidence of postoperative EP did not differ by age, we speculate that higher incidence of EP in infants might be associated with higher incidence of surgery, although further validation is necessary.

Refractory Hypertension in Infantile-Onset Denys-Drash Syndrome.

Denys-Drash syndrome is characterized by progressive nephropathy, gonadal dysgenesis, and Wilms tumor caused by a WT1 gene mutation. Infants with Denys-Drash syndrome frequently experience severe hypertension, but detailed clinical manifestations have yet to be clarified. Cases of infantile-onset Denys-Drash syndrome with severe hypertension at our hospital were retrospectively analyzed and the pathogenesis of hypertension was investigated. Six infants who received the diagnosis of Denys-Drash syndrome at the median age of 10 days (range: 2-182 days) were enrolled. Five infants had the complication of severe hypertension within a few days of diagnosis. All the patients showed rapid progression to end-stage renal disease and urgently required dialysis due to anuria/oliguria and hypervolemia with a median duration of 7.5 days (range: 0-17 days) on the day after diagnosis. Even under dialysis, all the patients continued to need antihypertensive treatment. Five patients underwent a preventive nephrectomy for Wilms tumor, and one patient underwent a nephrectomy due to progression to Wilms tumor. Two patients developed hypotension after a nephrectomy. The main causes of hypertension were hypervolemia in the predialysis stage, renin-associated hypertension in the dialysis stage, and multiple factors, including increased plasma catecholamine-associated hypertension in the postnephrectomy dialysis stage. At last the follow-up after bilateral nephrectomy, four of the five patients required antihypertensive treatment. Not all the patients showed target organ complications caused by hypertension. Severe hypertension is a common complication of infantile-onset Denys-Drash syndrome. The possibility of hypotension after nephrectomy should be considered in patients with Denys-Drash syndrome.

Abdominal paraganglioma in a young woman with 1p36 deletion syndrome.

1p36 deletion syndrome is the most common terminal deletion syndrome, and the genomic regions that contribute to specific 1p36 deletion syndrome-related phenotypes were recently identified. Deletions in the 1p36 region have been documented in various tumor tissues, which indicates correlation between loss of heterozygosity of 1p36 and tumor development, and the existence of tumor suppressors in this region. Therefore, it was suspected that patients with 1p36 deletion syndrome have a higher risk of tumor development; however, only a few child cases of neuroblastoma with 1p36 deletion syndrome have been reported. We report the first case of 1p36 deletion syndrome with paraganglioma (PGL) and include genetic investigation. The 24-year-old woman with 1p36 deletion syndrome had severe intellectual disability, dilated cardiomyopathy, and distinct dysmorphic features, and presented with persistent vomiting accompanied by hypertension (178/115 mmHg). Abdominal CT revealed a 40 × 50 mm retroperitoneal mass and substantial elevations of plasma and urine norepinephrine (15.4 nmol/L and 1022 µmol/mol creatinine, respectively); abnormal uptake of 123 I-MIBG in the tumor led to PGL diagnosis. The patient was not able to have surgery because of substantial surgical risks; however, a combination of α- and ß-blockade was effective for blood pressure control. Array CGH revealed a deletion over 4.5 Mb, from the 1p telomere but excluding the SDHB region. Comprehensive mutational analysis of PGL-associated genes (RET, VHL, TMEM127, MAX, and SDHA/B/C/D) was negative. These results indicate that the germline 1p36 deletion might be "1st hit" of tumor development, and PGL might be a novel complication of 1p36 deletion syndrome. © 2016 Wiley Periodicals, Inc.