Kimura's disease with recurrent bilateral lacrimal gland involvement in a male Japanese child successfully treated with cyclosporine A.

BACKGROUND: Kimura's disease (KD) is a rare chronic inflammatory disease of unknown etiology. Clinically, KD is characterized by nodular subcutaneous masses, that are typically localized to the neck and head. Involvement of the lacrimal glands and limbs is uncommon and seldom reported. CASE PRESENTATION: We report a case of a 4-year-old Japanese boy presenting with bilateral upper eyelid swelling with nodular subcutaneous lesions and peripheral eosinophilia. Based on clinical, histopathological, and laboratory findings, the patient was diagnosed with KD. An itchy subcutaneous mass on the left arm developed at the age of 14 years. Treatment with steroids was effective. However, as the steroids were tapered after the patient developed side effects, the masses relapsed within a few months. Treatment with cyclosporine A was then initiated, which led to an improvement of clinical features and serial levels of cytokines. CONCLUSIONS: We report a rare case of KD with a peculiar clinical presentation. The patient responded well to treatment with cyclosporine A.

Pathophysiological clinical features of an infant with hypertension secondary to multicystic dysplastic kidney: a case report.

BACKGROUND: The association of hypertension with congenital renal hypoplasia has been established. We report a case of an infant who underwent nephrectomy for hypertension. CASE PRESENTATION: Magnetic resonance imaging for the mother revealed fetal renal masses, and fetal multicystic dysplastic kidney was suspected. Following birth, the baby developed hypertension. Numerous investigations revealed that the left kidney was non-functional, and she was initiated on benazepril hydrochloride. However, because the drug response was poor, the left kidney was removed at the age of 7 months. Examination of the renal specimen revealed abrupt transition from normal to atrophic cortex with lobar atrophy and cysts. Tubular atrophy, marked abnormal blood vessels with wall thickening, gathered immature glomeruli, and parenchymal destruction were observed. Renin was partially localized in the proximal tubules and the parietal epithelium of the Bowman's capsule in the immature glomeruli. We speculated that an abnormal vascular structure and irregular renin localizations may be the cause of hypertension. Serum renin and aldosterone levels gradually reduced post-surgery, reaching normal levels on the 90th postoperative day. A long follow-up is needed due to the possibility of the child developing hypertension in the future. CONCLUSION: This is a case of an infant with MCDK, which discusses the clinicopathological features based on the pathophysiological analysis, including renin evaluation.

Nephrotic syndrome relapse in a boy with COVID-19.

Clinical data on coronavirus disease-19 (COVID-19) in children during the management of nephrotic syndrome (NS) is lacking. Patients on prednisolone are compromised hosts at the risk of severe infections. Some infections may induce NS relapse. We describe the clinical course of a child with NS and COVID-19. A 3-year-old boy was admitted with clinical and laboratory findings indicative of NS. Induction therapy with prednisolone (2 mg/kg/day) induced complete remission. While tapering the dose, he was infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). He developed a high fever and periorbital edema. Urinalysis revealed proteinuria (protein-creatinine ratio: 6.3 g/gCr). He was transferred to our hospital for the concurrent management of COVID-19 and NS relapse. As proteinuria worsened, the prednisolone dose was increased to 2 mg/kg/day. Proteinuria gradually improved, and remission was noted a week after initiating full-dose steroid treatment. The fever subsided after 2 days without treatment for COVID-19. Anti-SARS-CoV-2 antibody including IgG levels decreased in the early convalescent phase. To the best of our knowledge, this is the first reported case with the recurrence of NS triggered by the SARS-CoV-2 infection in Asia. SARS-CoV-2 infection may induce NS relapse. Daily administration of full-dose of prednisolone may be effective for managing the recurrence of NS associated with SARS-CoV-2 infection.

Donor-derived myelodysplastic syndrome after allogeneic stem cell transplantation in a family with germline GATA2 mutation.

Germline GATA2 heterozygous mutations were identified as complex immunodeficiency and hematological syndromes characterized by cytopenia (monocytes, B-cells, NK-cells), susceptibility to mycobacterium, fungus, or Epstein-Barr virus (EBV) infection, and myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) development. Herein, we report a patient with AML who had a fatal infection after allogeneic hematopoietic stem cell transplantation (HSCT) due to impaired immune reconstitution associated with GATA2 mutation. A 15-year-old man was diagnosed with AML with monosomy 7. His family history was negative for immunodeficiency and hematological disorders. He attained complete remission after HSCT from an HLA-identical sister. Post-HSCT examinations performed 15 months later revealed pancytopenia, especially monocytopenia and the absence of B and NK cells, resulting in the occurrence of donor-type MDS. Twenty-one months after HSCT, he developed central nervous system aspergillosis and finally died of the disease. Two months later (24 months after PBSCT), the donor was diagnosed with persistent EBV infection accompanied by MDS with multilineage dysplasia. Genetic analysis of GATA2 revealed a novel heterozygous mutation (c.1023_1026dupCGCC) in both siblings. GATA2 mutations were highly prevalent among adolescent MDS/AML patients with monosomy 7. Therefore, the screening of GATA2 mutations in relatives is necessary when performing HSCT from a relative donor.

The potentially therapeutic role of tonsillectomy in the alleviation of several renal diseases apart from IgA nephropathy.

Tonsils are located mainly at the gateway of the respiratory tract, and are reportedly one of the secondary lymphatic organs of the immune system. The development of several diseases including IgA nephropathy (IgAN) is associated with inflammatory stimulation and an aberrant immune response of the tonsils. Several studies have reported an improvement in and/or an increase in the stability of the clinicopathological findings of patients with IgAN post tonsillectomy. However, the efficacy in and precise mechanism of the alleviation of symptoms of other renal diseases by tonsillectomy remain unknown. We hypothesize that tonsillectomy may play a potentially therapeutic role in renal diseases apart from IgAN, which are thought to be caused by an impaired regulation of the immune system.

Real-world effectiveness and safety of tolvaptan in liver cirrhosis patients with hepatic edema: results from a post-marketing surveillance study (START study).

BACKGROUND: This large-scale post-marketing surveillance study (START study) evaluated the effectiveness and safety of tolvaptan in Japanese liver cirrhosis patients with hepatic edema in real-world clinical settings. Here, we present the final analysis outcomes. METHODS: A prospective, multicenter, non-interventional study involving patients who received tolvaptan for the treatment of liver cirrhosis with hepatic edema with an insufficient response to conventional diuretics. The observation period was up to 6 months. Effectiveness evaluation included changes in body weight and clinical symptoms. Safety analysis included evaluation of adverse drug reactions (ADRs). RESULTS: Case reports of 1111 patients were collected. Of these, 1109 were included in the safety analysis and 1098 in the effectiveness analysis. The mean age was 69.4 ± 11.5 years and 695 (62.7%) patients were male. After tolvaptan treatment, a decrease in body weight from baseline was - 2.6 ± 2.7 kg on day 7 and - 3.8 ± 4.1 kg on day 14. Moreover, clinical symptoms significantly improved over the 14-day treatment. Frequently reported ADRs were thirst (6.6%), hepatic encephalopathy (2.3%), dehydration (1.5%), and hypernatremia (1.2%). A serum sodium level of ≥ 150 mEq/L was reported in five patients (0.5%). Multivariate analyses showed that the baseline blood urea nitrogen (BUN) level (cut-off value: 22.4 mg/dL) was the predictive factor for tolvaptan treatment response. CONCLUSIONS: The results suggest that tolvaptan was effective and well-tolerated in liver cirrhosis patients with hepatic edema. In the real-world clinical setting, tolvaptan provides a useful option for the treatment of hepatic edema.

Early tonsillectomy for severe immunoglobulin A nephropathy significantly reduces proteinuria.

BACKGROUND: Early multiple-drug therapy for severe childhood immunoglobulin A (IgA) nephropathy prevents the progression of nephritis and improves the long-term prognosis. Recent studies have focused on the relationship between the pathophysiology of IgA nephropathy and tonsillar focal infection, and the efficacy of tonsillectomy with methylprednisolone pulse therapy in children has been demonstrated. However, no study has reported on the relationship between the period from diagnosis to tonsillectomy and the long-term prognosis of IgA nephropathy. METHODS: To clarify the long-term effects of an early tonsillectomy, 40 patients who were diagnosed with severe IgA nephropathy in childhood and underwent a tonsillectomy were divided into two groups based on the period from diagnosis to undergoing tonsillectomy: Group A, less than 3 years; and Group B, more than 3 years. The primary endpoint of this study was the change in the amount of proteinuria. Renal prognosis was evaluated 10 years after the diagnosis. RESULTS: This study enrolled 40 patients diagnosed with severe IgA nephropathy in childhood who underwent tonsillectomy after multiple-drug therapy with/without methylprednisolone pulse therapy at Kindai University Hospital; eight patients were excluded based on the exclusion criteria. Group A consisted of 18 patients and Group B, 14 patients. Proteinuria and hematuria levels were significantly reduced in the early surgery group (P < 0.01). No significant differences were found in serum creatinine, uric acid, and IgA/C3 ratio. CONCLUSIONS: High proteinuria levels worsen the renal prognosis in IgA nephropathy. Tonsillectomy in less than 3 years combined with multiple-drug therapy after the initial diagnosis could improve long-term prognosis.

Membranoproliferative glomerulonephritis related to a streptococcal infection in a girl with IgA deficiency: a case report.

BACKGROUND: IgA deficiency associated with glomerulonephritis is rare. In particular, there is no prior report regarding the association between IgA deficiency and membranoproliferative glomerulonephritis (MPGN) in children. Herein, we describe the case of a 5-year-old girl with selective IgA deficiency and MPGN. CASE PRESENTATION: The patient presented with persisting urinary abnormality and hypocomplementemia following a group A treptococcal infection. Renal biopsy revealed the presence of diffuse mesangial hypercellularity, endocapillary proliferation, and focal thickening of the walls of the glomerular capillaries using light microscopy, with IgG and moderate C3 deposits observed using immunofluorescence. Electron microscopy images revealed nodular deposits in the subendothelial areas, with hump-shaped subepithelial deposits. The pathological diagnosis was confirmed as MPGN. Treatment using oral prednisolone (PSL), mizoribine (MZR), and angiotensin-converting enzyme inhibitors reduced the proteinuria. The PSL dose was gradually tapered, with the low dose of PSL and MZR continued for 4 years. Histological findings were improved on repeated renal biopsy, and PSL and MZR administration was discontinued. CONCLUSIONS: We report a rare case of MPGN related to a streptococcal infection in a child. The clinical presentation included selective IgAD, with several pathological findings and a clinical course typical of glomerulopathy. The patient was successfully treated using multidrug therapy.