Background: Kimura’s disease (KD), also known as Eosinophilic Granuloma, is a benign, rare and chronic inflammatory disorder of unknown etiology and it affects subcutaneous tissues, lymph nodes, and salivary glands. Unusual presentations of KD might cause diagnostic difficulty or be misdiagnosed as malignancy if clinical suspicion is insufficiently high. Here, we aimed to explore the clinical characteristics, diagnosis and the therapeutic effect of children’s KD in China, in order to improve pediatricians’ knowledge of children’s KD. Methods: The Clinical data of 18 cases of KD diagnosed at Shenzhen Children's Hospital from January 2015 to January 2022 were analyzed retrospectively through case record review. Results: Of 18 cases, 17 were male and one is female. The masses appear as focal, painless, and immovable with an unclear boundary. The most common predilection is head-neck region (n=8, 44.4%). 12 patients showed cutaneous pruritus, 3 patients with nephrotic syndrome and 2 with simple hematuria. 16 patients showed peripheral blood eosinophilia. 12 of 13 patients presented with increased serum Immunoglobulin E (IgE) level. The prominent pathological characteristic is marked lymphoid hyperplasia accompanied by various degrees of vascular hyperplasia and eosinophil infiltration. Among the 18 patients followed for more than 6 months, 9 experienced recurrence of disease after treatment (surgical resection alone: 6/12; oral corticosteroids combined with immunosuppressants: 3/3; surgical resection followed by oral corticosteroids combined with immunosuppressants: 0/3). Through comparison with the clinical features of adult kimura disease, it showed that there was no significant difference between children and adults. Conclusion: KD is characterized by subcutaneous masses but it is also a systemic disease. The diagnosis should be confirmed by pathology. Surgical resection, radiotherapy, hormone or chemotherapy has definite therapeutic effects, but the rate of recurrence in children is high. Given the high rate of recurrence and reported association with lymphoma, patients require careful long-term follow-up.

Introduction: Aicardi-Goutières (AGS) is a rare immune dysregulated disease due to mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, or IFIH1. Clinical features include basal ganglia calcifications, white matter abnormalities, and cerebral atrophy. Severe systemic inflammation and chronic kidney disease (CKD) are extremely rare in AGS. Herein, we report a patient presenting with systemic inflammation and CKD to broaden the clinical phenotype spectrum of the RNASEH2B defect. Methods: All testing and molecular genetic analysis were performed after obtaining the informed consent of the parents. Demographic, clinical, and laboratory findings were abstracted from outpatient and inpatient encounters. Cerebral magnetic resonance imaging (MRI), computed tomography (CT) scans, and renal biopsy histopathology reports were reviewed and summarized. Whole exome sequencing (WES) was performed on peripheral blood cells. After exposure to cGAMP in vitro for 24 hours, mRNA expression of twelve IFN-stimulated cytokine genes in PBMCs was assessed. Serum cytokine levels were detected by Milliplex. Results: A 11-year-old girl presented with recurrent aseptic fever, arthritis, chilblains, failure to thrive, mild hearing loss, and neurological manifestations. Laboratory and immunologic findings demonstrated lymphopenia, low complement levels, positive autoantibodies, elevated levels of acute-phase reactants and inflammatory cytokines. Cerebral imaging showed cerebral atrophy, white matter abnormalities, and intracranial calcification. Renal biopsy showed glomerular sclerosis in three of fourteen glomeruli, infiltration of lymphocytes and other mononuclear cells. WES revealed a homozygous and heterozygous mutations in RNASEH2B . Over-expression of IFN-stimulated cytokine genes was observed, including IFI44, IFI27, IFIT1, IFIT2, IFIT3, ISG15, OAS1, and SIGLEC1. Conclusions: To date, only two cases with AGS have been reported to have renal disease. Here, we describe a patient with both homozygous and heterozygous variants in RNASEH2B, presenting with neurological manifestations, persistently systemic autoinflammation, and CKD. CKD has never been reported in patients with AGS due to the RNASEH2B defect .

Background Kikuchi-Fujimoto disease (KFD) is typically a benign, self-limiting inflammatory disease. However, some patients may have a prolonged or recurrent disease course, or present with life-threatening complications such as macrophage activation syndrome (MAS). In this study, we aimed to describe the incidence and clinical features of MAS in KFD and to access potential laboratory markers for the diagnosis of KFD-associated MAS. Methods Patients with KFD were retrospectively enrolled from January 2015 to November 2021 at Shenzhen Children’s Hospital. Clinical data were collected from inpatient or outpatient medical records. Data collected included clinical manifestations, laboratory and imaging findings, treatment, and clinical outcomes. Data were analyzed using GraphPad Prism 8.0 statistical software (GraphPad Software Inc., La Jolla, CA, USA). A receiver operating characteristic (ROC) curve analysis was further performed to access the potential predictors for the KFD-MAS diagnosis. Results Of 58 patients with a histological diagnosis of KFD, 15 (25.9%) patients had MAS. Compared to patients without MAS, patients with KFD-MAS presented with a higher proportion of skin rash (26.7%, p = 0.01), glucocorticoid treatment (80%, p = 0.003), and disease recurrence (33.3%, p = 0.04). KFD-MAS patients had lower absolute peripheral white blood cell (WBC, p = 0.02), platelet (p = 0.002), serum albumin levels (p = 0.01), and lymphocyte count (p < 0.0001), and higher lactate dehydrogenase (LDH) levels (p < 0.0001). ROC curve analysis showed that the cutoff values of absolute lymphocyte count, an absolute platelet count, serum albumin level, and serum LDH level for KFD-MAS diagnosis were < 1235/μL, < 171 × 106/μL, < 35.6 g/L, and > 679 IU/mL, respectively. Conclusions The presence of KFD-MAS in children may be more common than previously expected, especially in those with skin rash. KFD-MAS may be associated with a higher recurrence rate. An extremely elevated serum LDH level and moderate to severe lymphopenia may be useful diagnostic markers for MAS in KFD. Trial registration Not applicable; this was a retrospective study.

TYK2 deficiency is a rare Primary immunodeficiency disease caused by loss of function mutations of TYK2 gene, which is initially proposed as a subset of Hyper IgE syndrome (HIES). However, accumulating evidence suggest TYK2 deficient patients do not necessarily present with HIES characteristics, indicating a vacuum of knowledge on the exact roles of TYK2 in human immune system. Here we describe five more TYK2 deficient cases presenting with or without hyper IgE levels, atopy and distinct pathogen infection profile, which are caused by novel TYK2 mutations. These mutations were all found by high throughout sequencing and confirmed by Sanger sequencing. Pathogenic effects were confirmed by qRT-PCR and western blot. Peripheral blood mononulear cells (PBMCs) from these patients showed heterogenous responses to various cytokines treatment, including IFN-a/b/g, IL-6, IL-10, IL12 and IL-23. The homeostasis of lymphocytes is also disrupted. Based on our findings, we propose that TYK2 works as a multi-tasker in orchestrating various cytokines signaling pathways, differentially combined defects of which account for the expressed clinical manifestations.

Background Aicardi-Goutières (AGS) is a rare immune dysregulated disease due to mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1 or IFIH1. Severe systemic inflammation is not typically persistent in AGS. Chronic kidney injury (CKI) has been never reported in this syndrome. Herein, we report a patient presenting with systemic inflammation and CKI to broaden the clinical phenotype spectrum of RNASEH2B defect. Methods Clinical data extracted included medical history, clinical manifestations, laboratory results, radiological findings, management, and prognosis. Whole exome sequencing was performed on whole peripheral blood cells. After exposure to cGAMP in vitro for 24 hours, mRNA expression of twelve IFN-stimulated cytokine genes in PBMCs was assessed. Serum cytokine levels were detected by Milliplex. Results A 11-year-old female patient presented with recurrent aseptic fever, arthritis, chilblains, failure to thrive, mild hearing loss, and neurological manifestations. Laboratory and immunologic findings revealed lymphopenia, low complement levels, positive autoantibodies, elevated levels of acute phase reactants and inflammatory cytokines. Renal biopsy showed glomerular sclerosis in three of fourteen glomeruli, infiltration of lymphocytes and other mononuclear cells. Whole exome sequencing (WES) revealed a homozygous and heterozygous mutations in RNASEH2B.Over-expression of IFN-stimulated cytokine genes was observed in the patient, including IFI44, IFI27, IFIT1, IFIT2, IFIT3, ISG15, OAS1, and SIGLEC1. Conclusions Systemic autoinflammation and chronic renal injury may expand the clinical phenotype spectrum of RNASEH2B defect. Trial registration: Not applicable; this was a retrospective study.