Background: Macrophage activation syndrome (MAS) is a rare, life-threatening complication of Kawasaki disease (KD). Early recognition and treatment of MAS are very important, but sometimes it is difficult to distinguish MAS from a severe form of KD.

Data sources: A PubMed search was performed in Clinical Queries using the key terms “macrophage activation syndrome or secondary hemophagocytic lymphohistiocytosis (HLH)” and “Kawasaki disease”.

Results: KD patients with MAS show high intravenous immunoglobulin (IVIG) resistance and coronary complications. Mortality is also as high as MAS in other diseases. Persistent fever greater than 10 days is highly associated with development of MAS in KD. Splenomegaly is observed in more than two-thirds of KD patients with MAS. Thrombocytopenia is often the earliest laboratory finding of MAS. Hyperferritinemia is highly specific and sensitive for detecting MAS in KD; so, ferritin levels should be checked if there are unexplained clinical exacerbations in KD patients. Given the under-recognition of MAS in KD, it is prudent to consider resistant KD as occult/subclinical MAS. Many KD patients with MAS have good outcomes on immune modulators. However, if KD patients fulfill the HLH-2004 diagnostic criteria, they may undergo longer and more intensive treatment than needed.

Background: A20, a protein encoded by the tumor necrosis factor alpha-induced protein 3 gene (TNFAIP3), plays a vital role in the negative regulation of inflammation and immunity. Loss-of-function mutation in TNFAIP3 leads to a new described autoinflammatory disease-haploinsufficiency of A20 (HA20). Since HA20 was first described in 2016, a number of new cases have been described in this literature, however, the disease and its pathogenesis are poorly understood. This review seeks to improve clinical recognition of this disorder, and promote both earlier diagnosis and initiation of targeted therapies to improve patients’ outcomes.

Methods: We reviewed 26 papers about A20 and HA20, and we summarized genetic variants and clinical manifestations of a total of 61 reported patients from 26 families identified to have a genetic diagnosis of germline pathogenic variants in TNFAIP3/A20. Additionally, we discussed the pathogenesis and treatment of HA20.

Results: A total of 24 pathogenic variants of A20 had been reported. There was significant clinical heterogeneity, even among those with the same variants in TNFAIP3 . Prior to receiving a molecular diagnosis of HA20, patients had been diagnosed with Behcet’s disease, rheumatoid arthritis, rheumatic fever, juvenile idiopathic arthritis, systemic lupus erythematosus, and even adult-onset Stills’ disease. The patients with HA20 that presented with inflammatory signatures in NF-κB signaling were mostly responsive to treatment.

Background: To systematically evaluate the incidence characteristics of testicular microlithiasis (TM) in children and its association with primary testicular tumors (PTT).

Methods: A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A priori protocol was registered in the PROSPERO database (CRD42018111119), and a literature search of all relevant studies published until February 2019 was performed. Prospective, retrospective cohort, or cross-sectional studies containing ultrasonography (US) data on the incidence of TM or the association between TM and PTT were eligible for inclusion.

Results: Of the 102 identified articles, 18 studies involving 58,195 children were included in the final analysis. The overall incidence of TM in children with additional risk factors for PTT was 2.7%. In children, the proportion of left TM in unilateral cases was 55.7%, the frequency of bilateral TM was 69.0%, and proportion of classic TM was 71.8% [95% confidence interval (CI) 62.4–81.1%, P = 0.0, I² = 0.0%]. About 93.5% of TM remained unchanged, and newly detected PTT rate was very low (4/296) during follow-up. The overall risk ratio of TM in children with a concurrent diagnosis of PTT was 15.46 (95% CI 6.93–34.47, P < 0.00001).

Background: Perforin (PRF1) gene mutation can cause the onset of hemophagocytic lymphohistiocytosis (HLH). It has reported that PRF1 Ala91Val polymorphism was related with HLH risk. In the meta-analysis, we aim to evaluate the association between PRF1 Ala91Val polymorphism and HLH risk.

Methods: We accomplished a meta-analysis of six published case-control studies including 391 patients with HLH and 975 controls. We evaluated the quality of each study through Newcastle–Ottawa Scale (NOS). Data analysis was performed with Stata software.

Results: In general, all studies were of high quality (NOS score higher than 7). There were statistically significant between the PRF1 Ala91Val polymorphism and HLH risk though the pooled analysis [for Ala/Val vs. Ala/Ala: pooled odds ratio (OR) = 3.22, 95% confidence interval (CI) 1.08–9.56, P = 0.035, random model; for Ala/Val + Val/Val vs. Ala/Ala: pooled OR = 2.96, 95% CI 1.14–7.69, P = 0.025, random model]. Furthermore, sensitivity analysis also revealed a relationship between PRF1 Ala91Val polymorphism and HLH risk (for Ala/Val vs. Ala/Ala: pooled OR = 5.236, 95% CI 2.72–10.08, P < 0.000, I² = 12.1%, P heterogeneity = 0.332; for Ala/Val + Val/Val vs. Ala/Ala, pooled OR = 4.856, 95% CI 2.66–8.85, P < 0.000, I² = 5.9%, P heterogeneity = 0.373). Funnel plot and Egger’s test did not indicate obvious published bias (P = 0.841 for Ala/Val vs. Ala/Ala; P = 0.284 for Ala/Val + Val/Val vs. Ala/Ala).

Background: We aimed to explore predictive measures for intravenous immunoglobulin (IVIG) resistance in children with Kawasaki disease (KD).

Methods: Patients diagnosed with KD were enrolled in this study. Univariate analysis and multiple logistic regression were utilized to analyze the clinical features and laboratory results prior to IVIG-treatment of the two groups. Independent predictors of IVIG resistance were analyzed, and a predictive model for KD children with IVIG resistance was constructed.

Results: A total of 277 children with KD, 180 boys and 97 girls, aged 2-128 (median 23) months, were enrolled in the study. Compared with the IVIG-responsive group, the IVIG-resistant group had higher levels of the peripheral neutrophil count, mean platelet volume, mean platelet volume-to-lymphocyte ratio and C-reactive protein, and total serum bilirubin, but lower levels of peripheral lymphocyte count, serum albumin and serum prealbumin. Age (in months), peripheral neutrophil count, lymphocyte count and mean platelet volume and serum albumin were independent indicators for IVIG resistance by multivariate logistic regression analysis. A logistic regression model and a scoring system were set up, where cut-off values of - 0.46 and 6.5 points yielded sensitivities of 83.9% and 77.4%, and specificities of 74.8% and 61.0%, respectively. The areas under the curve (AUC) were 0.808 in the logistic regression model, and 0.750 in the scoring system.

Background: Coronavirus disease 2019 in children, or pediatric COVID-19, initially was described as an acute respiratory syndrome similar to the adult presentation but with less severe manifestations.

Methods: We describe the clinical characteristics, disease presentation, treatments and outcomes of all pediatric cases with COVID-19 admitted to the reference hospitals in Navarra, Spain during the first wave of the COVID-19 outbreak (February-May 2020).

Results: We found a low number of hospitalized cases in infants and children compared to adults with a hospitalization ratio of 1:180. Most of these hospitalized cases did not suffer from severe disease. Over 80% of infections reported household contacts, and the mother was the known-contact in 83% of these cases. 72% of hospitalized cases were previously healthy children. We describe how symptoms in pediatric cases are nonspecific and how COVID-19 can be presented with a wide range and variety of symptoms. Respiratory symptoms are not always present, and severe neurological and cardiac features can occur in previously healthy children.

Background: Although Kawasaki disease (KD) is known to cause anemia, the relationship between its prognosis and hemoglobin level is less well known.

Methods: We herein performed a secondary analysis of data from a previous study (Post-RAISE). Children aged 6 months to 2 years at the time of KD diagnosis were enrolled. Decreased hemoglobin was defined as a decrease > 10% on post-treatment day 2 compared with the level prior to the initial therapy.

Results: Of 1253 KD cases, treatment resistance was observed in 209 (17%) and was significantly more frequent in the decreased hemoglobin group (37/167 vs. 172/1086, P = 0.041). Multivariable logistic regression analysis revealed that decreased hemoglobin was associated with resistance to the initial treatment (odds ratio 1.53; 95% confidence interval 1.00-2.33; P = 0.048).

Background: To describe the cutaneous acral findings in a pediatric population noticed during this pandemic.

Methods: A retrospective descriptive study was performed collecting data on 36 patients under 14 years old, presenting suspicious acral skin manifestations for coronavirus disease 2019 (COVID-19).

Results: Patients were mostly male (63.8%). The mean age was 11.11 years. 66.67% of patients showed erythematous papules, and 44.44% purpuric macules. Feet were affected in 97.22% of patients and hands in 5.55%. Lesions were asymptomatic in 50% of patients. 30.55% of patients showed extracutaneous findings, preceding skin lesions in 12.62 days. Seven patients underwent specific severe acute coronavirus 2 (SARS-CoV-2) testing; all of these patients tested negative.