Revising the value of Antistreptolysin O titre in childhood and its interpretation in the diagnostic approach of rheumatic diseases.

The burden of group A streptococcus (GAS) infection and its rheumatic sequelae remains dramatically high, especially in low-income countries. Recently, an increased number of Acute Rheumatic Fever (ARF) cases was documented in many regions of Italy. The diagnosis of rheumatic sequelae relies on clinical signs and on the evaluation of the Antistreptolysin O titre (ASO), whose variations are globally reported. To re-examine the standard reference value of ASO titre, by measuring either its upper limit of normal (ULN) in a population of healthy children (HC) or comparing these values with streptococcal antibodies registered in a cohort of patients affected by the rheumatic sequelae of GAS infection. We performed a multicenter retrospective study. We enrolled 125 HC, aged 2-17 years, and a total of 181 patients affected by ARF, acute streptococcal pharyngitis, post-streptococcal arthritis, Henoch-Schönlein purpura and erythema nodosum, divided into four groups. The levels of ASO and anti-deoxyribonuclease B (anti-DNase B) titres were analyzed and compared among the various groups. Moreover, the 80th percentile value was calculated and established as the ULN for ASO titre in HC group. The ULN for ASO titre in overall HC group was 515 IU/mL, resulting in higher than used in the routine investigation. The ASO titre was significantly higher in patients with rheumatic sequelae compared with HC group, with a peak in the age between 5 and 15 years.    Conclusion: Our study established a new ULN normal value of streptococcal serology in a childhood and adolescent population of Italy, suggesting the need to extend this revaluation to the critical areas, in order to avoid underestimating ARF diagnosis. The correct interpretation of ASO and anti-DNase B values in the context of rheumatic diseases has been discussed. What is Known: • The global burden of disease caused by group A streptococcus is not known and remains an important cause of morbidity and mortality. Acute rheumatic fever continues to be a serious worldwide public health problem and a recent recurrence of group A streptococcus infection cases is observed. • The streptococcal sequelae requires evidence of preceding streptococcal infection, commonly elevated streptococcal antibody titre, but the upper limit for these titres varies considerably based on age group, region, and origin. What is New: • This study provides population-specific values for streptococcal antibody titres in Italy. • Interpret the results of group A streptococcal antibody tests within the clinical context.

Distinct Immunophenotypic Features in Patients Affected by 22q11.2 Deletion Syndrome with Immune Dysregulation and Infectious Phenotype.

The clinical expression of 22q11.2 deletion syndrome (22q11.2 DS) is extremely variable, as patients can present with recurrent or severe infections, immune dysregulation, atopic diseases, or extra-immunological manifestations. The immunological background underlying the different disease manifestations is not completely elucidated. The aim of this study was to identify the immunophenotypic peculiarities of 22q11.2 DS patients presenting with different disease expressions. This study included 34 patients with 22q11.2 DS, divided into three groups according to the clinical phenotype: isolated extra-immunological manifestations (G1), infectious phenotype with increased/severe infections (G2), and immune dysregulation (G3). The patients underwent extended immunophenotyping of the T and B lymphocytes and analysis of the circulating dendritic cells (DCs). In patients with an infectious phenotype, a significant reduction in CD3+ and CD4+ cells and an expansion of CD8 naïve cells was evidenced. On the other hand, the immunophenotype of the patients with immune dysregulation showed a skewing toward memory T cell populations, and reduced levels of recent thymic emigrants (RTEs), while the highest levels of RTEs were detected in the patients with isolated extra-immunological manifestations. This study integrates the current literature, contributing to elucidating the variability in the immune status of patients with 22q11.2DS with different phenotypic expressions, particularly in those with infectious phenotype and immune dysregulation.

AVNRT cryoablation in children <26 kg: efficacy and safety of electrophysiologically guided low-voltage bridge strategy.

The recently published "electrophysiologically guided low-voltage bridge (LVB) strategy" is effective in the ablation of atrioventricular nodal re-entry tachycardia (AVNRT) in children. This study aimed to evaluate its efficacy and safety in children <26 kgs. Fourteen children [64% males, median age 6.5 years (IQR 6-8 years), median weight 25.5 kg (IQR 24-26 kg)] with AVNRT were treated. In all patients, we detected a LVB associated to a typical slow pathway potential. The acute success rate was 100% with a mean of 5.5 cryoablation deliveries. All procedures were performed with near-zero fluoroscopic exposure (median time 0.15 min, IQR 0-0.7 min), in six patients fluoroscopy was 0 min. There were no complications or recurrences during the follow-up (median 20.91 months, IQR 11.7-26.7 months).

Clinical, Immunological, and Genetic Findings in a Cohort of Patients with the DiGeorge Phenotype without 22q11.2 Deletion.

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a primary immunodeficiency characterized by a broad and heterogeneous clinical presentation associated with various degrees of T-cell deficiency. We report the clinical, immunologic, and genetic findings of a cohort of eight patients presenting with a clinical phenotype that is highly suggestive of this syndrome but without the 22q11.2 deletion. The cardinal features of 22q11.2DS, such as congenital heart defects, hypoparathyroidism, and facial dysmorphisms, were observed in the majority of the patient cohort. The unusual features are described in detail. The immunologic assessment showed various degrees of immunodeficiency of the T-cell compartment, notably a reduction in the thymic output. Half of the patient cohort exhibited a reduction in total dendritic cells. Array comparative genomic hybridization (CGH) revealed six patients harboring copy number variations (CNVs) never reported in normal subjects. The gene content of these CNVs was carefully analyzed to understand the mechanisms leading to 22q11.2DS phenocopies. According to these results, we suggested that array-CGH should be used as a first-tier tool for patients resembling 22q11.2DS.

Toward the Knowledge of the Epidemiological Impact of Acute Rheumatic Fever in Italy.

Background: To estimate the incidence of Acute Rheumatic Fever (ARF) in Tuscany, a region of Central Italy, evaluating the epidemiological impact of the new diagnostic guidelines, and to analyse our outcomes in the context of the Italian overview. Methods: A multicenter and retrospective study was conducted involving children <18 years old living in Tuscany and diagnosed in the period between 2010 and 2019. Two groups were established based on the new diagnostic criteria: High-Risk (HR) group patients, n = 29 and Low-Risk group patients, n = 96. Results: ARF annual incidence ranged from 0.91 to 7.33 out of 100,000 children in the analyzed period, with peak of incidence registered in 2019. The application of HR criteria led to an increase of ARF diagnosis of 30%. Among the overall cohort joint involvement was the most represented criteria (68%), followed by carditis (58%). High prevalence of subclinical carditis was observed (59%). Conclusions: Tuscany should be considered an HR geographic area and HR criteria should be used for ARF diagnosis in this region.