Drugs for paediatric hyperinflammatory syndromes.

Background: Many syndromes are associated with exaggerated inflammation. Children with hyperinflammatory syndromes often present with vague and non-specific symptoms that pose diagnostic and management challenges. The recent literature seems biased towards referring these syndromes only to the multisystem inflammatory syndrome in children (MIS-C) that is associated with COVID-19. The purpose of this paper is to provide an updated narrative review on the pathophysiology, manifestations and management approaches for common hyperinflammatory syndromes. Methods: An extensive PubMed search of all publications in the English literature was performed with Clinical Queries for various hyperinflammatory syndromes and conditions using the undermentioned Medical Subject Headings: "hyperinflammation", "hyperinflammatory syndromes", "sepsis syndrome", "severe inflammatory response syndrome" and "acute respiratory distress syndrome". Categories were limited to reviews and clinical trials for the age range from birth to 18 years. Results: The criteria, presentation and management of these hyperinflammatory syndromes are described. Hyperinflammatory syndromes refer to a basket of inflammatory syndromes often associated with multisystem involvement and aberrant cytokine release and should be differentiated from autoinflammatory, autoimmune and hyperimmune syndromes. The major subtypes of hyperinflammatory syndromes, including macrophage activation syndrome, haemophagocytic lymphohistiocytosis, cytokine release syndrome and cytokine storm syndrome, are described. MIS-C associated with SARS-CoV-2 represents the latest addition. It must be understood that the syndrome is not exclusive to COVID-19 but could be caused by various viral infections. Early recognition, prompt and proactive treatment can reduce potential complications and improve outcomes and survival rates in paediatric patients. Anti-inflammatory medications for the management of these syndromes are described. Conclusion: The incidence of these hyperinflammatory conditions is generally low in comparison to other disease conditions. Except for paediatric inflammatory multisystem syndrome/MIS-C, the mortality is high and the hospital stay is prolonged in affected patients. Acute and critical care physicians must be aware of these conditions and their initial management. Corticosteroids are often used in the initial phrase but various disease-specific drugs and biologics are needed in subsequent management and expert management of these often-difficult conditions is crucial.

Risk factors for drug allergies in Chinese children.

BACKGROUND: Drug allergy, or drug hypersensitivity, is a potentially fatal disorder, and patients labeled with drug allergies have restricted access to first-line treatments. Full knowledge of the characteristics associated with drug allergies and severe reactions during allergy evaluation is beneficial for appropriate risk stratification. OBJECTIVE: We sought to determine whether certain clinical characteristics are associated with drug allergies in Chinese children. METHODS: Charts were reviewed for ethnic Chinese patients less than 18 years old referred to our tertiary allergy center for suspected drug allergies and completed skin and drug provocative testing between 2005 to 2017. Univariate and multivariate analyses were performed on the age of onset of drug allergies, gender, and other atopy versus drug allergies. RESULTS: Out of 75 children, 18 (24%) had IgE-mediated drug allergies, while 8 (10.7%) had delayed drug hypersensitivities, with a cumulative 26 subjects (34.7%) with any drug hypersensitivity. There were positive independent associations between drug hypersensitivities onset age vs IgE-mediated drug allergies (odds ratio (OR) = 14.9, 95% confidence intervals (CIs) = 1.5-148.3, P = 0.017) and between male gender and IgE-mediated drug allergies (OR = 4.4, CIs = 1.2-16.4, P = 0.019). Age 13 years was the best cut-off for IgE-mediated drug allergies according to the receiver operating characteristic curve (P = 0.026). Older age group (OR = 24.0, CIs = 1.4-417.8, P = 0.024) and atopic dermatitis (OR = 8.2, CIs = 1.4-49.8, P = 0.015) were correlated with delayed drug hypersensitivities. CONCLUSIONS: While several previous studies suggested a higher prevalence of IgE-mediated drug allergies in younger adult females, older boys were more likely to have drug allergies for Chinese children.

Disseminated Bacillus Calmette-Guérin and Susceptibility to Mycobacterial Infections-Implications on Bacillus Calmette-Guérin Vaccinations.

Bacillus Calmette-Guérin (BCG) is a live vaccine and has the potential to cause local disease and systemic dissemination in immunocompromised hosts, including infants who are infected with human immunodeficiency virus (HIV) through vertical transmission, and patients with primary immunodeficiencies (PID) such as severe combined immunodeficiency (SCID), chronic granulomatous disease (CGD), hyper-IgM syndrome, and defects of the IL12- IFNγ axis (Mendelian susceptibility to mycobacterial diseases, MSMD). Disseminated BCG is extremely difficult to treat. The chance of complete eradication is low unless functional immune response is restored by haematopoietic stem cell transplant. Prolonged use of anti-mycobacterial drugs often causes organ toxicities and drug resistance. Inflammatory complications which develop upon immunoreconstitution post-transplant may necessitate immunosuppressive treatment, which adversely affect immune recovery and increases risks of opportunistic infections. Multiple BCG reactivations can occur in patients with CGD and MSMD, and BCG can remain latent until reactivations take place in adulthood and manifest as disease. It is important for neonatologists, general practitioners, primary care clinicians and nurses working in maternal and child care centres to be aware of BCG-related complications, which may be the first sign of an underlying immunodeficiency. As neonatal BCG is included in standard vaccination schedule in many countries, it is a challenge to identify and avoid administration of BCG to infants who potentially have PIDs. Deferring BCG vaccination is recently advocated to protect highly vulnerable populations, but the appropriate strategy is yet to be determined. Newborn screening for SCID offers a potential to avoid this complication, if an integrated system of screening and vaccination can be organised.