Severe hypersensitivity reactions to biological drugs in children with rheumatic diseases

Abstract

Background: Hypersensitivity reactions (HSR) to biologic drugs (BD) may limit their use in children with rheumatic diseases. We aimed to analyze the incidence and clinical characteristics of immediate type I (IgE/non-IgE) hypersensitivity reactions to BD and the risk factors for these reactions.Methods: Children with rheumatic diseases using BD who were evaluated in the pediatric allergy department for possible drug hypersensitivity reaction (DHR) due to BD or any other drug were included in the study. Results: One hundred and twenty-eight children (49.2% boys; 14.6 years [9.9-16.9 years] with juvenile idiopathic arthritis [58%], familial Mediterranean fever [14%], vasculitis [14%], and other diseases [14%]) had used eight different BD with 32 494 infusions/injections. Fifteen patients were evaluated for DHR [injection-site reactions [n = 4], adverse events [n = 2], drug hypersensitivity other than BD [n = 3],and immediate BD hypersensitivity [n = 6]). The incidence of immediate BD HSR was 4.7%, with a clinical presentation of anaphylaxis in 3.9% (tocilizumab [n = 3], rituximab [n = 2], positive skin test with culprit BD [n = 3]). Among patients with BD HSR, the median follow-up was longer (84.5 vs 54 months, P = .048), and renal (33.3% vs 4.1%, P = .002), hematologic involvement (16.7% vs 0, P < .001), and active disease (83.3% vs 13.9%, P < .001) were more common. Logistic regression analysis revealed that renal involvement, more than 14 hospitalizations per lifetime, and more than two different BD used were associated with BD hypersensitivity. Conclusion:The frequency of severe immediate HSR due to BD was shown to be 3.9% in children with rheumatic diseases. Children with active rheumatic disease and who have exposure to multiple BD should be monitored for BD HSR, particularly during intravenous BD infusions. K E Y W O R D Sbiologic drugs, children, hypersensitivity, rheumatic diseases

Emergent high fatality lung disease in systemic juvenile arthritis

“…Drug hypersensitivity reactions can occur in children treated with biologic drugs for rheumatic disease 66. A subset of LD cases met the criteria for DReSS (online supplementary tables S1 and S8), a delayed form of severe drug-related hypersensitivity with organ involvement that can include lung 17 67 68.…”

Consensus statement of the Italian society of pediatric allergy and immunology for the pragmatic management of children and adolescents with allergic or immunological diseases during the COVID-19 pandemic

“…The diagnostic accuracy of skin tests to Azithromycin, Hydroxychloroquine, and Tocilizumab [22,31] is low, and to Remdesivir is unknown [32]. A confident diagnosis of drug hypersensitivity can be reached by performing a drug provocation test (DPT) with the culprit drug.…”

“…Azithromycin and Hydroxychloroquine co-treatment can be safely performed after a cardiological evaluation due to the risks of QT prolongation. Tocilizumab is mostly associated with a local reaction in the injection site, but it has been reported a prevalence of 3.9% of moderate-severe systemic reactions [31].…”

Diagnosis and management of the drug hypersensitivity reactions in Coronavirus disease 19: An EAACI Position Paper

“…This anti‐IL‐1 agent is normally well tolerated and indicated as an alternative in cases with an anaphylactic reaction to anakinra 138 . However, there is a recently reported case who developed immediate diffuse urticaria after the tenth canakinumab administration and was prevented from further reactions with cetirizine premedication 137 (Table 3).…”