Safety and efficacy of rapid drug desensitization in children.

BACKGROUND: Any drug taken at the recommended dosage may cause hypersensitivity reactions (DHR). Rapid drug desensitization (RDD) protocols have been developed in the case of a confirmed or highly suspected HSR to allow safe administration of the medicine when there is no alternative drug or in the presence of a less effective or more toxic alternative. The aim of this study was to evaluate the characteristics of children who underwent desensitization, the safety and efficacy of RDD in children, as well as, the characteristics and management of breakthrough reactions. METHOD: This retrospective study concerned children who underwent RDD due to physician-diagnosed HSRs during or up to 48 hours after the infusion of various drugs between February 2010-February 2021. Patients with a chronic disease needing chronic drug usage and acute infections seen in patients with chronic diseases were included. The results of RDD were documented. RESULTS: The study included 48 patients [8.1(IQR = 3.32-13.4) years, 60.4% male] with 58 HSRs of which 62.1% were classified as moderate and 5.2% as severe. Most of the patients were being treated for leukemia (41.7%), solid tumors (29.2%), and infections (6.3%). Skin tests were done for 41 out of 58 HSRs in 35 patients, and twenty of them were positive. A total of 269 RDDs were performed for 18 different drugs. Ninety percent of desensitizations were achieved with no reaction, and 3.7% and 5.6% with mild and moderate reactions, respectively. In multivariate analysis, skin test positivity was the only risk factor for breakthrough reactions (OR = 8.5, CI = 1.72-42.15, p = .009). CONCLUSION: We demonstrated the safety and efficacy of RDD in childhood, thereby offered the first line treatment options to children with chronic diseases with hypersensitivity reactions (HSRs).

A single-center study points to diverse features and outcome in patients with Hyperimmunoglobulin M Syndrome and Class- Switch Recombination defects.

Isotype class-switch recombination (CSR), somatic hypermutation (SHM), B cell signalling and DNA repair mechanisms defects are responsible for high IgM. The hyperimmunoglobulin M (HIGM) phenotype and CSR-related defects are now classified under primary antibody defects, combined immunodeficiencies or syndromic immunodeficiencies groups. The aim of the study is to evaluate the diverse phenotypic/genotypic/laboratory characteristics and outcome of patients with CSR defects and HIGM-related defects. We enrolled 50 patients. The most common gene defect was Activation-induced cytidine deaminase (AID) deficiency (n = 18), followed by CD40 Ligand (CD40L) (n = 14) and CD40 (n = 3) deficiency. Median ages at first symptom and diagnosis were significantly lower in CD40L deficiency (8.5 and 30 months, respectively) than AID deficiency (30 and 114 months, respectively) (p = .001 and p = .008, respectively). Frequent clinical symptoms were recurrent (66%) and severe (14.9%) infections, and/or autoimmune/non-infectious inflammatory features (48.4%). Eosinophilia and neutropenia were at a higher rate in CD40L deficiency patients (77.8%, p = .002 and 77.8%, p = .002, respectively) when compared to AID deficiency. Median serum IgM level was low in 28.6% of CD40L deficiency patients. It was significantly lower when compared to AID deficiency (p < 0.001). Six patients (CD40L deficiency n = 4, CD40 deficiency n = 2) underwent hematopoietic stem cell transplantation. Five were alive at the last visit. Four patients two patients with CD40L deficiency, one with CD40 deficiency and one with AID deficiency had novel mutations. In conclusion; patients with CSR defects and HIGM phenotype may present with a wide range of clinical manifestations and laboratory findings. Low IgM, neutropenia and eosinophilia were prominent in patients with CD40L deficiency. Characterization of genetic defect-specific clinical and laboratory features may ease the diagnosis, prevent the underdiagnoses of patients and ameliorate the outcome.

Hypersensitivity Reactions to Biologicals: from Bench to Bedside.

PURPOSE OF REVIEW: Biologic agents are new treatment options for chronic inflammatory diseases and cancers. As a result of their unique mechanism of action, they are more effective and less toxic treatment option and their clinical usage is increasing. While they are more commonly used, various adverse effects have been observed including life-threatening ones, including anaphylaxis. The aim of this review is to distinguish the anaphylaxis from other hypersensitivity reactions (HSR) and provide a management algorithm for the anaphylactic reactions induced by biological agents. RECENT FINDINGS: Many case reports and series have been published regarding anaphylaxis and other hypersensitivity reactions (concerning cytokine release syndrome, acute infusion-related reactions) due to biologic agents. Although acute treatment of HSR varies according to the clinical presentation, desensitization with the drug is the major management option for subsequent administrations in the case of anaphylactic reactions. SUMMARY: Anaphylaxis and other immediate onset hypersensitivity reactions are occasionally difficult to differentiate from each other, and mixed-type reactions may be observed. Immediate management of anaphylaxis includes discontinuation of infusion, immediate administration of adrenaline, antihistamines, corticosteroids, and other treatment options depending on the symptoms. After 30-120 min of the reaction, a blood sample for serum tryptase levels should be obtained and after 4-6 weeks skin testing with the culprit drug should be performed for decision of long-term management via either graded challenge or desensitization.