The following is a summary of the “Interleukin-6 and cytokine release syndrome: A new understanding in drug hypersensitivity reactions,” published in the February 2023 issue of Allergy and Clinical Immunology by Lee, et al.

Mast cell degranulation and the release of mediators like tryptase and histamine are traditionally assumed to be at the root of immediate drug hypersensitivity reactions (DHRs) caused by immunoglobulin E (IgE) cross-linking. However, as monoclonal antibodies have grown more common, it has become clear that some patients exhibit atypical features during immediate DHRs, such as the presence of fever, chills, rigors, and musculoskeletal pain, the absence of urticaria and angioedema, and the incidence during initial exposure. 

A new phenotype of immediate DHRs, cytokine release syndrome (CRS), was identified as a result of this finding. Infusion-related reactions (which manifest similarly to CRS) and mixed reactions are two more types of acute DHRs (which share overlapping features of both type 1 reactions and CRS). Those who develop rapid DHRs to first-line treatment may benefit significantly from desensitization to the offending medicines. However, even though drug desensitization is safe and effective in numerous studies, some patients may still experience a breakout reaction, with CRS being the most common cause. 

Tryptase, linked to type 1 reactions, is the only biomarker now available for immediate DHRs. New evidence suggests that interleukin six can be a potential biomarker, in addition to tryptase, to discriminate between different types of DHRs, and this link has been demonstrated repeatedly about higher serum interleukin six levels and DHR-related CRS. In today’s era of precision medicine, it is important to phenotype and endotype hypersensitivity reactions to chemotherapy and monoclonal antibodies with the help of validated biomarkers as part of standard drug allergy care.

Source: sciencedirect.com/science/article/abs/pii/S1081120622019056