Emerging Strategies for Delayed Hypersensitivity Reactions, With Jason Trubiano, PhD

In an interview at the American College of Allergy, Asthma & Immunology (ACAAI) Annual Meeting in Orlando, Florida, Jason A. Trubiano, PhD, MBBS, from Melbourne Medical School, discussed evolving strategies for managing delayed hypersensitivity reactions.

These T-cell–mediated reactions, including DRESS (drug reaction with eosinophilia and systemic symptoms), acute generalized exanthematous pustulosis (AGEP), and Stevens–Johnson syndrome (SJS), have long been managed with systemic corticosteroids. However, limited evidence supports corticosteroids for hypersensitivity reactions.

“It's a really difficult field because not a lot of new drugs and therapies [are] coming through,” Trubiano said. “There are rare conditions that don't get a lot of pharmaceutical attention, so we have to repurpose drugs from other diseases for this condition.”

Trubiano highlighted a shift toward exploring therapies originally developed for other immune-mediated conditions, such as hereditary angioedema (HAE), and repurposing them for severe cutaneous adverse reactions. He said the targeted mechanism of JAK inhibitors may offer a more precise way to interrupt immune pathways implicated in DRESS.

Another developing approach is T-cell modulation with agents such as etanercept. Trubiano cited a randomized controlled trial in Taiwan showing reduced mortality in SJS when etanercept was used. Many centers have begun integrating etanercept into management strategies for severe SJS cases requiring intensive care.

However, newer therapies appear unnecessary for AGEP. Patients generally recover rapidly with drug cessation and topical corticosteroids, and Trubiano noted that investigations continue to focus most heavily on conditions with greater morbidity.

A major component of Trubiano’s presentation centered on prevention. Many severe delayed hypersensitivity reactions are tied to known genetic risk factors, such as HLA-B*58:01 in allopurinol-induced reactions. He said that the next frontier will most likely combine pre-treatment genotyping with immunophenotyping to identify risk, guide drug selection, and enable precision-based interventions.

Trubiano anticipates a future where personalized medicine transforms outcomes in delayed hypersensitivity reactions. By integrating genetic testing with targeted immunomodulators, clinicians may one day prevent these reactions entirely or halt progression before patients experience critical illness.

“Rather than just blindly giving steroids, which attack everything, we should give very targeted therapies,” Trubiano said.

Trubiano has no reported disclosures.

References

Trubiano, J. Spectrum Of, and Novel Treatments for, Delayed Hypersensitivity Reactions. Presented at ACAAI 2025 in Orlando, Florida, on November 10.