Acetylsalicylic acid and montelukast block mast cell mediator–related symptoms during rapid desensitization

Background Rapid desensitization is a process in which drug-allergic patients receive their target dose in incremental steps, resulting in a state of temporary tolerization. In this manner, first-line therapy can be delivered safely, even in patients who present with severe hypersensitivity reactions (HSRs) to the given agent. A small subset of patients has persistent HSRs during rapid desensitization that can be refractory to antihistamines and corticosteroids. Objective To increase the safety and tolerability of rapid desensitization by prostaglandin and leukotriene blockade in patients with refractory mast cell mediator–related symptoms. Methods Fourteen adult patients developed HSRs to platinum chemotherapy that persisted during rapid desensitization. All patients had cutaneous symptoms (flushing, pruritus, or urticaria), many with associated systemic reactions. These patients were then pretreated with acetylsalicylic acid, 325 mg orally, and montelukast, 10 mg orally, 2 days before and on the day of desensitization. Response to subsequent desensitizations was assessed by medical record review and was compared with a group of matched historic control patients who received methylprednisolone for HSRs during desensitization. Results Seventy-eight desensitizations in 14 patients were performed. Using acetylsalicylic acid and montelukast, 86% of patients (12/14) experienced substantial improvement in symptoms (grade 0.5 vs grade 2.14, P < .0001). Reduction in symptoms during desensitization was also significantly greater than that experienced by historic control patients who received methylprednisolone pretreatment (grade 0.5 vs grade 1.75, P = .0008). All patients received their target dose of chemotherapy, and there were no severe systemic HSRs. Conclusions Pretreatment with acetylsalicylic acid and montelukast lessens the severity of HSRs during rapid desensitization.