Clinical classification of DHRs
Tiny changes were made through clinical classification of DHRs, but controversies still exist. Immediate reactions (IRs) appear within 1 hour up to 6 hours, after the first dose of the last therapeutic course. In general IRs are mediated by IgE antibodies. The clinical manifestation of those reactions ranges from benign urticaria with or without angioedema, up to potentially life-threatening anaphylaxis. Two clinical entities of IRs have been proposed: mild IRs (urticaria /angioedema), and severe IRs (anaphylaxis/anaphylactic shock). IRs can also be mediated by COX-1 inhibition or by MRGPRX2 (Mas-related G-protein-coupled receptor member X2). Clinical entities are: urticaria, angioedema, anaphylaxis and respiratory symptoms. Nonimmediate reactions (NIRs) occur more than 6 hours after the first dose of the last therapeutic course, which often start 2 to 5 days later. NIRs are mediated by T cells. Clinical manifestations of those reactions ranges from benign rashes (maculopapular exanthema-MPE or fixed drug eruption- FDE or serum sickness like reactions SSLR) to potentially life-threatening severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome-SJS and toxic epidermal necrolysis-TEN, drug reaction with eosinophilia and systemic symptoms-DRESS, acute generalized exanthematous pustulosis-AGEP or single organ reaction such as drug induced liver disease (DILI). Also two clinical entities of NIRs have been proposed: mild NIRs (MPE, SSLR) and severe NIRs (SCARs).1-3