Delayed cutaneous adverse drug reactions to sympathomimetics after oral intake of over-the-counter medications

Abstract

Sympathomimetics are a therapeutic class of drugs wich aim is to mimic adrenaline and noradrenaline, contained in many over-the-counter medications such as “Humex Cold”. To date, 32 cases of delayed hypersensitivity induced by pseudoephedrine have been reported in the literature ranging from MPE to severe cutaneous adverse drug reactions, including 3 PEAG and 4 EMP. Cross-reactivities within sympathomimetics are not yet well established. We describe here two case reports of delayed cutaneous drug reactions to sympathomimetics, one maculo-papular exanthema and one acute generalized exanthematic pustulosis. We evaluated cross-reactivity and review the sympathomimetic drugs to be able to make a summary table. We first did patch tests with the molecule that caused the initial skin reaction. Then, searching for cross-reaction: we tested with patch tests thirteen sumpathomimetics with different properties. We also performed skin biopsies on positive patch tests for histological analysis in RNA later for the patient who presented acute generalized exanthematic pustulosis. Patient who did maculopapular exanthema had a negative patch test to pseudoephedrine after two series of allergological tests but did a recurrence of maculo-papular exanthema after oral provocation to pseudoephedrine and with an emergency treatment with ephedrine. A new allergological workup revealed a positive ephedrine patch test at 72 h. The search for cross-reactivity had highlighted during a 3rd exploration positive patch tests at 72 h for: ephedrine, pseudoephedrine in three different molecules (Humex, Actifed, Rhinadvil) anda positive patch test to phenylephrine. Patient who did an acute generalized exanthematic pustulosis had a positive pseudephedrine patch test. No cross-reactivity with other sympathomimetics was found. Literature is weak regarding cases of delayed cross-hypersensitivity to sympathomimetics even if searching for cross-allergies seems to be necessary. We propose summary table and a list of of sympathomimetic drug to test when faced to a delayed cutaneous drug reaction.