**3. The skin clinical phenotypes of NSAID hypersensitivity**

The skin reactions are the most prevalent clinical phenotypes in patients with NSAID hypersensitivity. We have described at least 5 clinical phenotypes of immediate-type of skin NSAID hypersensitivity: [3, 7] NSAID-exacerbated cutaneous disease (NECD), NSAID-induced urticaria/angioedema (NIUA), two clinical phenotypes (NSAID induced isolated periorbital angioedema and NSAID induced recall urticarial) which are present exclusively in patients with respiratory allergy, mainly house dust mites; and a single NSAID induced urticaria/angioedema/ anaphylaxis (SNIUAA) (**Table 1**). The last mentioned is probably an IgE-mediated allergy. The remaining phenotypes do not have an immunological pathophysiology, but are caused by inhibiting COX-1 resulting in an imbalance in eicosanoid mediators, as above outlined.
