Multiple nonsteroidal anti-inflammatory drug-induced cutaneous disease: what differentiates patients with and without...

Multiple nonsteroidal anti-inflammatory drug (NSAID) cutaneous reactors may be otherwise normal or have underlying chronic spontaneous urticaria (CSU). This study compared these two phenotypes of NSAID-hypersensitive subjects.

A total of 97 multiple NSAID reactors underwent oral challenges with paracetamol, etoricoxib and tramadol. Atopic status was investigated in all patients, and autoreactivity was ascertained in some cases as well. Otherwise normal multiple NSAID reactors were reevaluated after 1-5 years in order to detect their proneness to CSU.

At the first visit, 41 patients had CSU and 56 had multiple NSAID intolerance without any underlying cutaneous disease. Altogether, 22, 10 and 6% of patients did not tolerate paracetamol, etoricoxib and tramadol, respectively, on oral challenge. Intolerance to these alternative drugs showed a strong association (p < 0.01 with all combinations). The two subgroups of patients did not show any difference in terms of mean age, gender distribution, prevalence of atopic diseases, prevalence of single offending NSAIDs and prevalence of intolerance to paracetamol, etoricoxib or tramadol on oral challenge. In all, 20% of multiple NSAID reactors without CSU at presentation developed CSU between 6 months and 5 years after the initial clinical evaluation.

Multiple NSAID cutaneous reactors with or without CSU seem identical from a clinical point of view, and some of the latter group show a propensity to acquire the former phenotype over time. A subset of patients apparently identical to the general population of multiple NSAID reactors also react to drugs exerting little or no cyclooxygenase-1 enzyme inhibition and might represent a distinct phenotype of NSAID-hypersensitive patients possibly characterized by a different underlying pathogenesis.