Three patients harbored the TYK2I684S variant.<h4>Study limitations</h4>The utility of using single markers for psoriasis diagnosis is limited due to the wide variability of results, but the utility of the simultaneous evaluation of a set of markers has promise.<h4>Conclusions</h4>The present study suggests an association between multiple TYK2 pathway markers and loss of systemic treatment response. Here, TYK2 is linked to psoriasis.