The possible mechanisms of psoriasis flare while on a saturating dose of efalizumab include (1) allergic hypersensitivity, (2) the development of anti-human neutralizing antibodies, (3) lowering of tissue concentration of the drug, or (4) an external trigger inducing other types of leukocytes to enter the skin via an LFA-1-independent mechanism causing inflammation. The gene discussed is ITGAL; the disease is psoriasis.