On comparing 32 patients with SCARs and 395 tolerant controls, we identified eight strong risk factors: increased age (OR 15.1 [95% CI 5.8–40.1], P < 0.0001), female sex (OR 333 [40–43,453], P < 0.0001), allopurinol for asymptomatic hyperuricemia (OR 955 [120–125,847], P < 0.0001), allopurinol starting dose > 150 mg (OR 316 [101–122], P < 0.0001), diuretics intake (OR 304 [35–40,018], P < 0.0001), eGFR < 60 ml/min/1.73 m2 (OR 100 [32–353], P < 0.0001), history of allopurinol-induced skin reaction (OR 78 [6–10,808], P = 0.004), and HLA-B*58:01 carriage (OR 147 [45–746], P < 0.0001). This evidence concerns the gene HLA-B and skin reaction.