Study Quantifies Cutaneous Reaction Risks of Some CKD Treatments
KEY TAKEAWAYS
Severe cutaneous adverse reactions (SCARs) after allopurinol remain rare but serious.
New research suggests Asian ethnicity, advanced CKD, and high initial dosing are strong predictors.
The model may have clinical utility in assist dermatologists weighing the risk of SCARs.
A newly validated risk prediction model in The Lancet Rheumatology could assist practitioners in estimating a patient’s short-term risk of developing severe cutaneous adverse reactions (SCARs) following initiation of allopurinol.
Involving over 215,000 allopurinol initiators across two UK databases (CPRD Aurum and GOLD), the retrospective cohort study focused on a 100-day risk window. SCARs, including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), occurred in 0.04% of patients in both development and validation cohorts.
The model, which integrates routinely available clinical variables, identified key dermatologic risk factors as Asian ethnicity (South Asian and Other Asian subgroups), initial allopurinol dose ≥300 mg/day (HR = 5.99 [95% CI, 3.56 to 10.08]), and moderate to advanced chronic kidney disease (CKD stages 3–5; the HR for CKD stage 5 was 18.85 [95% CI, 6.32 to 56.19]).
According to the researchers, the study findings reinforced known phenotype predictors of SCARs. The model’s discriminatory performance (Harrell’s C = 0.79–0.82) and calibration across low-risk thresholds (0.0001 to 0.003) suggests clinical utility for practicing dermatologist in helping to determine if and what alternatives are needed.
“This model has promising calibration and discrimination and has clinical utility,” the authors concluded. “It could be used to support an individualized risk-based choice between different urate-lowering drugs in patients for whom genetic screening for the HLA-B*58:01 polymorphism is not indicated.”
Source: Cipolletto E, et al. Lancet Rheumatology. 2025. doi:10.1016/S2665-9913(25)00165-1