Cutaneous adverse drug reactions to allopurinol: 10 year observational survey of the dermatology department--Cagliari University (Italy)

Background: Allopurinol is extensively prescribed for conditions associated with urate excess, despite being responsible for severe cutaneous adverse drug reactions (ADR).

Objective: A cross-sectional survey of allopurinol cases observed at the main Dermatology Department with inpatients facilities in southern Sardinia. (approx 560,836 inhabitants).

Material and methods: Data collection of all consecutive patients referred for ADR between 2001 and 2010. Causality assessment followed the WHO Collaborating Centre for Drug Monitoring criteria; illness severity score was adopted for toxic epidermal necrolysis (SCORTEN).

Results: Allopurinol was the culprit drug in 84 of 780 cutaneous ADR cases (10.7%; 8.4 cases/year). Mean age was 74 years, 58% of the patients were female, 95% of patients required hospitalization. Clinical forms were maculo-papular eruptions (34 cases), Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (31 cases), vasculitis (six cases), Drug Rash Eosinophilia and Systemic Symptoms (DRESS) (three cases), Acute Generalized Exanthematous Pustolosis (AGEP) (three cases), Pityriasis rosea-like eruption (three cases), lichenoid dermatitis (two cases), fixed drug eruption (one case), erythroderma (one case). The indication for allopurinol prescription was asymptomatic hyper-uricemia in 95% of the patients. Twelve patients were under allopurinol dosage adjustment according to creatinine clearance. Final causality assessment was definite for 12% of the cases and probable for the remaining 88%. Full recovery was achieved in 88% of subjects; ten SJS/TEN patients died (12% overall mortality; 32% mortality of the SJS/TEN cases).

Conclusion: Considering the populations size of Southern Sardinia, is plausible that 1.5/100,000 Sardinian will be affected by allopurinol related ADR per year. Advanced age, and inappropriate allopurinol prescription were the main conditions affecting morbidity and mortality.