Allopurinol-Induced Drug Hypersensitivity Syndrome 林世昌 醫師 國泰綜合醫院 過敏免疫科

Anaphylaxis CHARLES ROBERT RICHET The opposite of phylaxis or protection 1913 Nobel Laureate in Medicine in recognition of his work on anaphylaxis

Clinical Heterogeneity of Drug Hypersensitivity Drug reaction vs drug hypersensitivity Heterogeneity of skin lesions and skin pathology Heterogeneity of biological alterations: leukocytosis, eosinophilia, liver injury Heterogeneity of complications, prognosis and sequels Heterogeneity of drug causes: allopurinol is one of major causes of SJS or TEN (but only occasionally cause DRESS, but not AGEP (acute generalized exanthematous pustulosis)

Epidemiology of Allopurinol Hypersensitivity Cutaneous adverse reactions to allopurinol are common, affecting 2% of patients prescribed. Severe cutaneous adverse reaction: 0.4% of patients receiving therapy allopurinol  Allopurinol hypersensitivity syndrome Some hospital-based studies: allopurinol is one of most common drugs causing severe drug hypersensitivity syndrome associated with a high mortality of about 25%. The incidence of allopurinol hypersensitivity varies between different populations.

Diagnostic Criteria of Allopurinol Hypersensitivity Syndrome DRESS: Drug Reaction with Eosinophilia and Systemic Symptoms

Immune Mechanisms in Drug Hypersensitivity Immunologic memory with re-challenge Fit into 4 hypersensitivity classification of Gell and Coombs ?  drug specific T-cells What is the antigen  Parent drug or a reactive metabolite  Hapten and carrier Why is the immune response to medications leading to so diverse reactions? FROM OUR KNOWLEDGE OF MECHANISMS TO PREVENTION AND TREATMENT OF DRUG ALLERGY NOT CLOSE YET

Risk Factors of Drug Allergy Environmental factors  Viral infection  Bacterial infection Genetic factors Other systemic diseases: SLE

Genetic Studies on Drug Hypersensitivity The incidence of hypersensitivity varies according to the drug and the ethnicity of the patient Case reports of the familial occurrence of drug hypersensitivity reactions Determine the likelihood of drug hypersensitivity Determining the severity and pattern of clinical manifestations

HLA and Drug Hypersensitivity

The Recommendation for the Use of Allopurinol Clear indication Cautiously used in elderly, Chinese race, patients with underlying renal disease Allopurinol dosage should be corrected according to the renal function  Always start with a lower dose of allopurinol Monitored patients during the first two months for possible drug hypersensitivity Educate patients about early recognition of drug hypersensitivity and the importance of prompt withdrawal of the drug