Allopurinol-Induced Drug
Hypersensitivity Syndrome
林世昌 醫師
國泰綜合醫院
過敏免疫科
Anaphylaxis
The opposite of phylaxis or protection
1913 Nobel Laureate in
Medicine
in recognition of his work on
anaphylaxis
CHARLES ROBERT RICHET
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