Drug Sensitivity & Disease Association

Allopurinol is the most commonly used drug for the treatment of hyperuricemia and gout. However, allopurinol is also one of the most common causes of severe cutaneous adverse reactions (SCARs), which include drug hypersensitivity syndrome, Stevens–Johnson syndrome, and toxic epidermal necrolysis. A variant allele of the human leukocyte antigen (HLA)-B, HLA-B*58:01, associates strongly with allopurinol-induced SCAR.

The diagnosis of dampness and mold hypersensitivity syndrome (DMHS) is clinical and is based on the patient’s history and careful examination supplemented by risk assessment based on an HLA-DR test. A study has shown the following HLA gene combinations are implicated in mold hypersensitivity:

• HLA-DR7-DQ2-DR53
• DR7-DQ3-DR53
• DR13-DQ6-DR52
• DR17-DQ2-DR52
• DR18-DQ4-DR52

Carbamazepine is an important treatment for seizure disorders, bipolar disorder, trigeminal neuralgia and chronic pain. However, carbamazepine is also associated with hypersensitivity reactions that range from benign urticaria to life-threatening cutaneous disorders, including Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis. The latter two disorders carry a mortality that can be as high as 30% and require early diagnosis, with prompt withdrawal of all suspected potential causative drugs. The USA FDA has made a labeling change to the drug information for carbamazepine. Owing to recent data implicating the HLA allele HLA-A*31:01 and HLA-B*15:02 as markers for carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis, the FDA recommends genotyping for these alleles, particularly in populations with highest frequency of these alleles.

Phenytoin is a drug to treat epileptic seizures with a structural resemblance to carbamazepine, another antiepileptic drug. New studies have show when Asian patients who test positive for HLA-B*1502 are treated with phenytoin, they are at serious risks for developing adverse skin reactions. The occurrence of allele carriers with HLA-B*1502 is estimated to be 10-15% in patients from China, Thailand, Malaysia, Indonesia, the Philippines, and Taiwan.

High resolution HLA-B*55:01: This allele has been associated with an increased risk of developing a severe hypersensitivity reaction to penicillin in individuals positive for HLA-B*55:01.Penicillin Hypersensitivitycan range can range from mild skin rashes to severe and life-threatening reactions.