Millions of cases of adverse drug reactions (ADRs) are reported annually, many of which account for thousands of deaths. This makes the ADRs one of the leading causes of hospitalization and of death in the United States.
Knowing the patient’s genetic susceptibility to ADRs is instrumental in preventing serious drug related consequences. An example of a genetic marker associated with ADR is HLA-B*5701 genotype and hypersensitivity to abacavir, used to treat HIV infection. Variants of the HLA genes are reported to be associated with adverse reactions with several therapeutic drugs. To mitigate potentially adverse drug reactions, the FDA recommends testing for HLA typing before administering such drugs. Kashi Clinical Laboratories offers testing of a comprehensive battery of HLA biomarkers. The followings are examples of additional drugs associated with harmful reactions.
Abacavir is a nucleoside analog reverse transcriptase inhibitor (NRTI) used to treat HIV and AIDS. It is available under the trade name Ziagen and in two other formulations, Trizivir and Epzicom, both containing abacavir. Fatal hypersensitivity reactions have been associated with abacavir therapy. Symptoms include fever, skin rash, fatigue, nausea, vomiting, diarrhea or abdominal pain and respiratory symptoms such as pharyngitis, dyspnea or cough. Hypersensitivity is strongly associated with HLA-B*57:01, for which testing is now available in most countries. Screening for the HLA-B*57:01 has been convincingly shown to reduce the incidence of abacavir hypersensitivity reactions. Abacavir binds specifically to the peptide-binding groove of HLA-B*57:01 and thereby alters the spectrum of peptides that bind to this molecule. This leads to aberrant CD8 T-cell responses to self-antigens, which may explain the side effect. An FDA alert concerning abacavir and abacavir-containing medications was issued in July 2008 supporting pre-therapy screening for the presence of the HLA-B*57:01 allele and the selection of alternative therapy in positive subjects. Genetic tests for HLA-B*57:01 are available and all patients should be screened for the HLA-B*57:01 allele before starting or restarting treatment with abacavir or abacavir containing medications. Development of clinically suspected abacavir hypersensitivity requires immediate and permanent discontinuation of abacavir therapy in all patients, including patients negative for HLA-B*57:01.
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:
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.
Penicillin hypersensitivity is strongly associated with the presence of the HLA-B*55:01 allele in those with European ancestry. Due to the unpredictable and potentially severe nature of adverse drug reactions, it is recommended to consider testing for the presence of HLA-B*55:01 allele prior to initiating penicillin therapies. This test may also be used to further support a self-reported penicillin allergy. It is important to note that absence of the HLA-B*55:01 allele does not exclude a patient from possessing sensitivity to penicillin.
Kashi Clinical Laboratories uses a variety of techniques including Sanger Sequencing, Next Generation Sequencing, and Real-Time PCR to obtain the most reliable result.
To request environmental testing at Kashi Labs, please visit the Order Now page and contact us to get started.
To request toxicology testing at Kashi Labs, please visit the Order Now page and contact us to get started.
If you are an existing provider, please sign in to place an order through the online portal. If you are new to Kashi and would like to create an account, please contact us.
Place a one-time order by contacting us through the form at the link below, or get started by logging in to your online portal.
BoneMarrowTest.com is a service of Kashi Clinical Laboratories. For more information regarding Private HLA Testing or to order a test kit, please visit BoneMarrowTest.com.
*By clicking the link above you will be redirected to BoneMarrowTest.com.
Find more information regarding MMDx for Molecular Biopsy Assessment, sample reports, and free specimen collection kit orders.
*By clicking the link above you will be redirected to the ThermoFisher website.