From the Guidelines
Yes, carbamazepine can cause Stevens-Johnson Syndrome (SJS), a rare but serious and potentially life-threatening skin reaction. This adverse effect is more common in patients with certain genetic markers, particularly HLA-B15:02 and HLA-A31:01, which increase the risk for SJS and toxic epidermal necrolysis (TEN) 1. The risk of developing SJS with carbamazepine is highest during the first few months of treatment, typically within the first 8 weeks. Symptoms of SJS include fever, flu-like symptoms, followed by painful skin rash that spreads and blisters, affecting the mucous membranes. If you are prescribed carbamazepine, genetic testing for the HLA-B15:02 and HLA-A31:01 alleles is recommended before starting therapy if you have Asian ancestry 1. Some key points to consider:
- The US Food and Drug Administration approved labeling recommends avoiding carbamazepine in patients with HLA-B15:02 and HLA-A31:01 genotypes 1.
- Genetic testing for HLA-B*15:02 is also recommended before using carbamazepine to avoid life-threatening SJS and TEN 1.
- The mechanism behind carbamazepine-induced SJS involves an immune-mediated hypersensitivity reaction where the drug or its metabolites trigger an abnormal T-cell response in genetically susceptible individuals.
- If you develop any rash while taking carbamazepine, contact your healthcare provider immediately as early discontinuation of the medication can improve outcomes. It's essential to follow the guidelines for the management of SJS/TEN, which include discontinuing the culprit drug, providing supportive care, and considering alternative treatments 1.
From the FDA Drug Label
WARNINGS Serious Dermatologic Reactions Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have been reported with carbamazepine treatment.
- Yes, carbamazepine can cause Stevens-Johnson Syndrome (SJS) as stated in the drug label, with a risk estimated to be about 1 to 6 per 10,000 new users in countries with mainly Caucasian populations, and about 10 times higher in some Asian countries 2.
- The risk of SJS is strongly associated with the presence of the HLA-B*1502 allele, particularly in individuals of Asian ancestry.
- Patients who test positive for HLA-B*1502 should not use carbamazepine unless the benefits clearly outweigh the risks.
From the Research
Carbamazepine and Stevens-Johnson Syndrome
- Carbamazepine (CBZ) is a medication that can cause Stevens-Johnson Syndrome (SJS), a rare but severe mucocutaneous reaction 3, 4, 5, 6, 7.
- SJS is characterized by fever, painful sores, and blisters covering the body, along with mucous discharge from the eyes and other mucous membranes 3, 4.
- The risk of developing SJS is increased in individuals with certain genetic predispositions, such as the HLA-B*1502 allele, which is more common in South-East Asian populations 3, 4, 6.
- Other genetic markers, such as the HLA-A*3101 gene, have also been associated with an increased risk of CBZ-induced SJS, particularly in European and Japanese populations 7.
Clinical Presentation and Management
- The clinical presentation of CBZ-induced SJS can include prodromal symptoms such as flu-like symptoms, followed by the sudden onset of fever, painful sores, and blisters 3, 4.
- The diagnosis of SJS is based on clinical presentation and the extent of epidermal detachment, and can be confirmed by skin biopsy 6.
- Management of CBZ-induced SJS typically involves immediate cessation of the culprit drug, supportive care, and symptomatic treatment, such as intravenous immunoglobulins and wound care 3, 4, 6.
Prevention and Screening
- Screening for genetic markers such as HLA-B1502 and HLA-A3101 can help identify individuals at increased risk of developing CBZ-induced SJS 3, 4, 6, 7.
- Gradual titration of CBZ and close monitoring for adverse reactions can also help prevent the development of SJS 5.
- Avoiding readministration of CBZ in patients with a previous history of SJS or adverse skin reaction is also crucial 5.