HLA (human leukocyte antigen) genes play an important role in the immune system. They help the immune system to identify and respond to foreign substances, such as bacteria and viruses.
Certain DNA variations in the HLA-B gene can lead to the so-called HLA-B*1502 allele. This specific HLA-B*1502 allele can lead to hypersensitivity reactions as a result of treatment with lamotrigine, carbamazepine and related drugs like phenytoin and oxcarbazepine.
Carbamazepine is a drug that calms overstimulated nerves in the brain. It is used to treat epilepsy, manic depression, neuralgia, diabetes insipidus and alcohol withdrawal, amongst other things.
In around 10% of people treatment with lamotrigine, carbamazepine and related drugs leads to side effects in the form of skin problems. The severity and nature of these can vary. In patients who experience mild side effects red bumps and marks can appear on the skin, which spontaneously disappear once the medication is stopped.
However, severe side effects can also occur, such as itching, fever and inflammation of the liver or kidneys. These side effects are referred to by the term hypersensitivity syndrome (HSS/DRESS syndrome).
In rare cases a patient may even experience serious, sometimes life-threatening, side effects, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Genetic predisposition
Your individual risk of side effects in the event of treatment with carbamazepine, oxcarbazepine, phenytoin and lamotrigine may be partly explained by genetic variations. It is known, for example, that mutations in the HLA gene are partly responsible.
It has been demonstrated that carriers of the HLA-B*1502 allele are genetically predisposed to carbamazepine hypersensitivity. HLA-B*1502 positivity is found in varying percentages within the Asian population; the figures for different Asian population groups range from 1 to over 15%. In Europeans HLA-B*1502 positivity is less common (0-2%).
If a person is HLA-B*1502 positive, they have a significantly increased risk (more than 100 times greater) of serious side effects such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) as a result of a treatment with lamotrigine, carbamazepine and related drugs.*
Not everyone who is HLA-B*1502 positive experiences such serious side effects; they occur in roughly 1 in 20 positive individuals.
For safety reasons, the CPIC and KNMP recommend not starting a treatment with carbamazepine, oxcarbazepine, phenytoin and lamotrigine in the case of patients who are HLA-B*1502 positive. How you should ultimately proceed is a decision for an attending doctor.
*The risk of side effects as a result of carbamazepine treatment is also increased with HLA-A*3101 or HLA-B*1511-positivity.