HLA-B*15:02, carbamazepine and serious skin reactions

Stevens-Johnson syndrome is a serious skin and mucous-membrane reaction that needs urgent hospital care. The NHS says it is typically triggered by medicines, and lists carbamazepine, lamotrigine and phenytoin among epilepsy medicines that can cause it, along with sulfa antibiotics, some anti-inflammatory painkillers and allopurinol. In children, viral infections occasionally trigger it.

Most people who take carbamazepine never experience it. The reason a genetic test is useful is that HLA-B*15:02 identifies a subgroup with a much higher chance. MedlinePlus Genetics describes the allele as significantly raising the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis, particularly in Han Chinese and Southeast Asian populations.

The MHRA's safety update covers carbamazepine and the related medicines oxcarbazepine and eslicarbazepine. For HLA-B*15:02 it says the association is strong in Han Chinese, Hong Kong Chinese, Thai, Indian and Malaysian populations and that screening before treatment is advised in those groups, with sensitivity close to 100 per cent for the syndrome.

Because the medicines are structurally related, the guidance extends to oxcarbazepine and eslicarbazepine, although the agency notes the supporting evidence is more limited. A negative test lowers risk but does not remove the need to watch for skin changes, so the symptoms below matter for everyone.

• Screening applies to people from the populations the MHRA names, not to everyone.

• The test is performed before the first carbamazepine dose, because the reaction usually develops early in treatment.

• If screening is positive, an alternative anti-seizure or pain medicine is normally chosen by the specialist.

HLA-A*31:01 is a different variant, found in people of European descent at a frequency of 2 to 5 per cent and in about 10 per cent of Japanese people. The MHRA said it may raise the risk of carbamazepine-induced skin reactions from 5 per cent to 26 per cent in Europeans, but that the test detects only a minority of cases, with sensitivity of 42 per cent in Europeans and 83 per cent in Japanese people.

On that basis the agency concluded there were insufficient data to recommend screening for HLA-A*31:01 before carbamazepine. It is an example of how a gene can raise risk without being strong enough to justify a routine test.

For phenytoin the MHRA says HLA-B*15:02 is found in 8.2 to 9 per cent of the Thai population and 8.6 per cent of the Han Chinese population, against 1 to 2 per cent in Caucasians. Data were considered too limited to recommend routine screening, but for Thai or Han Chinese patients known to be positive, phenytoin should be avoided when alternative therapy can be given.

MedlinePlus Genetics adds that another variant, HLA-B*58:01, is linked with allopurinol reactions. The principle is the same across these examples: the test is used to avoid a medicine, because an immune reaction is not solved by a dose change.

The NHS describes early flu-like symptoms such as fever, sore throat and cough, followed days later by a rash of circular patches, darker in the middle, which spreads and develops into painful blisters and peeling skin. For people on carbamazepine it lists an itchy or painful rash, mouth ulcers or blisters and trouble breathing.

Call 999 immediately for these symptoms, as the NHS advises, especially after starting a new medicine. Treatment is in hospital, skin typically heals in two to three weeks and full recovery can take months. If a medicine caused the reaction, it and sometimes similar ones must be avoided permanently, so make sure it is recorded as an allergy.

If you are of a population named by the MHRA and have been offered carbamazepine, ask whether HLA-B*15:02 screening has been done. If your doctor has not mentioned it, it is reasonable to ask. If you are already taking carbamazepine without trouble beyond the first few months, the early-onset risk has largely passed, but any new rash still needs attention.

The NHS epilepsy page stresses not changing your dose or stopping your medicine without speaking to your specialist, so do not stop carbamazepine on your own for fear of a skin reaction unless you are developing symptoms and seeking urgent help.