Anticonvulsant hypersensitivity syndrome

Anticonvulsant hypersensitivity syndrome (AHS) is a rare but potentially fatal adverse drug reaction that occurs in response to certain anticonvulsant medications. The syndrome is characterized by a triad of symptoms: fever, skin rash, and internal organ involvement, most commonly affecting the liver and kidneys.

Etiology

AHS is most commonly associated with the use of aromatic antiepileptic drugs (AEDs), including phenytoin, carbamazepine, and phenobarbital. Other drugs, such as lamotrigine, oxcarbazepine, and zonisamide, have also been implicated. The exact mechanism of AHS is not fully understood, but it is believed to involve a complex interplay of genetic susceptibility, drug metabolism, and immune response.

Clinical Presentation

The onset of AHS typically occurs 1-8 weeks after initiation of the offending drug. The first symptom is usually a fever, followed by a skin rash that can range from a mild maculopapular rash to severe Stevens-Johnson syndrome or toxic epidermal necrolysis. Internal organ involvement can manifest as hepatitis, nephritis, or lymphadenopathy. In severe cases, AHS can lead to multi-organ failure and death.

Diagnosis

Diagnosis of AHS is primarily clinical, based on the characteristic triad of symptoms and a history of exposure to a potential offending drug. Laboratory tests can support the diagnosis and assess the extent of organ involvement. Skin biopsy may be performed in cases where the rash is severe or the diagnosis is uncertain.

Treatment

The first step in the treatment of AHS is immediate discontinuation of the offending drug. Supportive care, including hydration and fever control, is essential. In severe cases, systemic corticosteroids may be used to suppress the immune response. If organ failure occurs, intensive care and organ support may be necessary.

Prognosis

The prognosis of AHS varies widely, depending on the severity of the reaction and the extent of organ involvement. With prompt recognition and treatment, most patients recover fully. However, severe cases can be fatal, and some patients may have long-term organ damage.

Prevention

Prevention of AHS involves careful selection and monitoring of anticonvulsant therapy, particularly in patients with a known history of drug hypersensitivity. Genetic testing may be useful in identifying patients at increased risk.