Authors' objectives: Anticonvulsant hypersensitivity syndrome is a term used to describe the adverse drug reactions (ADRs) that may occur in patients taking anticonvulsant medications (also known as antiepileptic drugs [AEDs]). These adverse reactions are estimated to occur in 1 in 1000 to 1 in 10,000 AED exposures, and are commonly from the use of aromatic anticonvulsants (which are so named because of the process in which these medications are metabolized). These medications include carbamazepine (CBZ; also known by the brand name Tegretol), phenytoin (PHT; also known as fosphenytoin or by the brand name Dilantin), oxcarbazepine (OXC; also known by the brand name Trileptal), lamotrigine (LTG; also known by the brand name Lamictal), phenobarbital, and zonisamide (also known by the brand name Zonegran). CBZ is the most commonly prescribed firstline treatment for seizure disorders or epilepsy, and is also known to be effective in the treatment of bipolar disorder, trigeminal neuralgia (a chronic pain condition affecting the trigeminal facial nerve), neuropathic pain (pain due to damage or dysfunction of the nerves), and tinnitus (persistent noise or ringing in the ears). However, up to 10% of patients who are treated with CBZ may experience a cutaneous ADR (cADR; also known as a severe cutaneous adverse reaction, or SCAR). In addition, patients who are treated with other aromatic AEDs, such as PHT or LTG, may develop similar reactions. These reactions vary in severity, from nonbullous (nonblistering) maculopapular skin rashes (flat, red patches on the skin covered with small bumps) to severe bullous (blistering) skin reactions with fever and multisystem involvement. With regard to specific diagnoses, the nonbullous reactions to aromatic AEDs include maculopapular eruption (MPE) and hypersensitivity syndrome (HSS; also known as drug reaction with eosinophilia [increased number of eosinophils, a type of disease-fighting white blood cells] and systemic symptoms [DRESS] or drug-induced hypersensitivity syndrome [DIHS]). The more severe, bullous reactions include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap, although these diagnoses actually represent varying degrees of a single disease spectrum characterized by blistering erosions of the skin and mucosal membranes, skin detachment, and fever. Treatment of AED-related ADRs begins with the immediate withdrawal of the offending medication. In addition, it may include corticosteroid, immunosuppressant, or immunoglobulin therapy, and potentially admission to a burn center or intensive care unit. The most severe of these reactions are associated with increased mortality (up to 30% or more depending on the severity) and with longterm complications, such as blindness due to involvement of the eyes or cornea. Because of the chance of developing a severe reaction to CBZ and related medications, research has focused on identifying genetic variants that may be used to help assess the likelihood of an ADR prior to treatment initiation. Subsequently, it was discovered that some reactions to aromatic AEDs are associated with specific variants in the human leukocyte antigen (HLA) genes. The HLA genes encode cell surface proteins that function in immune response. The most common HLA allele (version of an HLA gene) linked to the development of ADRs in patients taking aromatic AEDs is the HLA-B*1502 allele, which is associated with an increased risk of developing SJS or TEN (or SJS/TEN overlap) in Asian patients taking CBZ. The HLA-B*1502 allele is most common among individuals from Southeast Asia. It is significantly less common among Japanese and Korean individuals, and is essentially absent in those of European, African, and Hispanic descent.

Project Status: Completed

Year Published: 2014

URL for published report: The report may be purchased from: http://www.hayesinc.com/hayes/crd/?crd=16511

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

Contact Address: 157 S. Broad Street, Suite 200, Lansdale, PA 19446, USA. Tel: 215 855 0615; Fax: 215 855 5218

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Contact Email: saleinfo@hayesinc.com

Copyright: 2014 Winifred S. Hayes, Inc