Lamotrigine hypersensitivity syndrome

Published and unpublished cases of Stevens-Johnson syndrome (n = 43) and toxic epidermal necrolysis (n = 14) associated with lamotrigine have been reviewed (44). The patients with Stevens-Johnson syndrome were younger than those with toxic epidermal necrolysis (21 versus 31 years) the median time to onset for both reactions was 17 days the median dosage at onset (50 mg for Stevens-Johnson syndrome, 87.5 mg for toxic epidermal necrolysis) did not differ significantly. Valproate comedication was present in 74% and 64% of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis respectively. In three patients, toxic epidermal necrolysis occurred in the context of the anticonvulsant hypersensitivity syndrome. 

A phenytoin-like hypersensitivity syndrome with skin rash, leukocytosis, and laboratory evidence of liver and kidney dysfunction has been attributed to lamotrigine (SEDA-22, 89). 

The manifestations of acute lamotrigine overdose can mimic the anticonvulsant hypersensitivity syndrome (68). 

Twenty-six lamotrigine-associated reactions consistent with the features of the anticonvulsant hypersensitivity syndrome have been reviewed, including nine previously published (54). The patients were aged 3.5-74 years (mean 28) and 14 were female. Valproate was used as co-medication in 60%. 

Schlienger RG, Knowles SR, Shear NH. Lamotrigine-associated anticonvulsant hypersensitivity syndrome. Neurology 1998 51(4) 1172-5. 

Fervenza FC, Kanakiriya S, Kunau RT, Gibney R, Lager DJ. Acute granulomatous interstitial nephritis and colitis in anticonvulsant hypersensitivity syndrome associated with lamotrigine treatment. Am J Kidney Dis 2000 36(5) 1034-40. 

Schaub N, Bircher AJ. Severe hypersensitivity syndrome to lamotrigine confirmed by lymphocyte stimulation in vitro. Allergy 2000 55(2) 191-3. 

Mylonakis E, Vittorio CC, HolUk DA, Rounds S. Lamotrigine overdose presenting as anticonvulsant hypersensitivity syndrome. Ann Pharmacother 1999 33(5) 557-9. 

Skin The clinical and laboratory findings of anticonvulsant hypersensitivity syndrome have been retrospectively evaluated using the medical records of 31 patients over a 12-year period [42 ]. The syndrome was related to carbamazepine in 48% of all cases, phe-nytoin in 35%, and lamotrigine in 9.6%, and in co-treatment with lamotrigine and valproic acid in 6.5% of cases. Symptoms appeared at 2-86 (mean 36) days after the start of treatment. The rashes were... 

Liver Three cases of anticonvulsant hypersensitivity syndrome or drug-related rash with eosinophilia and systemic symptoms (DRESS) have been described in conjunction with lamotrigine-associated hepatitis two recovered after withdrawal of lamotrigine [156, 157 ], but the third required liver transplantation [158 ]. 

Skin Stevens-Johnson syndrome [159 ] and anticonvulsant hypersensitivity syndrome [160" ] have been described in patients taking lamotrigine. 

Aouam K, Ben Romdhane F, Loussaief C, Salem R, Toumi A, Belhadjali H, Chaabane A, Boughattas NA, Chakroun M. Hypersensitivity syndrome induced by anticonvulsants possible cross-reactivity between carbamazepine and lamotrigine. J Clin Pharmacol 2009 49(12) 1488-91. 

A 30-year-old woman with lamotrigine-induced drug hypersensitivity syndrome (generalized, erythematous, morbilliform skin eruption with oral and ocular ulcerations) was refractory to dexamethasone treatment but was successfully treated with intravenous immxmoglobulin [86 ]. 

Comfere NI, Sartori-Valinotti JC, Bruce AJ, Drage LA. Successful treatment of lamotrigine-associated drug hypersensitivity syndrome with intravenous IgG. J Am Acad Dermatol June 2012 66(6) e249-50. 

Stevens-Johnson syndrome, and 3 as suggestive of Stevens-Johnson syndrome two deaths were reported. Rashes associated with one or more symptoms of hypersensitivity reactions occurred in 19 children. Of 29 patients with Stevens-Johnson syndrome, toxic epidermal necrolysis, or hypersensitivity reactions, for whom precise details were available, 83% were taking lamotrigine with concomitant valproate and 85% were taking lamotrigine dosages higher than recommended. 

Lamotrigine 22-36 h 200-500 mg Lethargy, dizziness, ataxia, stupor, nystagmus, hypertonia, seizures QRS prolongation nausea and vomiting hypokalemia hypersensitivity fever, rash (Stevens-Johnson syndrome) hepatitis, renal failure. 

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