Lamotrighe‐Induced Severe Cutaneous Adverse Reactions

Abstract

Summary: Purpose:We systematically reviewed and analyzed published and unpublished cases of Stevens-Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN) associated with lamotrigine (LTG) therapy to identify characteristics of these reactions.Methods: We performed a MEDLINE search (January 1985 to April 1998) and citation tracking for published reports. In addition, reports were requested from the Uppsala Monitoring Centre of the World Health Organization (WHO). Published and WHO cases of LTG-associated SJS or TEN were included if the causal relationship was assessed as either possible, probable, or definite.Results: We identified a total of 57 cases (43 cases of SJS, 14 cases of TEN), of which 13 (23%) were published. Cases in the SJS group were significantly younger-than in the TEN group (21 years vs. 31 years). The median time to onset (17 days for SJS and TEN) and the median dosage at onset (50 mg vs. 87.5 mg) for SJS and TEN did not differ significantly. Concomitant use of valproate (VPA) was reported in 74% of the SJS cases and 64% of the TEN cases. In three cases, TEN was the cutaneous manifestation of the antiepileptic drug hypersensitivity syndrome (AHS).Conclusions: The main features of severe cutaneous drug reactions, such as dosage, onset, and concomitant VPA use, do not differ in patients with LTG-induced SJS or TEN. SJS or TEN may also be the cutaneous manifestations of LTG-induced AHS. Further epidemiologic studies are needed to identify the incidence of severe LTG-induced cutaneous adverse reactions and the relative risk compared with other AEDs. Key Words: Lamotrigine-Antiepileptic drugs-Stevens-Johnson syndrome-Toxic epidermal necrolysis-Hypersensitivity .Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN, Lye11 syndrome) are severe albeit rare adverse drug reactions (ADRs) to several antiepileptic drugs (AEDs) such as phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), and valproate (VPA) (1-6). A recent cohort study indicated that the risks for severe cutaneous reactions in first-time users of PHT and CBZ are 9110,000 and 6.2/10,000, respectively (7). Severe cutaneous adverse reactions (SCARS) such as erythema multiforme (EM), SJS, or TEN may also represent the cutaneous manifestation of the antiepileptic drug hypersensitivity syndrome (AHS), which is defined by the triad of fever, a cutaneous reaction, and internal organ involvement (3,8).Lamotrigine (LTG), a phenyltriazine, is chemically unrelated to existing AEDs (9). It is extensively metabolized, predominantly by N-glucuronidation, whereas only minor fractions undergo N-oxidation and N-methylation

Severe Cutaneous Adverse Reactions

“…Lamotrigine when commenced at high doses can also overwhelm the detoxifying capacity resulting in an increased risk of SJS/TEN and DIHS [88]. The incidence has reduced significantly as a result of the now conventional practice of gradually titrating the dose [89].…”

Lyell – szindróma gyermekkorban

“…Lefolyása kiszámíthatatlan, igen magas mortalitási arány jellemzô. Elôfordulási gyakorisága a teljes populációt tekintve 0.4-1.8:1000000, enyhe nôi túl-súly figyelhetô meg (1)(2)(3)(4)(5) (3)(4)(5)(6)(7)(8)(9)(10)(11). Patomechanizmusa nem teljesen tisztázott, azonban a gyógyszer, illetve gyógyszermetabolitok által beindított immunológiai reakció eredményeként aktiválódott specifikus cytotoxikus T-sejtek igen fontos szerepet játszanak a hámsejtek károsodásában, emellett a TNF-α, IFN-γ, IL-2 fokozott expressziója révén közvetített, illetve a Fas-FasL interakció révén létrejövô keratinocyta apoptosis is szerepet játszik benne (1, 2).…”

Severe Cutaneous Adverse Reactions

“…Lamotrigine when commenced at high doses can also overwhelm the detoxifying capacity resulting in an increased risk of SJS/TEN and DIHS (Schlienger, Shapiro et al 1998). The incidence has reduced significantly as a result of the now conventional practice of gradually titrating the dose (Mockenhaupt, Messenheimer et al 2005).…”