Anticholinesterase activity of ß-carboline-1, 3, 5-triazine hybrids

Abstract The ß-carboline-1,3,5-triazine hydrochlorides 8-13 were evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The analysed compounds were selective to BuChE, with IC50 values in the range from 1.0-18.8 µM being obtained. The N-{2-[(4,6-dihydrazinyl-1,3,5-triazin-2-yl)amino]ethyl}-1-phenyl-ß-carboline-3-carboxamide (12) was the most potent compound and kinetic studies indicate that it acts as a competitive inhibitor of BuChE. Molecular docking studies show that 12 strongly interacts with the residues of His438 (residue of the catalytic triad) and Trp82 (residue of catalytic anionic site), confirming that this compound competes with the same binding site of the butyrylthiocholine

Levetiracetam and lamotrigine effects as mono- and polytherapy on bone mineral density in epileptic patients / Efeitos do levetiracetam e lamotrigina, em mono e politerapia, na densidade mineral óssea de pacientes epilépticos

ABSTRACT The purpose of this study was to determine the effect of lamotrigine (LTG) and levetiracetam (LEV) as mono- and polytherapy on biochemical markers of bone turnover and bone mineral density in Egyptian adult patients with epilepsy. Methods Forty-eight patients were divided into four groups: two received monotherapy of either LTG or LEV, and the other two groups received polytherapy comprising (valproate [VPA] + LTG or VPA + LEV). Thirty matched healthy participants were included in the study. Participants completed a nutritional and physical activity questionnaire. Biochemical markers of bone and mineral metabolism and bone mineral density of the lumbar spine were measured at baseline and at six months. Results In the LEV monotherapy group, the bone formation markers showed a significant decrease in serum alkaline phosphatase and serum osteocalcin levels while the bone resorption marker showed a significant increase in urinary deoxypyridinoline levels. After six months of treatment, bone mineral density showed a significant decrease in all treated groups, while among monotherapy groups, this significant decrease was more prevalent in the LEV monotherapy group compared with the LTG monotherapy group. Furthermore, there was significant negative correlation between urinary deoxypyridinoline levels and bone mineral density in the LEV monotherapy group. Conclusion Using new generation antiepileptics, LEV monotherapies and polytherapy showed harmful effects on bone but LTG did not.

RESUMO O objetivo deste estudo foi determinar o efeito da lamotrigina (LTG) e levetiracetam (LEV) como mono e politerapia em marcadores bioquímicos de remodelação óssea e densidade mineral óssea em pacientes adultos egípcios com epilepsia. Métodos Quarenta e oito pacientes foram divididos em quatro grupos: dois grupos receberam monoterapia de LTG ou LEV e os outros dois grupos receberam politerapia (valproato [VPA] + LTG ou VPA + LEV). Trinta participantes saudáveis controle foram incluídos no estudo. Os participantes preencheram um questionário nutricional e de atividade física. Marcadores bioquímicos do metabolismo ósseo e mineral e densidade mineral óssea da coluna lombar foram medidos no início e aos seis meses. Resultados No grupo de monoterapia LEV, os marcadores de formação óssea mostraram uma diminuição significativa nos níveis séricos de fosfatase alcalina e osteocalcina sérica, enquanto o marcador de reabsorção óssea mostrou um aumento significativo nos níveis de desoxipiridinolina urinária. Após seis meses de tratamento, a densidade mineral óssea mostrou uma diminuição significativa em todos os grupos tratados, enquanto entre os grupos de monoterapia, esta diminuição significativa foi mais prevalente no grupo de monoterapia LEV em comparação com o grupo de monoterapia LTG. Além disso, houve correlação negativa significativa entre os níveis de desoxipiridinolina urinária e densidade mineral óssea no grupo de monoterapia LEV. Conclusão Utilizando antiepilépticos de nova geração, as monoterapias LEV e a politerapia mostraram efeitos prejudiciais no osso, mas a LTG não.

Identifying the incidence of rash, Stevens-Johnson syndrome and toxic epidermal necrolysis in patients taking lamotrigine: a systematic review of 122 randomized controlled trials

ABSTRACT Lamotrigine is an antiepileptic drug used for the treatment of epilepsy, bipolar disorder and numerous off-label uses. The development of rash significantly affects its use. The most concerning of these adverse reactions is Stevens-Johnson syndrome/toxic epidermal necrolysis. We performed a systematic review of randomized controlled trials using lamotrigine as a monotherapy to quantify the incidence of cutaneous reactions, particularly Stevens-Johnson syndrome/toxic epidermal necrolysis. Of a total of 4,364 papers regarding lamotrigine, 122 studies met our inclusion and exclusion criteria. In total, 18,698 patients were included with 1,570 (8.3%) of patients experiencing an adverse dermatologic reaction. The incidence of Stevens-Johnson syndrome/toxic epidermal necrolysis was 0.04%.

HLA Allele Frequencies in 5802 Koreans: Varied Allele Types Associated with SJS/TEN According to Culprit Drugs

PURPOSE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are very serious forms of drug-induced cutaneous adverse reaction. SJS/TEN induced by certain drug is well known to be associated with some human leukocyte antigen (HLA) gene type. We aimed to explore HLA allele frequencies and their association with SJS/TEN according to culprit drugs in Korea. MATERIALS AND METHODS: We enrolled 5802 subjects who had results of HLA typing test from August 2005 to July 2014. Total 28 SJS/TEN patients were categorized based on culprit drugs (allopurinol, lamotrigine, carbamazepine) and identified the presence of HLA-B*58:01, HLA-B*44:03, HLA-B*15:02, and HLA-A*31:01. RESULTS: HLA-A*24:02 (20.5%), HLA-B*44:03 (10.0%), and HLA-Cw*01:02 (17.1%) were the most frequent type in HLA-A, -B, and -C genes, respectively. Allele frequencies of HLA-B*58:01, HLA-B*44:03, HLA-A*31:01, and HLA-B*15:02 were 7.0%, 10.0%, 5.0%, and 0.3%, respectively. In 958 allopurinol users, 9 subjects (0.9%) were diagnosed with SJS/TEN. Among them, 8 subjects possessed HLA-B*58:01 allele. SJS/TEN induced by allopurinol was more frequently developed in subjects with HLA-B*58:01 than in subjects without it [odds ratio: 57.4; confidence interval (CI) 7.12-463.50; p<0.001]. Allopurinol treatment, based on screening by HLA-B*58:01 genotyping, could be more cost-effective than that not based on screening. HLA-B*44:03 may be associated with lamotrigine-induced SJS/TEN (odds ratio: 12.75; CI 1.03-157.14; p=0.053). Among carbamazepine users, only two patients experienced SJS/TEN and possessed neither HLA-B*15:02 nor HLA-A*31:03. CONCLUSION: HLA gene frequencies varied in Korea. Screening of HLA-B*58:01 before the use of allopurinol might be needed to anticipate probability of SJS/TEN.

Liver dysfunction induced by systemic hypersensitivity reaction to lamotrigine: case report

Lamotrigine is an anticonvulsant drug used to treat partial and generalized seizure disorders. Hypersensitivity to lamotrigine usually causes mild symptoms such as fever, rash, and slight invasion of internal organs. However, a 33-year-old male patient who was admitted with Stevens-Johnson syndrome after taking lamotrigine for 15 days experienced hepatic failure and died 5 days after admission. This case demonstrates the importance of realizing that lamotrigine can lead to fatal hepatic failure, and that tests for the normal liver function should be performed when administering lamotrigine.

Meningoencefalitis aséptica como manifestación de un síndrome de rash con eosinofilia y síntomas sistémicos asociados a drogas por lamotrigina / Aseptic meningoencephalitis as infectation of a sindrome of rash with eosinophilia and systemic symptoms associated with drugs caused by lamotrigine

Aseptic meningitis (AM) is defined by the presence of cerebrospinal fluid findings consistent with meningitis, without achieving the isolation of a bacterium that produces it. Drugs are one of the diverse causes of AM. Drugs frequently associated with AM include immunoglobulin's, nonsteroidal anti-inflammatory, antibiotics, and aromatic anticonvulsants. When AM is part of a systemic response accompanying a cutaneous manifestation it may be a DRESS (Drug Rash with Eosinophilia and Systemic Symptoms), considered a serious adverse reaction to drugs. Lamotrigine is a non-aromatic anticonvulsant widely used for the treatment of epilepsy and bipolar disorder, which has been associated with AM. We report a case of aseptic meningoencephalitis as a manifestation of DRESS associated to lamotrigine.

La meningitis aséptica (MA) se define por la presencia de hallazgos en el líquido cefalorraquídeo compatibles con una meningitis, sin que se logre aislar una bacteria que la produzca. Las causas de MA son diversas, entre las que se encuentran las drogas. Entre los fármacos que más frecuentemente se han asociado a MA, se encuentran los antiinflamatorios no esteroidales, antibióticos, inmunoglobulinas y anticonvulsivantes aromáticos. Cuando la MA forma parte de una respuesta sistémica que acompaña a una manifestación cutánea, puede tratarse de un rash con eosinofilia y síntomas sistémicos asociado a drogas (DRESS, acrónimo derivado del inglés DrugRash with Eosinophilia and Systemic Symptoms), considerada una reacción adversa grave a medicamentos. La lamotrigina es un anticonvulsivante no aromático ampliamente utilizado para el tratamiento de la epilepsia y el trastorno bipolar que ha sido asociada con MA. Comunicamos un caso de meningoencefalitis aséptica como manifestación de DRESS asociado al uso de lamotrigina.

Possible teratogenic effects of antiepileptics in albino rats: comparative study between old and new generations: part I

All of the antiepileptic drugs [AEDs] are either known or suspected of being teratogenic. The possible mechanism of teratogenicity is likely to be multiple for the same drug. This is of major concern for all women with epilepsy using these drugs are delicately balanced between seizure control and the adverse effects the AEDs. The use of conventional AEDs eg. Carbamazepine control more than two thirds of the epileptic patients. In recent years, the number of commercially available AEDs has steadily increased eg. lamotrgine and levetiracetam.160 pregnant female albino rats were used in this study. Animals were classified randomly into eight groups; each group contained 20 pregnant female rats. Negative control group received nothing and positive control group received normal saline. Treated groups: each group received either the therapeutic dose or 1/4 LD50 of carbamazepine, lamotrigine or levetriacetam. The drugs were given by gastric tube from 6[th] day up to the 19[th] day of gestation. Teratological evaluation:the fetuses [both living and dead] in each group were weighted their crown rump length measured and morphological examination included: Head size and shape, orofacial development, vertebral column tail and abdomen, umbilicus and external genitalia Maternal findings showed high death rate in 1/4 LD50 of lamotrigine treated group; weight gain was dose dependant with highest effect in the lamotrigine treated groups. The fetal findings showed highest embrolethality and least litter siza in lamotrigine treated groups; while the fetal growth determined by weight gain and crown rumplength was retarded more in carbamazepine and lamotrigine treated groups than in levetiracetam treated groups. The morphological findings revealed that the highest percentage of congenital anomalies were in the dose of 1/4 LD50 of lamotrigine followed by carbamazepine and levetiracetam. The AEDs are potentially teratogenic and in utero exposure can increase the risk of adverse outcomes in off springs born epileptic mothers. The new AED lamotrigine caused gross fetal retardation even in therapeutic dose. Levetiracetam caused growth retardation in the therapeutic dose more than carbamazepine in the corresponding dose although it had the best effect on maternalparameters. As regard the congenital anomalies lamotrigine was the safest durg in the therapeutic dose

Presence of atrazine in the biological samples of cattle and its consequence adversity in human health

Cattle can be considered as an important source for herbicides through nutrition. Therefore, herbicide residue in animal products is a potential human exposure to herbicides causing public health problems in human life. Triazines are a group of herbicides primarily used to control broadleaf weeds in corn and other feed ingredients and are considered as possible human carcinogens. To evaluate trace residue of these pollutants molecular imprinted solid phase extraction [MISPE] method has been developed, using biological samples. Blood samples were taken from the jugular vein of 45 Holstein cows in 3 commercial dairy farms in Khuzestan Province, Iran. Urine samples were also taken from the cows. The mean +/- SD concentrations of atrazine in serum and urine samples of the study group [0.739 +/- 0.567 ppm and 1.389 +/- 0.633 ppm, respectively] were higher [P < 0.05] than the concentrations in serum and urine samples of the control group [0.002 +/- 0.005 ppm and 0.012 +/- 0.026 ppm, respectively]. Atrazine in the feed ingredients ingested by cattle could be transferred into the biological samples and consequently can be considered as a potential hazard for the public health

Reacciones cutáneas adversas a anticonvulsivantes y estabilizadores del ánimo / Adverse cutaneous reactions to anticonvulsants and mood stabilizers

Anticonvulsivantes y estabilizadores del ánimo principalmente el ácido valproico, lamotrigina y carbamazepina, poseen una alta incidencia de reacciones adversas a medicamentos (RAM) severas, como eritema multiforme, Síndrome Stevens- Johnson y necrolisis epidérmica tóxica, asociadas. Existen signos de alarma para su sospecha diagnóstica precoz, que permiten indicar la temprana suspensión del fármaco sospechoso e iniciar la terapia de soporte únicas medidas que han demostrado una clara disminución en la mortalidad. La inmunoglobulina G intravenosa se recomienda por su seguridad, sin embargo, su rol en disminuir la mortalidad es contradictorio. Los corticoides no han demostrado cambios en la mortalidad comparados con la terapia de soporte exclusiva. Se ha intentado mantener el tratamiento con lamotrigina, por sus cualidades terapéuticas, pese a la aparición de RAM cutáneas. De hecho, en estudios recientes en pacientes que han desarrollado RAM leves a este producto se ha demostrado un éxito de reexposición de 85 por ciento-87 por ciento mediante una lenta titulación de la dosis.

Anticonvulsants and mood stabilizers mainly valproic acid, lamotrigine and carbamazepine are medications that have a high incidence of severe adverse drug reactions (ADRs), such erythema multiforme, Stevens- Johnson syndrome and toxic epidermal necrolysis. Early diagnosis based in systemic and cutaneous alarm signs have been described, allowing premature discontinuation of suspected drugs and start supportive therapy; these are the only measures that have that have shown clear reduction in mortality. The use of intravenous immunoglobulin G is recommended for their safety, but studies regarding their role in reducing mortality are conflicting. Corticosteroids have not proved changes in mortality compared with exclusive supportive care. Due to therapeutic quality Lamotrigine is used despite the incidence of ADRs. In fact in recent studies patients with mild ADRs to this drug have shown between 85 percent-87 percent of success, when patients are re-exposed through a slow increasing in dosage.

Síndrome de DRESS: eritema cutáneo, fiebre y hepatitis asociado a lamotrigina: reporte de dos casos y revisión de la literatura / DRESS syndrome: skin rash, fever and acute hepatitis associated to lamotrigine: report of two cases and review of the literature

DRESS syndrome is an infrequent adverse drug reaction but in some cases may be life-threatening. It is characterized by cutaneous rash, systemic symptoms and eosinophilia. It is usually caused by aromatic anticonvulsants, sulfonamides and some antiviral drugs, among others. In this article we present two cases of drug induced hypersensitivity syndrome with rash, systemic symptoms (DRESS) associated to lamotrigine therapy with hepatic involvement and a review of the literature. The first case is a 78 year-old woman, presenting with myalgia, fever, abdominal pain and skin rash on her face and extremities. Labora¬tory tests revealed alteration of hepatic profile with hepatocellular pattern. After ruling out other causes, she recognized recent use of lamotrigine. The drug was withdrawn and she had a favourable evolution. The second case is a 30 year-old woman being treated for depression who presented with rash, adenopathies, fever and alteration of hepatic profile twenty four days after starting lamotrigine. Infectious causes were ruled out and she had a good response to corticosteroid treatment.

El síndrome de DRESS es una reacción adversa a medicamentos, poco frecuente pero potencialmente letal. Se caracteriza por eritema cutáneo, síntomas sistémicos y eosinofilia. Suele ser producido por los anticonvulsivantes aromáticos, sulfonamidas y algunos fármacos antivirales, entre otros. En este artículo presentamos dos casos de DRESS secundario a lamotrigina con compromiso hepático y revisión de la literatura. El primero de ellos, una mujer de 78 años, consulta por mialgias, fiebre, dolor abdominal y eritema maculopapular en cara y extremidades. Los exámenes de laboratorio revelaron alteración de pruebas de función hepática con patrón hepatocelular. Luego de descartar otras causas, la paciente reconoció uso reciente de lamotrigina. Se suspendió la droga y evolucionó favorablemente. El segundo caso es una mujer de 30 años en tratamiento por trastorno depresivo quien, veinticuatro días post-inicio de lamotrigina, comienza con eritema, adenopatías, fiebre y alteración de pruebas de función hepática, excluyéndose etiologías infecciosas; se inicia tratamiento corticoesteroidal con buena respuesta.

[Treatment effect of onion on sexual behavior after induces an antiepileptic drug [lamotrigine] in male rat]

The medicinal use of onion dates back to ancient China and India. Men with epilepsy have reduced fertility, and antiepileptic drugs may affect semen quality. Disturbances of reproductive endocrine hormones are more often found in men with epilepsy than in the general population. There is an ongoing debate whether this can be attributed to chronic use of antiepileptic drugs or to the epilepsy itself. The aim of the present study was to evaluate the beneficial degree of sexual behavior in male rats after inducement onion in lamotrigine receiving groups. Forty wistar rats, randomized into four groups [n=10], were used for this study, five of them male and five of them female. Animals in Group A served as the control and was drinking distilled water. Animals in Groups B: treated with 3cc/rat of onion juice, in Groups C: received10mg/kg/day lamotrigine, in Groups D: received10mg/kg/day lamotrigine plus 3cc/rat of onion juice. In All treatments were for 5 weeks. 48 hours before end of study estradiol benzoate [25 micro gr/kg/day, s.c.] and 6 hours before end of study progesterone 0.3muM were injected. Results showed the percentage of erections and couplings and serum testosterone in onion treated groups were significantly increased [p<0.01] when compared to other groups. onion and its constituents are stated to has antioxidant. Enhanced oxidative stress and changes in antioxidant capacity are considered to play an important role in the pathogenesis in diseases. These findings lead to the conclusion that onion significantly lowered the adverse effects of lamotrigine, and can do beneficial effect on sexual behavior in male rat

Síndrome de hipersensibilidad a anticonvulsivantes (síndrome de DRESS): comunicación de 4 casos / Anticonvulsant hypersensitivity syndrome (DRESS syndrome): report of 4 cases

El síndrome de hipersensibilidad a anticonvulsivante es una reacción frecuente y potencialmente fatal, que se caracteriza por fiebre, erupción cutánea y compromiso de órganos internos. Difenilhidantína, fenobarbital y carbamazepina son los anticonvulsivantes aromáticos que más frecuentemente lo producen. Comunicamos 4 pacientes adultos, 2 masculinos y 2 femeninos de entre 20 y 42 años que presentaron hallazgos clínicos, bioquímicos e histológicos compatibles con un síndrome de hipersensibilidad a drogas secundario a anticonvulsivantes que se inició luego de 4 a 8 semanas del inicio del fármaco. Las drogas causantes fueron difenilhidantoína, carbamazepina y la asociación de ácido valproico y lamotrigina.

Alteraciones hematológicas asociadas al síndrome de hipersensibilidad por anticonvulsivantes en una paciente tratada con lamotrigina / Hematological alterations associated to the hypersensitivity syndrome caused by anticonvulsants in patients treated with lamotrigine

El síndrome de hipersensibilidad por antiepilépticos es una reacción adversa grave de naturaleza idiosincrásica que cursa con distintas manifestaciones clínicas y cuyo mecanismo de producción se desconoce. Se presenta una paciente de 5 años con antecedentes de lesión estática y epilepsia, tratada durante dos años con politerapia anticonvulsivante con valproato de magnesio y topiramato, y reciente introducción de lamotrigina a dosis elevadas, fármaco del grupo de las feniltriazinas. A la cuarta semana de su inicio la paciente comenzó con fiebre, exantema maculopapular generalizado, conjuntivitis, linfadenopatías, edema periorbitario, hepatotoxicidad aguda, trombocitopenia severa y anemia megaloblástica, este último efecto no descrito en los casos reportados anteriormente. La lamotrigina es un inhibidor débil de la dihidrofolato reductasa y se describe la interferencia con el metabolismo del ácido fólico a largo plazo. El ácido valproico reduce el metabolismo de la lamotrigina, lo que puede explicar la aparición temprana de anemia megaloblástica en una paciente con controles hematológicos normales hasta el momento de la presentación del cuadro. Con la suspensión de la lamotrigina se alcanzó el valor normal de las plaquetas al séptimo día y la anemia desapareció progresivamente con la administración de ácido fólico.

The hypersensitivity syndrome caused by anti-epileptics is a serious adverse reaction of idiosyncratic nature that has several clinical manifestations, the production mechanism of which is unknown. We present a 5-years-old patient with antecedents of static lesion and epilepsy, treated during two years with anti-convulsive therapy of magnesium valproate and topiramate; recently high doses of lamotrigine, drug of the feniltrazine group, were introduced. In the fourth week after beginning the treatment, the patient had fever, generalized maculopapular exanthema, conjunctivitis, limphadenopathies, periorbital edema, acute hepatotoxicity, severe thrombocytopenia, and megaloblastic anemia. The last effect has not been described in the previously reported cases. Lamotrigine is a weak inhibitor of the dihydrofolate reductase, and we describe the interference of de folic acid with the metabolism. The valproic acid reduces the lamotrigine metabolism, and it might be the explanation of the megaloblastic anemia early appearance in a patient with normal hematological controls until the moment the disease presented. On the seven day after suspending lamotrigine, the normal value of platelets was reached and the anemia disappeared progressively administering folic acid.

Association of lamotrigine and valproate in refractory epilepsies of children and adolescents / Associação de lamotrigina e valproato de sódio no tratamento de epilepsia refratária em crianças e adolescentes

OBJECTIVE: To evaluate the efficacy or eventual side-effects of the association of lamotrigine and sodium valproate in the control of refractory epilepsies. METHOD: A retrospective analysis of 37 children with a mean age of 12 years taking exclusivelly lamotrigine and sodium valproate. Efficacy of seizure control was considered satisfactory if there was a reduction in seizures >50 percent or total control. RESULTS: The association of lamotrigine and sodium valproate was considered satisfactory in 65 percent of the studied children, independent of seizure type. Total seizure control was obtained in 33 percent and 35 percent had an unsatisfactory response or remained unchanged. Primary generalized tonic clonic seizures were the most common type with 84 percent of day-time seizures having a good response to treatment. Side-effects were seen in 11 percent of patients and the most common was tremor. CONCLUSION: Total or satisfactory control of seizures was seen in the majority of patients and side-effects were uncommon.

OBJETIVO: Avaliar a eficácia ou eventuais efeitos colaterais da associação de lamotrigina e valproato de sódio no controle de epilepsia refrataria. MÉTODO: Análise retrospectiva de 37 crianças e adolescentes com idade média de 12 anos tratadas exclusivamente com lamotrigina e valproato de sódio. A eficácia do controle de crises foi considerada satisfatória se o controle das crises foi >50 por cento ou total. RESULTADOS: A associação de lamotrigina e valproato de sódio foi considerada satisfatória em 65 por cento, independente do tipo de crise. O controle total de crises foi obtido em 33 por cento e em 35 por cento a resposta foi insatisfatória ou permaneceu inalterada. Crise generalizada primaria tônico clonica foi o mais comum, com 84 por cento das crises ocorrendo durante o dia, com boa resposta ao tratamento. Efeitos colaterais foram vistos em 11 por cento dos pacientes, sendo tremor o mais freqüente. CONCLUSÃO: Controle total ou satisfatório das crises ocorreu na maioria dos pacientes, sendo pouco freqüente os efeitos colaterais.

Intravenous immunoglobulin in the treatment of lamotrigine- induced toxic epidermal necrolysis

Toxic epidermal necrolysis is a potentially life-threatening disease, which needs necessary treatment. We present a 12 years old female who was a known case of idiopathic generalized tonic-clonic convulsion and presented with fever, diarrhea and generalized erythematous eruption after 2 weeks of being under treatment with maintenance doses of Lamotrigine [LTG] and Valproate [VPA]. The eruption led to more than 90% epidermal detachment of the total body surface area. However, she made a full recovery with few negligible sequelae regarding the severity of her disease and the symptomatic therapy and Intravenous Immunoglobulin [IVIG] administration which started soon after the bullae appeared. While IVIG might be beneficial in the treatment of TEN, controlled studies are needed to evaluate the efficiency of IVIG compared to other modalities

Síndrome de Stevens-Johnson: necrólisis epidérmica tóxica asociada a lamotrigina: presentación de un caso / Stevens-johnson syndrome: toxic epidermic necrolysis related to lamotrigina: case presentation

El síndrome de Stevens-Johnson/necrólisis epidérmica tóxica (SSJ/NET) corresponde a una forma clínica de superposición en el espectro del eritema multiforme. Es de presentación poco frecuente y pronóstico reservado. Los desencadenantes más comunes son los fármacos. Se presenta el caso de una paciente, de 50 años, que desarrolló un episodio de superposición (SSJ/NET) diez días después del agregado de lamotrigina a su tratamiento para la epilepsia iniciado con ácido valproico. La paciente fue internada en clínica médica, la relación causal para lamotrigina fue definida y el cuadro cursó una evolución favorable con la suspensión del fármaco y la instauración temprana de las medidas de sostén...

Anticonvulsant hypersensitivity syndrome to lamotrigine confirmed by lymphocyte stimulation in vitro.

Anticonvulsant hypersensitivity syndrome (AHS) developing to lamotrigine, a non-aromatic anticonvulsant, has rarely been reported. We present a two-year-old boy with refractory epilepsy on valproic acid and lamotrigine therapy who developed fever and a maculopapular itchy rash. Blood investigations detected lymphocytosis and thrombocytopenia. With a presumptive diagnosis of AHS, lamotrigine was discontinued. The fever and rash resolved over the next three days and the child was discharged on valproic acid and clobazam. The diagnosis was confirmed by in vitro lymphocyte toxicity assay, which not only demonstrated increased cell death following exposure to lamotrigine, but also to the three first-line aromatic anticonvulsants: phenytoin, phenobarbital and carbamazepine. The potential of first-line aromatic anticonvulsants to cause AHS should be remembered in a patient who has developed AHS on exposure to lamotrigine. Timely recognition of this rare but potentially fatal drug reaction is important.