High Risk for Hyperlipidemia and the Metabolic Syndrome after an Episode of Hypertriglyceridemia during 13-<i>cis</i> Retinoic Acid Therapy for Acne: A Pharmacogenetic Study

Rodondi, Nicolas; Darioli, R.; Ramelet, Albert‐Adrien; Hohl, Daniel; Lenain, Vincent; Perdrix, Jean; Wietlisbach, Vincent; Riesen, Walter; Walther, Thomas; Medinger, Laurent; Nicod, Pascal; Desvergne, Béatrice; Mooser, Vincent

doi:10.7326/0003-4819-136-8-200204160-00007

Cited by 99 publications

(65 citation statements)

References 15 publications

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“…15 The increase in triglyceride levels in patients being treated with oral isotretinoin may be related to a reduction in the removal rate of these lipids from plasma. 23 It also appears to be influenced by the increase in gene expression for Apo E. 24 In agreement with reports from other studies, no correlation was found between the oral dose of isotretinoin and the increase in triglycerides. 12,25 Furthermore, there appears to be no correlation between the cumulative dose of isotretinoin and the magnitude of the increase in triglycerides.…”

Section: Discussionsupporting

confidence: 85%

The effect of isotretinoin on triglycerides and liver aminotransferases

Vieira

Beijamini

Melchiors

2012

An. Bras. Dermatol.

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BACKGROUND:Isotretinoin has been used to treat the most severe cases of acne; however, it may provoke adverse events in mucocutaneous and hepatic tissues, lead to alterations in lipid levels and cause teratogenicity. OBJECTIVE: The objective of this study was to evaluate the profile of changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride levels in patients who had been treated with oral isotretinoin dispensed by the São Mateus/ES pharmacy for special drugs. METHODS: A retrospective, observational, longitudinal study was conducted by carrying out a secondary analysis of each patient's data. RESULTS: Of the 130 patients who received isotretinoin between January and December 2009, only 70 were actually treated for 3 months or more and handed in the results of their laboratory tests. Of these 70 patients, 39 (55.7%) were female. The mean age of the women (23.9 years) was higher than the mean age of the men (20.1 years). There was a statistically significant increase in the levels of triglycerides (87.01 ± 48.25 versus 105.32 ± 48.76 mg/dL), AST (20.44 ± 6.26 versus 24.38 ± 11.92 U/L) and ALT (18.24 ± 8.31 versus 23.34 ± 20.03 U/L) performed prior to and 3 months or more after oral isotretinoin treatment. After treatment with oral isotretinoin, triglyceride levels had increased beyond the normal range in 11% of the patients, while 8.6% had elevated AST levels and 7.3% had increased ALT levels. CONCLUSION:The results in this population show that the use of oral isotretinoin for the treatment of acne may result in altered triglyceride, AST and ALT levels. These findings are in accordance with data published previously in the scientific literature, confirming the need to monitor these patients. Keywords: Acne vulgaris; Aminotransferases; Dermatologic agents; Isotretinoin; Triglycerides Resumo: FUNDAMENTOS: A isotretinoína tem sido usada no tratamento dos casos mais graves de acne, embora possa induzir reações adversas nos tecidos mucocutâneos e hepáticos, alterações nos níveis lipídicos e teratogenicidade. OBJETIVOS: Este estudo avaliou o perfil de alterações nas concentrações de Alanina Aminotransferrase, Aspartato Aminotransferrase e triglicerídeos em pacientes que fizeram uso de isotretinoína oral fornecida pelo serviço Farmácia de Medicamentos Excepcionais de São Mateus/ES. MÉTODOS: Foi realizado estudo observacional longitudinal exploratório retrospectivo, utilizando coleta de dados secundários de cada paciente. Resultados: Dos 130 pacientes que receberam isotretinoína no período de janeiro a dezembro de 2009, somente 70 realizaram o tratamento por 3 meses ou mais e apresentaram os resultados dos exames. Desses 70 pacientes, 39 (55,7%) eram do sexo feminino. A média de idade das mulheres (23,9 anos) foi maior do que a média de idade dos homens (20,1 anos). Houve aumento estatisticamente significante nas dosagens de triglicerídeos (87,01±48,25 versus 105,32 ± 48,76), Aspartato Aminotransferrase (20,44 ± 6,26 versus 24,38 ± 11,92) e Alanina Aminotransferrase (18,24 ...

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Section: Discussionsupporting

confidence: 85%

The effect of isotretinoin on triglycerides and liver aminotransferases

Vieira

Beijamini

Melchiors

2012

An. Bras. Dermatol.

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“…5,6 Rodondi et al identified a propensity to develop the metabolic syndrome in patients who had a pronounced elevation in TG levels during use of oral isotretinoin, suggesting the participation of genetic factors. 7 These correlations may help explain the apparent propensity of women to develop high TG levels, as found in the present study, particularly in adult women with persistent acne. Possible inconsistencies in data that are inherent to retrospective studies may have affected the present findings.…”

Section: Comunicationsupporting

confidence: 65%

Mulheres adultas com acne apresentam maior risco de elevação de triglicerídeos ao uso de isotretinoína oral

Schmitt

Tavares

Cerci

2011

An. Bras. Dermatol.

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A isotretinoína apresenta restrições relacionadas a efeitos no perfil lipídico. Revisaram-se 90 pacientes tratados, em busca de fatores predisponentes a essas alterações. Houve elevação significativa do colesterol e triglicerídeos. Os pacientes em que estes últimos mostraram essa alteração foram, em sua maioria, do sexo feminino, predileção que não ocorria com as alterações iniciais. Mulheres com acne persistente talvez representem população de risco para tais efeitos colaterais

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“…23 This study shows the PD/Cub strain to be sensitive to modulation of triglyceride concentrations by isotretinoin, a phenomenon previously noted not only as a side effect of the treatment aimed at mostly dermatological disorders, 5 but also as a possible pharmacogenetic indicator of hereditary proneness to familial combined hyperlipidemia and metabolic syndrome. 24 Moreover, the increased adiposity and insulin resistance of skeletal muscle tissue in the isotretinoin-treated group are well in consent with the adverse reactions seen in the sensitive human subjects. 24 Therefore, this strain may well serve as a tool for dissection of the genetic component involved in the described pharmacogenetic interaction.…”

Section: Discussionmentioning

confidence: 84%

“…24 Moreover, the increased adiposity and insulin resistance of skeletal muscle tissue in the isotretinoin-treated group are well in consent with the adverse reactions seen in the sensitive human subjects. 24 Therefore, this strain may well serve as a tool for dissection of the genetic component involved in the described pharmacogenetic interaction. The mechanism of retinoic acid induced hypertriglyceridemia is unknown.…”

Section: Discussionmentioning

confidence: 84%

Isotretinoin and fenofibrate induce adiposity with distinct effect on metabolic profile in a rat model of the insulin resistance syndrome

et al. 2004

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OBJECTIVE:To investigate the effect of transcription-modulating drugs, fenofibrate and isotretinoin, on metabolic profile, insulin sensitivity of adipose and muscle tissues and gene expression in a genetic model of insulin resistance syndrome, polydactylous rat strain (PD/Cub). DESIGN: Administration of fenofibrate (100 mg/kg/day), isotretinoin (30 mg/kg/day) or vehicle to adult male PD/Cub rats fed standard laboratory chow for 15 days. MEASUREMENTS: Parameters of lipid and carbohydrate metabolismForal glucose tolerance test, serum concentrations of insulin, triglycerides (TG), free fatty acids (FFA), glycerol, total cholesterol (CH); morphometric variables, in vitro insulin sensitivity of adipose and muscle tissues, catecholamine-stimulated lipolysis and the expression of ApoC-III and Hnf-4 genes in liver. RESULTS: Both experimental groups displayed an increase in adiposity with contrasting effects on TG (lowered by fenofibrate and increased by isotretinoin) and gene expression (no change in fibrate-treated rats and increased expression of ApoC-III and Hnf-4 in isotretinoin-treated group). Fenofibrate-treated rats also showed decreased concentrations of FFA and CH with concomitant decrease of catecholamine-induced lipolysis in adipocytes, but also hyperinsulinemia and the highest insulin/ glucose ratio. Isotretinoin increased glycerol concentrations and decreased the insulin sensitivity of peripheral tissues. CONCLUSION: The PD/Cub rat showed a distinct pharmacogenetic reaction to fenofibrate and isotretinoin administration. Several lines of evidence now implicate specific variant(s) of ApoC-III and/or ApoA-V alleles as responsible for the dyslipidemia observed in this genetic model. The PD/Cub strain may also serve as a pharmacogenetic model for dissection of the retinoidinduced hypertriglyceridemia.

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High Risk for Hyperlipidemia and the Metabolic Syndrome after an Episode of Hypertriglyceridemia during 13-cis Retinoic Acid Therapy for Acne: A Pharmacogenetic Study

Abstract: Persons who develop hypertriglyceridemia during isotretinoin therapy for acne, as well as their parents, are at increased risk for future hyperlipidemia and the metabolic syndrome.

Cited by 99 publications

References 15 publications

The effect of isotretinoin on triglycerides and liver aminotransferases

The effect of isotretinoin on triglycerides and liver aminotransferases

Mulheres adultas com acne apresentam maior risco de elevação de triglicerídeos ao uso de isotretinoína oral

Isotretinoin and fenofibrate induce adiposity with distinct effect on metabolic profile in a rat model of the insulin resistance syndrome

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