Investigação da toxicidade da isotretinoína oral sobre a conjuntiva humana utilizando a citologia de impressão

Detalhes bibliográficos
Autor(a) principal: Queiroga, Isabella Bezerra Wanderley de
Data de Publicação: 2009
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFPB
Texto Completo: https://repositorio.ufpb.br/jspui/handle/tede/6770
Resumo: The physiological and pharmacological effects of isotretinoin are yet to be completely understood despite its widespread use in the treatment of acne vulgaris and the known adverse effects that it may cause, dry eyes being one of the most common. The objective of this study was to evaluate the toxicity of oral isotretinoin on the conjunctiva of patients submitted to treatment with this drug, using impression cytology. A prospective cohort clinical trial was conducted at the Ophthalmological Referral Center of the Federal University of Paraíba and at the Laboratory of External Eye Diseases of the Federal University of São Paulo. Twentyeight patients with acne vulgaris were selected. A questionnaire on symptoms was applied and biomicroscopy, tear film break-up time (TBUT), fluorescein staining, Shirmer s test, rose bengal staining and impression cytology (IC) were performed prior to and after three months of treatment with oral isotretinoin. Samples for IC were collected from the temporal, superior, nasal and inferior bulbar conjunctiva of both eyes. The doses of isotretinoin varied from 0.35 to 0.88 mg/kg/day. Compared to pretreatment, burning, pruritus and gritty eye sensation were significantly more common during treatment with this drug, as were the biomicroscopic changes of hyperemia and blepharitis. The percentage of positive results for dry eyes according to TBUT and for rose bengal conjunctival staining was also greater during treatment. Regarding Shirmer s test and fluorescein staining of the cornea, no statistically significant changes were found with exposure to the drug. With respect to IC performed on the samples obtained from the superior and temporal quadrants, there was a reduction in the percentage of normal results from 100% to 82% and from 75% to 43%, respectively, and an increase in the percentage of borderline results from 0 to 14% and from 21% to 47%, respectively, during treatment compared to baseline results. For the samples from the nasal quadrant, an increase occurred in the percentage of abnormal findings from 0 to 11%, while in the samples taken from the inferior quadrant, no changes were found with the use of isotretinoin. The parameters affected by this treatment were cell-to-cell contact, nucleus-tocytoplasm ratio and the distribution of goblet cells, the scores of which increased significantly. No significant correlation was found between the results of IC, symptom score and tear function tests. Therefore, the present findings show that acne treatment with oral isotretinoin results in changes in the conjunctival epithelium in a significant percentage of patients. These changes are seen both in the exposed region of the bulbar conjunctiva (temporal and nasal) and in the unexposed conjunctiva (superior) and reflect a trend towards squamous metaplasia as an adaptive response of the conjunctival epithelium, which tends to become nonsecretory under the effect of the drug.
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spelling Investigação da toxicidade da isotretinoína oral sobre a conjuntiva humana utilizando a citologia de impressãoInvestigation of the toxicity of oral isotretinoin on the human conjunctiva using impression cytologyIsotretinoínaEfeitos adversosOlho secoCitologia de impressãoIsotretinoinAdverse effectsDry eyeImpression cytologyCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAThe physiological and pharmacological effects of isotretinoin are yet to be completely understood despite its widespread use in the treatment of acne vulgaris and the known adverse effects that it may cause, dry eyes being one of the most common. The objective of this study was to evaluate the toxicity of oral isotretinoin on the conjunctiva of patients submitted to treatment with this drug, using impression cytology. A prospective cohort clinical trial was conducted at the Ophthalmological Referral Center of the Federal University of Paraíba and at the Laboratory of External Eye Diseases of the Federal University of São Paulo. Twentyeight patients with acne vulgaris were selected. A questionnaire on symptoms was applied and biomicroscopy, tear film break-up time (TBUT), fluorescein staining, Shirmer s test, rose bengal staining and impression cytology (IC) were performed prior to and after three months of treatment with oral isotretinoin. Samples for IC were collected from the temporal, superior, nasal and inferior bulbar conjunctiva of both eyes. The doses of isotretinoin varied from 0.35 to 0.88 mg/kg/day. Compared to pretreatment, burning, pruritus and gritty eye sensation were significantly more common during treatment with this drug, as were the biomicroscopic changes of hyperemia and blepharitis. The percentage of positive results for dry eyes according to TBUT and for rose bengal conjunctival staining was also greater during treatment. Regarding Shirmer s test and fluorescein staining of the cornea, no statistically significant changes were found with exposure to the drug. With respect to IC performed on the samples obtained from the superior and temporal quadrants, there was a reduction in the percentage of normal results from 100% to 82% and from 75% to 43%, respectively, and an increase in the percentage of borderline results from 0 to 14% and from 21% to 47%, respectively, during treatment compared to baseline results. For the samples from the nasal quadrant, an increase occurred in the percentage of abnormal findings from 0 to 11%, while in the samples taken from the inferior quadrant, no changes were found with the use of isotretinoin. The parameters affected by this treatment were cell-to-cell contact, nucleus-tocytoplasm ratio and the distribution of goblet cells, the scores of which increased significantly. No significant correlation was found between the results of IC, symptom score and tear function tests. Therefore, the present findings show that acne treatment with oral isotretinoin results in changes in the conjunctival epithelium in a significant percentage of patients. These changes are seen both in the exposed region of the bulbar conjunctiva (temporal and nasal) and in the unexposed conjunctiva (superior) and reflect a trend towards squamous metaplasia as an adaptive response of the conjunctival epithelium, which tends to become nonsecretory under the effect of the drug.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorAs ações fisiológicas e farmacológicas da isotretinoína ainda não são completamente conhecidas, apesar da sua ampla utilização no tratamento da acne vulgar e dos efeitos adversos que pode causar. Dentre esses, o quadro de olho seco é um dos mais frequentes. O objetivo deste estudo foi avaliar a toxicidade da isotretinoína oral sobre a conjuntiva de pacientes submetidos a tratamento com o fármaco, utilizando a citologia de impressão. Realizou-se estudo clínico prospectivo tipo coorte no Centro de Referência Oftalmológica da Universidade Federal da Paraíba e no Laboratório de Doenças Externas Oculares da Universidade Federal de São Paulo. Foram selecionados 28 pacientes portadores de acne vulgar. Realizou-se questionário de sintomas, biomicroscopia, teste do tempo de ruptura do filme lacrimal (TBUT), coloração por fluoresceína, teste de Shirmer, coloração por rosa bengala e citologia de impressão (CI) antes e aos 3 meses de tratamento com isotretinoína oral. Os espécimes para a CI foram coletados dos quadrantes temporal, superior, nasal e inferior da conjuntiva bulbar de ambos os olhos. As doses de isotretinoína variaram de 0,35 a 0,88 mg/kg/dia. Em relação ao pré-tratamento, os sintomas ardor ocular , prurido e sensação de areia nos olhos , assim como as alterações biomicroscópicas hiperemia e blefarite , ocorreram com uma frequência significantemente maior durante o tratamento com o fármaco. O percentual de resultados positivos para olho seco, para o TBUT e para a coloração conjuntival por rosa bengala também foi significantemente maior na vigência do tratamento. Para o teste de Shirmer e para a coloração da córnea por fluoresceína, não houve mudanças significantes com a exposição ao fármaco. Quanto à CI, para os espécimes obtidos dos quadrantes superior e temporal, houve diminuição do percentual de resultados normais (de 100 para 82 e de 75 para 43, respectivamente) e aumento do percentual de resultados limítrofes (de 0 para 14 e de 21 para 47, respectivamente) durante o tratamento, em relação aos resultados iniciais. Para os espécimes do quadrante nasal, houve aumento do percentual de resultados anormais (de 0 para 11), e para aqueles do quadrante inferior, não se observaram alterações com o uso de isotretinoína. Com o tratamento, foram afetados os parâmetros contato célula-célula , razão núcleo/citoplasma e distribuição das células caliciformes , que sofreram aumento significante em seus escores. Não houve uma correlação significante entre os resultados da CI, do escore de sintomas e dos testes da função lacrimal. Assim, de acordo com os resultados obtidos, o tratamento da acne com isotretinoína oral induz alterações no epitélio conjuntival de um percentual significante de pacientes. Essas alterações são observadas tanto na região exposta da conjuntiva bulbar (temporal e nasal), como na não exposta (superior) e representam uma tendência à metaplasia escamosa, como uma resposta adaptativa do epitélio conjuntival, que tende a se tornar não secretor sob efeito do fármaco.Universidade Federal da Paraí­baBRFarmacologiaPrograma de Pós Graduação em Produtos Naturais e Sintéticos BioativosUFPBDiniz, Margareth de Fátima Formiga Melohttp://lattes.cnpq.br/4173269414899195Vieira, Luiz AntônioQueiroga, Isabella Bezerra Wanderley de2015-05-14T12:59:47Z2018-07-21T00:25:04Z2010-01-062018-07-21T00:25:04Z2009-11-10info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfQUEIROGA, Isabella Bezerra Wanderley de. Investigation of the toxicity of oral isotretinoin on the human conjunctiva using impression cytology. 2009. 109 f. Tese (Doutorado em Farmacologia) - Universidade Federal da Paraí­ba, João Pessoa, 2009.https://repositorio.ufpb.br/jspui/handle/tede/6770porinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2018-09-06T01:53:51Zoai:repositorio.ufpb.br:tede/6770Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2018-09-06T01:53:51Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false
dc.title.none.fl_str_mv Investigação da toxicidade da isotretinoína oral sobre a conjuntiva humana utilizando a citologia de impressão
Investigation of the toxicity of oral isotretinoin on the human conjunctiva using impression cytology
title Investigação da toxicidade da isotretinoína oral sobre a conjuntiva humana utilizando a citologia de impressão
spellingShingle Investigação da toxicidade da isotretinoína oral sobre a conjuntiva humana utilizando a citologia de impressão
Queiroga, Isabella Bezerra Wanderley de
Isotretinoína
Efeitos adversos
Olho seco
Citologia de impressão
Isotretinoin
Adverse effects
Dry eye
Impression cytology
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
title_short Investigação da toxicidade da isotretinoína oral sobre a conjuntiva humana utilizando a citologia de impressão
title_full Investigação da toxicidade da isotretinoína oral sobre a conjuntiva humana utilizando a citologia de impressão
title_fullStr Investigação da toxicidade da isotretinoína oral sobre a conjuntiva humana utilizando a citologia de impressão
title_full_unstemmed Investigação da toxicidade da isotretinoína oral sobre a conjuntiva humana utilizando a citologia de impressão
title_sort Investigação da toxicidade da isotretinoína oral sobre a conjuntiva humana utilizando a citologia de impressão
author Queiroga, Isabella Bezerra Wanderley de
author_facet Queiroga, Isabella Bezerra Wanderley de
author_role author
dc.contributor.none.fl_str_mv Diniz, Margareth de Fátima Formiga Melo
http://lattes.cnpq.br/4173269414899195
Vieira, Luiz Antônio
dc.contributor.author.fl_str_mv Queiroga, Isabella Bezerra Wanderley de
dc.subject.por.fl_str_mv Isotretinoína
Efeitos adversos
Olho seco
Citologia de impressão
Isotretinoin
Adverse effects
Dry eye
Impression cytology
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
topic Isotretinoína
Efeitos adversos
Olho seco
Citologia de impressão
Isotretinoin
Adverse effects
Dry eye
Impression cytology
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
description The physiological and pharmacological effects of isotretinoin are yet to be completely understood despite its widespread use in the treatment of acne vulgaris and the known adverse effects that it may cause, dry eyes being one of the most common. The objective of this study was to evaluate the toxicity of oral isotretinoin on the conjunctiva of patients submitted to treatment with this drug, using impression cytology. A prospective cohort clinical trial was conducted at the Ophthalmological Referral Center of the Federal University of Paraíba and at the Laboratory of External Eye Diseases of the Federal University of São Paulo. Twentyeight patients with acne vulgaris were selected. A questionnaire on symptoms was applied and biomicroscopy, tear film break-up time (TBUT), fluorescein staining, Shirmer s test, rose bengal staining and impression cytology (IC) were performed prior to and after three months of treatment with oral isotretinoin. Samples for IC were collected from the temporal, superior, nasal and inferior bulbar conjunctiva of both eyes. The doses of isotretinoin varied from 0.35 to 0.88 mg/kg/day. Compared to pretreatment, burning, pruritus and gritty eye sensation were significantly more common during treatment with this drug, as were the biomicroscopic changes of hyperemia and blepharitis. The percentage of positive results for dry eyes according to TBUT and for rose bengal conjunctival staining was also greater during treatment. Regarding Shirmer s test and fluorescein staining of the cornea, no statistically significant changes were found with exposure to the drug. With respect to IC performed on the samples obtained from the superior and temporal quadrants, there was a reduction in the percentage of normal results from 100% to 82% and from 75% to 43%, respectively, and an increase in the percentage of borderline results from 0 to 14% and from 21% to 47%, respectively, during treatment compared to baseline results. For the samples from the nasal quadrant, an increase occurred in the percentage of abnormal findings from 0 to 11%, while in the samples taken from the inferior quadrant, no changes were found with the use of isotretinoin. The parameters affected by this treatment were cell-to-cell contact, nucleus-tocytoplasm ratio and the distribution of goblet cells, the scores of which increased significantly. No significant correlation was found between the results of IC, symptom score and tear function tests. Therefore, the present findings show that acne treatment with oral isotretinoin results in changes in the conjunctival epithelium in a significant percentage of patients. These changes are seen both in the exposed region of the bulbar conjunctiva (temporal and nasal) and in the unexposed conjunctiva (superior) and reflect a trend towards squamous metaplasia as an adaptive response of the conjunctival epithelium, which tends to become nonsecretory under the effect of the drug.
publishDate 2009
dc.date.none.fl_str_mv 2009-11-10
2010-01-06
2015-05-14T12:59:47Z
2018-07-21T00:25:04Z
2018-07-21T00:25:04Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv QUEIROGA, Isabella Bezerra Wanderley de. Investigation of the toxicity of oral isotretinoin on the human conjunctiva using impression cytology. 2009. 109 f. Tese (Doutorado em Farmacologia) - Universidade Federal da Paraí­ba, João Pessoa, 2009.
https://repositorio.ufpb.br/jspui/handle/tede/6770
identifier_str_mv QUEIROGA, Isabella Bezerra Wanderley de. Investigation of the toxicity of oral isotretinoin on the human conjunctiva using impression cytology. 2009. 109 f. Tese (Doutorado em Farmacologia) - Universidade Federal da Paraí­ba, João Pessoa, 2009.
url https://repositorio.ufpb.br/jspui/handle/tede/6770
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal da Paraí­ba
BR
Farmacologia
Programa de Pós Graduação em Produtos Naturais e Sintéticos Bioativos
UFPB
publisher.none.fl_str_mv Universidade Federal da Paraí­ba
BR
Farmacologia
Programa de Pós Graduação em Produtos Naturais e Sintéticos Bioativos
UFPB
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UFPB
instname:Universidade Federal da Paraíba (UFPB)
instacron:UFPB
instname_str Universidade Federal da Paraíba (UFPB)
instacron_str UFPB
institution UFPB
reponame_str Biblioteca Digital de Teses e Dissertações da UFPB
collection Biblioteca Digital de Teses e Dissertações da UFPB
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)
repository.mail.fl_str_mv diretoria@ufpb.br|| diretoria@ufpb.br
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