Luciana Bento

Doença do Refluxo Gastroesofágico (DRGE)

O refluxo gastroesofágico (REG), por definição, é a passagem de conteúdo gástrico para o esôfago, fazendo parte de um processo fisiológico e não apresenta sintomatologia. Entretanto, o REG com sintomatologia é o substrato da Doença do Refluxo Gastroesofágico (DRGE), requerendo tratamento na maioria das vezes. Na prática clínica, é muito difícil realizar o diagnóstico diferencial entre REG e DRGE, necessitando-se, muitas vezes, de testes diagnósticos de alta acurácia para diferenciá-los.

Epidemiologia

A DRGE é mais comum no Ocidente, particularmente quando se considera o sintoma mais comum, que é a pirose, com uma prevalência de 10-30% da população, sendo o tipo não-erosivo o mais comum, com uma prevalência maior que 70%.

No Brasil, as estatísticas apontam que a prevalência é de aproximadamente 12%. O sintoma pirose está intimamente relacionado com a obesidade, muito comum e crescente nos países ocidentais.

Outros fatores de risco:

  • Idade (prevalência diretamente proporcional à idade)
  • Gestação
  • Hérnia hiatal
  • Fatores genéticos
  • Tabagismo
  • Alcoolismo
  • Fármacos: anti-colinérgicos, inibidores da receptação de serotonina, beta-2-agonistas e bloqueadores de canais de cálcio

A infecção por H. pylori, importante etiologia das gastrites, não tem relação com a DRGE.

Etiopatogenia e Fisiopatologia

  • Episódios de refluxo gastroesofágico: frequência (pelo menos duas vezes por semana por, pelo menos 4 a 8 semanas), volume e extensão do material refluído e esfincter esofágico inferior: aberturas transitórias e hipotensão
  • Redução na capacidade de depuração esofágica
  • Agressividade do material refluído: ácido (mais comum), álcalis, pepsina e hiperosmolaridade
  • Redução na resistência tecidual ao material refluído
  • Natureza do material refluído: líquido ou gasoso

Classificação da DRGE

  • Doença do refluxo não-erosiva (DRGE-NE) – Tipo mais comum: sintomatologia presente e ausência de erosões ao exame endoscópico. A mucosa pode assumir aspecto normal, velamento dos vasos da submucosa ou mucosa nacarada (Figura 1).

Figura 1 - Doença do Refluxo GastroesofágicoFigura 1 – Paciente do sexo masculino de 67 anos, com sintomatologia de DRGE típica (pirose e regurgitação). À endoscopia digestiva alta, observa-se hérnia hiatal por deslizamento (quando a distância do pinçamento diafragmático e a transição esôfago-gástrica é maior ou igual a 2cm) associada a nacaramento da mucosa esofágica.

  • Doença de refluxo erosiva (DRGE-E) – Esofagites erosivas: exibe sintomatologia com erosões, que são definidas como solução de continuidade da mucosa. A classificação mais utilizada para esta enfermidade é a Classificação de Los Angeles.

Classificação de Los Angeles (classificação endoscópica)

  • Grau A: uma ou mais erosões menores que 5mm que não se estendem por duas pregas longitudinais (Figura 2)

Figura 2 - Doença do Refluxo Gastroesofágico

Figura 2 – Paciente do sexo masculino de 42 anos, tabagista, com sintomatologia de DRGE típica (regurgitação e pirose). À endoscopia digestiva alta, observa-se nacaramento da mucosa associada e erosões menores que 5mm que não se estendem por duas pregas longitudinais, sendo algumas recobertas por fibrina na mucosa esofágica.

  • Grau B: uma ou mais erosões maiores que 5mm em sua maior extensão, não contínuas entre os ápices de duas pregas longitudinais (Figura 3)

Figura 3 - Doença do Refluxo Gastroesofágico

Figura 3 – Paciente do sexo masculino, 54 anos, com sintomatologia de DRGE atípica (dor torácica não-cardíaca). À endoscopia digestiva alta, observa-se mucosa espessada e nacarada com erosões maiores que 5mm em sua maior extensão, não-contínuas entre os ápices de duas pregas longitudinais na mucosa esofágica.

  • Grau C: erosões contínuas ou convergentes entre os ápices de pelo menos duas pregas longitudinais, envolvendo pelo menos 75% da circunferência do órgão (Figura 4)

Figura 4 - Doença do Refluxo Gastroesofágico

Figura 4 – Paciente do sexo feminino, 60 anos, colecistectomizada, com sintomatologia de DRGE típica (regurgitação e pirose), rebelde ao tratamento com IBPs. À endoscopia digestiva alta, observa-se nacaramento e espessamento, além de erosões confluentes, recobertas por fibrina ocupando menos de 75% da circunferência do órgão da mucosa esofágica. Foi submetida a ph-Impedânciometria que evidenciou refluxo não-ácido.

  • Grau D: erosões contínuas ou convergentes entre os ápices de pelo menos duas pregas longitudinais, envolvendo pelo menos 75% da circunferência do órgão (Figura 5)

Figura 5 - Doença do Refluxo Gastroesofágico

Figura 5 – Paciente do sexo masculino, 62 anos, com sintomatologia de DRGE típica (regurgitação e pirose), rebelde ao tratamento com IBPs. À endoscopia digestiva alta, observa-se nacaramento e espessamento. Foi submetida à manometria esofágica, que evidenciou hipotonia do esfíncter esofagiano inferior.

Aspectos Clínicos – Sintomatologia 

A sintomatologia da DRGE pode ser classificada em típica e atípica.

Sintomas Típicos    

  • Pirose (queimação retrotesternal podendo irradiar para epigástrio e pescoço)
  • Regurgitação (percepção de restos alimentares na hipofaringe ou boca)

Sintomas Atípicos

  • Dor torácica não-cardíaca (DTNC)
  • Globus faringeus (sensação de corpo estranho na garganta)
  • Asma
  • Tosse crônica
  • Fibrose pulmonar idiopática
  • Apnéia do sono
  • Pneumonias de repetição
  • Otite média
  • Sinusite crônica
  • Rouquidão
  • Pigarro
  • Desgaste no esmalte dentário
  • Halitose
  • Aftas

Diagnóstico

Teste diagnóstico terapêutico

Consiste na administração de um dos fármacos inibidores de bomba de prótons (IBP) descritos a seguir, por um período de 4 semanas:

  • Omeprazol – 20mg -1 vez ao dia
  • Lanzoprazol – 30mg -1 vez ao dia
  • Pantoprazol – 40mg -1 vez ao dia
  • Rabeprazol – 20mg – 1 vez ao dia
  • Esomeprazol – 40mg -1 vez ao dia por um período de 4 semanas)

Indicação Esse teste só pode ser realizado em pacientes com idade menor que 45 anos, com sintomas típicos e sem sinais de alarme (disfagia, odinofagia, anemia, hemorragia digestiva e emagrecimento). Sendo o tratamento clínico satisfatório neste cenário, a endoscopia digestiva alta está dispensada.

Endoscopia digestiva alta

É o exame de escolha para avaliar o grau das esofagites e a existência de complicações da DRGE (estenoses pépticas, úlceras, esôfago de Barrett e adenocarcinoma – sempre devem ser biopsiadas). Indicação Para pacientes com sintomas atípicos, idade maior que 45 anos, sinais de alarme e falha terapêutica. Muitas vezes, o paciente é portador de Doença do Relfuxo Gastroesofágico com mucosa de aspecto normal.

Manometria esofágica

Consiste na instalação de um cateter via nasal que registra as pressões do esfíncter esofagiano inferior (EEI), do corpo esofagiano e do esfíncter esofagiano superior (EES). Indicações – no contexto da DRGE:

  • Pré-cirúrgico para se determinar o tipo de cirurgia de válvula antirrefluxo para o tratamento da DRGE
  • Localização precisa da parte proximal do EEI, condição essencial para o posicionamento da parte distal do cateter de pH-metria ou pH-impedanciometria – 5 cm acima da parte superior do EEI
  • Avaliação de doenças concomitantes como megaesôfago, doença do colágeno e espasmo esofagiano difuso, podendo estar relacionadas com a DRGE
  • Estudo do tônus do EEI em pacientes refratários ao tratamento clínico ou cirúrgico

pH-metria de 24 horas

Consiste na instalação de um cateter via nasal cuja parte distal deverá ficar posicionada a 5cm da parte superior do EEI. Indicações

  • Para pacientes com sintomatologia de DRGE e que não apresentam esofagite à endoscopia digestiva alta
  • Para caracterizar se o refluxo ocorre com mais frequência em posição supina, ortostática ou combinada (os do tipo ortostático respondem melhor às medidas clínicas)
  • Para avaliar se existe relação com refluxo e sintomatologia
  • Para avaliar a eficácia do tratamento clínico ou cirúrgico

A grande limitação deste exame é que ele detecta apenas refluxo ácido (pH<4). A pH-impedanciometria de 24 horas é similar à pH-metria, porém este exame classifica o refluxo em ácido (pH<4) ou não ácido (pH>4), sólido, líquido ou gasoso e anterógrado ou retrógrado. Este é o padrão-ouro para o diagnóstico da DRGE. Existe uma nova classificação proposta pelo Consenso da Doença do Refluxo Gastroesofágico do Porto que define a Doença do Refluxo Gastroesofágico Patológica de acordo com os achados endoscópicos, da pH-metria de 24hs e da impedâncio-pH-metria de 24hs:

  • Doença do Refluxo Gastroesofágico Patológica: esofagites graus C ou D de Los Angeles e/ou estenose péptica e/ou Esôfago de Barrett com extensão maior que 1cm e/ou Tempo de Exposição Ácido à pH-metria de 24hs ou impendâncio-pH-metria de 24hs maior que 6%
  • Borderline: esôfago com mucosa normal, hiperêmica, nacarada ou espessada; esofagites graus A ou B de Los Angeles ou Tempo de Exposição Ácido à pH-metria de 24hs ou impedâncio-pH-metria de 24hs entre 4-6%. Considerar o número de episódios de refluxo, linha de base da impedâncio-pH-metria de 24hs e esofagite microscópica (infiltração de eosinófilos, neutrófilos e linfócitos no epitélio; hiperplasia da camada basal, ultrapassando 20% da espessura do epitélio e alongamento das papilas da lâmina própria)
  • Doença de Refluxo Gastroesofágico Não-patológica: Tempo de Exposição Ácido menor do que 4%

Tratamento

Medidas Comportamentais

  • Elevação da cabeceira da cama (15cm)
  • Moderação no consumo de alimentos (se houver correlação com sintomatologia) gordurosos, cítricos, café, bebidas alcóolicas, bebidas gasosas, menta, hortelã, tomates e derivados
  • Atenção quanto aos medicamentos causadores de relaxamento do EEI, tais como anticolinérgicos, antidepressivos tricíclicos, bloqueadores de canais de cálcio, beta-2-adrenérgicos e alendronato
  • Respeitar o período pós-prandial: evitar deitar após as refeições (o período deve ser de no mínimo 2 horas)
  • Fracionamento das refeições impedindo a distensão gástrica excessiva
  • Redução drástica ou cessação do tabagismo
  • Normalização do Índice de Massa Corpórea (IMC)

Tratamento Farmacológico

É igual ao protocolo do teste terapêutico da DRGE. Havendo persistência dos sintomas, dobrar a dose de IBP por mais 12 semanas. O paciente é considerado refratário ao tratamento farmacológico se persistirem os sintomas, apesar do tratamento com dose dobrada de IBP por 12 semanas. ATENÇÃO: Todos os pacientes com classificação endoscópica de Los Angeles C ou D deverão se submeter à endoscopia digestiva alta para reestadiamento da DRGE.

Tratamento Cirúrgico

As indicações do tratamento cirúrgico consistem em

  • Refratariedade às medidas comportamentais e tratamento farmacológico
  • Necessidade de tratamento contínuo com IBP, principalmente nos pacientes com idade menor que 40 anos
  • Indisponibilidade de se manter financeiramente o tratamento com IBP a longo prazo

Complicações

Estenose Péptica

Figura 6 - Doença do Refluxo Gastroesofágico

Figura 6 – Paciente do sexo masculino, 75 anos, com sintomatologia de DRGE típica e disfagia para sólidos, em uso de Omeprazol há 10 anos, com melhora transitória da sintomatologia. À endoscopia digestiva alta, observa-se estenose péptica, com aspecto fibrótico e anelar, que não permitiu a transposição do gastroscópio. Realizadas biópsias que excluíram malignidade. O estudo radiológico contrastado do esôfago mostrou se tratar de uma estenose única com cerca de 1 cm de extensão. Realizada dilatação endoscópica balonada com sucesso.

Esôfago de Barrett

(Substituição do epitélio escamoso da transição esôfago-gástrica por epitélio colunar – condição pré-neoplásica para adenocarcinoma):

Figura 7 - Doença do Refluxo Gastroesofágico

Figura 7 – Paciente do sexo feminino, 54 anos, com obesidade grau 1, com sintomatologia atípica (globus faringeus). À endoscopia digestiva alta, observa-se hérnia hiatal por deslizamento, mucosa esofágica espessada e nacarada, com prolongamentos circulares e digitiformes de coloração vermelho-salmão, padrão vascular submucoso visível, sendo realizadas biópsias – cujo estudo histopatológico evidenciou metaplasia intestinal sem displasia. Submetida à manometria que revelou esfíncter esofágico inferior hipotônico e corpo esofágico compatível com a normalidade. Encaminhada para tratamento cirúrgico: confecção de válvula antirrefluxo. A Sociedade Britânica de Gastroenterologia recomenda realizar diagnóstico endoscópico de Barrett quando o epitélio colunar tenha no mínimo 1cm de extensão. Caso contrário, cogita-se irregularidade da transição esôfago-gástrica.

Adenocarcinoma

Figura 8 - Doença do Refluxo Gastroesofágico

Figura 8 – Paciente do sexo feminino, 58 anos, diagnóstica há 10 anos com Esôfago de Barrett sem displasia, por endoscopia digestiva alta e estudo histopatológico. Porém, abandonou o seguimento endoscópico e há 3 meses, começou a evoluir com disfagia para sólidos e síndrome consuptiva. À endoscopia digestiva alta, observa-se lesão elevada com componente cicatricial adjacente. Realizadas biópsias – cujo resultados histopatológicos evidenciaram adenocarcinoma bem diferenciado com invasão da camada submucosa. Realizadas ecoendoscopia e tomografia de tórax, abdome e pelve, que excluíram metástases locorregionais e à distância (T1N0M0). Paciente encaminhada para esofagectomia.

Sequência Biológica Evolutiva da DRGE – Adenocarcinoma:

Epitélio escamoso → Esofagite → Esôfago de Barrett → Displasia de baixo/alto grau → Adenocarcinoma

Considerações finais

A Doença de Refluxo Gastroesofágico representa grande impacto na qualidade de vida da população mundial com importância em termos de Saúde Pública, cujo tratamento é crucial para se interromper a evolução para as suas complicações.

Referências bibliográficas

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  2. Savarino E, Maraboto E, Bodini G et al. Epidemiology and natural history of gastro-oesophageal reflux disease. Minerva Gastroenterol Dietol. 2017; 72(2): 81-92.
  3. Moraes FJ, Domingues G. Doença do Refluxo Gastroesofágico. In: Zaterka S, Eisig JN, editors. Tratado de Gastroenterologia da Federação Brasileira de Gastroenterologia. São Paulo: Atheneu. 2016. p. 445-57.
  4. Herregoods T, Bredenoord A, Smout A. Pathophisiology of gastroesophageal reflux disease: new understanding in a new era. Neurogastroenterol Motil. 2015; 27: 1202-13.
  5. Hung WC, Wu JS, Sun ZJ et al. Gender diferences in the association of non-alcoholic fatty liver disease and metabolic syndrome with erosive oesophagitis: a cross-sectional study in a Taiwanese population. BMJ Open. 2016; 6(11): 2-7.
  6. Bortoli N, Martinucci L, Savarino E et al. Proton pump inhibitor responders who are not confirmed as GERD patients with impedance and ph monitoring: what are they? Neurogastroenterol Motil. 2014; 26: 28-35.
  7. Naik RD, Vaezi MF. Recents advances in diagnostic testing for gastroesophageal reflux disease. Expert Rev Gastroenterol Hepatol. 2017; Mar 27: 1-24.
  8. Dent J, Brun J, Frendrick AM et al. An evidence based appraisal of reflux disease management. The Genval Workshop Report. Gut. 1999; 44: 1-6.
  9. Jailwala JA, Shaker R. Oral and pharyngeal complications of gastroesophageal reflux disease: globus, dental erosions, chronic sinusitis. J Clin Gastroenterol. 2000; 30: 35-38.
  10. Moraes Filho JP, Navarro-Rodriguez T, Barbuti T et al. Guidelines for the diagnosis and management of gastroesophageal reflux disease: na evidence-based consensus. Arq Gantroenterol. 2010; 47(1): 99-115.
  11. Bortoli N, Martinucci I, Bertani L et al. Esophageal testing: What we have so far. World J Gatrointest Pathophysiol. 2016; 15(1): 72-85
  12. Filtzgerald RC, di Pietro M, Ragunnath K et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barretts’s oesopahgus. 2014; 63(1): 7-42.
  13. Inoue H, Fukami N, Yoshida T et al. Endoscopic mucosal resection for esophageal and gastric cancers. J Gastroenterol Hepatol. 2002; 17: 382-88.
  14. Roman S, Gyawali CP, Savarino E et al. Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: Update of the Porto consensus and recommendations from an international consensus group. Neurogatroenterol Motil. 2017; 1-15.
  15. Liu C, Crawford JM. O Trato Gatrointestinal. In: Kumar V, Abbas AK, Fausto N, editors. Patologia-Bases Patológicas das Doenças-Robbins e Cotran. Rio de Janeiro: Elsevier. 2013. p. 837-918.

IMAGENS: Figuras 1, 2, 3, 4, 5, 6, 7 e 8 – do acervo do autor.

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Dr. Marcio Correia Cazzamatta

Médico Endoscopista: Membro Titular da Sociedade Brasileira de Endoscopia Digestiva (SOBED). Médico-assistente do Serviço de Colonoscopia da Santa Casa de Misericórdia de Santos-SP, do Hospital do Bosque da Saúde (São Paulo – SP) e do AME (Santos – SP). Pós-graduando em Doenças Funcionais do Aparelho Digestivo, pH-metria, Manometrias Esofágica e Anorretal, pelo Núcleo de Fisiologia Gastrointestinal do Hospital Israelita Albert Einstein.

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