Upper gastrointestinal bleeding in a patient with Marfan’s disease

Ruiz-Rodríguez, Antonio José; García Robles, Adelina; Benavente Fernández, Alberto

doi:10.1016/j.medcle.2021.04.023

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The prevailing aetiological causes depend on the age range,<a class="elsevierStyleCrossRef" href="#bib0005">1</a> with NSAID gastritis, Dieulafoy’s lesion and caustic ingestion being the most common. Less commonly, they are also described in patients with structural abnormalities in blood vessels or internal organs, due to vascular disease (Wegener, microscopic polyangiitis), vascular malformations (Rendu–Osler–Weber) or connective tissue diseases (pseudoxanthoma elasticum, Marfan, Ehlers–Danlos, Loeys–Dietz).We report the case of a 14-year-old male with no history of interest who went to the emergency department for coffee ground vomitus. The patient’s past history included occasional use of NSAIDs in the previous week. Laboratory tests showed haemoglobin of 9 g/dl. An upper gastrointestinal endoscopy (UGE) in retroversion showed the mucosa of the upper body of stomach and fundus to be erythematous and congestive with several superficial linear ulcerations without active bleeding (Forrest III). The patient developed massive haematemesis after 48 h, and a second UGE was performed, which showed a 1 cm ulcer in the subcardial region with mild drooling bleeding (Forrest I-B) and adjacent denuded and friable mucosa of the fundus and upper body. Haemostatic treatment was applied to the ulcer and the bleeding was controlled. Again, 48 h later, he presented with new haematemesis and haemodynamic instability, which required a third UGE in the ICU: drooling bleeding was observed in the previously described subcardial ulcer, and, in addition, the adjacent mucosa of the upper body was very thin and friable, with spontaneous and diffuse bleeding. Given the recurrent nature of the bleeding, superselective embolization of the right gastric artery branches was finally performed using microcoils, without further episodes of bleeding.The patient’s physical examination revealed an antimongoloid palpebral fissure and eyelid scars, also highlighting generalized joint hyperlaxity. Beighton’s score was completed and was positive (4 points): passive dorsiflexion of the 5th finger exceeding 90° bilaterally and passive apposition of the thumbs to the flexor aspect of the forearm bilaterally. Suspecting a connective tissue disorder, a genetic study was requested, the results of which indicated the presence of a heterozygous p.Arg1125GIn mutation in the FBN1 gene, with this mutation being autosomal dominant, corresponding to Marfan syndrome.Although the gastrointestinal bleeding was initially attributed to NSAIDs, the course and recurrent nature of the bleeding, the atypical endoscopic findings (denuded and friable mucosa) and the patient’s features on physical examination led to the establishment of a differential diagnosis with connective tissue diseases, confirming a rare mutation of Marfan syndrome by genetic study.Marfan syndrome is an autosomal dominant type 1 fibrinopathy caused by a heterozygous mutation of the FBN1 gene that encodes the protein fibrillin-1, an essential component of the microfibrils that form part of the extracellular matrix, giving it strength and structural integrity, so that, when deficient, the connective tissue is fragile and unstructured, facilitating its rupture. Although any organ or system can be affected, giving rise to very varied manifestations, it is characterized by skeletal manifestations (tall stature with trunk-limb disproportion, scoliosis and/or pectus excavatum), ocular (ectopia lentis) and cardiovascular (aortic aneurysm and/or or mitral valve prolapse).<a class="elsevierStyleCrossRef" href="#bib0010">2</a>In the absence of family history and classic skeletal–ocular–cardiovascular manifestations, a positive systemic score or the presence of a FBN1 gene mutation is required for diagnosis, with the p.Arg1125GIn mutation of said gene being the basis of diagnosis in our case.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> This is especially important in paediatric or young adult patients as they potentially present incomplete conditions whose development is age-dependent, requiring high suspicion for early diagnosis to allow early detection of cardiovascular malformations that compromise prognosis.The gastrointestinal manifestations associated with Marfan’s disease are mainly functional and derive from abdominal wall or diaphragmatic hernias,<a class="elsevierStyleCrossRef" href="#bib0020">4</a> with gastrointestinal bleeding being rare and caused by arterial or visceral rupture mechanisms. In our patient, these causes were ruled out by angio-CT and arteriography, attributing the gastrointestinal bleeding to structural and functional alteration of the connective tissue, both of the gastric submucosa, since it is mainly made up of collagen fibres that surround and protect its abundant vasculature, as well as the lamina propria of the gastric mucosa, a tissue equally abundant in collagen.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>Ethical responsibilitiesProtection of people and animalsThe authors declare that no experiments on humans or animals have been performed for this research.Data confidentialityThe authors declare that they have followed their centre’s protocols on the publication of patient data.Right to privacy and informed consentThe authors declare that no patient data appear in this article. Informed consent was not requested for the publication of this case because no personal data enabling the identification of the patient are published in this article.FundingThis research has not received specific funding from public or private sector agencies or non-profit organisations.Conflict of interestsThe authors declare that there are no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:3 [ "identificador" => "sec0005" "titulo" => "Ethical responsibilities" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Protection of people and animals" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Data confidentiality" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Right to privacy and informed consent" ] ] ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of interests" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Ruiz-Rodríguez AJ, García Robles A, Benavente Fernández A. Hemorragia digestiva alta en un paciente con enfermedad de Marfan. Med Clin (Barc). 2022;158:237–238." ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pediatric gastrointestinal bleeding: perspectives from the Italian Society of Pediatric Gastroenterology" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C. Romano" 1 => "S. Oliva" 2 => "S. Martellossi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3748/wjg.v23.i8.1328" "Revista" => array:6 [ "tituloSerie" => "World J Gastroenterol" "fecha" => "2017" "volumen" => "23" "paginaInicial" => "1328" "paginaFinal" => "1337" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28293079" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The revised Ghent nosology for the Marfan síndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "B.L. Loeys" 1 => "H.C. Dietz" 2 => "A.C. Braverman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/jmg.2009.072785" "Revista" => array:6 [ "tituloSerie" => "J Med Genet" "fecha" => "2010" "volumen" => "47" "paginaInicial" => "476" "paginaFinal" => "485" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20591885" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Update of the UMD-FBN1 mutation database and creation of an FBN1 polymorphism database" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Collod-Beroud" 1 => "S. Le Bourdelles" 2 => "L. Ades" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/humu.10249" "Revista" => array:6 [ "tituloSerie" => "Hum Mutat" "fecha" => "2003" "volumen" => "22" "paginaInicial" => "199" "paginaFinal" => "208" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12938084" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gastrointestinal symptoms in Marfan syndrome and hypermobile Ehlers-Danlos syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "N. Inayet" 1 => "J. Hayat" 2 => "A. Kaul" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2018/4854701" "Revista" => array:2 [ "tituloSerie" => "Gastroenterol Res Pract" "fecha" => "2018" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Wheater’s functional histology: a text and colour atlas" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. Young" 1 => "O. Woodford" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:4 [ "edicion" => "6th ed." "fecha" => "2009" "editorial" => "Churchill Livingstone/Elsevier" "editorialLocalizacion" => "Edinburgh" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015800000005/v1_202203050916/S2387020622000717/v1_202203050916/en/main.assets" "Apartado" => array:4 [ "identificador" => "43311" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015800000005/v1_202203050916/S2387020622000717/v1_202203050916/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020622000717?idApp=UINPBA00004N"]

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Vol. 158. Issue 5.

Pages 237-238 (March 2022)

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