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Year : 2022  |  Volume : 2  |  Issue : 2  |  Page : 71-73

Rare genetic disorder unveiled on evaluation of occult gastrointestinal bleed

Department of Hepatology and Transplant Hepatology, Gleneagles Global Health City, Chennai, Tamil Nadu, India

Date of Submission24-Jan-2022
Date of Decision15-Feb-2022
Date of Acceptance15-Feb-2022
Date of Web Publication23-Mar-2022

Correspondence Address:
Jo Varghese
Department of Hepatology and Transplant Hepatology, Gleneagles Global Health City, Chennai - 600 100, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ghep.ghep_3_22

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The incidence of gastrointestinal (GI) bleed secondary to vascular ectasias in GI tract remains very less, accounting to only about 4%–5% of nonvariceal bleed. Most patients remain asymptomatic unless evident as iron deficiency anemia. We report of similar case scenario in a 65-year-old man who presented with recurrent anemia, treated with multiple blood transfusions for 6 years. The patient was found to have multiple lingual, nasal, gastric, and duodenal telangiectasias with arteriovenous malformations in the liver and lung. Considering the history, clinical findings, and investigations, a diagnosis of Osler-Weber-Rendu syndrome/hereditary hemorrhagic telangiectasia was made based on Curaçao criteria and the patient was treated with tamoxifen and argon plasma coagulation.

Keywords: Anemia, arteriovenous malformations, Curaçao criteria, hereditary hemorrhagic telangiectasia

How to cite this article:
Varghese J, Abirami PD. Rare genetic disorder unveiled on evaluation of occult gastrointestinal bleed. Gastroenterol Hepatol Endosc Pract 2022;2:71-3

How to cite this URL:
Varghese J, Abirami PD. Rare genetic disorder unveiled on evaluation of occult gastrointestinal bleed. Gastroenterol Hepatol Endosc Pract [serial online] 2022 [cited 2022 Aug 18];2:71-3. Available from: http://www.ghepjournal.com/text.asp?2022/2/2/71/340388

  Introduction Top

Occult gastrointestinal (GI) bleed remains to be a frequently ignored and underestimated cause of iron deficiency anemia, especially in developing countries. Most cases result from underlying GI malignancy, whereas vascular lesions such as telangiectasias causing occult GI bleed occur very rarely. We report one such case with an initial presentation of recurrent anemia, treated with multiple blood transfusions and on evaluation, was found to have an inherited disorder named Osler–Weber–Rendu syndrome.

  Case Report Top

A 65-year-old teetotaler presented with recurrent episodes of easy fatigability, loss of appetite, and generalized weakness over the past 6 years. There was no associated fever/night sweats/cough/breathlessness. There was no history of comorbid illness in the past except for pulmonary tuberculosis treated before 30 years.

Six years ago, he was evaluated and found to have severe anemia with hemoglobin of 4 g%. Further workup for anemia was suggestive of iron deficiency anemia, and hence he was treated with blood transfusion followed by iron supplements. Over the next 4 years, he was managed with repeated blood transfusions and parenteral iron therapy for recurrence of symptoms. His younger sister also had similar history of anemia and died at 50 years of age.

As his symptoms worsened further and the frequency of transfusion increased, he came to our institute for further evaluation. On clinical examination, the patient was thin built, pale, and few tiny and red spots were noted over the dorsal surface of the tongue [Figure 1]. Systemic examination was normal.
Figure 1: Dorsal surface of the tongue with few reddish spots-representing telangiectasia

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His basic laboratory investigations are depicted in [Table 1].
Table 1: Initial lab investigations

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Further workup for anemia showed normocytic admixed with microcytic erythrocytes with reticulocyte count of 3.6%, low serum ferritin levels and high total iron binding capacity. Thyroid function, B12 levels, and autoimmune profile were within normal limits. His stool for occult blood was positive, and further evaluation with gastroscopy and colonoscopy showed multiple reddish telangiectasias over the antrum, body of the stomach, and duodenum [Figure 2]a and [Figure 2]b. Few similar telangiectatic lesions were noted in the nasal mucosa in diagnostic nasal endoscopy.
Figure 2: Gastric mucosa (a) and duodenal mucosa (b) with reddish areas of telangiectasia

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Contrast-enhanced computer tomography abdomen revealed small hypervascular and hyperdense lesions with contrast enhancement of hepatic venules in arterial phase along segment II and VIII of the liver and hypertrophied hepatic artery suggestive of arteriovenous shunts. Similar hyperdense vascular lesions were noted in the lung suggestive of pulmonary arteriovenous shunts [Figure 3].
Figure 3: Contrast-enhanced computed tomography of the abdomen showing arteriovenous malformations appearing hyperdense in the liver

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The patient was diagnosed to have anemia secondary to GI bleed with multiple telangiectasias noted in GI mucosa and nasal mucosa. In addition, arteriovenous malformations were noted in both liver and lungs. All the above-mentioned findings fulfilled the CURACAO criteria for diagnosis of hereditary hemorrhagic telangiectasia (HHT). Hence, the patient was started on trial of tamoxifen and underwent argon plasma coagulation for telangiectasia noted in GI mucosa. The patient is currently on follow-up with static hemoglobin levels, and further management with newer options such as bevacizumab has been planned in case of recurrence of symptoms.

  Discussion Top

The initial appearance of our patient's telangiectatic lesions in the tongue remained unnoticed and there were no cutaneous telangiectasias. The cause for telangiectatic lesions along GI tract includes hereditary HHT, blue rubber bleb nevus syndrome, progressive systemic sclerosis (CREST syndrome), Klippel-Trenaunay syndrome, Parkes-Weber syndrome, gastric antral vascular ectasia, angiodysplasia secondary to radiation-induced mucosal injury, etc.

GI mucosal telangiectasias in HHT are more common with increasing age but rarely bleed, and affect 70% of patients by age 30 years. Recurrent GI bleeding occurs in up to 30% of patients as a result of telangiectasias.[1]

Hereditary HHT, also named Osler–Weber–Rendu syndrome, is characterized by vascular dysplasia manifesting with telangiectasias and arteriovenous malformation in any internal organ.[1] This syndrome is inherited in autosomal dominant patterns and has worldwide prevalence of 1 in 10,000.[2] It is characterized by mutation in genes encoding for transmembrane proteins involved in the transforming growth factor (TGF)-β signaling pathway and is expressed predominantly on vascular endothelium.[3] Based on the gene involved, five main types of HHT with varying clinical picture have been described to date.[3]

The most common manifestation of HHT is recurrent spontaneous epistaxis seen in almost 90% of patients.[4] Telangiectasias in GI mucosa causing GI bleed are more commonly located in the stomach and duodenum.[5] They are usually >3 mm in diameter and >10 in number.

The diagnosis of this rare syndrome is mainly based on Curaçao criteria which necessitates the presence of at least three of four main clinical features: epistaxis, cutaneous or mucosal telangiectasias, visceral involvement, and a family history of HHT.[6] Genetic testing allows confirmation of the diagnosis in families with clinical features of HHT.

There have been several case reports on the successful management of epistaxis in HHT with various endoscopic techniques. Although the incidence of GI bleed is less compared to epistaxis, HHT patients with GI bleeding often require repeated blood transfusions and iron supplementation. Recurrent GI bleed in HHT patients should be addressed with either endoscopic/surgical interventions or pharmacotherapy. GI bleeding in HHT patients could be reduced by the administration of hormonal therapy such as tamoxifen/raloxifene.[7] Newer medications targeting TGF-β and VEGF such as thalidomide, pomalidomide, pazopanib, and bevacizumab have been found to be successfully advocated in patients with severe and recurrent GI bleed.[8]

Patient consent

This is to state that proper informed consent has been obtained from the patient for publishing his clinical details and images. Patient identity has not been revealed anywhere in the images submitted for publication.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

McDonald JE, Miller FJ, Hallam SE, Nelson L, Marchuk DA, Ward KJ. Clinical manifestations in a large hereditary hemorrhagic telangiectasia (HHT) type 2 kindred. Am J Med Genet 2000;93:320-7.  Back to cited text no. 1
Begbie ME, Wallace GM, Shovlin CL. Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): A view from the 21st century. Postgrad Med J 2003;79:18-24.  Back to cited text no. 2
Cole SG, Begbie ME, Wallace GM, Shovlin CL. A new locus for hereditary haemorrhagic telangiectasia (HHT3) maps to chromosome 5. J Med Genet 2005;42:577-82.  Back to cited text no. 3
Plauchu H, Chadarévian D, Bideau A, Robert JM. Age-related clinical profile of hereditary hemorrhagic telangiectasia in an epidemiologically recruited population. Am J Med Genet 1989;32:291-7.  Back to cited text no. 4
Mora-Luján JM, Iriarte A, Alba E, Sánchez-Corral MÁ Berrozpe A, Cerdà P, et al. Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia: Risk factors and endoscopic findings. J Clin Med 2020;9:82.  Back to cited text no. 5
Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, et al. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet 2000;91:66-7.  Back to cited text no. 6
Bauditz J, Lochs H. Angiogenesis and vascular malformations: Antiangiogenic drugs for treatment of gastrointestinal bleeding. World J Gastroenterol 2007;13:5979-84.  Back to cited text no. 7
Flieger D, Hainke S, Fischbach W. Dramatic improvement in hereditary hemorrhagic telangiectasia after treatment with the vascular endothelial growth factor (VEGF) antagonist bevacizumab. Ann Hematol 2006;85:631-2.  Back to cited text no. 8


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]


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