Osler-Weber-Rendu Syndrome - The Gastrointestinal Atlas

This is a 62 Year-old male, from the republic of Guatemala with severe recurrent GI bleeding since 2 years previous, in this period has received 60 blood transfusions. At the age of 35 was observed the tongue lesions. Patient also has a recurrent epistaxis since childhood.
Transfusion-dependent GI bleeding and multiple gastrointestinal telangiectasias the majority are in the stomach.

The gastrointestinal bleeding manifestations were with melena and bright red blood.

Gastrointestinal bleeding was managed with argon plasma coagulator to the vast majority of angiodysplasias except the angiodysplasia of the cecum needed a combination of two therapeutic procedures with injections of absolute alcohol and argon plasma coagulation (APC).

Recurrent gastrointestinal tract hemorrhage occurs in up to one-third of individuals with HHT. The risk of such hemorrhage increases with advancing age, typically appearing in the fifth or sixth decade of life. (Gastrointestinal telangiectasias can be multiple and are found throughout the gastrointestinal tract, most commonly in the stomach and duodenum.( The severity of anemia is related to the number of telangiectasias, which are diagnosed through digestive endoscopy.

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Characteristic Mucocutaneous Telangiectasia

Pictures and Photos of Hereditary Hemorrhagic

Telangiectasias on his ears, face, lips, tongue, and oral and nasal mucosa.

Osler-Weber-Rendu syndrome, or hereditary hemorrhagic telangiectasia (HHT), is a rare genetically determined disorder that affects blood vessels throughout the body and results in a tendency for bleeding. HHT is an autosomal dominant disorder characterized by vascular dysplasia and hemorrhage. but about 20% develop spontaneously in the absence of evidence of genetic transmission.

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Close-up view of typical symptoms of patient with Osler-Weber-Rendu syndrome with red nodules and starry telangiectasia on the lips.

HHT is an autosomal dominant disorder manifested by mucocutaneous telangiectases and arteriovenous malformations (AVMs), a potential source of serious morbidity and mortality. Lesions can affect the nasopharynx, central nervous system (CNS), lung, liver, and spleen, as well as the urinary, GI tract, conjunctiva, trunk, arms, and fingers. Epistaxis is the most common manifestation, and GI bleeding is also prevalent. Onset of symptoms may be delayed until the fourth decade of life (approximately 90% of patients manifest by age 40 y) or later decades.

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Telangiectatic lesions on tongue and lips

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Hereditary Hemorrhagic Telangiectasia Image

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Hereditary Hemorrhagic Telangiectasia Image

In 1864, Sutton described a disorder of epistaxis and degeneration of the vascular system that would later bear the names Osler-Weber-Rendu disease (OWRD) and hereditary hemorrhagic telangiectasia (HHT).Benjamin Guy Babington noted the syndrome’s familial nature in his
1865 paper "Hereditary Epistaxis.".

In 1876, Sir John Legg described a case of "hemophilia" with recurrent epistaxis and multiple nevi. However, Henri Rendu was the first to emphasize the hallmark blanching cutaneous and mucous membrane angiomata of HHT and differentiated this disease from hemophilia.Subsequently,
Sir William Osler and Frederick Parks Weber published detailed descriptions of the syndrome that along with Rendu, bears their names.

The term hereditary hemorrhagic telangiectasia (HHT) was coined by the pathologist Hanes in 1909. With the development of gastrointestinal endoscopy, Renshaw described the "millet seed to pinhe.

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The underlying disorder in HHT is abnormal vascular architecture at discrete sites. Unaffected areas show normal vessel architecture based on ultrastructural analysis. Thus, researchers postulate that an initiating event combined with abnormal repair results in HHT
lesions.

Interactions with transforming growth factor-beta (TGF-b) signaling result in disorganized cytoskeletal structure and poor vascular tubule formation. The gene expression profiles of the vascular endothelial cells grown from HHT patients reveals dysregulation of genes involved with the following:

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Hereditary Hemorrhagic Telangiectasia Image

Angiogenesis
Cytoskeletal integrity
Cell migration
Proliferation
Nitric oxide synthesis

Blanching round and reticulated reddish-purple plaques.

There are totally 3 types of telangiectasia. People with Type 1 and 2 will show symptoms early and type 2 and 3 will have liver abnormalities to large extent. Nosebleeds are quite common in all people with this disorder and it becomes serious when there is internal bleeding in liver or
lungs or brain. In another type of Juvenile telangiectasia there will be a tendency for the growth of polyps in the gastrointestinal tract.

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Hereditary Hemorrhagic Telangiectasia

Telangiectases of the skin and mucous membranes, epistaxis, and a positive family history comprise the classic triad of Osler-Weber-Rendu syndrome, or hereditary hemorrhagic telangiectasia (HHT). Visceral and central nervous system (CNS) involvement may be asymptomatic but are of importance due to associated complications that may be preventable. The estimated frequency of manifestations in patients with HHT is as follows:

Spontaneous, recurrent epistaxis - 90%
Skin telangiectases - 75%
Hepatic or pulmonary involvement (AVMs) - 30%
GI bleeding 15%
CNS lesions

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It is recognized that the manifestations of HHT are not generally present at birth, but develop with increasing age. Data suggest that by age 16 years, 71% of individuals will have developed some sign of HHT, rising to over 90% by age 40 years. However, these data mean that during their childbearing years, an apparently unaffected child of an HHT patient still has a 5-20% chance of actually carrying the HHT disease gene.

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Hereditary Hemorrhagic Telangiectasia

A known progression in the onset of symptoms over time begins with epistaxis, then pulmonary AVM, followed by cutaneous and mucous telangiectases.

Skin lesions begin as dark red lines or punctate, pulsating vascular papules the size of match heads. These may be found on the skin, oral mucosa, nasal mucosa, and conjunctiva More rarely, skin lesions are star shaped and 1-3 mm in diameter; alternatively, they are nonpulsating
telangiectases similar to those of araneus nevi.

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Hereditary Hemorrhagic Telangiectasia

Eighty percent present as spontaneous epistaxis Arteriovenous malformations (AVMs) occur throughout the body including the gastrointestinal (GI) tract, lungs, liver, brain/spinal cord Cutaneous lesions start to appear in adulthood and increase with age Lesions appear as small macular telangiectasia that are
1–2 mm in diameter and blanch Telangiectasia commonly occur on lips, tongue, palate, face (sun-exposed areas), nares, ears, conjunctiva, chest, hands, and feet Fingertips can develop painful ulcers from the telangiectasia.

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Hereditary Hemorrhagic Telangiectasia Image

Half of patients manifest cutaneous lesions by age 30, although lesions may arise during the teenage years. The face, lips and mouth, nares, tongue, ears, hands, chest, and feet are most often affected, in descending order of frequency and in any combination. Lesions are multiple and may be of cosmetic concern, and the number of lesions may increase with age. Bleeding israrely clinically significant.

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Osler-Weber-Rendu Syndrome

Autosomal dominant —A pattern of inheritance in which only one of the two copies of an autosomal gene must be abnormal for a genetic condition or disease to occur. An autosomal gene is a gene that is located on one of the autosomes or non-sex chromosomes. A person with an autosomal dominant disorder has a 50% chance of passing it to each of their offspring.

Chromosome —A microscopic thread-like structure found within each cell of the human body and consisting of a complex of proteins and DNA. Humans have 46 chromosomes arranged into 23 pairs. Chromosomes contain the genetic information necessary to direct the
development and functioning of all cells and systems in the body. They pass on hereditary traits from parents to child (like eye color) and determine whether the child will be male or female.

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Hereditary Hemorrhagic Telangiectasia Video Clip

Recurrent gastrointestinal tract hemorrhage occurs in up to one-third of individuals with HHT. The risk of such hemorrhage increases with advancing age, typically appearing in the fifth or sixth decade of life. Gastrointestinal telangiectasias can be multiple and are found throughout the gastrointestinal tract, most commonly in the stomach and duodenum. The severity of anemia is related to the number of telangiectasias, which are diagnosed through digestive endoscopy.

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Osler-Weber-Rendu Syndrome Video Clip

Endoscopic Management of Severe Gastrointestinal Bleeding in Hereditary Hemorrhagic Telangiectasia

Telangiectasia causing acute haemorrhage

A history of gastrointestinal bleeding is common in patients with HHT (33%). 25% of HHT patients > or =60 yr suffer from severe gastrointestinal bleeding.

Almost invariably, all of the mucous membranes are involved, including membranes throughout the GI, respiratory, and urinary tracts and those in the nasal septum, oral cavity, and nasopharynx.

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Hereditary Hemorrhagic Telangiectasia, Gastric Telangiectasia.

Mirror effect due to immersion in water

Control of intermittent GI bleeding may be managed medically. However, brisk hemorrhage may require endoscopic treatment or surgical resection.

GI bleeding treatment may include the following:

Estrogen-progesterone therapy
Transfusion
Aminocaproic acid
Endoscopic photoablation or electrocautery
Bevacizumab

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Hereditary Hemorrhagic Telangiectasia

Duodenal Angiodysplasia in a Hereditary Hemorrhagic Telangiectasia.

Although 80% of patients with HHT have gastric or small intestinal telangiectasia on endoscopy or capsule examination, only 25-30% of patients will develop symptomatic GI bleeding which usually does not present until the fifth or sixth decades of life. Patients rarely develop significant GI bleeding before 40 years of age
Women are affected with GI bleeding in a ratio of 2-3:1

Recurrent gastrointestinal tract hemorrhage occurs in up to one-third of individuals with HHT. The risk of such hemorrhage increases with advancing age, typically appearing in the fifth or sixth decade of life. Gastrointestinal telangiectasias can be multiple and are found throughout the gastrointestinal tract, most commonly in the stomach and duodenum. The severity of anemia is related to the number of telangiectasias, which are diagnosed through digestive endoscopy.

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Hereditary Hemorrhagic Telangiectasia

Endoscopic Treatment with Argon Plasma Coagulation of a severe case of bleeding due to a Hereditary Hemorrhagic Telangiectasia

GI bleeding develops in 25-30% of patients with HHT Usually manifesting in the fifth or sixth decade, lesions can arise in any portion of the GI tract, although they most commonly involve the stomach and small bowel. Nodular angiomas are visualized on endoscopy and are similar to cutaneous telangiectases in appearance.

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Hereditary Hemorrhagic Telangiectasia Video Clip therapy with Argon Plasma Coagulation.

GI bleeding is the most common visceral manifestation of HHT; it presents later than epistaxis and has been shown to occur in both HHT-1 and HHT-2 families.Massive transfusion requirements of more than 100 units of blood have been reported. The presence and number of lesions
detected in the stomach and duodenum on upper endoscopy correlates with the detection of lesions in the jejunum, although large (greater or equal to 5mm) upper tract lesions do not necessarily suggest the presence of large jejunal lesions.

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Hereditary Hemorrhagic Telangiectasia

Hereditary Hemorrhagic Telangiectasia: Continuous Challenges of a Well Described Disease.

Severe cases of HHT, recurrent GI Bleeding due to multiple Telangiectasias.Hereditary Hemorrhagic Telangiectasia Video Clip therapy with Argon Plasma Coagulation.

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Endoscopic Management of Severe Gastrointestinal Bleeding in Hereditary Hemorrhagic Telangiectasia

Indications for intervention in Osler-Weber-Rendu syndrome, or hereditary hemorrhagic telangiectasia (HHT), vary according to site of involvement and presentation. One third of cases of are mild, one third are moderate, and one third are severe. In mild cases of HHT, no treatment is necessary. Individual skin lesions may be obliterated with cautery, hypertonic saline sclerotherapy, or dye laser surgery.

$Endoscopic Management of Severe Gastrointestinal Bleeding in Hereditary Hemorrhagic Telangiectasia with Argon Plasma Coagulation. In severe cases of HHT, recurrent epistaxis refractory to ablative treatment is treated surgically with nasal septum skin transplants by using skin taken from the lower trunk. Severe cases of HHT may respond to estrogen therapy.$

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Hereditary Hemorrhagic Telangiectasia

Endoscopic Management of Severe Gastrointestinal Bleeding in Hereditary Hemorrhagic Telangiectasia with Argon Plasma Coagulation.

In severe cases of HHT, recurrent epistaxis refractory to ablative treatment is treated surgically with nasal septum skin transplants by using skin taken from the lower trunk. Severe cases of HHT may respond to estrogen therapy.

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Hereditary Hemorrhagic Telangiectasia Video Clip

Patients with HHT and GI bleeding may or may not be symptomatic, as the bleeding is usually in a slow, chronic and intermittent fashion, often without notable melena. Patients often have few symptoms until they become anemic. In severe cases, HHT GI bleeding causes
morbidity, dependency on blood transfusions and increased mortality.

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Hereditary Hemorrhagic Telangiectasia Video Clip

Endoscopic application of a heater probe, bicap, argon photocoagulation or laser are used by some to treat symptomatic GI bleeding. In some trials, hormonal treatment with estrogen-progesterone has decreased transfusion needs. Like telangiectases of the nose and skin, GI tract telangiectases will usually recur over time regardless of treatment.

$Esophagogastroduodenoscopy is the recommended initial test for evaluation of GI bleeding in HHT patients with anemia or iron deficiency, particularly when out of keeping with the severity of epistaxis. Though the majority of patients with HHT will have GI telangiectasia, the utility of endoscopic evaluation is in the anemic or iron-deficient patient. The International HHT Guidelines recommended aggressive management of anemia and iron deficiency, with consideration of limited endoscopic therapy and potential medical therapies (hormonal therapy, anitfibrinolytics) in refractory cases, though evidence is limited.$

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Hereditary Hemorrhagic Telangiectasia

Esophagogastroduodenoscopy is the recommended initial test for evaluation of GI bleeding in HHT patients with anemia or iron deficiency, particularly when out of keeping with the severity of epistaxis. Though the majority of patients with HHT will have GI telangiectasia, the utility of
endoscopic evaluation is in the anemic or iron-deficient patient. The International HHT Guidelines recommended aggressive management of anemia and iron deficiency, with consideration of limited endoscopic therapy and potential medical therapies (hormonal therapy, anitfibrinolytics) in refractory cases, though evidence is limited.

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Hereditary Hemorrhagic Telangiectasia

The most common manifestation of HHT is epistaxis caused by spontaneous bleeding from telangiectasias in the nasal mucosa, which can be seen in individuals as young as
10 years of age and occur in most affected individuals.

The telangiectasia can be so severe that multiple transfusions and oral iron supplementation are required or so mild that HHT is never suspected. Although recurrent epistaxis becomes more severe with advancing age in approximately two-thirds of all individuals with HHT,the
disorder can also go undetected for many years and might be less common in adults.

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Colonoscopy; Telangiectasia of the colon before coagulation.

A big telangiectasia of the cecum, causing acute haemorrhage with bright red bleeding, this was the only angiodysplasia throughout the course of the colon.

Besides the patient had melena and rectal bleeding with bright red blood and this is the cause of severe bleeding (bright red).

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Hereditary Hemorrhagic Telangiectasia

Colonic arteriovenous malformation (AVM) is one of the causes of lower GI bleeding. Unlike small vascular ectasia or angiodysplasia, colonic AVM tends to be solitary, large in size, and identified endoscopically as flat or as an elevated bright red lesion.

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Hereditary Hemorrhagic Telangiectasia

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After injection acute hemorrhage iniciates

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Hereditary Hemorrhagic Telangiectasia

Final Status of the therapeutic treatment with combination of absolute alcohol and argon plasma coagulation.

Argon coagulation appears the best endoscopic option at the moment to control bleeding in these patients with a low rate of adverse effects and complications and relatively lower costs. Hereditary Hemorrhagic Telangiectasia: Continuous Challenges of a Well Described Disease.

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Hereditary Hemorrhagic Telangiectasia

Terminal Ileum

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Hereditary Hemorrhagic Telangiectasia
A follow up endoscopy was performed the next day

Some angiodysplasias were found and some of they with the status post ablative therapy.

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Hereditary Hemorrhagic Telangiectasia

Retroflexed view of the gastric fundus

There are some active angiodysplasia “red spot” and some that has been underwent ablative therapy with argon plasma coagulation “white spot”

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Hereditary Hemorrhagic Telangiectasia Video Clip

Second endoscopy performed the next day

Continuing with the ablative therapy of remnants of angiodysplasia with APC.

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Hereditary Hemorrhagic Telangiectasia

GI bleeding occurs from telangiectasias in 25-33% of patients with HHT, itis one of the challenging problems of the disease. Most of the available therapies are good forshort-term control of bleeding, but are unlikely to be effective in the long term. Bevacizumab is amonoclonal
antibody that binds to and inhibits the biological activity of VEGF. Nasal injection ofthis medication was shown to be effective in decreasing the frequency and the transfusionrequirement in nasal bleed; however, up to now it was not tested or used for GI bleeding. Withrecent
advances in genetic testing and better understanding of the nature of the disease we might beable to find more targeted therapy.

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Duodenal Angiodysplasia in a Hereditary Hemorrhagic Telangiectasia.

Our patient also has Duodenal Angiodysplasia

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Hereditary Hemorrhagic Telangiectasia Video Clip

In this second endoscopy performed the next day, It practiced the same therapy with argon plasma coagulation for the angiodysplasia of the duodenum.

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Hereditary Hemorrhagic Telangiectasia

The treatment was successful, the patient stopped bleeding, we expect the long-term outcome.

These treatments were successful and the Gi bleeding stopped, pending treatment to stop nosebleeds.

Antibiotic prophylaxis should be considered during treatment procedures because transient bacteremia may seed arteriovenous malformations.

Some HHT patients with GI bleeding improve on drug therapies, but others fail. Transfusion-dependent GI bleeding is difficult to manage, and optimal management may include both medical and endoscopic treatments

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Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu syndrome).

The images showing here are tiny multiple, telangiectatic vessels 1 mm. across the duodenum Jejuno and ileum.

This 62-year-old lady has suffered of ferropenic anemia during 10 years. Her average hemoglobin has been of 10.3 gr/dl, Fecal Occult Blood Test was positive multiple times the enteroscopy shows multiple tiny 1 mm. vascular lesions

Hereditary hemorrhagic telangiectasia (HHT) is a genetic condition associated with vascular malformations throughout the body. HHT patients commonly present with recurrent gastrointestinal bleeding and iron-deficiency anemia.

Gastrointestinal involvement in HHT is common.

Telangiectasias, the typical vascular anomaly in this disease, appear in the intestinal mucosa as an irregular distribution of red macules that have been reported to range in size from 1 to 10 mm in diameter

For more endoscopic details download the video clip by clicking on the endoscopic image.

Wait to be downloaded complete, then if you wish to appreciate in full screen press Alt and Enter for windows media. any image or video clip can be storage in your computer for multimedia.

All endoscopic images of this atlas contain a video clip.

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Multiple tiny 1 mm. vascular lesions at the jejuno

Telangiectases in the gastric mucosa of a patient with Osler-Weber-Rendu syndrome. The lesions can be seen most prominently at the 11-o'clock position proximally.

The endoscopic evidence of vascular lesions in patients with bleeding confirms the role of GI telangiectasias in the bleeding episodes.

The researchers do not, however, address the more frequent scenario of occult GI blood loss that occurs without melena or hematemesis, and they may have underestimated the role of GI lesions in HHT anemia.

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Forms of hereditary hemorrhagic telangiectasia include type 1, type 2, type 3, and juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome.

People with type 1 tend to develop symptoms earlier than those with type 2, and are more likely to have blood vessel malformations in the lungs and brain. Type 2 and type 3 may be associated with a higher risk of liver involvement.

Women are more likely than men to develop blood vessel malformations in the lungs with type 1, and are also at higher risk of liver involvement with both type 1 and type 2. Individuals with any form of hereditary hemorrhagic telangiectasia, however, can have any of these problems.

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Multiple tiny 1 mm. vascular lesions at the jejuno and duodenum.

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Examination revealed capillary telangiectases

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Multiple tiny 1 mm. vascular lesions and subepithelial hemorrhages

Systemic estrogen-progesterone at doses used for oral contraception may eliminate bleeding in symptomatic HHT and is a reasonable initial option in fertile women.

There is no information on possible effects of lower-dose estrogen -progesterone used in postmenopausal women for hormone replacement therapy.

Tamoxifen has dramatically eliminated HHT-related bleeding in two cases. It is well tolerated in postmenopausal women and should be considered for randomized clinical trials.

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At the gastric antrum also has some gastric antral vascular ectasias and also some tiny 1mm. capillary telangiectases that was treated by argon plasma coagulation as well as the jejuno and duodenum lesions.

The concept of Rendu-Osler-Weber disease was first proposed by Rendu (1896), Osler (1901), and Weber (1907) In most cases a pattern of autosomal dominant inheritance is evident, but about 20% develop spontaneously in the absence of evidence of genetic transmission.