Life-Threatening Oral

BleedA Rare Presentation of Hereditary

Hemorrhagic Telangiectasia
Syed Kowsar Ahamed, MDS,* and Yasser Al-Thobaiti, MDSy
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder of fibrovascular tissues.
Patients with HHT often develop life-threatening bleeds from telangiectasias in the nasal or gastrointestinal
mucosa or from visceral arteriovenous malformations. Recurrent oral bleeds are rare presentations in these
patients and are seldom reported. This report describes a rare case of 72-year-old man with a known history of HHT who presented with a recurrent life-threatening oral bleed from telangiectasia of the palate
and reviews the literature for current trends of medical and dental management. This study is an effort
to draw the attention of oral physicians and surgeons to such drastic complications of the disease and
various current treatment modalities.
2015 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg 73:1465.e1-1465.e5, 2015
Pathologic life-threatening oral bleeds are rare; the most
common oral bleeds result from arteriovenous malformations (AVMs) of the jaws and facial trauma in hemophiliac patients. Hereditary hemorrhagic telangiectasia
(HHT) also can cause postoperative bleeding complications. Osler-Weber-Rendu syndrome (or HHT) is a rare,
autosomal dominant, inherited, fibrovascular disorder;
it is characterized by vascular malformations in mucocutaneous tissues, internal organs, and the central nervous
system. The disease has an incidence rate of 1:5,000.1-5
Although Benjamin Green Babington was the first to
describe the symptoms of HHT in 1865, it is named
after 3 physicians, Marie Rendu, Bert Osler, and
Fredrick Parks Weber, who extensively reported similar
cases.1 In 2000, diagnostic criteria were developed and
named the Curacao criteria: 1) epistaxis, 2) cutaneous
and mucosal telangiectasias, 3) visceral AVMs, and 4) a
positive family history. A minimum of 2 of the 4 criteria
should be present for the diagnosis.5

Report of Case
A 72-year-old male patient was admitted to the intensive care unit (ICU) with acute respiratory distress
*Assistant Consultant, Department of Maxillofacial Surgery, King

syndrome, acquired pneumonia, and septic shock. He

was intubated and put on ventilator support. The department of oral and maxillofacial surgery was consulted for
a severe recurrent oral bleed and hemoptysis. The patient was known to have HHT with a 2-year history of
chronic epistaxis and minor oral bleeds; he was admitted
to the ICU for acute respiratory distress resulting from
aspiration pneumonia. One month previously, he underwent intranasal laser cauterization and was administered
bevacizumab (Avastin; Genentech, South San Francisco,
CA). His hemoglobin level was 4.3 mg/dL. The patient
had a strong positive family history, with an affected
aunt, 2 sons, 1 daughter, and 1 grandson (Fig 1). There
were telangiectatic lesions over his lips, face, and fingers, and he had profuse bleeding from palatal telangiectasias (Fig 2). The telangiectatic spots were spread
widely over the palatal, gingival, and lingual mucosa. A
chest computed tomogram showed bilateral multiple
small AVMs in the lungs (Figs 3, 4). Genetic analysis for
the endoglin (ENG) and ACVLR1 genes showed a
mutation in the ENG gene (exon 3, nucleotide
c.277 C>T, amino acid p.Arg93X [p.R93X]). A
mutation in the ACVRL1 gene was not detected. Thus,
he was diagnosed with HHT type 1 disease.
Received November 21 2014

Abdullah Medical City, Makkah, Saudi Arabia.

Accepted March 13 2015

ySwedish Board, Consultant, Department of Maxillofacial Surgery,

Abdullah Medical Center, Makkah, Saudi Arabia; Assistant Professor,

2015 American Association of Oral and Maxillofacial Surgeons

Consultant, Department of Oral & Maxillofacial Surgery, Faculty of

http://dx.doi.org/10.1016/j.joms.2015.03.043

0278-2391/15/00335-3

Dentistry, Taif University, Taif, Saudi Arabia.

Address correspondence and reprint requests to Dr Ahamed:
Department of Maxillofacial Surgery, King Abdullah Medical City,
Makkah, Saudi Arabia; e-mail: dr_syed03@yahoo.co.in

1465.e1

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HEREDITARY HEMORRHAGIC TELANGIECTASIA

FIGURE 1. Pedigree of patient (purple square) and affected family members.

Ahamed and Al-Thobaiti. Hereditary Hemorrhagic Telangiectasia. J Oral Maxillofac Surg 2015.

The bleeding did not respond to conservative topical

hemostatic measures; therefore, he underwent diode
laser application over the oral telangiectatic spots and
an intralesional injection of Avastin, after which the
bleeding stopped. A blood transfusion was administered, his hemoglobin level increased to 13 mg/dL,
and his condition improved. After his discharge, he
was followed in the outpatient department. Informed
surgical consent was taken from the patient after he
was provided with detailed information regarding
the procedure. This study was approved by the
ethics committee.

FIGURE 2. Telangiectasias with engorged vessels in the hard palate.

Ahamed and Al-Thobaiti. Hereditary Hemorrhagic Telangiectasia.
J Oral Maxillofac Surg 2015.

Discussion
HHT is an autosomal dominant disorder of the
vascular endothelium resulting from AVMs and causing
recurrent epistaxis. Based on the mutated gene, it is
classified as HHT1 or HHT2. HHT1 is more aggressive
and caused by a mutant ENG gene on chromosome
9q33-34.6-8 The patient showed an ENG mutation in
the 93p arm; no activin receptor-like kinase-1 (ALK1)
mutations were detected. HHT2 is a relatively mild
variant with a mutant ALK1 gene on chromosome
12q-13. Sabba9 and Abdalla and Letarte10 reported
that the SMAD4 gene is associated with juvenile polyposis HHT or HHT3.9,10 These genes are responsible for
endothelial cells signaling for proteins that act as
surface receptors for transforming growth factor-b
and vascular endothelial growth factor (VEGF).
Therefore, increased levels of VEGF are observed
in patients with HHT, which forms a basis for using
bevacizumab, an anti-VEGF monoclonal antibody.11,12
Recurrent epistaxis is the most common clinical
presentation of HHT and is a presenting symptom
in 90% of patients.5,9 Eighty percent show
mucocutaneous telangiectatic spots in the face,
fingers, and oral mucosa. According to the literature
review, despite the commonness of oral mucosal
telangiectasias, only 2 cases with minor oral bleeds
have been reported.13 Pulmonary and cerebral AVMs
have been observed in 13 to 15% and 9 to 10% of patients, respectively.14 Gastrointestinal telangiectasias
have been reported in 13 to 45% of patients.15 Hepatic
involvement is rare and is present in approximately 8%
of patients with HHT.1 AVMs in the liver can produce a
left-to-right shunt leading to heart failure or portal

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AHAMED AND AL-THOBAITI

FIGURE 3. Chest computed tomogram in axial view shows pulmonary arteriovenous malformations (red circles).
Ahamed and Al-Thobaiti. Hereditary Hemorrhagic Telangiectasia. J Oral Maxillofac Surg 2015.

hypertension; occasionally, patients present with

cirrhosis of the liver, causing coagulopathies.
HHT treatment options are mainly therapeutic and
should be tailored for each patient. Epistaxis and its
management in patients with HHT is thoroughly

discussed and documented in the literature. Treatment

ranges from medical, surgical, to medical and surgical,
based on the location and severity of the bleed. An
estrogen and progesterone combination helps to
modulate nasal mucosa by metaplasia and increase

FIGURE 4. Chest computed tomogram in sagittal view shows pulmonary arteriovenous malformations (red circles).
Ahamed and Al-Thobaiti. Hereditary Hemorrhagic Telangiectasia. J Oral Maxillofac Surg 2015.

1465.e4
the mucosas thickness. However, its use is restricted
because of the side effects of hormonal therapy.
Antifibrinolytic agents, such as tranexamic acid and
aminocaproic acid, can be used as a supportive and
local measure in controlling mild recurrent bleeds,
but their efficiency is questionable.16 Topical or intravenous (IV) bevacizumab (Avastin) is a well-proven
promising option. Bevacizumab binds to circulating
VEGF and decreases the stimulation of VEGF, thereby
decreasing angiogenesis.3
Surgical options include the Young procedure (surgically closing the nostrils, making the nose nonfunctional), thermo- or laser coagulation or dermoplasty
of the nasal mucosa. Symptomatic large pulmonary
and cerebral AVMs are treated with a balloon, coil embolotherapy, or sclerosing agents and can be followed
with surgery. However, this treatment poses the risk
of a distant thrombosis leading to cerebrovascular
accidents or ischemia.3 It is well understood that
multimodal therapies yield better results than a single
therapy.2,11,17 A combination of laser application and
Avastin is a well-documented therapeutic modality
for controlling nasal bleeds. Lasers act specifically on
vascular telangiectatic spots, causing minimal damage
to adjacent mucosa. The efficacy of a diode laser is
comparable to that of a KTP laser or an Nd:YAG laser.2
These IV and local (topical) bevacizumab preparations
have been tried and resulted in successful improvement in quality of life by decreasing the severity and
frequency of nasal bleeds. IV bevacizumab (10 mg/
kg once every 2 weeks) is associated with a considerable number of serious side-effects, such as anaphylaxis, hypertension, and pulmonary hemorrhage.11,18
Hence, submucosal injection of Avastin at a dose of
100 mg followed by a topical spray at a dose of
100 mg/4 mL is a better option for long-term control
of epistaxis.11 Treatment options for oral bleeds have
not been reported to date. The authors experience
with such a severe bleed was the first of its kind, and
they used photocoagulation with a diode laser and a
submucosal injection of Avastin in the palate under
general anesthesia. This resulted in prolonged relief
from severe oral bleeds and decreased the frequency
of minor oral bleeds to once every 10 to 12 weeks.
The authors believe a long-term IV or topical spray
or mouthwash of bevacizumab would have been
better, but this was not possible because there was
no clinical evidence or internationally approved trials
for such use in HHT. In addition, there were no
available topical oral preparations of the drug; hence,
they could not obtain the benefit of the drug. Because
oral telangiectasias are common presentations, oral
and maxillofacial surgeons can play a key role in the
recognition of this disease. Patients with HHT and
pulmonary AVMs have higher chances of septic
embolization through a right-to-left shunt and thus

HEREDITARY HEMORRHAGIC TELANGIECTASIA

are predisposed to develop brain abscesses. Invasive

dental procedures in such patients should be
performed with endocarditis prophylaxis because
there is a risk of developing brain abscesses.1,19,20
The American Heart Association states that the
risks from antibiotics exceed the benefits from
prophylaxis, and prophylaxis should be reserved for
high-risk conditions. One high-risk condition is cardiac
malformation with a right-to-left shunt similar to situations observed in patients with HHT and pulmonary
AVMs.18 Despite the controversy, certain HHT centers,
such as the Irish HHT center, advocate the use of
antibiotic prophylaxis for dental and surgical procedures in patients in whom pulmonary AVMs are not
excluded by negative echo findings.14
Oral and maxillofacial surgeons can help in the early
diagnosis of such patients. There are notably few
reported HHT cases with oral bleeds. The treatment
options for oral complications are limited because
there are no reports of such cases. Hence, it is essential
to report such encounters to accumulate wellaccepted evidence-based treatment protocols for oral
complications of this disorder. Oral mouth rinses of
Avastin for chronic oral bleeds in patients with HHT
could be a novel treatment. Long-term preventive
efforts for nasal and oral bleeds can improve the quality of life and life expectancy of such patients.

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