Life-Threatening Oral Bleed—A 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 his- tory 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. Ó 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 malfor- mations (AVMs) of the jaws and facial trauma in hemo- philiac patients. Hereditary hemorrhagic telangiectasia (HHT) also can cause postoperative bleeding complica- tions. Osler-Weber-Rendu syndrome (or HHT) is a rare, autosomal dominant, inherited, fibrovascular disorder; it is characterized by vascular malformations in mucocu- taneous 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 inten- sive care unit (ICU) with acute respiratory distress syndrome, acquired pneumonia, and septic shock. He was intubated and put on ventilator support. The depart- ment of oral and maxillofacial surgery was consulted for a severe recurrent oral bleed and hemoptysis. The pa- tient 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 under- went 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 fin- gers, and he had profuse bleeding from palatal telangiec- tasias (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. *Assistant Consultant, Department of Maxillofacial Surgery, King Abdullah Medical City, Makkah, Saudi Arabia. ySwedish Board, Consultant, Department of Maxillofacial Surgery, Abdullah Medical Center, Makkah, Saudi Arabia; Assistant Professor, Consultant, Department of Oral & Maxillofacial Surgery, Faculty of Dentistry, Taif University, Taif, SaudiArabia. Address correspondence and reprint requests to Dr Ahamed: Department of Maxillofacial Surgery, King Abdullah Medical City, Makkah, Saudi Arabia; e-mail: [email protected]Received November 21 2014 Accepted March 13 2015 Ó 2015 American Association of Oral and Maxillofacial Surgeons 0278-2391/15/00335-3 http://dx.doi.org/10.1016/j.joms.2015.03.043 1465.e1
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Ab
Ab
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Life-Threatening OralBleed—A Rare Presentation of Hereditary
Hemorrhagic Telangiectasia
*Assista
dullah M
ySwedi
dullah M
nsultan
ntistry,
Addres
partme
kkah, S
Syed Kowsar Ahamed, MDS,* and Yasser Al-Thobaiti, MDSy
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder of fibrovascular tissues.Patients with HHToften develop life-threatening bleeds from telangiectasias in the nasal or gastrointestinal
mucosa or from visceral arteriovenousmalformations. 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 his-
tory 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; themost
common oral bleeds result from arteriovenous malfor-
mations (AVMs) of the jaws and facial trauma in hemo-
should be tailored for each patient. Epistaxis and itsmanagement in patients with HHT is thoroughly
FIGURE 4. Chest computed tomogram in sagittal view show
Ahamed and Al-Thobaiti. Hereditary Hemorrhagic Telangiectasia. J Ora
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 tomodulate nasal mucosa by metaplasia and increase
s pulmonary arteriovenous malformations (red circles).
l Maxillofac Surg 2015.
1465.e4 HEREDITARY HEMORRHAGIC TELANGIECTASIA
the mucosa’s 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 intra-
venous (IV) bevacizumab (Avastin) is a well-proven
promising option. Bevacizumab binds to circulatingVEGF and decreases the stimulation of VEGF, thereby
decreasing angiogenesis.3
Surgical options include the Young procedure (sur-
gically closing the nostrils, making the nose nonfunc-
tional), thermo- or laser coagulation or dermoplasty
of the nasal mucosa. Symptomatic large pulmonary
and cerebral AVMs are treated with a balloon, coil em-
bolotherapy, or sclerosing agents and can be followedwith 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 damageto adjacent mucosa. The efficacy of a diode laser is
comparable to that of a KTP laser or an Nd:YAG laser.2
These IVand local (topical) bevacizumab preparations
have been tried and resulted in successful improve-
ment 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 consider-
able number of serious side-effects, such as anaphy-laxis, 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 asubmucosal 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 trialsfor 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
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 cardiacmalformation with a right-to-left shunt similar to situa-
tions 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 proce-
dures in patients in whom pulmonary AVMs are not
excluded by negative echo findings.14
Oral and maxillofacial surgeons can help in the earlydiagnosis 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 well-
accepted evidence-based treatment protocols for oral
complications of this disorder. Oral mouth rinses of
Avastin for chronic oral bleeds in patients with HHTcould be a novel treatment. Long-term preventive
efforts for nasal and oral bleeds can improve the qual-
ity of life and life expectancy of such patients.
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