Patient With Nose Bleeding and Septum Perforation: Osler-Weber-Rendu Disease

Risk Factors for Acute Otitis Media (AOM) in Children

Nosebleeds (epistaxis) are one of the most common symptoms encountered in ENT practice. Although there are usually simple underlying causes; in some patients, especially recurrent and severe bleeding, it may be a symptom of an underlying systemic disease. Osler-Weber-Rendu (OWR) disease, or hereditary hemorrhagic telangiectasia (HHT), is a rare but important genetic vascular disease. In this article, the diagnosis, differential diagnosis and management processes will be discussed in a 46-year-old female patient diagnosed with septum perforation after cauterization due to nosebleeds.

Synonyms for Osler-Weber-Rendu disease (OWR):

• Hereditary Hemorrhagic Telangiectasia (HHT)
• Rendu-Osler-Weber disease
• Osler-Rendu-Weber syndrome
• Familial Hemorrhagic Telangiectasia
• Angiomatous Telangiectasia
• Congenital Hemorrhagic Telangiectasia
• Telangiectasia hemorrhagica hereditaria

Case Report

Patient: 46-year-old female

Reason for Application: Recurrent nosebleeds on both sides and nasal dryness

History: The patient has been experiencing intermittent nosebleeds for the last 6 years, and a cauterization procedure was performed 5 years ago at another clinic to control nasal bleeding. After the procedure, the patient continued to have nasal congestion, air leakage and bleeding complaints, and a septum perforation was detected during the examination. This patient had a septum perforation closure operation at another clinic 2 years ago and the perforation reoccurred.

Examination Findings:

Nasal endoscopy revealed a 4x5 cm ellipsoid-shaped perforation in the posterior septum, widespread telangiectatic lesions in bilateral inferior turbinates, red dots (telangiectasis) on the lip mucosa and tongue, mild cyanosis on the fingertips, and several petechiae-like lesions on the skin.

Family History: It was learned that her mother and uncle had similar nosebleeds and digestive system bleeding.

What is Osler-Weber-Rendu Disease?

HHT is an autosomal dominantly transmitted vascular anomaly disease. Arteriovenous malformations (AVM) occur due to the lack of capillary network between the arterial and venous systems. These malformations can often be located in the nasal mucosa, skin, gastrointestinal system, lungs, liver and brain.

Clinical Findings

The most common symptoms in OWR disease:

Nosebleeds (epistaxis): Seen in 90% of patients. It starts in adolescence and increases in severity with age. Bleeding usually originates from the anterior septum region.

Mucocutaneous telangiectasias: Common in the lips, tongue, nasal mucosa and fingers. Becomes apparent over time.

Internal organ AVMs: Pulmonary AVM: Dyspnea, cyanosis, risk of cerebral embolism

Hepatic AVM: Heart failure, high-output circulation

Gastrointestinal bleeding: Seen with iron deficiency anemia

Cerebral AVM: Headache, seizure, risk of stroke

Diagnostic Criteria (Curacao Criteria) For Osler-Weber-Rendu Disease

At least 3 of the following 4 criteria must be present for the diagnosis of OWR:

• Spontaneous and recurrent epistaxis
• Mucocutaneous telangiectasias
• Visceral lesions (pulmonary, cerebral, hepatic AVM)
• Positive family history (autosomal dominant transmission)

In this case, at least 3 criteria (epistaxis, mucosal lesions and family history) were present and clinical diagnosis was made.

Risks of Nasal Cauterization

Anterior cauterization performed on this patient caused repetitive trauma and mucosal ischemia, leading to septum perforation. Since the mucosa is fragile and vascular-rich in OWR patients, classical cauterization procedures carry a risk of complications.

Alternative recommendations:

• Moisturizing and antibacterial nasal creams
• Superficial laser therapy (KTP, PDL)
• Endonasal septodermoplasty
• Embolization (in advanced cases)

Treatment and Follow-up

Management of Nose Bleeding:

First Step: Topical ointments (Bactroban, creams containing vitamin A+D), moisturizers

Second Step: Laser photocoagulation

In Severe Cases: Septal skin graft application (septodermoplasty), Young procedure (nasal closure)

Systemic Follow-up:

• Imaging: Thorax CT (pulmonary AVM), MRI (cerebral AVM)
• Gastroscopy/Colonoscopy: In those with GI bleeding
• Echocardiography and Doppler USG: Investigation of liver AVM
• Genetic counseling: Screening of family members

Patient Education and Preventive Approach

• Traumatic nose picking and nose Intranasal manipulations should be avoided
• Nasal mucosa should be kept moist
• Drugs that may increase bleeding such as aspirin and NSAIDs should be avoided
• Female patients planning pregnancy should be screened for pulmonary AVM in advance

Osler-Weber-Rendu disease is a hereditary vascular disease that can lead to serious systemic complications if not diagnosed early. As in this case, HHT should definitely be considered in an adult patient presenting with recurrent nosebleeds, especially in the presence of septum perforation after anterior cauterization. Diagnosis is vital not only for managing nosebleeds, but also for preventing potential internal organ AVMs.

When patients have nosebleeds, tranexamic acid IV and TB can be given. This treatment can also be given to close a perforation inside the nose or to reduce bleeding during procedures such as dermal grafting and cauterization. Unfortunately, patients are prone to nasal bleeding and at risk for mucosal circulation disorders, and the chance of complete successful perforation closure is reduced.

Pazopanib Use in Osler-Weber-Rendu (OWR) Disease

Osler-Weber-Rendu disease is a genetic disease that disrupts vascular structure and is characterized by frequent nosebleeds, telangiectasias in the mucosa and skin. Angiogenesis (vessel formation) and vascular stabilization are impaired in this disease.

Scientific Relationship Between Pazopanib and HHT

In recent years, a number of studies have been conducted investigating angiogenesis inhibitors, especially anti-VEGF (vascular endothelial growth factor) effective drugs in the treatment of HHT. In this context, pazopanib has also been studied.

Pazopanib inhibits receptors such as VEGF receptors (VEGFR-1, -2, -3), PDGFR and c-kit.

These receptors play an important role in the formation of vascular structures that are impaired in OWR.

Scientific Publications and Clinical Observations:

Case reports and small series have shown that pazopanib can reduce nosebleeds and gastrointestinal bleeding.

Alternative anti-VEGF drugs, bevacizumab and thalidomide, have been studied and used more frequently.

Pazopanib is not FDA approved for HHT, its use can only be considered off-label, and this decision requires a multidisciplinary approach.

Chugh R, et al. “Use of pazopanib for management of bleeding in hereditary hemorrhagic telangiectasia.”

Cancer Med. 2019;8(4):1704–1710.

→ This study reported positive observations that pazopanib suppressed bleeding.

https://doi.org/10.1002/cam4.2037

⚠️ Clinical Use and Cautions

The balance of benefits and harms should be carefully evaluated.

Pazopanib has serious side effects such as liver toxicity, hypertension and thromboembolic complications.

Off-label use requires ethics committee approval and patient consent.

Pazopanib (Votrient) is considered a potential option for Osler-Weber-Rendu disease, especially in cases of severe bleeding, according to theoretical and limited clinical observations. However:

It is not in routine clinical practice.

Its use is off-label and requires careful patient selection and monitoring.

Agents such as bevacizumab have stronger evidence.

Search result link where you can find articles prepared by Dr. Murat Enöz about epistaxis and published on this website (you can also reach previous articles by clicking "more posts" at the end of the page) >> https://www.ent-istanbul.com/search?q=epistaxis 

Sources >>

• Guttmacher AE, Marchuk DA, White RI Jr. Hereditary hemorrhagic telangiectasia. N Engl J Med. 1995 Jun 1;332(14):918-24. https://doi.org/10.1056/NEJM199504063321407
• Faughnan ME, Palda VA, Garcia-Tsao G, et al. International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia. J Med Genet. 2011 Feb;48(2):73–87. https://doi.org/10.1136/jmedgenet-2010-100562
• Shovlin CL. Hereditary haemorrhagic telangiectasia: pathophysiology, diagnosis and treatment. Blood Rev. 2010 Sep;24(6):203–219. https://doi.org/10.1016/j.blre.2010.07.001
• Donaldson JW, McKeever TM, Hall IP, Hubbard RB. Complications and mortality in hereditary hemorrhagic telangiectasia: a population-based study. https://doi.org/10.1164/rccm.201202-0196OC

Murat Enoz, MD, Otorhinolaryngology, Head and Neck Surgeon

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