Portuguese Version

Year:  2003  Vol. 69   Ed. 4 - (22º)

Relato de Caso

Pages: 577 to 580

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Rendu-Osler-Weber Disease: clinical and surgical treatment

Author(s): Roberta I. D. Garcia1,
Suzana B. Cecatto1,
Kátia S. Costa1,
Fernando Veiga A. Jr.2,
Ivan P. Uvo3,
Priscila Bogar Rapoport4

Keywords: hereditary haemorrhagic teleangiectasia, Osler-Weber-Rendu syndrome, epistaxe

Abstract:
Hereditary Haemorrhagic Telangiectasia (Rendu-Osler-Weber disease) is a rare disease with and incidence of 1-2/100000, affecting blood vessels of the skin, mucous membrane, lungs and gastrointestinal tract. It is recognized as a classic triad of teleangiectasia in face, hands and cavity; recurrent epistaxe and family occurrence. We reported three patients with Rendu-Osler-Weber disease and discussed about clinical manifestations and treatment.

INTRODUCTION

Hereditary hemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu syndrome is an autosomal dominant disease with high degree of penetration, affecting all races and presenting the same distribution in both genders. It is a rare syndrome, with incidence of 1-2/100,000 1.

The initial lesion is based on structural deficiency of the blood vessel walls, characterized by abnormalities of the elastic lamina and muscle layer, making them more vulnerable to trauma and spontaneous rupture 1, 2.

Despite the autosomal dominant transmission, in 15 to 23% f the cases there is no family history, despite sporadic mutations. Many genes were implied in the pathogenesis of the disease, being that two of them were identified: Endoglin (9q:33-34), associated with central nervous system (CNS) and pulmonary manifestations, and receptor of the BII growth transformer (3p 32), related with blood vessels. The homozygous states seem to be lethal, but there are few reported cases. Moreover, chromosome 12q is associated with telangiectasias and recurrent epistaxis 3, 4.

ENT manifestations are the most frequent ones, being that the main symptom is recurrent epistaxis, present in 93% of the patients 1.

The disease may affect other regions of the body, such as the eyes, skin, lungs, brain, central nervous system, gastrointestinal tract and genitourinary tract. Otorhinolaryngologists are normally the first physicians that provide care to such patients and they should be prepared to make the diagnosis, so that treatment can be early to prevent complications 1, 2.

CASE REPORT

D.D., 65-year-old male patient, came to the Service of Otorhinolaryngology, Medical School ABC, complaining of recurrent epistaxis for 40 years. He reported initial bleedings of small amount, controlled with anterior and posterior nasal packing. As time went by, there was increase in frequency and intensity of the episodes, and other therapies became necessary, such as nasal cauterization, which led to septal perforation owing to repetitive procedures.

Twenty years before, he presented tongue hemangioma and after cauterization, there was only mild and sporadic bleeding. Thirteen years before there was a severe episode of nasal bleeding, requiring hospitalization and blood transfusion. Ten years before he was submitted to nasal surgery and they used a skin graft (septodermoplasty) which resulted in symptom improvement. For the two previous years, he presented recurrent epistaxis and it was necessary to perform thermal coagulation in addition to nasal packing. He did not refer bleeding in other organs.

At the physical examination, presence of disseminated telangiectasia through the thorax, tip of the fingers and lips, anterior rhinoscopy showed septal perforation and presence of crusts. The patient presented hemangioma of the tongue.

He was referred to pneumology and gastroenterology, aiming at assessing the existence of possible malformations in other systems, and after careful investigation we did not find any affections. He is currently being followed up by the hematologist to compensate anemia.

The patient is frequently submitted to anterior and/or posterior packing in our unit.

The patient's family came to the visit upon our request and his son, 38 years old, referred episodes of recurrent epistaxis for the past 15 years, controlled with digital compression. The physical examination revealed telangiectasias of the septal mucosa only, with no bleeding points. His grandson, 8 years old, presented only a mild episode of easy to control epistaxis. Physical examination with no findings. Both did not show other systemic complications. They were informed about the pathology and possible future complications. They are currently being followed up in our service, but both remain asymptomatic.

DISCUSSION

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disease that affects the wall of blood vessels. It was described for the first time in 1864 by Sutton.1,5.

Clinical manifestations are secondary to bleedings, which may affect any part of the body. The Otorhinolaryngologist is normally the first physician to see the patient, because in 90% of the cases the most common symptom is recurrent epistaxis; bleeding is secondary to telangiectasias being that in 50% of the cases, the first episodes takes place at the age of 10 and in 80 to 90% of the cases up to the age of 30 years 5. One third of the patients present severe epistaxis, requiring hospitalization and blood transfusion 1, such as the case of the described patient. The severity of the epistaxis is worsened by aging, pregnancy and after menopause, owing to fluctuating levels of estrogen in the nasal mucosa. Other influencing factors are puberty, menses, use of oral contraceptive drugs, as well as stress, alcohol and changes in temperature 6.

Mucous-cutaneous impairment includes macular telangiectasias of 1 to 3mm in diameter and in 60% of the patients they are detected 10 to 30 years after the epistaxis episodes. In 71% of the cases, the lesions are manifested in the hand palms and ungueal beds, in 66% in the lips and tongue and the remaining 20 to 40% affect the face, extremities, conjunctiva and the trunk. They rarely lead to bleeding and treatment is basically esthetical and performed with laser. Conjunctival telangiectasia of the retina affects 45% of the patients being that 16 to 35% of them have blood tears 5.

Pulmonary manifestations of HHT include hemoptisis, hemothorax, right-left shunting and paradoxical embolism. There are arterial-venous malformations and fistulae, present in 5 to 23% of the patients. Paradoxical embolism is found in 40 to 50% of the patients and can cause transient ischemic and cerebral vascular accidents. In 8% of the patients, there can be massive pulmonary hemorrhage. Other symptoms include hypoxemia, dyspnea, cyanosis, polycytemia and distal phalanx clubbing. The diagnosis is made using high resolution spiral CT scan and angiogram; treatment includes surgical resection, arterial ligation and embolization.

Complications of the central nervous system vary from transient ischemic accident to intracranial abscess or bleeding. It is estimated that 8 to 41% of the patients with HHT will have some form of neurological complication during life. Clinical manifestations can include seizures, headache, coma and varied grades of neurological deficit. In most cases, the diagnosis is made with high resolution CT scan and angiogram 5, 6, 7. The treatment options are surgical resection, embolization and radiosurgery.

In the gastrointestinal tract the manifestations include telangiectasias, arterial-venous malformations and varicose veins, which may lead to upper digestive hemorrhage, dysfunction and hepatic encephalopathy. Bleeding tends to be recurrent and progressive and normally occurs after the age of 40 years. Notoya et al. reported a case of spleen lesion associated with HHT 8. The diagnosis can be made by endoscopy or angiogram, and treatment includes estrogen therapy, laser, cauterization or surgical resection 5.

The diagnosis of HHT is based on the clinical assessment of the patient. The criteria include the classical triad of epistaxis, telangiectasia and family history, however the triad is not present in all cases. Many authors defined the diagnosis of HHT in the presence of at least two manifestations of the triad and some other kind of well-documented visceral involvement 2, 9.

Among differential diagnosis, we should refer to epistaxis secondary to trauma, tumors, coagulation pathologies and mainly those of unknown causes 5.

The treatment of HHT is palliative. There is no consensus as to the best therapeutic option. The objective of treatment is to promote disease control as long as possible, with few interventions and trying to prevent sequelae 10.

Some acute bleeding episodes can be controlled by manual compression, anterior and/or posterior nasal packing, as well as cauterization. The latter, when used repetitively, may lead to necrosis, synechia and even septal perforation 1, 11, which was observed in the reported case. The patients learn how to prevent and threat their own epistaxis. In general, they should avoid digital trauma, maintain the appropriate level of moisture, and be trained to self-pack with absorbable material in emergencies. For more severe bleedings, there is embolization and arterial ligation, which generally lead to good short-term results. However, the methods are ineffective when the disease has collateral circulation in the nasal mucosa, which generally happens because it has a persistent course. Other treatment options include the use of aminocaproic acid, estrogen therapy, laser photocoagulation, as well as intranasal brakytherapy with 192 Ir 10.

Estrogen therapy leads to squamous metaplasia of the nasal epithelium, which prevents local traumas and bleedings, but it has side effects such as female signals in men and increased risk of endometrial cancer in post-menopause women 1, 2.

Laser cauterization can replace the drugs and it has become an effective treatment for moderate HHT, especially when combined to septodermoplasty 1, 2.

In severe and chronic cases of epistaxis, we can use septodermoplasty, Young's modified technique and cutaneous and myocutaneous flaps.

Septodermoplasty is considered the gold standard for treatment when all the other forms are ineffective. The technique consists of removing the nasal septum mucosa that is replace by a thin skin graft. The procedure promotes temporary improvement of symptoms owing to the resurge of telangiectasias of the flap, a fact observed in our case. The use of amniotic membrane in the surgery has proved to be successful 1, 2, 11, 12.

The Young's modified technique has shown to be effective. It consists of closing uni or bilaterally the nasal cavity, preventing turbulence and dryness caused by the constant airflow through the telangiectasia. The disadvantage is to maintain permanent nasal obstruction 1, 2, 11.

Another important fact is the need to control chronic anemia.

The prognosis is good in cases in which we can control bleeding and mortality caused by complications resultant from the disease is found in 10% of the cases 5.

CLOSING REMARKS

Epistaxis resultant from Rendu-Osler-Weber syndrome, even though rare, should always be considered when facing a case of repetitive and severe bleeding. Early diagnosis is necessary, promoting investigation of associated pulmonary and CNS malformations, preventing and avoiding dramatic consequences. In addition, being a syndrome to which no therapy has proven to be 100% satisfactory, it is important to report the cases in order to compare clinical manifestations and therapeutic management, trying to find the best evolution and quality of life to the patients.

REFERENCES

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1 Resident Physician, Discipline of Otorhinolaryngology, Medical School, ABC (FMABC).
2 Assistant Professor, Discipline of Otorhinolaryngology, FMABC; Doctorate studies under course, Discipline of Otorhinolaryngology, FMUSP.
3 Assistant Professor, Discipline of Otorhinolaryngology, FMABC.
4 Faculty Professor, Discipline of Otorhinolaryngology, FMABC.
Address correspondence to: Rua Professor Filadelfo Azevedo,400
Vila Nova Conceição Sao Paulo 04508-010
Study conducted by the Discipline of Otorhinolaryngology, Medical School ABC-2002.
Article submitted on September 18, 2002. Article accepted on October 24, 2002.

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