Review
Management of patients with hereditary angio-oedema in dental, oral, and maxillofacial surgery: a review

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Abstract

Hereditary angio-oedema (HEA) is an autosomal dominant, life-threatening genetic disorder that is caused by insufficiency or dysfunction of the C1 esterase inhibitor that develops coincidentally with recurrent oedema in the skin, internal organs, and upper respiratory tract. Increased production of bradykinin secondary to increased plasma kallikrein activity is the primary cause of attacks. Dental procedures cause emotional stress and mechanical trauma and may also initiate attacks. The most feared complication is asphyxiation as a result of laryngeal oedema. Cases that resulted in death after tooth extraction have been reported, so dentists and oral and maxillofacial surgeons should take maximum care in the treatment of patients with HAO, consult with the patient’s doctor, and ensure that prophylaxis is given before the procedure. They should work as atraumatically as possible and use procedures to minimise stress. In the event of an attack of HAO, despite all the correct measures having been taken, the procedure should be terminated immediately and treatment of the attack started as soon as possible. The first drugs for the treatment of acute attacks are C1-INH (C1 inhibitor), ecallantide, or icatibant.

Introduction

Hereditary angio-oedema (HAO) is an autosomal-dominant, life-threatening genetic disorder that develops when the C1 esterase inhibitor is insufficient or does not function correctly coincidentally with recurrent oedema of the skin, internal organs, and upper respiratory tract. Its incidence ranges from 1/50 000 to 1/100 000.1 The disease does not discriminate between sexes or among races.

Section snippets

Classification

Three types of the disease have been described: type 1, type 2, and HAO with normal C1-inhibitor (C1-INH) activity. A total of 85% of all cases are type 1, and present with low C1-INH activity. Type 2 includes the remaining15% of cases, and the C1-INH activity of this type may be normal or raised, but the present C1-INH is non-functional.2 In the HAO with normal C1-INH activity all measurements are normal, but attacks of angio-oedema are similar to those of type 1 and type 2. This type is more

Pathophysiology

C1-INH is a serine protease inhibitor that is synthesised mainly in the liver (SERPING1 family).14 This inhibitory protein not only inhibits C1s and C1r (the components of the classical complement pathway), but also inhibits the mannan-binding lectin pathway of the complement system, FXIa, FXIIa, thrombin, plasmin, and kallikrein.15, 16, 17, 18, 19, 20, 21 Increased bradykinin production secondary to increased plasma kallikrein activity is the primary cause of attacks of HAO.22 Bradykinin is a

Clinical presentation

Patients with HAO usually have their first attacks during childhood, and the frequency of attacks increases in puberty when the disease is usually diagnosed.24 Local trauma and emotional stress are the most important triggers of attacks, but mechanical compression, infection, dental procedures, menstruation, ovulation, drugs such as angiotensin-converting enzyme inhibitors (ACE), angiotensin II receptor blockers (ARB), and oestrogen may also cause attacks.7, 25, 26 Inhibition of ACE causes

Laryngeal and lingual oedema

The most feared complication of the disease is asphyxiation as a result of laryngeal oedema, and more than half of all patients with HAO have an attack at least once in their lifetime.39 This can result in death if it is not properly diagnosed and treated, and is the most common cause of death in patients with HAO.41 In the past, 30% of patients with HAO have been reported to have died from laryngeal oedema.41 During the attack, there may be changes such as deepening of the sound, wheezing, and

Laboratory tests

The most commonly used tests for hereditary angioedema are the C4 and C1-INH activity and the C1-INH function test. Serum C4 activity is low in type 1 and type 2 HAO, and is within normal limits in those with allergic angio-oedema and HAO with normal C1-INH activity.47 The concentration of C1 inhibitor protein is low in patients with type 1 HAO, and within normal limits or high in patients with type 2 HAO. For the diagnosis of patients with type 2 HAO, C1 inhibitor activity should also be

Management of an attack

There are three stages in the management of HAO: treatment of the acute attack (on-demand treatment), short-term prophylaxis, and long-term prophylaxis (Table 1). Early intervention is essential in attacks of HAO. When the interval between the onset of the attack and the beginning of the treatment is shortened, the resolution of the symptoms is facilitated and the total duration of the attack is shortened.50, 51, 52, 53

Oedema that develops in patients with HAO does not respond to

Prophylaxis

Dental procedures, oral and maxillofacial surgery, and endotracheal intubation may result in swelling of the lips and tongue, and obstruction of the airway by laryngeal oedema. Cases that resulted in death after tooth extraction have been reported.42, 59, 60, 61 Patients who died had often been misdiagnosed as having allergic angio-oedema, had been treated with adrenaline, steroids, and antihistamines, and (as these drugs are not effective in hereditary angio-oedema) unfortunately died of

Dental and oral and maxillofacial procedures

Patients with HAO are among those who require a special procedure by dentists and oral and maxillofacial surgeons, and if the practitioners do not have sufficient knowledge about the disease and cannot manage the treatment correctly, they may face serious complications. Consultation should be requested from the patient’s allergy specialist/immunologist before starting treatment. The patient should be informed in detail about the risks and possible complications of the procedure. Emotional

Conclusion

HAO is a serious, life-threatening disease and requires special procedures. Dentists and oral and maxillofacial surgeons should therefore take maximum care in the treatment of patients with HAO, consult with the patient’s doctor, ensure that prophylaxis is given before the procedure, should work as atraumatically as possible, and should minimise stress.

Conflict of interest

We have no conflicts of interest.

Ethics statement/confirmation of patients’ permission

No ethics permission or patients’ permission required.

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