3. Management of dental-oral, maxillofacial and ENT procedures (DOMFOPs) in patients with C1-INH-HAE

1. Introduction

178 A Comprehensive Review of Urticaria and Angioedema

inhabitants in Norway [5].

angioedema attacks

Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is a genetic autosomal dominant disease characterized by a deficiency of the functionally active C1 esterase inhibitor (C1-INH) protein [1]. This deficiency results in an excess of bradykinin (BK), which increases

The minimum prevalence of C1-INH-HAE is 1.09 per 100,000 inhabitants in Spain [2], 1.41 per 100,000 inhabitants in Denmark [3], 1.54 per 100,000 inhabitants in Italy [4] and 1.75 per 100,000

Other forms of BK-mediated AE are: acquired angioedema due to C1-INH deficiency (C1-INH-AAE), hereditary angioedema with normal C1-INH (C1-INH-nC1-INH), with/without mutation in the F12 gene that encodes Factor XII coagulation (HAE-FXII/HAE-D) and acquired angioedema associated with angiotensin converting enzyme inhibitors (ACEi) (AAE-ACEi). ACEis are drugs that inhibit the metabolic pathways of BK and thus produce an increase in BK. Other drugs that inhibit BK catabolism have been implicated in the development of AE. These include dipeptidyl peptidase IV (DPPIV) inhibitors, aminopeptidase P (APP) inhibitors, neutral endopeptidase (NEP) inhibitors and others. In this chapter, we will focus on C1-INH-HAE.

2. The importance of cervicofacial anatomical location in C1-INH-HAE

or glucocorticoids is not effective in this type of BK-mediated AE [8].

Oestrogens, trauma, infections or stress has been described as triggers for AE attacks in 21 patients with C1-INH-HAE [6]. Microtrauma can precipitate the onset of acute AE attacks, and thus, dental-oral procedures carry a high risk of triggering them and also an increased risk of death from asphyxiation due to the AE location [7]. Treatment with adrenaline, antihistamines

In the past, without proper specific treatment, overall mortality after dental surgery in patients with C1-INH-HAE was up to 30–40% [9–12]. Some dental-oral, medical and/or surgical procedures are susceptible to receive "short-term prophylaxis" (STP) (also called "pre-procedural prophylaxis") [8, 13–15] in order to reduce the risk of AE. Such prophylaxis in patients with C1-INH-HAE usually consists of introducing oral antifibrinolytics or attenuated androgens (AAs) or administering intravenous pdhC1INH before the procedure [8, 13]. There are currently two brands of pdhC1INH available: Berinert® (CSL-Behring, Marburg, Germany) and Cinryze® (Shire-HGT, Zug, Switzerland). Since upper airway AE can cause death from asphyxiation [13, 16], adequate monitoring of upper airway permeability is imperative, so that appropriate emergency treatment (endotracheal intubation and/or tracheotomy) is performed if the upper airway is threatened despite medical treatment [8, 17]. Nevertheless, the availability of specific drugs for the treatment of acute AE attacks and of plasma-derived human C1-inhibitor concentrates (pdhC1INH) (Berinert®, CSL Behring, Marburg, Germany and Cinryze®, Shire HGT, Zug, Switzerland) for STP, together with the increased awareness of

vascular permeability and produces angioedema (AE) [1].

A review of published case reports of dental-oral, maxillofacial and ear, nose and throat (ENT) procedures in patients with C1-INH-HAE is shown in Table 1.



FFP = fresh frozen plasma, IU = International Unit, N.AD = not administered, pdhC1INH = plasma-derived human C1 esterase inhibitor, SC = subcutaneous, STP = short-term prophylaxis and y.o. = years old.

Table 1. Literature review of dental-oral, maxillofacial and ENT procedures in patients with C1-INH-HAE.
