Angioneurotic edema (familial)

[MIM 106 100610 618]

(Hereditary angioedema, familial bradykininic angio-edema, C1 esterase deficiency)

Prevalence: 1/100,000 in France. Transmission: autosomal dominant. Mutation in the SPING1 gene on 11q 11 - q13.1 but 30% of the cases are sporadic. C1 esterase deficiency (inhibitor of the C1 complement fraction: C1- INH) explains the symptomatology. The role of C-1 esterase is to inhibit the formation of kallikrein (and thus bradykinin) by the activated factor XII  in presence of tissular trauma. Its deficiency causes  localized and non-itchy edema (airway, bowel...) triggered by a minimal trauma or stress. The first symptoms appear generally before 10 years of age. In girls the first manifestations most often occur at the time of menarche. These crises are characterized by the inefficiency of corticosteroids, anti-inflammatory drugs, antihistaminics and epinephrine. In certain patients, the gastrointestinal involvement is revealed by repeated episodes of pancreatitis without evident cause.

There are 3 types:

-         Type I (> 80%): low levels of protein C1- INH in plasma (< 30% of normal level)

-         Type II: normal levels of protein C1- INH in plasma but its function is diminished or absent

-         Type III: the plasma level and activity of C1-INH are normal but there is an excess of activity of kininogenase due to a mutation of factor XII (Hageman); crises are caused by estroprogestative contraception.

There are also acquired forms in adulthood . They are due:

-         to hyperactivity of the classical pathway of the complement: asociation with benign or malignant type B lymphoproliferation

-         the presence of  anti-C1- INH autoantibodies: association with a lymphoproliferative disorder

-         to a medication: AEC inhibitors (1 to 3/1000), oral contraceptives (Diane ©)

Crisis :

-        C1-esterase purified from plasma  (Berinert © 20 IU/kg IV) or Cinryze ©) [500 U if < 10 years; 1000 U if > 10 years or 50 kg], slow IV administration (> 5 minutes) in 2 doses separated by more than > 5 minutes: clinical response in about 30 minutes. This initial dose can be repeated after 1 h if the effect is insufficient. Cinryze © is currently preferred because its half-life is longer (58 h) than that of Berinert © (18 h).

-        bradykinin B2 receptor inhibitors (icatibant or Firazyr ©)  30 mg subcutaneously to repeat 6 hours later if necessary h (no experience in childhood)

-        if nothing else is available: fresh frozen plasma (but risk of aggravation as the consumed complement factors are replaced); tranexamic acid is no more recommended.

prophylaxis : purified C1-esterase  (Berinert © or Cinryze © (see supra for doses) or tranexamic acid 20 to 50 mg/kg in 2 or 3 doses; or preoperative treatment of 5 days with Danazol © (10 mg/kg 3 x/day); or 30 mg subcutaneous icatibant (adult dose). )

chronic treatment : Danazol © at the lowest possible dose  (25-200 mg/d, sometimes 1j/2) or tranexamic acid 20 to 50 mg/kg in 2 or 3 doses


Anesthetic implications: 

Take advice with the personal doctor of the patient (alert card?) or contact a reference centre.

Be attentive: the appearance of dysphagia or changes of the voice: beginning of laryngeal edema ? Significant risk of edema after instrumental manipulation of the airways. Hypovolemic shock. If chronic treatment with Danazol ©: liver function tests (cholestasis?). 

Emergency: Berinert © or Cinryze © IV slowly over 60 minutes before a procedure susceptible to induce edema. Prophylactic treatment with icatibant has been effective in an adult.

Centres of reference: in France

creak@chu-grenoble.fr; in Belgium : Cliniques universitaires St Luc, Service d’Hématologie (Profs C Hermans et C Lambert)

Patients' Association : www.haebelgium.be


References : 

-          Jensen NF, Weiler JM. 
C1 esterase inhibitor deficiency, airway compromise, and anesthesia. 
Anesth Analg 1998; 87:480- 8.

-         Levy JH, Freiberger DJ, Roback J. 
Hereditary angioedema : current and emergong treatment options. 
Anesth Analg 2010; 110: 1271-80.

-         Ebo DG, Verweij MM, De Knop KJ, Hagendorens MM, Bridts CH, De Clerck LS, Stevens WJ. 
Hereditary angioedema in childhood: an approach to management. 
Pediatr Drugs 2010; 12: 257-68.

-         Yazawa T, O’higashi T, Daijo H, Shinomura T. 
Anesthesia management for emergency laparotomy in a pediatric patient with suspected hereditary angioedema. 
J Anesth 2010; 24: 121-3.

-         Senaratne KT, Cottrell AM, Prentice RL. 
Successful perioperative management of a patient with C1 esterase inhibitor deficiency with a novel bradykinin receptor B2 antagonist. 
Anaesth Intensive Care 2012; 40: 523-6.

-         Wahn V, Aberer W, Eberl W, Fasshauer M et al. 
Hereditary angioedema (HAE) in children and adolescents: a consensus on therapeutic strategies. 
Eur J Pediatr 2012; 171: 1339-48.

-        MacGinnitie AJ. 
Pediatric hereditary angioedema. 
Pediatr Allergy & Immunology 2014 ; 25 : 420-7.

-        Berger TD, Garty B-Z.
Hereditary angioedema presenting as recurrent acute pancreatitis.
Pediatrics 2016; 137(2): e20150620

-        Hartopp A, Moran P, King W.
Sudden-onset trismus after respiratory arrest in a patient with an acute exacerbation of hereditary angioedema.
Eur J Anaesthesiol 2018 ; 35 :710-1

-        Dewachter P, Kopac P, Laguna JJ, Mertes PM et al.
Anaesthetic management of patients with pre-existing allergic conditions: a narrative review.
Br J Anaesth 2019; 123 (1): e65-81.


Updated: August 2019