treatment of hereditary angioneurotic oedema

Last edited 10/2021 and last reviewed 10/2021

Therapy for hereditary angioedema is aimed at

• relieving acute attacks
• preventing an attack (short term prophylaxis)
• to reduce the frequency and severity of recurrent attacks

Relieving acute attacks:

• treatment of choice is C1 esterase inhibitor replacement therapy - usually symptoms begins to resolve within 30-60 minutes
• fresh frozen plasma - contains C1 inhibitor (use of FFP is controversial since the presence of contact system proteins may aggravate the situation)
• epinephrine - may help in providing a temporary relief
• corticosteroids and antihistamines - should not be used in acute attacks
• narcotic analgesics (for abdominal attacks), antiemetic agents and aggressive fluid replacement therapy - for gastrointestinal symptoms
• rapid intubation or tracheotomy - for oropharyngeal attacks (1)

Short term prophylaxis:

• is indicated in angioedema patients who are likely to be exposed to a clinical situation which may provoke an acute attack. (Dental procedure, invasive medical procedures, and surgical procedures) Treatment options include:
  • treatment with C1 inhibitor - 500 to 1500 U/ I hour before the event
  • if C1 inhibitor is unavailable high-dose 17 -alkylated androgens - 5 -10 prior to the event
  • fresh-frozen plasma - 1 to 12 hours before the event

Long term prophylaxis:

• 17 -alkylated androgens - Danazole, Stanozolol, Methyltestosterone
• antifibrinolytic drugs - Epsilon aminocaproic acid (EACA), tranexamic acid

NICE state (2):

• Berotralstat is recommended as an option for preventing recurrent attacks of hereditary angioedema in people 12 years and older, only if:
  • they have at least 2 attacks per month, and
  • it is stopped if the number of attacks per month does not reduce by at least 50% after 3 months

Special situations: Pregnant women and children

• due to adverse effects of androgen on the growing fetus and children, antifibrinolytic drugs have been recommended as the first line of treatment in this group of patients

Avoidance of stimuli that might precipitate attacks:

• angiotensin converting enzyme inhibitor - slows down the catabolism of bradykinin
• exogenous oetrogens - oral contraceptive pills
• stress (1)

Notes:

• anabolic steroids - these increase C1 esterase inhibitor concentrations - however they are not effective in the acute attack
• idiopathic angio-oedema, that is not associated with C1 esterase deficiency, may respond well to anti - fibrinolytic therapy e.g. tranexamic acid. However, anti- fibrinolytics are not generally used in hereditary angio-oedema because of side effects such as vascular thrombosis
• berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein recently approved for prevention of angioedema attacks in adults and adolescents with hereditary angioedema (HAE)
  • study evidence shows that both berotralstat doses, 150  and 110 mg once daily, were generally well tolerated. Effectiveness results support the durability and robustness of berotralstat as prophylactic therapy in patients with HAE (3)

Reference:

• Zuraw B.L. Hereditary angioedema. NEJM 2008: 359:1027-1036
• NICE (October 2021). Berotralstat for preventing recurrent attacks of hereditary angioedema
• Farkas H, Stobiecki M, Peter J, et al. Long-term safety and effectiveness of berotralstat for hereditary angioedema: The open-label APeX-S study. Clin Transl Allergy. 2021;11(4):e12035. doi:10.1002/clt2.12035