Update of International Recommendations for the Diagnosis and Treatment of Hereditary Angioedema from 2021

Introduction

Hereditary angioedema (HAE) is a rare genetic immune disorder that manifests with attacks of massive swelling of the subcutaneous tissues and mucous membranes. Swellings can appear in any location, including the respiratory or digestive tract mucosa. The most common cause is a deficiency or dysfunction of the C1 inhibitor (C1-INH), which leads to an uncontrolled increase in bradykinin levels. This results in increased vascular permeability and subsequent painful swelling.

Early diagnosis and treatment are crucial in HAE. In 2021, an international panel of experts revised the previous recommendations for the diagnosis and treatment of this condition from 2018, creating 28 recommendations based on current knowledge and evidence to support and facilitate the use of appropriate diagnostic procedures and therapeutic options in practice.

We present an overview of the recommendations, including the percentage agreement of experts and the quality of the data from which the recommendations are derived (grade A–D, where A represents high-quality data obtained from randomized studies, and D represents expert opinion).

What the expert panel recommends or suggests

1. Assess C1-INH function, C1-INH protein level, and C4 level in the blood of all patients with suspected HAE. (92%, D)
2. Repeat the assessment (C1-INH function, C1-INH protein, and C4) in patients with a positive result to confirm the diagnosis of HAE-1/2. (87%, D)
3. Examine known mutations causing HAE with normal C1 inhibitor (HAE-nC1-INH) in patients with suspected HAE and normal C1-INH function and level. (91%, D)
4. Consider on-demand treatment for all HAE attacks. (98%, D)
5. Treat all attacks affecting or potentially affecting the upper respiratory tract. (100%, C)
6. Treat attacks as early as possible. (100%, C)
7. Treat attacks with i.v. C1 inhibitor, ecallantide, or icatibant. (96%, A)
8. Consider early intubation or surgical intervention for progressing upper respiratory tract swelling. (100%, D)
9. Provide all patients with enough on-demand medication for at least 2 attacks to carry with them at all times. (100%, D)
10. Consider short-term prophylaxis before surgical, dental, or other procedures and events triggering angioedema attacks. (94%, C)
11. Use i.v. C1 inhibitor derived from human plasma as first-line short-term prophylaxis. (91%, C)
12. Consider prophylaxis before events causing angioedema in specific patients. (90%, D)
13. Aim for complete disease control and ensure a normal life for the patient as a treatment goal. (100%, D)
14. Evaluate the need for long-term prophylaxis at each control based on disease activity, consequent burden, achieved control, and patient preferences. (96%, D)
15. Administer human plasma-derived C1 inhibitor as the first-line long-term prophylaxis. (87%, A)
16. Administer lanadelumab as first-line long-term prophylaxis. (98%, A)
17. Administer berotralstat as first-line long-term prophylaxis. (81%, A)
18. Administer androgens alone as second-line long-term prophylaxis. (89%, C)
19. Routinely monitor disease activity, its impact, and control in all patients on long-term prophylaxis to possibly optimize dosing and improve outcomes. (98%, A)
20. Examine children from families affected by HAE as early as possible, as well as all offspring of parents with HAE. (98%, D)
21. Administer C1 inhibitor or icatibant to treat attacks in children under 12 years of age. (94%, A)
22. Prefer human plasma-derived C1 inhibitor for treatment during pregnancy and breastfeeding. (100%, D)
23. Ensure all patients have an action plan. (98%, D)
24. Ensure the availability of specific, comprehensive, and integrated care for all HAE patients. (100%, D)
25. Ensure HAE patients are treated by a specialist experienced in managing this condition. (100%, D)
26. Teach all patients equipped with on-demand treatment approved for self-administration to apply this therapy independently. (98%, C)
27. Educate all patients about triggers that can cause an attack. (100%, D)
28. Screen family members of HAE patients. (100%, D)

The full text of these recommendations in English is freely available here. 

(zza)

Source: Maurer M., Magerl M., Betschel S. et al. The international WAO/EAACI guideline for the management of hereditary angioedema − the 2021 revision and update. Allergy 2022 Jan 10, doi: 10.1111/all.15214 [Epub ahead of print].