Current status of the management of hereditary angioedema in China: a patient-based, cross-sectional survey



Hereditary angioedema (HAE) is a rare, inherited disorder characterized by unpredictable and recurrent cutaneous and mucosal oedema.


This study aimed to identify the current status of HAE management in China.

Materials and Methods

An internet-based survey was sent to 129 patients with type 1 and 2 HAE diagnosed between 1983 and 2017; a total of 107 patients provided complete disease management information.


The survey response rate was 82.9% (107 responders). Ten patients reported 18 fresh frozen plasma (FFP) transfusions for the main purpose of treating lethal laryngeal oedema. Two patients reported adverse events. Eighty-nine (83.2%) patients had taken danazol for long-term prophylaxis, and 74 (69.2%) were on long-term danazol prophylaxis. Among patients on long-term prophylaxis, 56 (75.7%) patients reported a decrease in their annual attack frequency after taking danazol. Twenty-five (33.8%) patients had an attack frequency of no more than once per year. The most common side effects were menstrual disorders, weight gain, osteoarticular pain, acne, and sebaceous hypersecretion. Patients with higher education levels, positive family histories, and laryngeal oedema attacks before medication tended to show better adherence. Patients maintaining high or medium adherence showed better control of laryngeal and gastrointestinal involvement than patients with low adherence. Four (3.7%) patients reported current or past use of tranexamic acid.


Attenuated androgen and FFP transfusions remain the mainstay in China, where specifically targeted drugs are currently lacking. Maintaining good medication adherence should be recommended to achieve improved disease control.

This is a preview of subscription content, log in to check access.


  1. 1.

    Betschel S, Badiou J, Binkley K, et al. Canadian hereditary angioedema guideline. Allergy Asthma Clin Immunol 2014; 10: 50.

    Article  Google Scholar 

  2. 2.

    Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-the 2017 revision and update. World Allergy Organ J 2018; 11: 5.

    Article  Google Scholar 

  3. 3.

    Walford HH, Zuraw BL. Current update on cellular and molecular mechanisms of hereditary angioedema. Ann Allergy Asthma Immunol 2014; 112: 413–8.

    CAS  Article  Google Scholar 

  4. 4.

    Zuraw BL, Bernstein JA, Lang DM, et al. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema. J Allergy Clin Immunol 2013; 131: 1491–3.

    CAS  Article  Google Scholar 

  5. 5.

    Bork K. A decade of change: recent developments in pharmacotherapy of hereditary angioedema (HAE). Clin Rev Allergy Immunol 2016; 51: 183–92.

    CAS  Article  Google Scholar 

  6. 6.

    Liu S, Xu Y, Liu Y, Zhi Y. Hereditary angioedema: a Chinese perspective. Eur J Dermatol 2019; 29: 14–20.

    PubMed  Google Scholar 

  7. 7.

    Gelfand JA, Sherins RJ, Alling DW, Frank MM. Treatment of hereditary angioedema with danazol. Reversal of clinical and biochemical abnormalities. N Engl J Med 1976; 295: 1444–8.

    CAS  Article  Google Scholar 

  8. 8.

    Bork K, Bygum A, Hardt J. Benefits and risks of danazol in hereditary angioedema: a long-term survey of 118 patients. Ann Allergy Asthma Immunol 2008; 100: 153–61.

    CAS  Article  Google Scholar 

  9. 9.

    Riedl MA. Critical appraisal of androgen use in hereditary angioedema: a systematic review. Ann Allergy Asthma Immunol 2015; 114: 281–8.e7.

    CAS  Article  Google Scholar 

  10. 10.

    Wu MA, Zanichelli A, Mansi M, Cicardi M. Current treatment options for hereditary angioedema due to C1 inhibitor deficiency. Expert Opin Pharmacother 2016; 17: 2740.

    Article  Google Scholar 

  11. 11.

    Busse PJ, Farkas H, Banerji A, et al. Lanadelumab for the prophylactic treatment of hereditary angioedema with C1 inhibitor deficiency: a review of preclinical and phase I studies. BioDrugs 2019; 33: 33–43.

    CAS  Article  Google Scholar 

  12. 12.

    Aberer W, Maurer M, Bouillet L, et al. Breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis are responsive to icatibant: findings from the icatibant outcome survey. Allergy Asthma Clin Immunol 2017; 13: 31.

    Article  Google Scholar 

  13. 13.

    Liu S, Wang X, Xu Y, Xu Q, Zhi Y. Risk factors for diagnostic delay in Chinese patients with hereditary angioedema. Allergy Asthma Proc 2019; 40: 343–9.

    CAS  Article  Google Scholar 

  14. 14.

    Morisky DE, Ang A, Krousel-Wood M, Ward HJ. Predictive validity of a medication adherence measure in an outpatient setting. J Clin Hypertens (Greenwich) 2008; 10: 348–54.

    Article  Google Scholar 

  15. 15.

    Castellucci LA, Shaw J, van der Salm K, et al. Self-reported adherence to anticoagulation and its determinants using the Morisky medication adherence scale. Thromb Res 2015; 136: 727–31.

    CAS  Article  Google Scholar 

  16. 16.

    Kane S, Becker B, Harmsen WS, Kurian A, Morisky DE, Zinsmeister AR. Use of a screening tool to determine nonadherent behavior in inflammatory bowel disease. Am J Gastroenterol 2012; 107: 154–60.

    CAS  Article  Google Scholar 

  17. 17.

    Yan J, You LM, Yang Q, et al. Translation and validation of a Chinese version of the 8-item Morisky medication adherence scale in myocardial infarction patients. J Eval Clin Pract 2014; 20: 311–7.

    Article  Google Scholar 

  18. 18.

    Xu YY, Jiang Y, Zhi YX, et al. Clinical features of hereditary angioedema in Chinese patients: new findings and differences from other populations. Eur J Dermatol 2013; 23: 500–4.

    Article  Google Scholar 

  19. 19.

    Caballero T, Baeza ML, Cabanas R, et al. Consensus statement on the diagnosis, management, and treatment of angioedema mediated by bradykinin. Part II. Treatment, follow-up, and special situations. J Investig Allergol Clin Immunol 2011; 21: 422–41.

    CAS  PubMed  Google Scholar 

  20. 20.

    Tang R, Chen S, Zhang H. Analysis on treating hereditary angioedema acute attack with fresh frozen plasma in 16 case-times. J Regional Anat Operative Surg 2012; 21: 283–4.

    CAS  Google Scholar 

  21. 21.

    Longhurst HJ. Emergency treatment of acute attacks in hereditary angioedema due to C1 inhibitor deficiency: what is the evidence? Int J Clin Pract 2005; 59: 594–9.

    CAS  Article  Google Scholar 

  22. 22.

    Zotter Z, Veszeli N, Csuka D, Varga L, Farkas H. Frequency of the virilising effects of attenuated androgens reported by women with hereditary angioedema. Orphanet J Rare Dis 2014; 9: 205.

    Article  Google Scholar 

  23. 23.

    Caballero T, Farkas H, Bouillet L, et al. International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency. J Allergy Clin Immunol 2012; 129: 308–20.

    Article  Google Scholar 

  24. 24.

    Giannitrapani L, Soresi M, La Spada E, Cervello M, D’Alessandro N, Montalto G. Sex hormones and risk of liver tumor. Ann N Y Acad Sci 2006; 1089: 228–36.

    CAS  Article  Google Scholar 

  25. 25.

    Bork K, Pitton M, Harten P, Koch P. Hepatocellular adenomas in patients taking danazol for hereditary angio-oedema. Lancet 1999; 353: 1066–7.

    CAS  Article  Google Scholar 

  26. 26.

    Crampon D, Barnoud R, Durand M, et al. Danazol therapy: an unusual aetiology of hepatocellular carcinoma. J Hepatol 1998; 29: 1035–6.

    CAS  Article  Google Scholar 

  27. 27.

    Gower RG. HAE update: determining optimal patient specific therapy. Allergy Asthma Proc 2013; 34: 7–12.

    CAS  Article  Google Scholar 

  28. 28.

    Nordenfelt P, Nilsson M, Bjorkander J, Mallbris L, Lindfors A, Wahlgren CF. Hereditary angioedema in Swedish adults: report from the national cohort. Acta Derm Venereol 2016; 96: 540–5.

    CAS  Article  Google Scholar 

  29. 29.

    Jung JW, Suh DI, Park HJ, et al. Clinical features of hereditary angioedema in Korean patients: a nationwide multicenter study. Int Arch Allergy Immunol 2018; 176: 272–9.

    Article  Google Scholar 

  30. 30.

    Bouillet L, Gompel A. Hereditary angioedema in women: specific challenges. Immunol Allergy Clin North Am 2013; 33: 505–11.

    Article  Google Scholar 

  31. 31.

    Bygum A, Fagerberg CR, Ponard D, Monnier N, Lunardi J, Drouet C. Mutational spectrum and phenotypes in Danish families with hereditary angioedema because of C1 inhibitor deficiency. Allergy 2011; 66: 76–84.

    CAS  Article  Google Scholar 

Download references

Acknowledgements and disclosures

Acknowledgements: We thank all the patients for their support with this research. Conflicts of interest: none. Funding sources: This work was supported by the National Natural Science Fund (No. 81472870), the CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2016-I2M-1-002), the Undergraduate Innovation Program (No. 2018zlgc0632) and the National Key Research and Development Program of China (No. 2016YFC0901501).

Author information



Corresponding author

Correspondence to Yuxiang Zhi.

Supplementary material

About this article

Verify currency and authenticity via CrossMark

Cite this article

Liu, S., Xu, Q., Xu, Y. et al. Current status of the management of hereditary angioedema in China: a patient-based, cross-sectional survey. Eur J Dermatol 30, 169–176 (2020).

Download citation

Key words

  • adherence
  • danazol
  • fresh frozen plasma
  • hereditary angioedema
  • tranexamic acid