How do we treat patients with hereditary angioedema

https://doi.org/10.1016/S1473-0502(03)00164-2Get rights and content

Abstract

Hereditary angioedema (HAE) is due to the inherited deficiency of C1-Inhibitor (C1-Inh). When specific treatment was not available, the mortality rate for this disease was as high as 50% and the disability up to 100–150 days per year [Agostoni and Cicardi, Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients. Medicine (Baltimore) 71 (1992) 206]. Such a worrying scenario dramatically improves upon appropriate treatment. Nevertheless, the disease still frequently goes undiagnosed or misdiagnosed as an allergic condition. Both circumstances prevent patients from receiving drugs that could save and/or improve the quality of their life. The interest of our group for patients with HAE goes back to the early seventies [Agostoni and Martignoni, Hereditary angioneurotic oedema. Lancet 2 (1973) 325]. Since that time, 441 such patients have been examined and treated at our department; 403 are still actively followed. Here we present our experience on the treatment of HAE.

Section snippets

The approach

Hereditary angioedema (HAE) treatment is usually divided into three parts:

  • 1.

    long term prophylaxis,

  • 2.

    short term prophylaxis,

  • 3.

    treatment of acute attacks.


While parts 2 and 3 apply to any HAE patient, patients eligible for a long-term prophylaxis should be carefully selected. Criteria for this selection should take into account how much the disease affects the quality of life and/or carries risk of fatality on one side, and what are the risks related to long-term treatment on the other.

Long-term prophylaxis

The endpoint of this treatment is to render angioedema symptoms sporadic, i.e. approximately 2 attacks per year. Two classes of drugs have been proven to be effective in this type of prophylaxis: antifibrinolytic agents and androgen derivatives [3], [4], [5]. The first have been proposed for HAE due to their inhibitory activity on plasmin, a fibrinolytic enzyme that seems to be involved in the pathogenesis of attacks. Two preparations, epsilon-aminocaproic acid (EACA) and tranexamic acid (AMCA)

Short term prophylaxis

It is intended to guarantee absence of symptoms for a period of days or weeks. It is effectively performed using attenuated androgens that, given for a short time, do not raise safety problems even in children and in pregnant women during the last trimester. In our experience, HAE patients, after 1 week of danazol treatment on high doses (600 mg/day), are protected from swelling. Hence, we recommend that patients exposed to conditions that can trigger life threatening attacks (manipulation of

Treatment of acute attacks

We mentioned at the beginning the high mortality rate of HAE when appropriate treatment is not available. Deaths are due to laryngeal edema, which does not respond to corticosteroids and adrenaline. At present, this emergency can be overcome only by substitution therapy either with C1-Inh concentrate or with fresh frozen plasma [28], [29]. The first one has several advantages: (i) it can be kept at home by the patients and even self infused if needed; (ii) it has reduced risks of blood-borne

Drugs to be avoided in HAE patients

HAE is frequently misdiagnosed as an allergic condition and even when the correct diagnosis is made, physicians approaching these patients remain very concerned about using drugs. The axiom: “angioedema equals allergic drug reaction” is difficult to eradicate. As an example, many of our patients have been treated by the dentists without anesthesia, on the wrong, but firm belief, that angioedema results from allergy to anesthetics and not from the trauma. Hence, it is important to stress that

Conclusions

In this review we tried to share with the readers our clinical practice in treating HAE patients. We recognize, while giving therapeutic options to newly diagnosed patients that we are not just offering to them tools to fight a potentially lethal condition, but we are rather showing a way out from the feeling of uncertainty that marks their lives. A major complaint for HAE patients is the difficulty to find physicians who are adequately informed on the different aspects of their disease. In

References (42)

  • M Cicardi et al.

    Long-term treatment of hereditary angioedema with attenuated androgens: a survey of a 13-year experience

    J. Allergy Clin. Immunol.

    (1991)
  • R.J Pickering et al.

    Replacement therapy in hereditary angioedema. Successful treatment of two patients with fresh frozen plasma

    Lancet

    (1969)
  • K Bork et al.

    Recurrent episodes of skin angioedema and severe attacks of abdominal pain induced by oral contraceptives or hormone replacement therapy

    Am. J. Med.

    (2003)
  • A Agostoni et al.

    Contraindications to the use of ace inhibitors in patients with C1 esterase inhibitor deficiency

    Am. J. Med.

    (1991)
  • M Cugno et al.

    Bradykinin and the pathophysiology of angioedema

    Int. Immunopharmacol.

    (2003)
  • H Sumino et al.

    Hormone replacement therapy in postmenopausal women with essential hypertension increases circulating plasma levels of bradykinin

    Am. J. Hypertens.

    (1999)
  • M Lansink et al.

    Increased clearance explains lower plasma levels of tissue-type plasminogen activator by estradiol: evidence for potently enhanced mannose receptor expression in mice

    Blood

    (1999)
  • A Agostoni et al.

    Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients

    Medicine (Baltimore)

    (1992)
  • M.M Frank et al.

    Epsilon aminocaproic acid therapy of hereditary angioneurotic edema. A double-blind study

    N. Engl. J. Med.

    (1972)
  • G Blohme

    Treatment of hereditary angioneurotic oedema with tranexamic acid. A random double-blind cross-over study

    Acta Med. Scand.

    (1972)
  • J.A Gelfand et al.

    Treatment of hereditary angioedema with danazol. Reversal of clinical and biochemical abnormalities

    N. Engl. J. Med.

    (1976)
  • Cited by (65)

    • Hereditary Angioedema

      2023, Immunology and Allergy Clinics of North America
    • Hereditary Angioedema

      2022, Emergency Medicine Clinics of North America
    • Prophylactic Therapy for Hereditary Angioedema

      2017, Immunology and Allergy Clinics of North America
    • Life-threatening complications following orthognathic surgery in a patient with undiagnosed hereditary angioedema

      2013, Journal of Oral and Maxillofacial Surgery
      Citation Excerpt :

      Several treatments have been published for acute attacks in patients with suspected or confirmed diagnosis of HAE. Treatment is divided into 3 categories: acute prophylaxis before triggers and procedures; acute treatment for attacks; long-term suppression.3,5,11 While short-term prophylaxis and treatment of acute attacks apply to any HAE patient, individuals who are eligible for long-term prophylaxis should be carefully selected.11

    View all citing articles on Scopus
    View full text