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Hilary J Longhurst, MA, PhD, FRCP, FRCPath
Consultant in Clinical Immunology,
Barts and the London NHS Trust
Hereditary angioedema (HAE) is an autosomal dominant condition that has an estimated prevalence of 1:50,000. It occurs in both men and women with no predilection for any particular ethnic group. It is characterised by episodic, non-pruritic, localised subcutaneous and sub-mucosal swellings that, untreated, typically last for 1–5 days. While the trigger for most attacks of angioedema is not known, minor trauma, surgery, infection, menstruation, bleeding and stress are all known to exacerbate the disease. In some cases an attack is heralded by a prodromal rash or feeling of malaise. Untreated, patients average 1–2 attacks per month, but there is considerable variability between patients with regard to the frequency and severity of their attacks.
What clinical symptoms and/or medical history should indicate a potential diagnosis of HAE?
In any patient with angioedema not associated with urticaria, unexplained abdominal pain (which may be associated with bowel angioedema) or reversible swellings of hands, feet or genitals should be considered. Anyone with a first degree relative who has HAE is potentially at risk even if asymptomatic and should be screened for HAE, as the first attack could potentially (rarely) be fatal.
How has the treatment of HAE evolved over the past decade?
We have a choice of licensed treatments for acute attacks and home therapy/self-administration programmes have been set up. These two developments have enabled us to move from the treatment of established attacks in hospital or ‘accident and emergency’ to the treatment of early symptoms at home, thus aborting the attack. Both intravenous (C1-inhibitor) and subcutaneous (icatibant) options are available, meaning that almost anyone interested can self-treat. This has enabled patients to avoid pain and the reversible but damaging disability associated with HAE, and to ensure that they can fulfil their potential in education and at work.
As far as prophylaxis is concerned, we are more aware of the potential for side-effects with higher doses of attenuated androgens and are more likely to manage suitable patients on low dose prophylaxis. Stanozolol or oxandrolone can often be tolerated by patients who do not tolerate or do not find danazol effective. We also have the option of C1-inhibitor prophylaxis, where androgens are not tolerated or contraindicated. This has been particularly helpful for those with very frequent attacks, and during pregnancy and breastfeeding. Although unlicensed for pregnant women, C1-inhibitors are the option recommended by experts for acute treatment and, where necessary, prophylaxis for this group.
Is the HAE patient a candidate for personalised prophylaxis and personalised treatment?
Absolutely. HAE is such a variable disease that each patient has different requirements and responses to treatment. This is one reason why we recommend referring all patients to a specialist centre, who will share care with the local centre.
Has the introduction of the new therapeutic agents significantly improved patient quality of life?
They have great potential and, for the lucky patients who have full access to these agents, they have made a big improvement in quality of life. However, access to treatment is variable, because of lack of understanding by funding authorities, or sometimes by patients themselves, who are used to accepting the limitations, risks and difficulties associated with suboptimal treatment.
How should the prescriber approach the management of patients with HAE?
Should certain steps be taken and certain healthcare personnel (for example, pharmacists) included to optimise clinical outcomes? Traditionally, lower doses of C1-inhibitor were used to treat attacks. While patients reported benefit, double-blind randomised controlled trials suggest that higher doses (1000–2000 units for Cinryze; 20U/kg for Berinert; and 50U/kg or 4200 units, whichever is higher, for Ruconest) are more effective. Pharmacists could play a vital role in encouraging use of licensed doses, which are likely to have better outcomes and to reduce the need for admission to hospital. They could also suggest alternatives, such as icatibant, self-administration of C1-inhibitor, or optimisation of prophylaxis, which might facilitate home treatment and/or reduce the need for emergency care.