Angioedema

Severe local swelling of the skin might indicate a case of angioedema. The condition mainly affects the arms and legs but can also affect the face and the genital area.

Common in the occurrence of angioedema are swollen lips, shown here in a man.

Our skin is made up of three layers: epidermis, dermis and hypodermis (or subcutaneous layer). Angioedema – also known as Quincke’s oedema or angioneurotic oedema – means accumulations of fluid in the subcutaneous tissue that lead to swelling. Two basic forms of angioedema can be distinguished: mast cell-mediated and bradykinin-mediated angioedema, the latter being less common.

Causes and forms

Mast cell-mediated angioedema

Most cases of angioedema that occur spontaneously are mast-cell-mediated – (also known as mast cell mediator-mediated). The causes of activation of the mast cells are diverse: e.g. allergic reactions, viral or bacterial infections, medications or even stress factors.

Bradykinin-mediated angioedema

Bradykinin is a tissue hormone that increases vessel permeability. The protein C1-inhibitor normally regulates the formation of bradykinin. If C1-inhibitor is available in insufficient quantities, if it is deficient or too much of it is consumed, the result is an excess of bradykinin. This also happens if degradation of bradykinin is blocked. Due to this excess, more fluid passes from the blood vessels into the surrounding tissue, resulting in angioedema.

Subforms of this group are:

  • hereditary angioedema (HAE), triggered by, for example, stress, physical exertion, injury, surgery or secondary to hormonal changes
  • acquired angioedema, relatively rare, triggered in most cases by an autoimmune disease, a disease of the lymphocytes and lymphatic tissue
  • drug-induced angioedema (triggered by certain blood pressure-lowering drugs, especially ACE-inhibitors or even blood sugar-lowering drugs such as gliptins)

Symptoms

Swellings occur in both forms of angioedema, often combined with a feeling of pressure or a burning sensation in different parts of the body, e.g.

  • Head: swelling of the eyelids, lips, facial skin, headaches, dizziness
  • Genital organs: swelling of the penis, testicles, vulva and vagina
  • Extremities: swellings on hands, feet, arms and legs; normal sequences of movement are restricted, walking impeded

In mast cell-mediated angioedema, itchy hives (urticaria) may appear on the body at the same time. This is not the case in the bradykinin-mediated form.

In hereditary angioedema (HAE) swellings frequently occur in the gastrointestinal tract (especially in the small and large bowel), which can result in severe abdominal pains, nausea, vomiting and diarrhoea even lasting several days. Swellings in the airways can be very dangerous. However, life-threatening situations can be averted in most cases because effective medicines are available nowadays.

Diagnosis

If the swelling is visible, the clinical diagnosis is relatively straightforward. On the other hand, searching for the cause is often a challenge, which is why it is important for the doctor to question the individual thoroughly when investigating the symptoms. In addition, specific laboratory tests (e.g. measurement of the level of C1-inhibitor) can provide further information to help clarify matters.

A symptom diary kept by the sufferer may prove helpful to the doctor when making the diagnosis. In this diary, the sufferer should write down when and for how long the swelling occurred and what other symptoms were also present (such as pain, itching, rash, breathlessness and abdominal pain). Photographs of the swellings are also very useful to the doctor.

Treatment

Mast cell-mediated angioedema

If the angioedema is induced by allergy, the trigger should be avoided as far as possible. If a medication is responsible for the reaction, the individual should stop taking the drug. If a bacterial infection or some other illness is the cause, it is important to treat this appropriately.

In most cases – irrespective of the cause – antihistamines and cortisone preparations are used to relieve the symptoms. In the case of life-threatening swellings, these drugs are also used as emergency medication, if necessary combined with a prefilled adrenaline syringe

Bradykinin-mediated angioedema

In hereditary angioedema (HAE), the primary aim should also be to avoid the triggers. There is also the option of preventive therapy with certain drugs. The protein C1-inhibitor and icatibant (active substance) – a bradykinin receptor antagonist – can be used to treat an acute angioedema attack.

In acquired angioedema it is important to ensure that the underlying disease is treated.

In drug-induced angioedema, administration of a C1-inhibitor and of icatibant is also useful. The drugs that cause the angioedema must be withdrawn and can be replaced where necessary with medicines from a different class of active substance.

Tips & tricks

  • Drug-induced angioedema can occur for the first time even though the drug has already been taken for a lengthy period of time (weeks or months). Consult a doctor immediately if the relevant symptoms appear.
  • Hereditary angioedema (HAE) runs in families. Therefore family members should also be tested when a case of HAE is confirmed.

Facts and figures

  • Up to 20 per cent of the population are affected by an acute swelling at some time in their lives.
  • In Switzerland there are about 160 people suffering from hereditary angioedema (HAE). The incidence is roughly 1 in 50,000.
  • Angioedema can occur in one area or several areas of the body.

Editors: aha! Swiss Allergy Centre in co-operation with the Scientific Advisory Board. For prevalence figures, see source references.