Causes of the development of angioedema

A distinction is made between non-allergic and allergic causes. The former can be inherited (so-called hereditary angioedema), caused by medication or caused by so-called lymphoproliferative diseases. An idiopathic form is also known, i.e. the trigger is not known.

All forms of oedema are based on the same mechanism: fluid flows from the vascular system into the interstitial space due to a pathological process. The interstitial space describes a space between different types of cells. In allergic angioedema, the substance histamine is responsible for this, which is released by the mast cells of the immune system during an allergic reaction.

Histamine changes the permeability of the vascular system and allows the aqueous components of the blood to pass into the connective tissue space. The same mechanism is present, for example, when an allergic reaction develops “wheals” (so-called urticaria). In non-allergic angioedema, no urticaria is developed.

This form is most often caused by drugs such as ACE inhibitors (against high blood pressure), less frequently by AT-1 blockers (against high blood pressure) and aspirin (ASA, for example after a heart attack). The other two forms (hereditary and acquired) are less common. Acquired angioedema is caused by lymphoproliferative diseases following organ transplantation.

The hereditary (hereditary) form is caused by an enzyme deficiency in the C1 esterase inhibitor enzyme. The mechanism involves the protein bradykinin, which normally mediates vascular opening during inflammation and promotes the passage of water from the blood into the surrounding tissue. Angioedema is a common side effect of ACE inhibitors.

These drugs are often used to treat high blood pressure. ACE inhibitors are used according to the “start low, go slow” principle because of their side effects. This means that a low dosage is prescribed first.

If angioedema occurs, it is kept within limits because the dose is low. If angioedema occurs, ACE inhibitors should be discontinued and replaced by another blood pressure medication. Treatment of the edema may be necessary. In general, however, it is sufficient to eliminate the triggering factor. .

What is hereditary angioedema?

Hereditary angioedema is a special form of conventional angioedema (also known as Quincke’s edema) because it is an autosomal-dominantly inherited disease. Those affected show an increased tendency to develop edema, the cause of which is a deficiency of the C1 esterase inhibitor enzyme. This enzyme is responsible for the activation of a component of the immune system and acts as a bradykinin mediator.

Bradykinin is a peptide hormone that binds to receptors located in the vessel. This principle of action causes vessels to be dilated and permeability to be increased. Fluid now escapes from the vessel and edema develops.

The enzyme can be completely absent or only partially restricted in its function. If the enzyme is completely lost, the immune system is activated excessively, which changes the permeability of all blood vessels and makes them more permeable. Affected people usually suffer from childhood and extensive oedema, which is mainly localised on the skin, but can also occur in the gastrointestinal tract and in the respiratory tract.

Even the smallest injuries such as cuts or tooth extractions can cause an exaggerated immune reaction. The oedemas only slowly recede on their own and require drug therapy. This can be, for example, enzyme substitution or FFP (fresh frozen plasma with corresponding enzymes). Androgens, which intervene in the circulation of sex hormones, also act via previously unknown mechanisms and can be used.