The angioedema

introduction

Angioedema (swelling of the blood vessel) or Quincke's edema is a sudden swelling of the skin and subcutaneous tissue, some of which lasts for several days.
Swellings on the lip, tongue and eyes are relatively harmless. Swelling of the glottis (the voice-forming part of the larynx), on the other hand, can be life-threatening.

Concomitant symptoms

Classic angioedema is typically associated with generalized itching and a feeling of tension in the skin. Depending on which other parts of the body are affected, swelling of the connective tissue can cause unspecific symptoms.
For example, hereditary angioedema can cause pain or indigestion because edema can form in the gastrointestinal tract. However, this is more of a rare symptom.

Symptoms from the allergic group would be more obvious. The vessels in our body relax and widen. The vasodilatation can lead to a sudden drop in central venous pressure. Blood pressure drops so much that it can make you pass out (so-called hypotonic syncope). This can be preceded by symptoms such as malaise, dizziness, sweating, racing heart and "weak knees".
Like any allergic reaction, this can be excessive and result in an allergic shock.

Untreated angioedema, perhaps combined with edema from other diseases, for example right heart failure, can lead to watery tension blisters in the skin or other skin changes.

Locations of the angioedema

Angioedema of the lip

The lips are a preferred place for edema to develop because they have a thin layer of skin and delicate connective tissue with few tight collagen fibers.
Usually the lips do not swell so much that the oral passage is not obstructed. However, massive swelling can become uncomfortable and appear unaesthetic. Since the skin and mucous membrane of the lips are rapidly regenerating cell layers, no permanent damage is to be expected.

You may also be interested in this topic: Swollen lips.

Angioedema of the face

Apart from the aesthetic aspects, angioedema of the face is no more dangerous than other forms of edema.
The skin of the face is a predilection for the development of edema, as the skin and subcutaneous tissue are a little more delicate. For example, there is less tight connective tissue there than in the legs or feet. In addition, the skin of the face is exposed to less mechanical stress than the skin on the hands.
In addition, the skin on the face and the subcutaneous tissue are particularly well supplied with blood. The number of blood vessels is important in the formation of edema and promotes it.

Find out more about the topic here: Swelling of the face.

Angioedema of the eye or eyelid

The eyelid is also a site of predilection for edema due to its anatomy. Padded with little subcutaneous fatty tissue and delicate connective tissue, it swells up more than other parts of the face.

It usually swells so much that it is impossible to see through one eye or even both eyes. This fact naturally harbors its own dangers and limitations (e.g. inability to drive) and should be remedied as soon as possible.
If one eye swells so much that the vitreous humor (lat. bulb) compresses the eye or increases the pressure in the eye, it can lead to an acute glaucoma attack or cause pain.

Find out more about the topic here:

• Edema of the eye
• Swelling of the eyes.

Angioedema of the neck

The most dreaded complication of angioedema is glottic edema, i.e. swelling of the glottis. This is located in the middle tier of the larynx and represents the opening between the mouth / throat and lungs.
The glottic edema manifests itself as sudden shortness of breath and difficulty speaking, like a lumpy or hoarse language.

Angioedema of the tongue

Swelling of the tongue can become problematic as it makes it difficult to speak and allows saliva to drain down the throat. It can also cause breathing difficulties. The swelling of the tongue, especially at the back of the tongue, can cut off the air's path.
Medicines can no longer be taken in by mouth either, but must be administered through the vein.

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 drugs or caused by so-called lymphoproliferative diseases. An idiopathic form is also known, i.e. the reason for this is unknown.

All forms of edema are based on the same mechanism:
Fluid escapes from the vascular system into the interstitial space due to a pathological process. The interstitial space describes a space between different cell types.
In allergic angioedema, the substance histamine is responsible for this, which is released by the mast cells of the immune system in the event of 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, if the allergic reaction is "wheals" (so-called urticaria) developed.

In non-allergic angioedema, urticaria will not develop. This form is most commonly caused by drugs such as ACE inhibitors (for high blood pressure), less often by AT-1 blockers (for high blood pressure) and aspirin (ASA, for example after a heart attack).

The other two forms (hereditary and acquired) are rarer. Acquired angioedema occurs as a result of lymphoproliferative diseases after organ transplantation. The hereditary (inheritable) form arises from an enzyme deficiency in the C1 esterase inhibitor enzyme. The mechanism involves the protein bradykinin, which normally mediates a vascular opening in the course of inflammation and promotes the passage of water from the blood into the surrounding tissue.

ACE inhibitors as the cause

Angioedema is a common side effect of ACE inhibitors. These drugs are often used for high blood pressure.
Because of their side effects, ACE inhibitors are used according to the “start low, go slow” principle. This means that a low dosage is prescribed initially. If angioedema occurs, this is limited because the dose was chosen to be low.

If angioedema occurs, ACE inhibitors should be discontinued and replaced with another blood pressure medication. Treatment of the edema may be necessary if necessary. In general, however, it is sufficient to eliminate the triggering factor.

Read more about this: Side effects of ACE inhibitors.

What is hereditary angioedema?

Hereditary angioedema is a special form of conventional angioedema (also Quincke edema), as it is an autosomal dominant inherited disease. Those affected show an increased tendency to develop edema, the cause of which is a deficiency in the C1 esterease inhibitor enzyme.
This enzyme is responsible for activating a component of the immune system and has a bradykinin-mediating effect. Bradykinin is a peptide hormone that binds to receptors that are located in the blood vessel. Due to this active principle, vessels are made wider and permeability is 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 overly activated, which changes the permeability of all blood vessels and makes them more permeable.

Those affected usually already suffer in childhood and extensive edema, which is mainly localized on the skin, but can also occur in the gastrointestinal and respiratory tract. Even the smallest injuries such as cuts or tooth extractions can result in an excessive immune reaction.

The edema only slowly regresses on its own and requires drug therapy. This can be, for example, an enzyme substitution or FFP (fresh frozen plasma with corresponding enzymes). Androgens, which intervene in the circulation of the sex hormones, work via previously unknown mechanisms and can be used.

Find out more about the topic here: Hereditary angioedema.

The diagnosis of angioedema

Angioedema is diagnosed clinically, i.e. based on the complaints and through targeted inspection and questioning by the doctor.
In the case of known, similar cases in the family, a genetic test for a C1 esterase inhibition deficiency can be considered as a further diagnosis.

Otherwise the diagnosis is made "ex juvantibus" i.e. through healing. The substance that is suspected to be the trigger is avoided here. If the patient no longer develops any further edema, the diagnosis can be confirmed.

therapy

Treatment depends on the cause:

Angioedema that is triggered by a certain drug can be cured by stopping the drug.

In allergic angioedema, antihistamines and glucocorticoids are most effective, as they modulate the immune system. Both the vascular permeability and the inflammation reaction can be reduced.
Antihistamines and glucocorticoids are injected intravenously for quick and far-reaching effects. In the case of minor allergic reactions, an oral antihistamine can also be taken, provided that the act of swallowing is still possible.

Hereditary edema can be treated with enzyme substitution as already described. Alternatively, a drug called icatibant, a bradykinin receptor antagonist, can be used. As an antagonist, it counteracts bradykinin and blocks the receptors so that bradykinin can no longer bind to it. This prevents the increased vessel permeability and the liquid kit remains in the vessel.
Enzyme substitution via plasma substitution can also be considered. Fresh frozen plasma (FFP) would be used for this.

Androgens, which intervene in the hormone metabolism, have proven effective as prophylaxis. Its mechanism in relation to angioedema has not yet been clarified.

In the case of glottic edema, intensive care management is necessary to ensure the supply of oxygen and breathing. Appropriate therapy is intravenous high-dose glucocorticoids.

Duration of angioedema

Depending on the mechanism by which the edema develops and how it has spread, angioedema can persist for days to weeks if untreated.

In the case of allergic edema, the edema can be treated directly with the help of acute therapy with antihistamines and should be addressed shortly, i.e. regress within a few hours. The same applies to the use of glucocorticoids, which are extremely effective as a decongestant.

The course of angioedema

Angioedema can be harmless to life-threatening.

Singular swellings of the eyelids and lips are relatively harmless.
If swellings on the tongue or on the glottis (so-called glottis) move the airways, these can be life-threatening. Rapid securing of the airway supply through drug treatment or intubation or tracheotomy are then necessary. As soon as drug treatment is started at the same time, the angioedema should subside and resolve within several days to weeks.

The course of the disease can be accelerated positively, for example, by punctually and correctly taking prescribed medication or in severe cases by administering glucocorticoids via the vein, as this can reach the site of action more quickly.

Find out more about this: Quincke's edema.

Which doctor treats angioedema?

If angioedema occurs simultaneously with shortness of breath, an emergency doctor should be called as soon as possible.
Otherwise, antihistamines, for example, which are administered in the case of allergic angioedema, are part of the standard repertoire of a medical institution. The application of local anesthetics can also trigger an allergic reaction at the dentist's. In this case, the dentist would have to treat the angioedema.
The family doctor or the medical on-call service are also suitable contact points.

If angioedema occurs more frequently, which is suspected to be an allergic cause, an allergist, who is usually a pulmonologist (pulmonologist) specialist, is suitable. If there is a tendency to edema in the family and this has occurred since childhood, a human geneticist should be consulted to rule out the described enzyme deficiency.