What is angioedema? Symptoms
Angioedema, a.k.a. Quincke’s, was first described in 1882 by the German physician of that name. It is usually a sudden, marked swelling of the skin, subcutaneous tissue and/or mucous membranes that is associated with an increase in blood vessel permeability [1,8]. It predominantly affects the skin of the face (particularly the lips and eyelids), and less commonly the torso, limbs and genitals [1]. The oedema may be ‘migratory’ in nature [4]. It usually takes the form of a single focus with clear boundaries (involving only the hand, for example) [7]. It is sometimes preceded by paresthesias, i.e. a sensation of tingling, numbness, pricking, burning, squeezing [2].
Angioedema is in many cases accompanied by the presence of urticaria [1,2,3,4,5]. Occasionally, it is also accompanied by changes in the gastrointestinal tract manifested by nausea, vomiting, abdominal pain and diarrhoea. This type of swelling resolves spontaneously, usually after 48-72 hours [1]. However, when it involves the tongue, larynx and mucous membranes of the upper respiratory tract, it becomes fatal. It can result in closure of the larynx and cause a tightening sensation in the throat, resulting in an inability to breathe [6].
Therefore, in cases of severe or rapidly progressive angioedema, the emergency services should be called immediately [2].
Congenital or acquired? Allergic or non-allergic?
Quincke’s oedema has two main varieties – acquired (AAE) and congenital (HAE), which are subdivided into further subtypes. Whereby acquired does not always mean allergic, although this is one of the most common. The allergic form is triggered, for example, by food, insect venom and other environmental allergens (even pollen [9]). Acquired non-allergic oedema, on the other hand, may result, among others:
- from the presence of certain diseases, especially autoimmune diseases such as systemic lupus erythematosus [1],
- exposure to physical agents, e.g. ultraviolet radiation, cold,
- use of certain medications, e.g. non-steroidal anti-inflammatory drugs or angiotensin-converting enzyme inhibitors (these preparations are used to treat hypertension, heart failure, coronary artery disease, metabolic syndrome) [4,9],
- chronic infections [9].
In contrast, congenital angioedema is genetically determined and is most often caused by abnormalities in the production or function of a C-1 inhibitor detectable in blood plasma. The disease is usually diagnosed as early as childhood (in children aged 5-11 years), although some people experience their first episode of oedema only in adulthood [1]. HAE is a rare disease, with fewer than 500 patients diagnosed in Poland to date [9]. At the same time, it is assumed that there is a large group of undiagnosed cases (these are mainly people with uncharacteristic symptoms).
HAE seizures are triggered by factors such as:
- medical procedures,
- mechanical trauma,
- physical exertion,
- infections,
- stress,
- pregnancy [1].
Angioedema can also be idiopathic (when the cause is unknown) [1,4].
Attention, anaphylaxis!
Angioedema can occur alone, simultaneously with or as part of an anaphylactic reaction. It is associated with approximately 40% of all cases of anaphylaxis [4]. Distinguishing its allergic from non-allergic form is a significant difficulty.
Angioedema per se, even if involving the tongue and throat, is not a systemic reaction and so should not be classified as anaphylaxis [3]. However, it is often confused with it and treated according to the management appropriate for anaphylaxis (antihistamines, GCS, adrenaline) [4]. Such treatment in patients with congenital angioedema is unsuccessful [1].
According to the 2020 WAO criteria, anaphylaxis is present when mucosal and/or skin symptoms are acute, start suddenly and progress rapidly. In addition, at least one of the following criteria must be met:
- impairment of respiratory function (e.g. dyspnoea, bronchospasm, wheezing),
- decreased blood pressure or symptoms indicative of organ dysfunction (e.g. fainting, involuntary urination),
- severe gastrointestinal symptoms (e.g. repeated vomiting, spasmodic abdominal pain) [10].
Anaphylaxis is diagnosed even when there are no typical skin lesions, but the patient has a significant drop in blood pressure or obstruction, i.e. bronchospasm, after contact with an identified or very likely allergen [10].
People with diagnosed allergy or other atopic disease (either in themselves or in their immediate family) are particularly at risk of allergic angioedema [3]. Pruritus (local or generalised) is a symptom that may indicate an allergic reaction, including anaphylaxis [1]. However, the answer to the causes of angioedema is only provided by a thorough diagnosis.
Angioedema – diagnosis
Quantitative determination of serum C1-esterase inhibitor (C1INH) levels is applicable in the diagnosis of angioedema [1]. If AAEC1-INH is found, additional tests are performed to confirm or exclude comorbidities [1]. This includes, for example, the determination of complement C4 protein (its decreased concentration is an indicator of lupus erythematosus activity) [9]. In order to identify the cause of angioedema, a standard allergy diagnosis is also performed [9].
