May occur as an independent symptom or be associated with urticaria Hives (Urticaria).
Angioedema without urticaria is usually either associated with an underlying drug reaction or idiopathic.
The treatment is symptomatic. If the triggering factor can be identified, it should be avoided.
It is important to identify laryngeal oedema and patients requiring acute hospital treatment.
Angioedema may be an anaphylactic symptom Anaphylaxis.
Clinical picture and symptoms
Sudden-onset circumscribed oedema of deeper skin structures and/or mucosa.
The superficial skin is usually normal; there may be erythema.
The duration of symptoms varies from less than a day to even up to 5 days.
Typical sites include the lips, tongue, eyelids, face (picture 2); may also occur on the limbs (e.g. backs of the hands), trunk or genital area (such as the testes).
The oedema feels doughy on palpation, and there is no pitting.
There is usually tingling and pain, less often itching. Oedema may occur without any other symptoms.
There may be urticaria.
Oedema in the upper respiratory tract (laryngeal oedema) may lead to sudden respiratory insufficiency and may be fatal.
Symptoms of laryngeal oedema include a sensation of tight throat, voice change and respiratory difficulty.
During the attack, there may be gastrointestinal oedema and other gastrointestinal symptoms; these may rarely be the sole symptoms of angioedema.
Causes
Drugs (ACE inhibitors, ARBs, non-steroidal anti-inflammatory analgesics, possibly also other drugs)
Association with urticaria, such as acute urticaria triggered by infections Hives (Urticaria)
Physical urticarias (pressure, vibration, heat or cold) Hives (Urticaria)
Idiopathic (e.g. autoimmune angioedema)
About 10% of chronic urticarias present only as paroxysmal angioedema without wheals.
Allergic reactions: food allergies Food Allergy in Adults (oral allergy syndrome), allergy to Hymenoptera, latex allergy
Angioedema may be the first symptom of an anaphylactic reaction Anaphylaxis.
It is important to exclude angioedema of the upper respiratory tract (e.g. laryngeal oedema) and to identify patients requiring emergency hospital treatment (with intubation available during treatment and monitoring).
Clinical examination
Pharyngeal and oral mucosa (uvular oedema, mucosal oedema?); palpation of the neck
Auscultation of the neck; inspiratory stridor?
Respiratory rate (more than 25/min usually abnormal); does dyspnoea prevent speaking?
Pulse oximetry (< 92% clearly abnormal)
Exclusion of anaphylactic reaction: blood pressure, lung auscultation (bronchial obstruction?)
Hot erythema, ulcers or symptoms of infection do not indicate angioedema.
Patient history
Development of the disease, medication, allergies, food, family history
Is there a temporal association with any drug (new drug started before the onset of the symptoms)?
Erysipelas or cellulitis (glowing, hot erythema, fever, chills) Erysipelas; recurring erysipelas may also occur, for instance in the genital area
Incipient shingles (pain, erythema in the area of the dermatome, precisely restricted to one side of the median line, unilateral) Shingles (Herpes Zoster)
Acute allergic contact dermatitis Allergic Contact Dermatitis (itching, papules and vesicles on the skin, eczematous clinical picture, restricted to area of exposure to contact allergen)
Local reaction to insect sting or bite Insect Stings and Bites (history of insect sting or bite, sting or bite mark and petechia in the centre of the oedema)
Other conditions causing oedema
Oedema caused by hypoproteinaemia (e.g. nephrotic syndrome, enteropathies)
Myxoedema (in most cases associated with hypothyroidism)
Factors obstructing veins and/or lymph vessels (e.g. compression of superior vena cava)
Inflammation parameters (CRP, basic blood count with platelet count), as necessary for differential diagnosis, to exclude infection
In the case of recurring attacks (can be performed in the interim):
Targeted examination for IgE-mediated allergy (specific IgE antibodies, prick tests) if an allergic reaction (food allergy, for example) is suspected
If an autoimmune disease is suspected, thyroid tests TSH, free T4, TPO antibodies, as necessary, or other targeted examinations
Serum C1 esterase inhibitor, C1 esterase inhibitor biological activity, C3 and C4 (if hereditary angioedema is suspected)
Treatment
In patients who are in a good general condition and have no risk factors or signs of upper respiratory tract obstruction, monitoring and symptomatic treatment, as necessary, may be sufficient.
The triggering factor (e.g. drug) should be withdrawn, as far as possible, and a follow-up visit arranged, as necessary
If angioedema is suspected of being caused by an ACE inhibitor or ARB, this should be replaced by another antihypertensive drug, such as a calcium-channel blocker and/or diuretic. If the ACE inhibitor has been paused for 6 months and the patient has remained asymptomatic, an ARB can be tried based on case-by-case judgement, if this is necessary for the treatment.
An antihistamine at 1-4 times the normal dose (1-2 tablets in the morning and in the evening, with sic! written in the prescription) for 1-2 weeks at a time
This is effective for urticaria (histaminergic angioedema), in particular.
However, antihistamines are often ineffective (so-called non-histaminergic angioedema, usually bradykinin-mediated).
If the oedema is severe and disturbing, adults can be given oral glucocorticoids, such as prednisolone at a dose of 30-40 mg once daily (0.5 mg/kg in courses of 1-3 days), for example.
In some cases, tranexamic acid may help, given at doses of 1-1.5 g 2-3 times daily for a few days (until angioedema subsides).
Emergency hospital care (transportation with intubation available); further treatment and monitoring in a unit with intubation and tracheostomy available.
Adrenaline will reduce the oedema: for adults 0.3-0.5 mg i.m. (0.01 mg/kg if patient weighs < 50 kg), repeated every 10-20 min, as necessary. See Anaphylaxis Anaphylaxis.
For patients with hypoxaemia symptomatic treatment with oxygen
Glucocorticoid i.v., such as a 40-80 mg bolus of i.v. methylprednisolone
I.v. fluid administration (Ringer or NaCl)
Causal treatment, as far as possible (such as withdrawal of ACE inhibitor)
For life-threatening ACE inhibitor-induced angioedema, in addition to the aforementioned treatments, also spesific therapies for HAE (e.g. C1 inhibitors) have been used.
Avoid the cause (drugs, allergies) as far as possible
In idiopathic angioedema, it is worth trying regular prophylactic medication with an antihistamine. If the treatment does not work, it is suggestive of so-called non-histaminergic, i.e. usually bradykinin-mediated, angioedema.
Prophylactic antihistamines: 1-4 times the normal dose (1-2 tablets every morning and evening), with the patient titrating the dose according to the response and symptoms
For attacks, a glucocorticoid at doses of, for example, 30-40 mg once daily (0.5 mg/kg in courses of 1-3 days) and an oral antihistamine
In severe cases, the patient may be prescribed a disposable adrenaline syringe for use as needed. Instructions for its use must be given to the patient and the family.
For patients with respiratory tract obstruction, emergency hospital care and monitoring (preparedness for intubation and tracheostomy)
Specialized care should be consulted if symptoms are persistent or severe (unit with special expertise in the treatment and diagnosis of angioedema)
An allergologist should be consulted if allergy is suspected but its cause remains unclear.
For hereditary angioedema, monitoring and treatment in a specialized care unit specializing in familiar angioedema
References
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