- 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
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 (picture (Swelling around the eye in an HAE patient)), face (picture (Angio-oedema)); may also occur on the limbs (e.g. backs of the hands; picture (Swollen hand of an HAE patient)), 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.
- 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))
- 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
- Physical urticarias (pressure, vibration, heat or cold) (Hives (urticaria))
- Hereditary angioedema (Hereditary angioedema (HAE) and ACE inhibitor-induced angioedema); very rare, with a prevalence of about 1:50,000
- The diagnosis is based on clinical findings.
- 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)?
- Angioedema due to ACE inhibitors or ARBs (Hereditary angioedema (HAE) and ACE inhibitor-induced angioedema) may have a sudden onset even after long-term use. Symptoms may continue for 1–6 months after withdrawing the medication.
- Angioedema may be the first symptom of an anaphylactic reaction (Anaphylaxis).
- Angioedema associated with ACE inhibitor therapy or, more rarely, with other pharmacotherapy (Hereditary angioedema (HAE) and ACE inhibitor-induced angioedema).
- Very rare hereditary angioedema (HAE) (Hereditary angioedema (HAE) and ACE inhibitor-induced angioedema).
- Erysipelas or cellulitis (glowing, hot erythema, fever, chills) (Erysipelas and cellulitis); 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) (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)
- Macroglossia (acromegaly, amyloidosis, hypothyroidism, Melkersson–Rosenthal syndrome)
- Inflammation parameters (CRP, basic blood count with platelet count, SR), as necessary for differential diagnosis, to exclude infection
- In the case of recurring attacks (can be performed in the interim):
- Serum C1 esterase inhibitor, C1 esterase inhibitor biochemical activity, C3 and C4 (if hereditary angioedema is suspected)
- 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
- 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).
- Tranexamic acid may increase tendency for venous thrombosis (Evaluation of thrombophilia); remember to investigate risk factors for thromboembolism.
- Analgesics, as necessary (if there is no sign of a reaction triggered by non-steroidal anti-inflammatory analgesics)
- Topical application of cold or a cooling gel may alleviate the symptoms.
- For treatment of hereditary angioedema (HAE) and ACE inhibitor-induced angioedema, see (Hereditary angioedema (HAE) and ACE inhibitor-induced angioedema).
If there are signs of upper respiratory oedema
If there are signs of upper respiratory oedema
- Emergency hospital care (transportation with intubation available); further treatment and monitoring in a unit with intubation and tracheostomy available.
- Adrenaline will reduce the oedema: 0.3–0.5 mg i.m. (0.01 mg/kg), repeated every 10–20 min, as necessary.
- 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 hereditary angioedema, specific treatment (Hereditary angioedema (HAE) and ACE inhibitor-induced angioedema)
- For ACE inhibitor-induced angioedema that is unresponsive to treatment, the bradykinin receptor blocker icatibant has been used (off-label use for treatment of HAE).
- 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.
- Tranexamic acid may also be useful for attacks.
- 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
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TY - ELEC T1 - Angioedema ID - 1305192 BT - Evidence-Based Medicine Guidelines UR - https://evidence.unboundmedicine.com/evidence/view/EBMG/1305192/all/_________Angioedema______ PB - Duodecim Medical Publications Limited DB - Evidence Central DP - Unbound Medicine ER -