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Angioedema is edema of the deep dermis and subcutaneous tissues. It is caused by exposure to drug, venom, dietary, or extracted allergens. The main symptom is diffuse, painful swelling that can be severe. Diagnosis is by examination. Treatment is elimination or avoidance of the allergen and H1 blockers.
Acute angioedema is essentially anaphylaxis of the subcutaneous tissues. It is sometimes accompanied by urticaria (local wheals and erythema in the skin—see Approach to the Dermatologic Patient: Urticaria); the two have similar causes (eg, drug, venom, dietary, or extracted allergens). Also, angioedema is pathogenetically related to urticaria, which occurs at the epidermal-dermal junction.
Chronic (> 6 wk) angioedema is rarely IgE-mediated and is more difficult to explain. Cause is usually unknown (idiopathic), but chronic ingestion of an unsuspected drug or chemical (eg, penicillin in milk, a nonprescription drug, preservatives, other food additives) is sometimes the cause. A few cases are hereditary (see Allergic and Other Hypersensitivity Disorders: Hereditary Angioedema).
Symptoms and Signs
Angioedema may be slightly pruritic or nonpruritic. It is characterized by locally diffuse and painful soft-tissue swelling that may be asymmetric, especially on the eyelids, lips, face, and tongue but also on the back of hands or feet and on the genitals. Edema of the upper airways may cause respiratory distress, and the stridor may be mistaken for asthma. Complete airway obstruction may occur.
Diagnosis
The cause is often obvious, and diagnostic tests are seldom required because reactions are self-limited and nonrecurrent. No test is particularly useful. Erythropoietic protoporphyria may mimic allergic forms of angioedema and can be distinguished by measuring blood and fecal porphyrins (see Porphyrias: Diagnosis).
Treatment
For acute angioedema, treatment is removing or avoiding the allergen and relieving symptoms (eg, with H1 blockers—see Allergic and Other Hypersensitivity Disorders: Antihistamines; Table 2: Allergic and Other Hypersensitivity Disorders: Oral H1 Blockers ). Prednisone 30 to 40 mg po once/day is indicated for more severe reactions. Topical corticosteroids are useless. If a cause is not obvious, all nonessential drugs should be stopped. Pharyngeal or laryngeal angioedema requires epinephrine 0.3 mL of a 1:1000 solution sc. It may be supplemented with an IV antihistamine (eg, diphenhydramine 50 to 100 mg). Long-term treatment may involve H1 and H2 blockers and occasionally corticosteroids.
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Table 2
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| Oral H1 Blockers |
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Drug
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Usual Adult Dosage
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Usual Pediatric Dosage
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Available Preparations
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Sedating*
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Azatadine
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1–2 mg bid
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< 2 yr: Contraindicated
2–11 yr: Not recommended
≥ 12 yr: Adult dose
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1-mg tablets†
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Brompheniramine
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4 mg q 4–6 h
or 8 mg q 8–12 h
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< 2 yr: Contraindicated
2–6 yr: 0.125 mg/kg q 6 h (maximum dose 6–8 mg/day)
6–11 yr: 2–4 mg q 6–8 h (maximum dose 12–16 mg/day)
≥ 12 yr: Adult dose
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4-, 8-, and 12-mg tablets
2 mg/5 mL elixir
8- and 12-mg tablets (sustained-release)
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Chlorpheniramine
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2–4 mg q 4–6 h
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< 2 yr: Contraindicated
2–6 yr: Not recommended
6–11 yr: 2 mg q 4–6 h (maximum dose 12 mg/day)
≥ 12 yr: Adult dose
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2-mg chewable tablets
4-, 8-, and 12-mg tablets
2 mg/5 mL syrup
8- and 12-mg tablets or capsules (timed-release)
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Clemastine
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1.34 mg bid to 2.68 mg tid
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< 6 yr: Contraindicated
6–11 yr: 0.5 mg q 12 h (maximum dose 3 mg/day)‡
≥ 12 yr: Adult dose
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1.34- and 2.68-mg tablets
0.67 mg/5 mL syrup
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Cyproheptadine
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4 mg tid or qid (maximum 0.5 mg/kg/day)
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< 2 yr: Contraindicated
2–6 yr: 2 mg bid to tid (maximum 12 mg/day)
7–14 yr: 4 mg bid to tid (maximum 16 mg/day)
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4-mg tablets†
2 mg/5 mL syrup
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Dexchlorpheniramine
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2 mg q 4–6 h
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< 2 yr: Contraindicated
2–5 yr: 0.5 mg q 4–6 h (maximum dose 3 mg/day)
6–11 yr: 1 mg q 4–6 h (maximum dose 6 mg/day)
≥ 12 yr: Adult dose
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2-mg tablets
2 mg/5 mL syrup
4- and 6-mg tablets (extended-release)
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Diphenhydramine
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25–50 mg q 4–6 h
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< 2 yr: Contraindicated
2–11 yr: 1.25 mg/kg q 6 h (maximum dose 300 mg/day)
≥ 12 yr: Adult dose
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25- and 50-mg capsules or tablets
12.5 mg/mL syrup
12.5 mg/5 mL elixir
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Hydroxyzine
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25–50 mg tid or qid
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< 2 yr: Not recommended
2–11 yr: 0.7 mg/kg tid
≥ 12 yr: Adult dose
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25-, 50-, and 100-mg capsules
10-, 25-, 50-, and 100-mg tablets
10 mg/5 mL syrup
25 mg/5 mL oral suspension
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Promethazine
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12.5–25 mg bid
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< 2 yr: Contraindicated
≥ 2 yr: 6.25–12.5 mg bid or tid
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12.5-, 25-, and 50-mg tablets†
6.25 mg/5 mLand 25 mg/5 mL syrup
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Nonsedating
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Acrivastine/pseudoephedrine
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8/60 mg bid or tid
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< 12 yr: Not recommended
≥ 12 yr: Adult dose
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8-mg acrivastine plus 60-mg pseudoephedrine capsules
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Cetirizine
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5–10 mg once/day
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6–11 mo: 2.5 mg once/day
12–23 mo: 2.5 mg bid
2–5 yr: 5 mg once/day
≥ 6 yr: Adult dose
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5- and 10-mg tablets
1 mg/mL syrup
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Desloratadine
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5 mg once/day
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6–11 mo: 1 mg/day
1–5 yr: 1.25 mg/day
6–11 yr: 2.5 mg once/day
≥ 12 yr: Adult dose
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5-mg tablets
0.5 mg/mL syrup
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Fexofenadine
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60 mg bid or 180 mg once/day
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6–23 mo: 15 mg bid
2–11 yr: 30 mg bid
≥ 12 yr: Adult dose
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30-, 60-, and 180-mg tablets
6 mg/mL oral suspension
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Levocetirizine
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5 mg once/day
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< 6 yr: Contraindicated
6–11 yr: 2.5 mg once/day
≥ 12 yr: Adult dose
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5-mg tablets
0.5 mg/mL oral suspension
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Loratadine
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10 mg once/day
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2–5 yr: 5 mg once/day
≥ 6 yr: Adult dose
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10-mg tablets, 1 mg/mL syrup
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Mizolastine
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10 mg once/day
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< 12 yr: Not recommended
≥ 12 yr: Adult dose
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10-mg tablets
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*All sedating antihistamines have strong anticholinergic properties. Generally, they should not be used in the elderly or in patients with glaucoma, benign prostatic hyperplasia, delirium, dementia, or orthostatic hypotension. These drugs commonly cause dry mouth, blurred vision, urinary retention, constipation, and orthostatic hypotension.
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†Do not increase frequency in children.
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‡
Clemastine is not approved for children < 6 yr, but a dose of 0.05 mg/kg/day (maximum dose 1 mg/day) has been safely used in this age group.
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Hereditary Angioedema
Hereditary angioedema is caused by deficiency or dysfunction of C1 inhibitor, a protein that regulates the classical complement activation pathway (see Biology of the Immune System: Complement System).
Hereditary angioedema has 2 types:
Inheritance is autosomal dominant. C1 inhibitor deficiency may also be acquired: when complement is consumed in neoplastic disorders (eg, B-cell lymphoma), when C1 inhibitor autoantibody is produced in monoclonal gammopathy, or, rarely, when the autoantibody is produced in other disorders (eg, SLE, dermatomyositis). Attacks can be precipitated by mild trauma (eg, dental work, tongue piercing), viral illness, cold exposure, pregnancy, or ingestion of certain foods or may be aggravated by emotional stress.
Symptoms and signs are similar to those of angioedema except that edema progresses until complement components have been consumed; the GI tract is often involved, causing nausea, vomiting, colic, and signs of intestinal obstruction. Other common anatomic locations include the skin and the larynx. Episodes of swelling are self-limited; however, laryngeal involvement can lead to death.
Diagnosis
Diagnosis is based on detection of low levels of C2 and C4, normal levels of C1q (a fragment of C1), and decreased C1 inhibitor function. In type 1, C1 inhibitor protein levels are low; in type 2, levels are normal or increased. In acquired C1 inhibitor deficiency, C1q levels are low.
Treatment
Attenuated androgens (eg, stanozolol 2 mg po tid, danazol 200 mg po tid) are used to stimulate hepatic C1 inhibitor synthesis. This treatment may be less effective for the acquired form. Some experts advocate giving fresh frozen plasma immediately before dental or medical procedures to prevent attacks, but this approach could theoretically provoke an attack by providing substrate for angioedema.
Purified C1 inhibitor and recombinant C1 inhibitor are being developed for acute treatment. Corticosteroids and antihistamines are not effective. Epinephrine can be of transient benefit in cases of airway involvement. Symptomatic relief can be provided by analgesics, antiemetics, and fluid replacement.
Last full review/revision September 2008 by Peter J. Delves, PhD
Content last modified September 2008
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