eMedicine Specialties > Allergy and Immunology > Urticaria and Angioedema
Angioedema: Treatment & Medication
Updated: Oct 20, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Acute attacks
- Voice changes (eg, hoarseness, stridor, muffling) are indications that airway intervention should be strongly considered. In urgent but nonemergent cases, orotracheal intubation is the preferred method. When laryngeal edema is severe, a surgical airway must be created via cricothyrotomy or tracheotomy.
- Attain intravenous access with large-bore line.
- Fluid resuscitation may be necessary.
- Continuously monitor vital signs.
- Epinephrine, corticosteroids, and antihistamines are not effective in patients with HAE, AAE, and ACE inhibitor–induced angioedema. These agents are recommended as second-line therapy. In cases of angioedema due to allergic causes, these medications are first-line therapies (see Anaphylaxis).
- Vapor-heated C1-INH concentrate (recommended dosage 500-2000 U IV) is the first-line therapy for acute attacks of HAE or AAE, and was recently approved by the FDA in the United States for routine prophylaxis. When vapor-heated C1-INH concentrate is unavailable, fresh frozen plasma (FFP) (2 U IV) may be used. FFP may worsen an attack by providing substrates of complement that may exacerbate angioedema; however, this treatment is being used by many centers in this situation, given the lack of other available therapies, and most do not report any difficulties.
- Other treatment options for acute attacks include antifibrinolytic agents (eg, tranexamic acid, epsilon-aminocaproic acid). These agents probably act by inhibiting plasmin, which plays a role in initiating the complement cascade. Tranexamic acid is not approved for treatment of HAE or AAE in the United States.
- Long-term prophylaxis
- Long-term prophylaxis is indicated when a person is experiencing more than 2 attacks per month or if the airway is compromised continuously. Some authors recommend that long-term prophylaxis be considered in any patient with HAE affecting any organ system, regardless of the number of previous episodes.
- The agents of choice are the synthetic androgens danazol and stanozolol. Androgenic agents are effective because they induce messenger-RNA synthesis in the liver and directly increase C1-INH levels. Stanozolol and danazol have the same efficacy, but stanozolol has less masculinizing potential. In pediatric patients, antifibrinolytic agents are recommended as the first choice because of their favorable safety profile.
- Epsilon-aminocaproic acid and tranexamic acid have been used successfully to prevent bouts of HAE and AAE.
- Short-term prophylaxis
- Dental procedures or elective surgery of the oropharyngeal region often precipitates acute bouts of HAE or AAE. Therefore, short-term prophylaxis is necessary.
- A combination of FFP, vapor-heated C1-INH concentrate (if available), and androgen therapy is the regimen of choice.
- Treatment of the underlying disorder associated with AAE (ie, malignancy) usually results in correction of the abnormality.
- Patients who have had angioedema related to an ACE inhibitor must be cautioned against resuming that drug or using another drug in the class at any time. In addition, it is becoming recognized that these patients may be at risk for angioedema if taking an angiotensin receptor antagonist; their use should be considered only if no other option is available.
- Therapies currently under investigation for HAE and AAE include the following (For more information, see United States Hereditary Angioedema Association.):
- C1 inhibitor concentrates (Pharming and Lev Pharmaceuticals) are currently undergoing clinical testing.
- A kallikrein inhibitor, DX-88 (Dyax/Genzyme), is currently undergoing an open-label trial for use in HAE and AAE.
- B2 bradykinin receptor antagonist, Icatibant (Jerini Pharmaceutical), is also undergoing clinical trials.
Consultations
Consultation with an allergist or an immunologist is recommended in the management of HAE or AAE.
Medication
The goal of medical treatment for HAE and AAE is to either increase levels of C1-INH (eg, C1-INH concentrate, androgens) or to limit mediators of the complement cascade (eg, antifibrinolytic agents).
Androgens
Induce messenger-RNA synthesis in the liver and directly increase C1-INH. Agents of choice for long- and short-term prophylaxis.
Danazol (Danocrine)
Increases levels of C4 component of complement and reduces attacks associated with angioedema.
Adult
50-600 mg/d PO (usually 200 mg PO tid)
Short-term prophylaxis: 200 mg PO tid for 5-10 d preoperatively and 3 d postoperatively
Pediatric
Not established
Decreases insulin requirements and increases effects of anticoagulants (monitor PT); carbamazepine levels may increase
Documented hypersensitivity; seizure disorders, renal or hepatic insufficiency, pregnancy, breastfeeding, conditions influenced by edema
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Caution in cardiac insufficiency, epilepsy, migraines, undiagnosed abnormal vaginal bleeding; women should be observed for virilization
Stanozolol (Winstrol)
Synthetic androgen with immunosuppressive properties.
Adult
1-4 mg/d PO
Short-term prophylaxis: 1 mg qid for 5-10 d preoperatively and 3 d postoperatively
Pediatric
Not established
Increases hypoprothrombinemic effects of oral anticoagulants and hypoglycemic effects of insulin and sulfonylureas
Documented hypersensitivity; nephrosis; breast or prostate cancer; pregnancy, breastfeeding
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
May cause peliosis hepatitis, liver cell tumors, and blood lipid changes with increased risk of arteriosclerosis; caution in cardiac, renal, or hepatic disease and epilepsy; women should be observed for virilization
Hemostatic agents
Mechanism of action in the treatment of HAE and AAE is unknown. Most likely related to inhibition of plasmin.
Aminocaproic acid (Amicar)
Inhibits fibrinolysis via inhibition of plasminogen activator substances and, to a lesser degree, through antiplasmin activity. Main problem is that the thrombi that form during treatment are not lysed, and effectiveness is uncertain.
Adult
8 g IV q4h, then 16 g/d in acute attacks;
6-10 g/d PO maintenance
Pediatric
8-10 g/d PO
Coadministration with estrogens may cause an increase in clotting factors, leading to a hypercoagulable state
Documented hypersensitivity; evidence of active intravascular clotting process; DIC
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not administer unless a definite diagnosis of hyperfibrinolysis is made; caution in cardiac, hepatic, or renal disease and thrombosis and myonecrosis
Tranexamic acid (Cyklokapron)
Alternative to aminocaproic acid. Inhibits fibrinolysis by displacing plasminogen from fibrin.
Adult
Up to 8 g PO/IV for acute attacks, 1-2 g PO for maintenance
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal impairment or thrombosis
Vasopressors
In angioedema caused by drugs and foods, catecholamines improve vascular permeability, vascular resistance, and bronchodilation. Less effective in HAE and AAE, but used as second-line therapy.
Epinephrine (EpiPen, Adrenalin)
Has alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Beta-agonist effects include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.
Adult
0.3-0.5 mL IM/SC of 1:1000 dilution
Pediatric
0.01 mL/kg IM/SC of 1:1000 dilution; not to exceed 0.5 mL
Increases toxicity of beta- and alpha-blocking agents and that of halogenated inhalational anesthetics; effects potentiated by TCAs, levothyroxine, certain antihistamines, and MAOIs
Documented hypersensitivity; cardiac arrhythmia or angle-closure glaucoma; not for use during labor (may delay second stage of labor)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in elderly persons and persons with prostatic hypertrophy, hypertension, cardiovascular disease, diabetes mellitus, hyperthyroidism, and cerebrovascular insufficiency; rapid IV infusions may cause death from cerebrovascular hemorrhage or cardiac arrhythmia
Antihistamines
Histamine causes increased vascular permeability. Blocking this effect at the receptor level provides symptomatic relief.
Diphenhydramine (Benadryl)
For symptomatic relief of symptoms caused by release of histamine.
Adult
50 mg PO/IV/IM q6h; infuse slowly
Pediatric
1 mg/kg PO/IV/IM q6h; not to exceed 50 mg; infuse slowly
Potentiates effect of CNS depressants; due to alcohol content, do not administer syrup to patients taking medications that can cause disulfiramlike reactions
Documented hypersensitivity; MAOIs
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction; caution in pregnancy, breastfeeding and premature infants
Ranitidine (Zantac)
H2 antagonist that, when combined with an H1 type, may be useful in treating allergic reactions that do not respond to H1 antagonists alone.
Adult
50 mg IV over 5 min
Pediatric
0.5 mg/kg IV over 5 min
May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin; may increase PT with concurrent use of warfarin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment
Glucocorticoids
Anti-inflammatory actions inhibit the late-phase response to allergens. Inhibit inflammatory cell proliferation and release of mediators that can cause increased capillary permeability and bronchoconstriction observed in anaphylaxis.
Methylprednisolone (Solu-Medrol, Depo-Medrol)
Steroids ameliorate delayed effects of anaphylactoid reactions and may limit biphasic anaphylaxis.
Adult
125 mg IV
Pediatric
1-2 mg/kg IV
Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking concurrently with diuretics; concurrent use with cyclosporine may cause convulsions; decreased clearance with concurrent use of ketoconazole; possible increase in PT with warfarin coadministration
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use
Serine Proteinase Inhibitors (serpins)
Used for routine prophylaxis against angioedema attacks.
C1 inhibitor, human (Cinryze)
C1 inhibitor is a normal constituent of human blood and is one of the serine proteinase inhibitors (serpins). Regulates activation of pathway for complement and intrinsic coagulation. Also regulates fibrinolytic system. Available as a sterile, lyophilized preparation derived from human plasma. Specific activity is 4-9 U/mg protein. One unit corresponds to the mean quantity of C1 inhibitor present in 1 mL of normal fresh plasma. Indicated for routine prophylaxis against angioedema attacks in adolescents and adults with hereditary angioedema.
Adult
1000 U IV infused over 10 min; repeat every 3-4 d
Pediatric
Neonates and children: Not established
Adolescents: Administer as in adults
Data limited; none reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Severe hypersensitivity may occur and result in hives, urticaria, chest tightness, wheezing, hypotension, and/or anaphylaxis (discontinue and administer epinephrine if warranted); thrombotic events have been reported with high doses; as with all products derived from human blood, universal precautions for infection transmission should be used; common adverse effects (ie, >5%) include URTIs, sinusitis, rash, and headache
More on Angioedema |
| Overview: Angioedema |
| Differential Diagnoses & Workup: Angioedema |
 Treatment & Medication: Angioedema |
| Follow-up: Angioedema |
| Multimedia: Angioedema |
| References |
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Further Reading
Keywords
angioneurotic edema, oedema, laryngeal edema, hereditary angioedema, HAE, acquired angioedema, AAE, allergic reactions, hereditary angioneurotic edema, airway obstruction, swelling
