Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

acute urticaria ± angioedema

1st line – epinephrine (adrenaline) + airway protection

Back
ACUTE
|
acute urticaria ± angioedema
|
with airway involvement
1st line – 

epinephrine (adrenaline) + airway protection

Episodes of urticaria with angioedema affecting the head and neck, which could potentially compromise the airway, should be treated promptly with epinephrine.

The status of the airway should be assessed and closely monitored in all patients with angioedema, and all necessary steps must be taken to ensure the airway is always secured. Consultation with an anesthesiologist may be necessary.

If available, flexible fiberoptic laryngoscopy can rapidly determine the extent of involvement of the base of the tongue or the larynx. This can determine the most appropriate airway management strategy.[26]

Beta-blockers can interfere with the action of epinephrine, and discontinuing this drug in patients with urticaria and angioedema can be considered if comorbid conditions allow. However, for most medical indications, the risk of stopping or changing the drug may exceed the risk of more severe anaphylaxis if the drug is continued, particularly in patients with insect sting anaphylaxis.[28]

For patients with a history of urticaria associated with angioedema, two self-injectable epinephrine pens should be prescribed.[27] Patients must be instructed how to use them. Patients who have administered epinephrine outside a medical setting will often require immediate medical attention at an emergency facility, although this may not be required if the patient experiences prompt, complete, and durable response to treatment.[28]

Primary options

epinephrine (adrenaline): consult local protocol for guidance on dose

Plus – intravenous antihistamine

Back
ACUTE
|
acute urticaria ± angioedema
|
with airway involvement
Plus – 

intravenous antihistamine

Treatment recommended for ALL patients in selected patient group

Antihistamines are the mainstay of therapy in acute urticaria.[37] Treatment of angioedema of the neck, face, tongue, or lips is with an intravenous antihistamine.

Primary options

diphenhydramine: 10-50 mg intravenously every 4-6 hours when required, maximum 400 mg/day

Plus – trigger identification and avoidance

Back
ACUTE
|
acute urticaria ± angioedema
|
with airway involvement
Plus – 

trigger identification and avoidance

Treatment recommended for ALL patients in selected patient group

Acute urticaria is generally self-limited. Triggers can often be identified and need to be strictly avoided if possible. This can involve dietary modifications, the discontinuation or substitution of causative drugs, and the removal of physical stimuli.

Central to the treatment for drug-induced angioedema without urticaria is the identification and cessation of the drug responsible.

Consider – systemic corticosteroid

Back
ACUTE
|
acute urticaria ± angioedema
|
with airway involvement
Consider – 

systemic corticosteroid

Treatment recommended for SOME patients in selected patient group

If an episode of urticaria is severe, a short course of corticosteroids can be considered in addition to antihistamines. Administration of an intravenous corticosteroid may be considered for angioedema of the neck, face, tongue, or lips.

Primary options

methylprednisolone sodium succinate: 10-40 mg by intravenous infusion initially, followed by 40-120 mg once daily thereafter

1st line – trigger identification and avoidance

Back
ACUTE
|
acute urticaria ± angioedema
|
without airway involvement
1st line – 

trigger identification and avoidance

Acute urticaria is generally self-limited. Triggers can often be identified and need to be strictly avoided if possible. This can involve dietary modifications, the discontinuation or substitution of causative drugs, and the removal of physical stimuli.

Central to the treatment for drug-induced angioedema without urticaria is the identification and cessation of the drug responsible.

Plus – antihistamine

Back
ACUTE
|
acute urticaria ± angioedema
|
without airway involvement
Plus – 

antihistamine

Treatment recommended for ALL patients in selected patient group

Second-generation, nonsedating antihistamines are the mainstay of therapy in acute urticaria.[37] Examples of this class of drug include loratadine, desloratadine, cetirizine, levocetirizine, and fexofenadine.

Second-generation antihistamines have a good safety profile and can be taken for several years continously.[1] They cross the blood-brain barrier to a lesser extent than first-generation antihistamines and may be less likely to lead to sedation and impaired cognitive function.[44][45] Cetirizine has been reported to cause a slightly greater rate of sedation compared with other agents.[46]

Choice of agent should be based on individual responses in both efficacy and adverse-effect profile.

First-generation antihistamines and doxepin, a tricyclic antidepressant and an antihistamine, are also used in the treatment of acute urticaria. Although efficacious, their use is often limited by adverse effects, particularly sedation.[50][51] Choice of agent is dictated by individual variations in response in both efficacy and adverse-effect profile.

Primary options

loratadine: 10 mg orally once daily

OR

desloratadine: 5 mg orally once daily

OR

cetirizine: 10 mg orally once daily

OR

levocetirizine: 5 mg orally once daily

OR

fexofenadine: 180 mg orally once daily

Secondary options

diphenhydramine: 25-50 mg orally every 4-6 hours when required

More

OR

hydroxyzine: 25 mg orally every 6-8 hours when required

More

OR

chlorpheniramine: 4 mg orally every 4-6 hours when required

More

OR

doxepin: 10-100 mg orally once daily at bedtime when required

More

Consider – systemic corticosteroid

Back
ACUTE
|
acute urticaria ± angioedema
|
without airway involvement
Consider – 

systemic corticosteroid

Treatment recommended for SOME patients in selected patient group

If an episode of urticaria is severe, a short course of corticosteroids can be considered in addition to antihistamines. However, the addition of prednisone to an antihistamine failed to improve symptomatic and clinical response of acute urticaria compared to antihistamine alone in one randomized controlled study.[41] The use of systemic corticosteroids is limited by their adverse effects. It is imperative that all efforts are made to treat patients with other agents first. Topical corticosteroids have no role in the management of urticaria.

Primary options

prednisone: 0.5 to 1 mg/kg/day orally given in 1-2 divided doses for 5-7 days

Consider – epinephrine (adrenaline)

Back
ACUTE
|
acute urticaria ± angioedema
|
without airway involvement
Consider – 

epinephrine (adrenaline)

Treatment recommended for SOME patients in selected patient group

If there is extensive angioedema of the torso or limbs, epinephrine may be indicated to bring it under control.

Beta-blockers can interfere with the action of epinephrine, and discontinuing this drug in patients with urticaria and angioedema can be considered if comorbid conditions allow. However, for most medical indications, the risk of stopping or changing the drug may exceed the risk of more severe anaphylaxis if the drug is continued, particularly in patients with insect sting anaphylaxis.[28]

All patients with a history of urticaria associated with angioedema should be prescribed two self-injectable epinephrine pens and instructed on their use.[27] If epinephrine is required to treat an episode, the patient should be instructed to seek medical care swiftly, unless they experience prompt, complete, and durable response to treatment.[28]

Primary options

epinephrine (adrenaline): consult local protocol for guidance on dose

hereditary angioedema

1st line – airway protection

Back
ACUTE
|
hereditary angioedema
|
with airway involvement
1st line – 

airway protection

The status of the airway should be assessed and closely monitored in all patients with angioedema, and all necessary steps must be taken to ensure the airway is always secured. Consultation with an anesthesiologist may be necessary.

If available, flexible fiberoptic laryngoscopy can rapidly determine the extent of involvement of the base of the tongue or the larynx. This can determine the most appropriate airway management strategy.[26]

Although epinephrine (adrenaline), antihistamines, and systemic corticosteroids have no proven efficacy in hereditary angioedema, they may be administered to patients if there is doubt over the type of angioedema involved. Treatment of angioedema of the neck, face, tongue, or lips is with an intravenous antihistamine; administration of an intravenous corticosteroid may be considered. If angioedema is elsewhere on the body, oral antihistamines may be used initially, with oral corticosteroids and epinephrine as adjuncts if angioedema is particularly severe. See patient group (acute urticaria ± angioedema) for more detail.

Plus – C1 esterase inhibitor or ecallantide or icatibant

Back
ACUTE
|
hereditary angioedema
|
with airway involvement
Plus – 

C1 esterase inhibitor or ecallantide or icatibant

Treatment recommended for ALL patients in selected patient group

C1 esterase inhibitor concentrates (plasma-derived or recombinant), plasma kallikrein inhibitors (e.g., ecallantide), and bradykinin B2 receptor antagonists (e.g., icatibant) are effective in curbing acute attacks.[71][72][73][74]

All three drug classes have been approved by the Food and Drug Administration (FDA) for use in acute attacks.

Primary options

C1 esterase inhibitor (human): consult specialist for guidance on dose

OR

C1 esterase inhibitor (recombinant): consult specialist for guidance on dose

OR

ecallantide: consult specialist for guidance on dose

OR

icatibant: consult specialist for guidance on dose

2nd line – fresh frozen plasma

Back
ACUTE
|
hereditary angioedema
|
with airway involvement
2nd line – 

fresh frozen plasma

Fresh frozen plasma (FFP) may be considered if other therapies are not readily available.[75] Its use, however, is controversial because FFP contains complement proteins that can theoretically worsen an attack.

1st line – C1 esterase inhibitor or ecallantide or icatibant

Back
ACUTE
|
hereditary angioedema
|
without airway involvement
1st line – 

C1 esterase inhibitor or ecallantide or icatibant

C1 esterase inhibitor concentrates (plasma-derived and recombinant), plasma kallikrein inhibitors (e.g., ecallantide), and bradykinin B2 receptor antagonists (e.g., icatibant) are effective in curbing acute attacks.[71][72][73][74]

All three drug classes have been approved by the Food and Drug Administration (FDA) for use in acute attacks.

Although epinephrine (adrenaline), antihistamines, and systemic corticosteroids have no proven efficacy in hereditary angioedema, they may be administered to patients if there is doubt over the type of angioedema involved. See patient group (acute urticaria ± angioedema) for more detail.

Depending on the areas involved, symptomatic treatment may be required. For example, extremity swelling can be disabling and may require therapy with analgesics. Gastrointestinal involvement may require antiemetics.

Primary options

C1 esterase inhibitor (human): consult specialist for guidance on dose

OR

C1 esterase inhibitor (recombinant): consult specialist for guidance on dose

OR

ecallantide: consult specialist for guidance on dose

OR

icatibant: consult specialist for guidance on dose

2nd line – fresh frozen plasma

Back
ACUTE
|
hereditary angioedema
|
without airway involvement
2nd line – 

fresh frozen plasma

Fresh frozen plasma (FFP) may be considered if other therapies are not readily available.[75] Its use, however, is controversial because FFP contains complement proteins that can theoretically worsen an attack.

1st line – C1 esterase inhibitor

Back
ACUTE
|
hereditary angioedema
|
undergoing invasive medical procedures
1st line – 

C1 esterase inhibitor

Individuals with hereditary angioedema are particularly susceptible to attacks with certain triggers, such as invasive medical procedures, (e.g., extensive dental work). Prior to these events, short-term prophylaxis is recommended with plasma-derived C1 esterase inhibitor concentrate.​[38]

Primary options

C1 esterase inhibitor (human): consult specialist for guidance on dose

ONGOING

chronic urticaria ± angioedema

1st line – trigger identification and avoidance

Back
ONGOING
|
chronic urticaria ± angioedema
1st line – 

trigger identification and avoidance

Management should include the identification and avoidance of known triggers wherever possible. This may be particularly important with inducible urticaria.

Although the mechanism is unclear, psychosocial stress may play a role in patients with chronic urticaria.[42] Patients are encouraged and educated on how to manage their stresses in the hope of better controlling symptoms of the disease.

Plus – treatment of underlying illnesses

Back
ONGOING
|
chronic urticaria ± angioedema
Plus – 

treatment of underlying illnesses

Treatment recommended for ALL patients in selected patient group

Management of any other underlying illness should be optimized. Although underlying conditions do not cause urticaria directly, they are generally felt to play a role in exacerbating the disease and making symptomatic management more difficult.

Plus – antihistamine

Back
ONGOING
|
chronic urticaria ± angioedema
Plus – 

antihistamine

Treatment recommended for ALL patients in selected patient group

Second-generation, nonsedating antihistamines are the mainstay of therapy in chronic urticaria.[37] Examples of this class of drug include loratadine, desloratadine, cetirizine, levocetirizine, and fexofenadine. It should be stressed to patients that antihistamines have their greatest efficacy if taken prophylactically, rather than reactively after lesions develop.

Second-generation antihistamines have a good safety profile and can be taken for several years continously.[1] They cross the blood-brain barrier to a lesser extent than first-generation antihistamines and may be less likely to lead to sedation and impaired cognitive function.[44][45] Cetirizine has been reported to cause a slightly greater rate of sedation compared with other agents.[46]

Choice of agent should be based on individual responses in both efficacy and adverse-effect profile.

There is some evidence to suggest that higher than typical doses of desloratadine and levocetirizine are more efficacious than typical doses.[47][48][49]

If symptoms are not adequately controlled by second-generation antihistamines, addition of a night-time dose of a first-generation antihistamine or doxepin, a tricyclic antidepressant, should be considered.[17]

Although efficacious, their use is often limited by adverse effects, particularly sedation.[50][51] Choice of agent is dictated by individual variations in response in both efficacy and adverse-effect profile.

Primary options

loratadine: 10 mg orally once daily

OR

desloratadine: 5 mg orally once daily

OR

cetirizine: 10 mg orally once daily

OR

levocetirizine: 5 mg orally once daily

OR

fexofenadine: 180 mg orally once daily

Secondary options

diphenhydramine: 25-50 mg orally every 4-6 hours when required

OR

hydroxyzine: 25 mg orally every 6-8 hours when required

OR

chlorpheniramine: 4 mg orally every 4-6 hours when required

OR

doxepin: 10-100 mg orally once daily at bedtime when required

Consider – H2 antagonist

Back
ONGOING
|
chronic urticaria ± angioedema
Consider – 

H2 antagonist

Treatment recommended for SOME patients in selected patient group

Although these agents have no role as monotherapy, they may provide a modest amount of additional benefit to therapy in combination with full-dose antihistamines.[52][53]

Famotidine has fewer drug interactions compared with cimetidine and is generally a safer choice.

Once urticaria is controlled, H2 antagonists should be discontinued before attempting to discontinue the antihistamine.

Primary options

famotidine: 20-40 mg orally once or twice daily

Secondary options

cimetidine: 200-800 mg orally twice daily

Consider – systemic corticosteroid

Back
ONGOING
|
chronic urticaria ± angioedema
Consider – 

systemic corticosteroid

Treatment recommended for SOME patients in selected patient group

Short courses of systemic corticosteroids may be necessary for some patients to achieve symptom control during an exacerbation. However, the use of systemic corticosteroids is limited by their adverse effects. It is imperative that all efforts are made to treat patients with other agents first.

Topical corticosteroids have no role in the management of urticaria.

Primary options

prednisone: 0.5 to 1 mg/kg/day orally given in 1-2 divided doses for 5-7 days

Consider – leukotriene receptor antagonist

Back
ONGOING
|
chronic urticaria ± angioedema
Consider – 

leukotriene receptor antagonist

Treatment recommended for SOME patients in selected patient group

These agents are used in addition to full-dose antihistamines, although their additional effect is marginal.[57][58] They have no role as monotherapy for this condition.

Leukotriene receptor antagonists in combination with antihistamines may be effective in patients with a history of adverse reactions to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs).[59][60]

Once urticaria is controlled, leukotriene receptor antagonists should be discontinued before attempting to discontinue the antihistamine regimen.

Montelukast may be associated with adverse neuropsychiatric events (e.g., mood changes, aggression, depression, and suicide, among others).[61] The risks and benefits should be carefully considered when prescribing this drug.

Primary options

zafirlukast: 20 mg orally twice daily

OR

montelukast: 10 mg orally daily

2nd line – omalizumab

Back
ONGOING
|
chronic urticaria ± angioedema
2nd line – 

omalizumab

Omalizumab is effective in chronic inducible and chronic spontaneous urticaria, can be used long term, and is effective at treating relapses after discontinuation.[62][63][64][65] It is recommended for use in patients who have persistent symptoms despite maximum antihistamine therapy.[1][35]

Primary options

omalizumab: consult specialist for guidance on dose

Consider – antihistamine

Back
ONGOING
|
chronic urticaria ± angioedema
Consider – 

antihistamine

Treatment recommended for SOME patients in selected patient group

Second-generation, nonsedating antihistamines are the mainstay of therapy in chronic urticaria.[37] Examples of this class of drug include loratadine, desloratadine, cetirizine, levocetirizine, and fexofenadine. It should be stressed to patients that antihistamines have their greatest efficacy if taken prophylactically, rather than reactively after lesions develop.

Second-generation antihistamines have a good safety profile and can be taken for several years continously.[1] They cross the blood-brain barrier to a lesser extent than first-generation antihistamines and may be less likely to lead to sedation and impaired cognitive function.[44][45] Cetirizine has been reported to cause a slightly greater rate of sedation compared with other agents.[46]

Choice of agent should be based on individual responses in both efficacy and adverse-effect profile.

There is some evidence to suggest that higher than typical doses of desloratadine and levocetirizine are more efficacious than typical doses.[47][48][49]

First-generation antihistamines and doxepin, a tricyclic antidepressant and an antihistamine, are also used in the treatment of chronic urticaria. Although efficacious, their use is often limited by adverse effects, particularly sedation.[50][51] Choice of agent is dictated by individual variations in response in both efficacy and adverse-effect profile.

Primary options

loratadine: 10 mg orally once daily

OR

desloratadine: 5 mg orally once daily

OR

cetirizine: 10 mg orally once daily

OR

levocetirizine: 5 mg orally once daily

OR

fexofenadine: 180 mg orally once daily

Secondary options

diphenhydramine: 25-50 mg orally every 4-6 hours when required

OR

hydroxyzine: 25 mg orally every 6-8 hours when required

OR

chlorpheniramine: 4 mg orally every 4-6 hours when required

OR

doxepin: 10-100 mg orally once daily at bedtime when required

Consider – systemic corticosteroid

Back
ONGOING
|
chronic urticaria ± angioedema
Consider – 

systemic corticosteroid

Treatment recommended for SOME patients in selected patient group

Short courses of systemic corticosteroids may be necessary for some patients to achieve symptom control during an exacerbation. However, the use of systemic corticosteroids is limited by their adverse effects. It is imperative that all efforts are made to treat patients with other agents first.

Topical corticosteroids have no role in the management of urticaria.

Primary options

prednisone: 0.5 to 1 mg/kg/day orally given in 1-2 divided doses for 5-7 days

3rd line – cyclosporine

Back
ONGOING
|
chronic urticaria ± angioedema
3rd line – 

cyclosporine

Cyclosporine prevents the release of histamine from mast cells.[66] Randomized controlled trials have demonstrated that it is an effective add-on therapy for patients with chronic urticaria who do not respond to maximum antihistamine therapy.[67][68][69] It is not licensed for urticaria and is associated with dose-dependent adverse effects.[69] International guidelines recommend that omalizumab is used before cyclosporine.[1][35]

Primary options

cyclosporine modified: consult specialist for guidance on dose

Consider – antihistamine

Back
ONGOING
|
chronic urticaria ± angioedema
Consider – 

antihistamine

Treatment recommended for SOME patients in selected patient group

Second-generation, nonsedating antihistamines are the mainstay of therapy in chronic urticaria.[37] Examples of this class of drug include loratadine, desloratadine, cetirizine, levocetirizine, and fexofenadine. It should be stressed to patients that antihistamines have their greatest efficacy if taken prophylactically, rather than reactively after lesions develop.

Second-generation antihistamines have a good safety profile and can be taken for several years continously.[1] They cross the blood-brain barrier to a lesser extent than first-generation antihistamines and may be less likely to lead to sedation and impaired cognitive function.[44][45] Cetirizine has been reported to cause a slightly greater rate of sedation compared with other agents.[46]

Choice of agent should be based on individual responses in both efficacy and adverse-effect profile.

There is some evidence to suggest that higher than typical doses of desloratadine and levocetirizine are more efficacious than typical doses.[47][48][49]

First-generation antihistamines and doxepin, a tricyclic antidepressant and an antihistamine, are also used in the treatment of chronic urticaria. Although efficacious, their use is often limited by adverse effects, particularly sedation.[50][51] Choice of agent is dictated by individual variations in response in both efficacy and adverse-effect profile.

Primary options

loratadine: 10 mg orally once daily

OR

desloratadine: 5 mg orally once daily

OR

cetirizine: 10 mg orally once daily

OR

levocetirizine: 5 mg orally once daily

OR

fexofenadine: 180 mg orally once daily

Secondary options

diphenhydramine: 25-50 mg orally every 4-6 hours when required

OR

hydroxyzine: 25 mg orally every 6-8 hours when required

OR

chlorpheniramine: 4 mg orally every 4-6 hours when required

OR

doxepin: 10-100 mg orally once daily at bedtime when required

Consider – systemic corticosteroid

Back
ONGOING
|
chronic urticaria ± angioedema
Consider – 

systemic corticosteroid

Treatment recommended for SOME patients in selected patient group

A short to moderate course of systemic corticosteroids is commonly required on the initiation of alternative agents, in hopes of controlling ongoing lesions.

Systemic corticosteroids should be promptly tapered to minimize adverse effects once control of urticaria is achieved with corticosteroid-sparing immunomodulatory agents.

Topical corticosteroids have no role in the management of urticaria.

Primary options

prednisone: 0.5 to 1 mg/kg/day orally given in 1-2 divided doses for 5-7 days

drug-induced angioedema without urticaria

1st line – trigger identification and avoidance

Back
ONGOING
|
drug-induced angioedema without urticaria
1st line – 

trigger identification and avoidance

Central to the management of drug-induced angioedema without urticaria is the identification and cessation of the drug responsible. Meantime, patients receive antihistamines (and sometimes corticosteroids) for symptomatic relief. Treatment can be stopped once symptoms resolve, so long as the drug responsible is avoided. If ongoing therapy is needed for a comorbid condition, a drug from a different class should be prescribed.

idiopathic angioedema without urticaria

1st line – antihistamine

Back
ONGOING
|
idiopathic angioedema without urticaria
1st line – 

antihistamine

Second-generation, nonsedating antihistamines are the mainstay of therapy in chronic idiopathic angioedema.[37] Examples of this class of drug include loratadine, desloratadine, cetirizine, levocetirizine, and fexofenadine. It should be stressed to patients that antihistamines have their greatest efficacy if taken prophylactically, rather than reactively after lesions develop.

Second-generation antihistamines have a good safety profile and can be taken for several years continously.[1] They cross the blood-brain barrier to a lesser extent than first-generation antihistamines and may be less likely to lead to sedation and impaired cognitive function.[44][45] Cetirizine has been reported to cause a slightly greater rate of sedation compared with other agents.[46]

Choice of agent should be based on individual responses in both efficacy and adverse-effect profile.

There is some evidence to suggest that higher than typical doses of desloratadine and levocetirizine are more efficacious than typical doses.[47][48][49]

First-generation antihistamines and doxepin, a tricyclic antidepressant and an antihistamine, are also used in the treatment of chronic idiopathic angioedema. Although efficacious, their use is often limited by adverse effects, particularly sedation.[50][51] Choice of agent is dictated by individual variations in response in both efficacy and adverse-effect profile.

Primary options

loratadine: 10 mg orally once daily

OR

desloratadine: 5 mg orally once daily

OR

cetirizine: 10 mg orally once daily

OR

levocetirizine: 5 mg orally once daily

OR

fexofenadine: 180 mg orally once daily

Secondary options

diphenhydramine: 25-50 mg orally every 4-6 hours when required

OR

hydroxyzine: 25 mg orally every 6-8 hours when required

OR

chlorpheniramine: 4 mg orally every 4-6 hours when required

OR

doxepin: 10-100 mg orally once daily at bedtime when required

Plus – trigger identification and avoidance

Back
ONGOING
|
idiopathic angioedema without urticaria
Plus – 

trigger identification and avoidance

Treatment recommended for ALL patients in selected patient group

Triggers cannot be identified in most cases of idiopathic angioedema without urticaria. However, if a trigger is identified, the patient should be counseled on how to avoid it.

Plus – H2 antagonists

Back
ONGOING
|
idiopathic angioedema without urticaria
Plus – 

H2 antagonists

Treatment recommended for ALL patients in selected patient group

Although these agents have no role as monotherapy, they may provide a modest amount of additional benefit to therapy in combination with full-dose antihistamines.[52][53]

Once angioedema is controlled, H2 antagonists should be discontinued before attempting to discontinue the antihistamine regimen.

Primary options

famotidine: 20-40 mg orally once or twice daily

Secondary options

cimetidine: 200-800 mg orally twice daily

Consider – systemic corticosteroid

Back
ONGOING
|
idiopathic angioedema without urticaria
Consider – 

systemic corticosteroid

Treatment recommended for SOME patients in selected patient group

Short courses of systemic corticosteroids may be necessary for some patients to achieve symptom control during an episode of idiopathic angioedema. However, the use of systemic corticosteroids is limited by their adverse effects. It is imperative that all efforts are made to treat patients with other agents first.

Primary options

prednisone: 0.5 to 1 mg/kg/day orally given in 1-2 divided doses for 5-7 days

Consider – leukotriene receptor antagonist

Back
ONGOING
|
idiopathic angioedema without urticaria
Consider – 

leukotriene receptor antagonist

Treatment recommended for SOME patients in selected patient group

These agents are adjunctive therapy, used in addition to full-dose antihistamines, although their additional effect is marginal.[57][58] They have no role as monotherapy for this condition.

Once angioedema is controlled, leukotriene receptor antagonists should be discontinued before attempting to discontinue the antihistamine regimen.

Montelukast may be associated with adverse neuropsychiatric events (e.g., mood changes, aggression, depression, and suicide, among others).[61] The risks and benefits should be carefully considered when prescribing this drug.

Primary options

zafirlukast: 20 mg orally twice daily

OR

montelukast: 10 mg orally daily

2nd line – alternate anti-inflammatory or immunomodulating agents

Back
ONGOING
|
idiopathic angioedema without urticaria
2nd line – 

alternate anti-inflammatory or immunomodulating agents

If acquired angioedema proves refractory to treatment with maximal doses of antihistamines and leukotriene receptor antagonists, specialists may use one of a number of alternate anti-inflammatory and immunomodulatory agents, including omalizumab, cyclosporine, hydroxychloroquine, sulfasalazine, colchicine, dapsone, azathioprine, methotrexate, and intravenous immune globulin (IVIG).[33][62][63][70] Although case reports suggest beneficial effects for all of these agents, only cyclosporine and omalizumab have been shown to be effective in double-blind, placebo-controlled studies.[62][63][67][68][81] In patients with refractory urticaria, omalizumab has the most robust safety and efficacy data.[82] The use of anti-inflammatory and immunomodulatory agents is limited by their adverse-effect profiles and/or cost, and these issues must be carefully weighed against potential benefits of therapy.

Primary options

omalizumab: consult specialist for guidance on dose

OR

cyclosporine modified: consult specialist for guidance on dose

OR

hydroxychloroquine sulfate: consult specialist for guidance on dose

OR

sulfasalazine: consult specialist for guidance on dose

OR

colchicine: consult specialist for guidance on dose

OR

dapsone: consult specialist for guidance on dose

OR

azathioprine: consult specialist for guidance on dose

OR

methotrexate: consult specialist for guidance on dose

OR

mycophenolate mofetil: consult specialist for guidance on dose

OR

immune globulin (human): consult specialist for guidance on dose

Consider – systemic corticosteroid

Back
ONGOING
|
idiopathic angioedema without urticaria
Consider – 

systemic corticosteroid

Treatment recommended for SOME patients in selected patient group

Short courses of systemic corticosteroids may be necessary for some patients to achieve symptom control during an episode of idiopathic angioedema. However, the use of systemic corticosteroids is limited by their adverse effects. It is imperative that all efforts are made to treat patients with other agents first.

Topical corticosteroids have no role in the management of idiopathic angioedema.

Primary options

prednisone: 0.5 to 1 mg/kg/day orally given in 1-2 divided doses for 5-7 days

hereditary angioedema

1st line – C1 esterase inhibitor

Back
ONGOING
|
hereditary angioedema
1st line – 

C1 esterase inhibitor

Plasma-derived C1 esterase inhibitor is the preferred long-term prophylaxis treatment.[38]​ Intravenous plasma-derived C1 esterase inhibitor, compared to placebo, significantly reduced the number of attacks over a 12-week period in one randomized controlled trial. When attacks occurred, the severity and the duration were reduced.[71] Subcutaneous C1 esterase inhibitor, compared to placebo, significantly reduced the rate of attacks and the need for rescue therapy in one randomized controlled trial.[79]

Primary options

C1 esterase inhibitor (human): consult specialist for guidance on dose

2nd line – attenuated androgens

Back
ONGOING
|
hereditary angioedema
2nd line – 

attenuated androgens

Attenuated androgens (e.g., danazol) are the second-line option for long-term prophylaxis and have been used for prophylaxis for many years.[38]​​[75]

Androgens are thought to work by increasing hepatic production of C1 esterase inhibitor. Danazol reduces the frequency of acute attacks by 83%. However, dose-dependent adverse effects are common and include weight gain, virilization, menstrual irregularities, headache, depression, and/or liver adenomas.[80]

Primary options

danazol: consult specialist for guidance on dose

3rd line – tranexamic acid

Back
ONGOING
|
hereditary angioedema
3rd line – 

tranexamic acid

Tranexamic acid is primarily used when C1 esterase inhibitor concentrate is not available and attenuated androgens are contraindicated.[80] Tranexamic acid is less efficacious than C1 esterase inhibitor concentrate and attenuated androgens.

Primary options

tranexamic acid: consult specialist for guidance on dose

back arrow

Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer