Approach Considerations
Identify the etiology of the acute urticaria if possible. If an inciting agent can be identified, instruct the patient to avoid it. The major goal is to control the severity of acute urticaria lesions until the process resolves over 4-6 weeks.
Inpatient therapy may be required rarely if the urticaria is severe and does not respond to antihistamine therapy, or if the patient's condition progresses to laryngeal angioedema and/or anaphylactic shock.
Pharmacologic Therapies
As advised in the 2022 EAACI/GA2LEN/EDF/WAO management guideline, due to the fluctuating nature of acute urticaria and the chance that spontaneous remission can occur at any time, continued or alternative drug treatment should be reevaluated every 3-6 months. [5]
In children, if a case is confirmed to involve streptococcal infection, penicillin G should be given either orally or by injection, depending on the patient’s age and circumstances. [18]
H1 antagonists (first-generation antihistamines)
Antihistamines are the primary agents used to treat urticaria. [17] The older, first-generation H1 antagonists (eg, diphenhydramine, hydroxyzine) are effective in reducing the lesions and pruritus but can produce a number of adverse effects, such as drowsiness, anticholinergic effects, and cognitive effects, which may continue until the next day. [49] Thus, these agents can be useful if administered at bedtime.
According to the EAACI/GA2LEN/EDF/WAO management guideline, first-generation sedating antihistamines should no longer be used as the first choice therapy except where second-generation antihistamines are not available or where their benefits outweigh their risks. The guideline advises against using older, sedating first-generation antihistamines in patients with urticaria who have no special indications. [5]
Any patient who is taking a medication that has potential sedative effects should be cautioned about driving and operating heavy machinery. Commonly used first-generation agents include diphenhydramine, hydroxyzine, chlorpheniramine, and cyproheptadine.
Most patients with urticaria can be treated with oral (PO) H1 antihistamines. Modern second-generation antihistamines are the first choice. Increasing the dose up to fourfold is permitted in patients who do not respond sufficiently to the standard dosing. For refractory cases, use a combination of H1 and H2 antihistamines.
The experimental evidence comparing the various possible regimens and rates of adverse effects in the long term is still minimal.
H1 antagonists (second-generation antihistamines)
The newer second-generation antihistamines are nonsedating in most patients, with very few adverse effects reported (cetirizine can cause drowsiness in up to 10% of patients). [50, 5] Therefore, many specialists prefer the use of these agents for chronic urticaria, with first-generation agents reserved for acute or refractory cases. Commonly used second-generation antihistamines are cetirizine, levocetirizine, desloratadine, loratadine, and fexofenadine. Four times the approved doses can be used if needed in cases where standard dose is insufficient to control the symptom.
H2 antagonists
These drugs are usually used to decrease gastric acid secretion. H2 antagonists are not effective when used as single agents for urticaria; however, the combination of an H1 antagonist with an H2 antagonist has been shown to be more effective than an H1 antagonist alone. [51, 52] Any of the H2 blockers can be used. Two of the most commonly used agents are ranitidine and cimetidine.
Corticosteroids
In some instances of acute or chronic urticaria, antihistamines may fail, even at high doses, or adverse effects may be problematic. In addition, mediators other than histamine may be involved. In such situations, corticosteroids can be highly effective. Corticosteroids may also be used in urticarial vasculitis, which usually does not respond to antihistamines.
The EAACI/GA2LEN/EDF/WAO management guideline recommends the use of corticosteroids only in severely affected patients. [5]
A short course of an oral corticosteroid (administered daily for 5-7 d, with or without a taper) or a single dose of a long-acting injectable steroid is not usually associated with long-term sequelae and can be helpful when used for an acute episode of urticaria nonresponsive to antihistamines. [30] Examples of corticosteroid preparations include prednisolone, methylprednisolone, and prednisone
Because of adverse effects of chronic or recurrent use of systemic corticosteroids, the long-term use of these agents should be avoided, when possible. If urticaria is severe and cannot be safely controlled with other medications, low-dose therapy and/or alternate-day therapy can be considered.
Corticosteroids stabilize mast cell membranes and inhibit further histamine release, as well as reduce the inflammatory effect of histamine and other mediators. The efficacy of corticosteroids in acute urticaria remains controversial. In one study, acute urticaria improved more quickly in the group treated with prednisone than in the group treated with placebo. [53]
In adults, 40-60 mg daily of prednisone for 5 days is a reasonable therapeutic regimen. In children, the treatment is 1 mg/kg/d for 5 days. Tapering of the corticosteroid dose is not necessary in most cases of acute urticaria. [6]
Sympathomimetic agents
Sympathomimetic agents cause vasoconstriction and reduction in vascular dilation, which contributes to urticaria formation.
The efficacy of epinephrine in acute urticaria is controversial. [5] If angioedema is present with urticaria, epinephrine should be administered via the IM route. Remember that converting enzyme inhibitor (ACEI)–induced angioedema usually does not respond to epinephrine or most other common therapies, as it is not an IgE-mediated process. [54]
Immunomodulatory and anti-inflammatory therapy
Cyclosporine has been shown to be effective in 2 double-blind placebo-controlled studies. [55, 56] IV gammaglobulin and plasmapheresis have been described as useful in a limited number of case studies. [57, 58] These therapies can be a consideration in severe urticaria, particularly of the autoimmune type that is unresponsive to medications, but such treatment is usually only initiated by specialists with considerable expertise in urticaria.
Colchicine and dapsone have also been reported to be useful for refractory urticaria and urticarial vasculitis, [59, 60] perhaps because of their ability to modulate polymorphonuclear lymphocyte (PMN) function. PMNs and a mixed infiltrate can be present in some urticarial lesions, particularly urticaria that is severe or refractory to antihistamine treatment.
Some reports describe the effectiveness of the antileukotriene agents in urticaria, [61, 62] but extensive clinical trials have not been performed, so their usefulness is still questionable. Clinical trials might in the future support the theory that the antileukotriene agents can provide a synergistic response when used in conjunction with antihistamines.
Omalizumab (monoclonal antibody to IgE) is a recombinant biologic molecule effective for chronic urticaria based on two large positive phase III studies and is currently FDA approved for treatment of chronic urticaria. Patients can be treated with 150 or 300 mg subcutaneously every four weeks. [63] The role in acute urticaria has not been determined and further studies are needed.
Because the use of the aforementioned agents is not widespread, details of dosage and administration are not provided, but references are listed in the bibliography. The use of corticosteroids is more common and is discussed in Medication.
Tricyclic antidepressants
Tricyclic antidepressants (TCAs) are a complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects. TCAs block the active reuptake of norepinephrine and serotonin; and some (eg, doxepin) have antihistamine effects, blocking both the H1 and H2 receptors, and have been used in the treatment of allergic reactions, especially urticaria.
Nonpharmacologic Therapies
Food and symptom diaries
Suspected food allergies can be confirmed or disproved with the use of food diaries. A food or symptom diary for a fixed duration (eg, 2-4 wk) may be helpful. Note all activities in which the patient was involved for 6-8 hours before the onset of urticaria. Cases have been reported in which a food or activity (such as jogging) by itself results in no symptoms but when combined (eg, eating a shrimp cocktail and then jogging) may result in urticaria with or without progression to anaphylaxis. Excessive or prolonged use of a food or symptom diary is unlikely to be of benefit.
Avoidance
If a trigger can be identified, avoidance is the most effective form of management. This would include any food, medication, physical agent, or other factor that triggers the urticaria.
Aspirin, [64, 65] NSAIDs, [66] opiates, and alcohol have been reported to be nonspecific triggers of urticaria and might lower the threshold for urticaria in selected patients. Therefore, some specialists advise all patients with urticaria to avoid these agents. However, little experimental evidence is available to support this recommendation.
Removing offending ectoparasites can prevent papular urticaria, and insect repellent may lessen the chance of bites or stings from offending insects. Desensitization strategies are not recommended, except for stinging insect venoms.
Although the need for cold cardiopulmonary bypass surgery in patients with cold-induced urticaria is uncommon, one study reported success using an anti-inflammatory regimen before surgery and during recovery to prevent a systemic reaction of urticaria. [67]
Emergency Care and Complications
Acute urticaria is a common disorder that often prompts patients to seek treatment in the emergency department (ED). In fact, acute urticaria is the most common cutaneous disease treated in the ED. [68] Determining whether urticaria is part of an anaphylactic reaction is important. If an anaphylactic reaction occurs, the patient needs prompt treatment and careful monitoring
The management of urticaria in the ED is straightforward and typically is not altered by underlying etiology. The mainstay is avoidance of further exposure to the antigen and antihistamines.
Most cases of acute urticaria respond to pharmacotherapy (see Medication). Modern second-generation antihistamines are effective as first-line treatment. [5] Diphenhydramine (25 mg IV or 50 mg IM or PO) or hydroxyzine (50 mg IM or PO) can be administered also and have benefit in helping patients sleep at nights. [5]
If any features of anaphylaxis (eg, hypotension, respiratory distress, stridor, gastrointestinal distress, swallowing problems, joint swelling, joint pain) are present, immediate medical intervention should occur.
Acute urticaria may progress to life-threatening angioedema and/or anaphylactic shock in a very short time, although it usually presents as rapid-onset shock with no urticaria or angioedema. [69]
If associated angioedema is present, especially if laryngeal angioedema (eg, hoarseness, stridor) is suspected, prehospital administration of 0.3-0.5 mg of intramuscular [IM] epinephrine may be warranted. If associated bronchospasm is present, prehospital nebulized albuterol may be warranted.
Other measures may be appropriate, such as continuous electrocardiography (ECG); blood pressure and pulse oximetry monitoring; administering IV crystalloids if the patient is hypotensive; and administering oxygen. If the patient has angioedema that is treated successfully in the ED, the patient should be sent home with an EpiPen prescription. The patient should be instructed to keep the EpiPen with him or her at all times and to use it if swelling of the lips, tongue, or face develops or if his or her voice becomes acutely hoarse.
Diet
Dietary modification is only necessary if food allergy or food additive hypersensitivity has been established. If such hypersensitivity is identified, the patient should avoid the offending food or food additive.
Activity
If the patient has physical urticaria, activity should be carefully monitored, depending on the trigger (eg, cold or hot temperatures, exposure to sun or water, pressure or vibration).
Individuals with cold urticaria must be particularly cautious and not immerse themselves suddenly in cold water. Patients should avoid swimming in lakes, streams, or oceans.
Consultations
A primary care provider can manage most cases of acute urticaria. If a trigger is easily identified and avoidance leads to resolution, then referral is not necessary. If an allergic trigger is suspected but not easily identified, then referral to an allergy specialist is warranted. [70] Similarly, if avoidance of a trigger does not lead to resolution or if the patient does not respond well to antihistamines, then referral to an allergist or dermatologist is warranted. [70]
Long-term Monitoring
Identify the etiology of the acute urticaria if possible. If an inciting agent can be identified, instruct the patient to avoid it. The major goal is to control the severity of acute urticaria lesions until the process resolves over 4-6 weeks.
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Urticaria associated with a drug reaction.
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Urticaria developed after bites from an imported fire ant.
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Local urticaria on a patient with latex allergy who was touched with a latex glove.
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Urticaria from drug reaction.
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Photograph of dermographism.
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Pressure urticaria (dermatographia) developed after strokes.
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Acute urticaria associated with dermatographism.
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Urticaria associated with acute group A beta-hemolytic streptococci infection.
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Acute urticaria in a toddler affecting the face. Likely cause is postviral syndrome.
