Timely transport to the emergency department (ED) for any patient with signs or symptoms of an allergic reaction, including urticaria, angioedema, or anaphylactic shock is essential. Acute urticaria may progress to life-threatening angioedema and/or anaphylactic shock in a very short period, although it usually presents as rapid-onset shock with no urticaria or angioedema. (See Anaphylaxis.)
If associated angioedema is present, especially if laryngeal angioedema (eg, hoarseness, stridor) is suspected, prehospital administration of 0.3-0.5 mg of intramuscular 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 intravenous (IV) crystalloids if the patient is hypotensive; and administering oxygen. Diphenhydramine (25 mg IV or 50 mg intramuscularly [IM] or orally [PO]) or hydroxyzine (50 mg IM or PO) should be administered if they are available.
Emergency department care
The management of urticaria is straightforward and typically is not altered by underlying etiology. The mainstay is avoidance of further exposure to the antigen. Pharmacologic treatment also plays a role. In selecting medications for urticaria, it is important to avoid prescribing those that may have significant drug-drug interactions (especially true with ranitidine and cimetidine, which are both inhibitors of the P450 enzyme system in the liver).
Antihistamines, primarily the older sedating H1 antihistamines, are the first line of therapy for urticaria. Most cases of simple acute urticaria can be treated with H1 antihistamines. These agents block the histamine response in sensory nerve endings and blood vessels through competitive inhibition of histamine at the H1 receptor, which mediates wheal and flare reactions, bronchial constriction, mucus secretion, smooth muscle contraction, and edema.
Diphenhydramine and hydroxyzine are the most commonly used H1-blocking antihistamines. They act more rapidly than the minimally sedating H1-blocking antihistamines (see below). These medications are potentially sedating, and the patient should not be allowed to drive within 6 hours of their administration.
H1-blocking antihistamines are effective in relieving the pruritus and rash of acute urticaria in most cases. Their effects are dose related, but higher doses may cause excessive sedation, as well as serious anticholinergic side effects, such as hypotension, central nervous system (CNS) depression, urinary retention, and cardiac arrhythmias.
Newer H1-blocking minimally sedating antihistamines are now available and include fexofenadine, loratadine, desloratadine, cetirizine, and levocetirizine. These are used primarily in the management of chronic urticaria rather than acute urticaria. However, if acute urticaria persists for more than 24-48 hours, the minimally sedating antihistamines should be prescribed, with supplementation with the sedating antihistamines if the pruritus and urticaria are refractory to the longer-acting, minimally sedating antihistamines.
In cases of severe or persistent urticaria, H2 antihistamines, such as cimetidine, famotidine, and ranitidine, may be added. H2 antihistamines are reversible, competitive blockers of histamine at H2 receptors, particularly those in gastric parietal cells. These H2 antagonists are highly selective, do not affect H1 receptors, and are not anticholinergic agents. They block the vasodilation mediated by the H2 receptors in blood vessels, possibly leading to less edema formation in urticaria.
H1 and H2 antihistamines are thought to have a synergistic effect and often result in a more rapid and complete resolution of urticaria than H1 antihistamines alone, especially if given simultaneously IV. The combination of H1 and H2 antagonists may be useful in acute urticaria as well as chronic idiopathic urticaria not responding to H1 antagonists alone.[24, 28] This combination in IV form also may be useful for itching and flushing in anaphylaxis, pruritus, urticaria, and contact dermatitis.
If a patient with chronic urticaria is refractory to nonsedating antihistamines, doses up to 4 times the recommended maximal dose may be effective. If maximum doses of nonsedating antihistamines are not effective, other therapies should be tried.[29, 30]
Tricyclic antidepressants are a complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects, and block the active reuptake of norepinephrine and serotonin. Some, such as doxepin, have antihistamine effects, blocking both the H1 and H2 receptors, and have been used in the treatment of allergic reactions, especially urticaria. Doxepin may be effective in refractory cases of urticaria in doses of 25-50 mg at bedtime or 10-25 mg 3-4 times a day.
Glucocorticoids stabilize mast cell membranes and inhibit further histamine release. They also reduce the inflammatory effect of histamine and other mediators. In particular, they decrease the inflammation associated with urticaria resistant to H1- and H2-receptor antihistamine therapy. They do not inhibit mast cell degranulation.
The efficacy of glucocorticoids in acute urticaria remains controversial. In one study, acute urticaria improved more quickly in a prednisone-treated group than in the placebo group. In adults, prednisone 40-60 mg/d for 5 days is a reasonable 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. In chronic urticaria, glucocorticoids are often effective, but they should be tapered to the lowest effective dose to prevent long-term complications.
The efficacy of epinephrine in acute urticaria is controversial. If angioedema is present with urticaria, 0.3-0.5 mg of epinephrine should be administered intramuscularly. Remember that ACE-inhibitor–induced angioedema usually does not respond to epinephrine or most other common therapies, since it is not an IgE-mediated process.
The use of methotrexate, colchicine, dapsone, indomethacin, and hydroxychloroquine may be effective in the management of vasculitic urticaria.
Chronic or recurrent urticaria
Refractory cases of chronic urticaria may improve with glucocorticosteroids. Chronic urticaria may benefit from treatment with doxepin. Because of its significant sedative properties, it should be given at bedtime. Topical therapy with 5% doxepin cream or capsaicin may also be used in refractory cases. Cyproheptadine may be useful to suppress recurrent cold urticaria.
One study showed that the combination of a leukotriene receptor antagonist and a nonsedating antihistamine was superior to the antihistamine alone in treating chronic idiopathic urticaria. Cyclosporine and omalizumab have been shown to be effective in cases of refractory chronic urticaria.[35, 6, 36]
Patients with chronic or recurrent urticaria should be referred to a dermatologist for further evaluation and management.
Consultation with or referral to a dermatologist, allergist, immunologist, or rheumatologist may be appropriate in selected cases, particularly in cases of complicated, recurrent, refractory, severe, or chronic urticaria. Dermatology referral is mandatory if vasculitic urticaria is suspected.
Further inpatient care
In general, patients with urticaria do not require further inpatient care unless their urticaria is severe and does not respond to antihistamine therapy or unless they progress to laryngeal angioedema and/or anaphylactic shock or have comorbidities that necessitate inpatient therapy.
Further outpatient care
Most patients with urticaria can be treated at home on H1 antihistamines (ie, diphenhydramine 50 mg q6h or hydroxyzine 50 mg q6h for 24-48 h) or, in refractory cases, use a combination of H1 and H2 antihistamines plus oral glucocorticoids.
If the patient has angioedema that is treated successfully in the ED, the patient should be sent home with an EpiPen prescription and told to keep it with him or her at all times and to use it if swelling of the lips, tongue, face develops or if his or her voice acutely become hoarse.
Consultation with or referral to a dermatologist, allergist, immunologist, or rheumatologist may be appropriate in cases of suspected urticarial vasculitis and in cases of chronic or recurrent urticaria.
Patients with urticaria should avoid any medication, food, or other allergen that has precipitated urticaria or other serious allergic reaction previously.