Urticaria

(Hives; Wheals)

ByJulia Benedetti, MD, Harvard Medical School
Reviewed/Revised Jan 2024
View Patient Education

Urticaria consists of migratory, well-circumscribed, erythematous, pruritic plaques on the skin.

Urticaria also may be accompanied by angioedema, which results from mast cell and basophil activation in the deeper dermis and subcutaneous tissues and manifests as edema of the face and lips, extremities, or genitals. Angioedema can occur in the bowel and manifest as colicky abdominal pain. Angioedema can be life-threatening if airway obstruction occurs because of laryngeal edema or tongue swelling.

(See also Evaluation of the Dermatologic Patient.)

Pathophysiology of Urticaria

Urticaria results from the release of histamine, bradykinin, kallikrein, and other vasoactive substances from mast cells and basophils in the superficial dermis, resulting in intradermal edema caused by capillary and venous vasodilation and occasionally caused by leukocyte infiltration.

The process can be immune mediated or nonimmune mediated.

Immune-mediated mast cell activation includes

  • Type I hypersensitivity reactions, in which allergen-bound IgE antibodies bind to high-affinity cell surface receptors on mast cells and basophils

  • Autoimmune disorders, in which antibodies to an IgE receptor functionally cross-link IgE receptors and cause mast cell degranulation

Nonimmune-mediated mast cell activation includes

  • Direct nonallergic activation of mast cells by certain medications or substances

  • Drug-induced cyclooxygenase inhibition that activates mast cells by poorly understood mechanisms

  • Activation by physical or emotional stimuli; mechanism is poorly understood but possibly involves the release of neuropeptides that interact with mast cells

Etiology of Urticaria

Urticaria is classified as acute (< 6 weeks) or chronic (> 6 weeks); acute cases (70%) are more common than chronic (30%).

Acute urticaria (see table Some Causes of Urticaria) most often results from

  • Type I hypersensitivity reactions

A presumptive trigger (eg, medication, food ingestion, insect bite or sting, infection) occasionally can be identified.

Chronic urticaria most often results from

  • Idiopathic causes

  • Autoimmune disorders

Chronic urticaria often lasts months to years, eventually resolving without a cause being found.

Table
Photos of Urticaria
Urticaria
Urticaria
Urticarial lesions (wheals or hives) are migratory, elevated, pruritic, reddish plaques caused by local dermal edema.

Photo provided by Thomas Habif, MD.

Cold-Induced Urticaria
Cold-Induced Urticaria
This photo shows a positive ice cube test in a patient with idiopathic cold-induced urticaria. This photo was taken 5 m... read more

© Springer Science+Business Media

Urticaria Pigmentosa (Thorax)
Urticaria Pigmentosa (Thorax)
Urticaria pigmentosa may manifest as erythematous plaque-like lesions on the skin.

© Springer Science+Business Media

Urticaria Pigmentosa (Leg)
Urticaria Pigmentosa (Leg)
Systemic mastocytosis can cause yellowish tan to reddish brown macules and papules.

© Springer Science+Business Media

Urticaria Pigmentosa (Child)
Urticaria Pigmentosa (Child)
This photo shows reddish brown macules on the back of a school-aged child.

© Springer Science+Business Media

Urticaria Pigmentosa (Infant)
Urticaria Pigmentosa (Infant)
The infant shown here has profuse papulonodular and plaque lesions of urticaria pigmentosa.

© Springer Science+Business Media

Solar Urticaria
Solar Urticaria
This photo shows solar urticaria in a woman who had been wearing a tank top. These hives appear within minutes of sun e... read more

© Springer Science+Business Media

Dermatographism
Dermatographism
Dermatographism, or skin-writing, may occur when the skin is lightly scratched and results in raised red lines.

© Springer Science+Business Media

Evaluation of Urticaria

Because there are no definitive diagnostic tests for urticaria, evaluation largely relies on history and physical examination.

History

History of present illness should include a detailed account of the individual episodes of urticaria, including distribution, size, and appearance of lesions; frequency of occurrence; duration of individual lesions; and any prior episodes. Activities and exposures during, immediately before, and within the past 24 hours of the appearance of urticaria should be noted. Clinicians specifically should ask about recent exercise; exposure to potential allergens (see table Some Causes of Urticaria), insects, or animals; new laundry detergent or soaps; new foods; recent infections; or recent stressful life events. The patient should be asked about the duration between any suspected trigger and the appearance of urticaria and which particular triggers are suspected. Important associated symptoms include pruritus, rhinorrhea, swelling of the face and tongue, and dyspnea.

Review of systems should seek symptoms of causative disorders, including fever, fatigue, abdominal pain, and diarrhea (infection); heat or cold intolerance, tremor, or weight change (autoimmune thyroiditis); joint pain (cryoglobulinemia, systemic lupus erythematosus [SLE]); malar rash (SLE); dry eyes and dry mouth (Sjögren syndrome); cutaneous ulcers and hyperpigmented lesions after resolution of urticaria (urticarial vasculitis); small pigmented papules (mastocytosis); lymphadenopathy (viral illness, cancer, serum sickness); acute or chronic diarrhea (viral or parasitic enterocolitis); and fevers, night sweats, or weight loss (cancer).

Past medical history should include a detailed allergy history, including known atopic conditions (eg, allergies, asthma, eczema) and known possible causes (eg, autoimmune disorders, cancer). All medication use should be reviewed, including over-the-counter medications and herbal products, specifically any agents particularly associated with urticaria (see table Some Causes of Urticaria). Family history should elicit any history of systemic rheumatic disease, other autoimmune disorders, or cancer. Social history should cover any recent travel and any risk factors for transmission of infectious disease (eg, hepatitis, HIV).

Physical examination

Vital signs should note the presence of bradycardia or tachycardia and tachypnea. General examination should immediately seek any signs of respiratory distress and also note cachexia, jaundice, or agitation.

Examination of the head should note any swelling of the face, lips, or tongue; scleral icterus; malar rash; tender and enlarged thyroid; lymphadenopathy; or dry eyes and dry mouth. The oropharynx should be inspected and the sinuses should be palpated and transilluminated for signs of occult infection (eg, sinus infection, tooth abscess).

Abdominal examination should note any masses, hepatomegaly, splenomegaly, or tenderness. Neurologic examination should note any tremor or hyperreflexia or hyporeflexia. Musculoskeletal examination should note the presence of any inflamed or deformed joints.

Skin examination should note the presence and distribution of urticarial lesions as well as any cutaneous ulceration, hyperpigmentation, small papules, or jaundice. Urticarial lesions usually appear as well-demarcated transient swellings involving the dermis. These swellings are typically erythematous and vary in size from pinprick to covering wide areas. Some lesions can be very large. In other cases, smaller urticarial lesions may become confluent. However, skin lesions also may be absent at the time of the visit. Maneuvers to evoke physical urticaria can be done during the examination, including exposure to vibration (tuning fork), warmth (tuning fork held under warm water), cold (stethoscope, chilled tuning fork, or ice cube), water, or pressure (lightly scratching an unaffected area with a fingernail).

Red flags

The following findings are of particular concern:

  • Angioedema (swelling of the face, lips, or tongue)

  • Stridor, wheezing, or other respiratory distress

  • Hyperpigmented lesions, ulcers, or urticaria that persist > 48 hours

  • Signs of systemic illness (eg, fever, lymphadenopathy, jaundice, cachexia)

Interpretation of findings

Acute urticaria is nearly always due to some defined exposure to a medication, substance, or physical stimulus or an acute infectious illness. However, the trigger is not always clear from the history, particularly because allergy may develop without warning to a previously tolerated substance.

Most chronic urticaria is idiopathic. The next most common cause is an autoimmune disorder. The causative autoimmune disease is sometimes clinically apparent. Urticarial vasculitis sometimes is associated with systemic rheumatic diseases (particularly SLE or Sjögren syndrome). In urticarial vasculitis, urticaria is accompanied by findings of leukocytoclastic vasculitis on histopathology; it should be considered when the urticaria is painful rather than pruritic, lasts > 48 hours, does not blanch, or is accompanied by vesicles or purpura.

Testing

Usually, no testing is needed for an isolated episode of urticaria unless symptoms and signs suggest a specific disorder (eg, infection).

Unusual, recurrent, or persistent cases warrant further evaluation. Referral for allergy skin testing should be done, and routine laboratory tests should consist of complete blood count, blood chemistries, liver tests, and thyroid-stimulating hormone (TSH). Further testing should be guided by symptoms and signs (eg, of autoimmune disorders) and any abnormalities on the screening tests (eg, hepatitis serologies and ultrasonography for abnormal liver tests; ova and parasites for eosinophilia; cryoglobulin titer for elevated liver tests or elevated creatinine; thyroid autoantibodies for abnormal TSH).

Skin biopsy should be done if there is any uncertainty as to the diagnosis or if wheals persist > 48 hours (to rule out urticarial vasculitis).

Clinicians should be cautious when recommending the patient do an empiric challenge (eg, “Try such and such again and see whether you get a reaction”) because subsequent reactions may be more severe.

Treatment of Urticaria

Any identified causes are treated or remedied. Implicated medications or foods should be stopped.

Nonspecific symptomatic treatment (eg, taking cool baths, avoiding hot water and scratching, wearing loose clothing) may be helpful.

Systemic treatment

Antihistamines remain the mainstay of treatment. They must be taken on a regular basis, rather than as needed. Newer oral antihistamines often are preferred because of once-daily dosing and because some are less sedating. Appropriate choices include

1).

Angioedema

Treatment reference

  1. 1. Zhao ZT, Ji CM, Yu WJ, et al: Omalizumab for the treatment of chronic spontaneous urticaria: A meta-analysis of randomized clinical trials. J Allergy Clin Immunol 137(6):1742-1750.e4, 2016. doi: 10.1016/j.jaci.2015.12.1342

Geriatrics Essentials: Urticaria

Key Points

  • Urticaria can be caused by allergic or nonallergic mechanisms.

  • Most acute cases are caused by an allergic reaction to a specific substance.

  • Most chronic cases are idiopathic or result from autoimmune disease.

  • Concomitant systemic symptoms require a thorough evaluation for the etiology.

  • Treatment is based on severity; nonsedating antihistamines and avoidance of triggers are first-line options.

  • Topical corticosteroids and topical antihistamines are not beneficial.

Drugs Mentioned In This Article
quizzes_lightbulb_red
Test your KnowledgeTake a Quiz!
Download the free Merck Manual App iOS ANDROID
Download the free Merck Manual App iOS ANDROID
Download the free Merck Manual App iOS ANDROID