Urticaria consists of migratory, well-circumscribed, erythematous, pruritic plaques on the skin.
Urticaria also may be accompanied by angioedema Angioedema Angioedema is edema of the deep dermis and subcutaneous tissues. It is usually an acute but sometimes a chronic mast cell–mediated reaction caused by exposure to a drug (eg, angiotensin-converting... read more , 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 present 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 Evaluation of the Dermatologic Patient History and physical examination are adequate for diagnosing many skin lesions. Some require biopsy or other testing. Important information to obtain from history includes Personal or family... read more .)
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 Type I Allergic (including atopic) and other hypersensitivity disorders are inappropriate or exaggerated immune reactions to foreign antigens. Inappropriate immune reactions include those that are... read more 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 drugs
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 Some Causes of Urticaria ) most often results from
Type I hypersensitivity reactions
A presumptive trigger (eg, drug, food ingestion, insect bite or sting, infection) occasionally can be identified.
Chronic urticaria most often results from
Chronic urticaria often lasts months to years, eventually resolving without a cause being found.
Evaluation of Urticaria
Because there are no definitive diagnostic tests for urticaria, evaluation largely relies on history and physical examination.
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 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 Hashimoto Thyroiditis Hashimoto thyroiditis is chronic autoimmune inflammation of the thyroid with lymphocytic infiltration. Findings include painless thyroid enlargement and symptoms of hypothyroidism. Diagnosis... read more ); joint pain (cryoglobulinemia, systemic lupus erythematosus [SLE] Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more ); malar rash (SLE); dry eyes and dry mouth (Sjögren syndrome Sjögren Syndrome Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more ); cutaneous ulcers and hyperpigmented lesions after resolution of urticaria (urticarial vasculitis); small pigmented papules (mastocytosis Mastocytosis and Mast Cell Activation Syndrome Mastocytosis is mast cell proliferation with infiltration of skin or other tissues and organs. Mast cell activation syndrome is increased and inappropriate activation of mast cells without clonal... read more ); 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 drug use should be reviewed, including over-the-counter drugs and herbal products, specifically any agents particularly associated with urticaria ( see Table: Some Causes of Urticaria Some Causes of Urticaria ). Family history should elicit any history of rheumatoid disease, autoimmune disorders, or cancer. Social history should cover any recent travel and any risk factors for transmission of infectious disease (eg, hepatitis, HIV).
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 red 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 or chilled tuning fork), water, or pressure (lightly scratching an unaffected area with a fingernail).
The following findings are of particular concern:
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 drug 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 connective tissue disorders (particularly SLE or Sjögren syndrome). In urticarial vasculitis, urticaria is accompanied by findings of cutaneous vasculitis; 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.
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 Biopsy Diagnostic tests are indicated when the cause of a skin lesion or disease is not obvious from history and physical examination alone. These include Patch testing Biopsy Scrapings Examination... read more 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 drugs or foods should be stopped.
Nonspecific symptomatic treatment (eg, taking cool baths, avoiding hot water and scratching, wearing loose clothing) may be helpful.
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
Cetirizine 10 mg once/day
Fexofenadine 180 mg once/day
Desloratadine 5 mg once/day
Levocetirizine 5 mg once/day
Older oral antihistamines (eg, hydroxyzine 10 to 25 mg every 4 to 6 hours; diphenhydramine 25 to 50 mg every 6 hours) are sedating but inexpensive and sometimes quite effective.
Systemic corticosteroids (eg, prednisone 30 to 40 mg orally once/day) are given for severe symptoms but should not be used long term. Topical corticosteroids or topical antihistamines are not beneficial.
Patients with chronic idiopathic urticaria often do not respond to antihistamines or other drugs commonly used. Omalizumab, a monoclonal antibody that can suppress certain allergic reactions, may help relieve symptoms, but experience with this use is limited.
Patients who have angioedema involving the oropharynx or any involvement of the airway should receive epinephrine 0.3 mL of 1:1000 solution sc and be admitted to the hospital. On discharge, patients should be supplied with and trained in the use of an auto-injectable epinephrine pen.
The older oral antihistamines (eg, hydroxyzine, diphenhydramine) are sedating and can cause confusion, urinary retention, and delirium. They should be used cautiously to treat urticaria in older patients.
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.
Treatment is based on severity; nonsedating antihistamines and avoidance of triggers are first-line options.
Topical corticosteroids and topical antihistamines are not beneficial.
Concomitant systemic symptoms require a thorough evaluation for the etiology.