Chapter: Urticaria
McMaster Section Editor(s): Judah A. Denburg
Section Editor(s) in Interna Szczeklika: Marek L. Kowalski, Agnieszka Padjas
McMaster Author(s): Mary Messieh, Samuel Ian Yung
Author(s) in Interna Szczeklika: Jacek Szepietowski, Agnieszka Padjas, Wiesław Gliński†
† Deceased.
Additional Information

Definition, Etiology, PathogenesisTop

Urticaria is a condition characterized by transient wheals (hives), angioedema, or both. Various triggers can lead to the final common pathway of skin mast cell activation. When this occurs, histamine and other mediators are released, leading to local cell recruitment (eg, lymphocytes), vasodilation, increased vascular permeability, and sensory nerve activation. Wheals result from edema of the upper and mid dermis, and angioedema involves a similar change in the lower dermis and subcutis.

Based on the duration of symptoms, urticaria may be classified as acute urticaria (≤6 weeks; two-thirds of cases) or chronic urticaria (>6 weeks).

Acute urticaria must be differentiated from anaphylaxis. If wheals or angioedema occur with changes in other organs besides the skin, such as the cardiovascular system (hypotension), nervous system (presyncope/syncope), respiratory distress, or gastrointestinal upset (emesis/diarrhea), then anaphylaxis should be suspected.

Acute urticaria may be categorized based on etiology:

1) IgE-mediated allergy, such as allergy to a food (common allergenic foods are tree nuts, peanuts, fish, shellfish, wheat, eggs, dairy, soy, or sesame), medication, or Hymenoptera sting.

2) Non–IgE-mediated reaction:

a) Foods, for example, those containing proteases, or fish of the Scombridae family (tuna, mackerel) containing histamine-producing bacteria.

b) Medications, particularly acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs), and direct mast cell activators such as opioids, skeletal muscle relaxants, and radiocontrast dye.

c) Infection: Commonly viral illnesses.

3) Idiopathic.

4) Early presentation of chronic urticaria (for causes, see below).

Chronic urticaria may be further classified as:

1) Chronic spontaneous urticaria (CSU), which involves a spontaneous appearance of wheals, angioedema, or both lasting >6 weeks because of an unknown or known cause, such as:

a) Autoimmunity mediated by autoantibodies against the high-affinity IgE receptor or directly against IgE.

b) Bacterial, viral, parasitic, and fungal infections.

c) Serum sickness.

d) Autoimmune disease (eg, Hashimoto thyroiditis, systemic lupus erythematosus, or mixed connective tissue disease).

e) Malignancy (eg, lymphoproliferative disorders–see Schnitzler syndrome under Differential Diagnosis, below).

f) Causes of acute urticaria (see above).

g) Idiopathic (most common).

2) Inducible (or physical) urticaria:

a) Dermatographism, caused by pressure applied to the skin. Wheals appear 1 to 5 minutes after the stimulus (occurs in ~5% of the general population).

b) Cold urticaria, caused by cold air, water, wind. Cold urticaria can be associated with anaphylaxis if there is systemic cold exposure (eg, aquatic activities).

c) Delayed pressure urticaria, caused by pressure on the skin. Wheals and edema of deeper skin layers usually appear after 4 to 6 hours (but up to 12-24 hours) and may be painful.

d) Vibratory angioedema (vibratory urticaria), caused by, for instance, vibrations of a lawnmower or pneumatic hammer.

e) Heat urticaria, caused by a local source of heat.

f) Solar urticaria, caused by ultraviolet or visible light.

g) Exercise-induced anaphylaxis (EIA) and urticaria, provoked by exercise and occurring as a manifestation of anaphylaxis. It develops within minutes of starting exercise. The patient can experience any symptoms of anaphylaxis (cutaneous, gastrointestinal, respiratory, cardiovascular).

h) Cholinergic urticaria, associated with elevated core body temperature, for instance, after exercise or heating the body. It manifests as “pinpoint” hives from 1 to 3 mm in diameter that appear after 2 to 20 minutes of exposure. The condition is not related to anaphylaxis and occurs in ~11% of the general population.

i) Aquagenic urticaria, caused by contact with water, independent of temperature.

j) Contact urticaria, following exposure to, for instance, latex, foods (tree nuts, fish, shellfish), chemical agents (formaldehyde present in clothes, resins, animal saliva, ammonium persulfate in cosmetics and foods).

Currently, urticarial vasculitis is not classified as urticaria.

Clinical Features and Natural HistoryTop

Wheals are usually itchy (sometimes causing pain or a burning sensation), porcelain-white or pink, almost always surrounded by erythema, and elevated over the surrounding skin. They develop and usually also resolve rapidly (<24 hours). Wheals may become confluent, forming different shapes, and may cover extensive areas of the skin. Angioedema is nonpitting, nondependent, erythematous or skin-colored swelling of the lower dermis and subcutis or mucous membranes that is present in 40% of patients with chronic urticaria; 10% have angioedema alone.

Some characteristic features of the wheals may suggest the etiology of urticaria:

1) Appearance (size, shape): For instance, wheals that are initially small (1-3 mm) and have a wide red halo suggest cholinergic urticaria, whereas very large wheals may indicate exercise-induced or contact urticaria.

2) Location: Wheals developing at the site of contact with an allergen suggest contact urticaria. Wheals on uncovered skin areas exposed to cold or sunlight indicate cold or solar urticaria. Wheals at the site of compression are associated with delayed pressure urticaria.

3) Time from contact with the causative factor to the onset of urticaria: Lesions developing after several minutes to several hours are suggestive of allergic or physical urticaria. Lesions developing after 3 to 12 hours suggest pressure urticaria. Lesions appearing after several days may indicate urticaria in the course of serum sickness.

4) Duration of lesions: Lesions lasting from 1 to 4 hours are associated with allergic urticaria; 30 minutes to 2 hours, with most of physical urticarias; from 6 to 12 hours, with pressure urticaria.

Acute urticaria may appear suddenly, within a few minutes or hours. Typically lesions resolve rapidly. In chronic urticaria lesions may develop daily or periodically (eg, once a week or month); spontaneous remissions frequently occur within a year, but urticaria may also be periodic and last several years.


Diagnostic Criteria

The diagnosis of urticaria is based on typical cutaneous features (as described under Clinical Features and Natural History, above), identifying triggers of exacerbation or underlying causes, and exclusion of differential diagnoses. The cause of chronic urticaria can be established only in ~20% of patients.

As acute urticaria is usually self-limiting, it usually does not require a diagnostic workup. However, if there is suspicion for an IgE-mediated food allergy or existence of eliciting factors (eg, NSAIDs), allergy testing and patient education on avoidance measures may be undertaken.

The patient’s history plays a crucial role in establishing the cause of chronic urticaria. Key questions include:

1) Timing (onset, duration, frequency): Typical individual lesions do not last more than 24 to 48 hours.

2) Lesion characteristics (distribution, shape, size, pruritic or painful, residual pigmentation): Typical lesions are pruritic and do not leave pigmentation after resolution of the initial lesions (except from excoriation).

3) Associated angioedema: Typical urticaria can occur with or without angioedema.

4) Other associated features that may suggest atypical causes (eg, arthralgias/arthritis, fever, abdominal cramps, family history).

5) Triggers:

a) Allergic, for instance, medications, foods, insect bites/stings.

b) Physical stimuli, for instance, scratching, cold, heat, sweating.

c) Cofactors, for instance, infection.

6) Response to therapy: Typical lesions should respond to antihistamines.

Physical examination is the next step in diagnosis.

Diagnostic Tests

Diagnostic testing should be guided by the patient’s history. In acute urticaria routine testing is not recommended. Testing would be appropriate to establish a cause suggested by history (eg, skin testing or specific IgE testing for a suspected allergen).

For CSU, the recommended routine diagnostic tests are a complete blood count with differential count as well as erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) levels (or both).

Extensive general screening is not advised in typical cases of CSU. If the etiology is important and in doubt or the history suggests atypical features, referral to a specialist in allergology/clinical immunology or dermatology is advised. One important consideration is lesional biopsy, especially in suspected urticarial vasculitis (dark-red or violet wheals lasting >24 hours, frequently painful).

In cases of suspected inducible (physical) urticaria, the history is key. Provocation testing may also be considered. For example, dermatographism may be elicited by stroking the skin with moderate pressure using a smooth item (eg, a wooden spatula) and cold urticaria may be elicited by placement of an ice cube in a thin plastic bag on the skin for 5 minutes.

Differential Diagnosis

Start from excluding serious diseases that may present with urticaria (see Definitions, Etiology, Pathogenesis, above). Other conditions that should be part of differential diagnosis:

1) Maculopapular cutaneous mastocytosis (also known as urticaria pigmentosa): Rubbing the red-brown papules can produce bead-like wheals (Darier sign).

2) Urticarial vasculitis.

3) Bradykinin-mediated angioedema.

4) Anaphylaxis.

5) Cryopyrin-associated periodic syndromes, which can present with urticarial rash, recurrent fever attacks, arthralgia or arthritis, ocular inflammation, fatigue, and headaches. Examples include familial cold autoinflammatory syndrome and Muckle-Wells syndrome.

6) Schnitzler syndrome, which can present with recurrent urticarial rash, monoclonal gammopathy, recurrent fever, bone or muscle pain, arthralgia or arthritis, and lymphadenopathy.

7) Gleich syndrome, which features episodic angioedema with eosinophilia.

8) Wells syndrome, which features granulomatous dermatitis with eosinophilia (eosinophilic cellulitis).

9) Bullous pemphigoid.

10) Mild erythema multiforme: Patients often have prodromal symptoms (weakness, fever, sore throat, myalgia, arthralgia) followed by annular lesions on the hands, feet, outer surfaces of extremities, and oral mucosa.


General Measures

1. Avoidance of causative factors (allergens, physical factors), if identified.

1) In case of food-induced urticaria, an elimination diet should be used.

2) Patients with cold urticaria are at increased risk of anaphylaxis and should be advised to exercise caution with aquatic activities (and completely avoid cold bodies of water), avoid cold foods and beverages, and their IV fluids should be prewarmed. If they are undergoing surgery, the surgical team should be made aware of their condition and they must be kept warm throughout the procedure.

2. Avoidance of nonspecific factors inducing or worsening urticaria: Drugs (ASA, NSAIDs, opioids), alcohol, stress.

3. Treatment of the underlying condition in secondary urticaria.


1. Antihistamines are the mainstay of symptomatic treatment in the majority of patients. Administer modern second-generation H1 antihistamines (dosage: Table 2 in Allergic Rhinitis); if this is not effective, higher doses of second-generation antihistamines can be used (up to quadruple of the standard dose).Evidence 1Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias and heterogeneity. Guillén-Aguinaga S, Jáuregui Presa I, Aguinaga-Ontoso E, Guillén-Grima F, Ferrer M. Updosing nonsedating antihistamines in patients with chronic spontaneous urticaria: a systematic review and meta-analysis. Br J Dermatol. 2016 Dec;175(6):1153-1165. doi: 10.1111/bjd.14768. Epub 2016 Oct 19. Review. PubMed PMID: 27237730. In chronic urticaria continuous treatment with H1 antihistamines is strongly recommended (rather than intermittent use). The only exception is some forms of inducible (physical) urticaria, where on-demand treatment may be more useful, such as 2 hours prior to cold exposure in patients with cold urticaria.

Antihistamines with documented efficacy in treatment of urticaria are bilastine, cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, and rupatadine. Do not use multiple antihistamines in combination.

Standard treatment with one antihistamine agent is effective in <50% patients with CSU; in one-fourth to one-third of such patients, the urticarial lesions relapse despite treatment with high doses of antihistamines.

2. The following other drugs should be considered in patients with urticaria resistant to treatment with high-dose modern second-generation H1 antihistamines:

1) Omalizumab, a monoclonal antibody against IgE. A dose of 150 to 300 mg/mo is effective—regardless of baseline serum IgE levels—in treatment of CSU, pressure urticaria, heat urticaria, solar urticaria, and cold urticaria. It is generally well tolerated. The strongest evidence of efficacy is present for CSU.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). High Quality of Evidence (high confidence that we know true effects of the intervention). 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. 2016 Jun;137(6):1742-1750.e4. doi: 10.1016/j.jaci.2015.12.1342. Epub 2016 Mar 31. PubMed PMID: 27040372.

2) If the above treatments are ineffective, then cyclosporine (INN ciclosporin) should be considered as the next step in treatment. Although often effective, it is reserved for more resistant urticaria because of its adverse effects.

3. The following drugs may also be considered in treatment of urticaria:

1) Glucocorticoids may be considered for acute urticaria and acute exacerbations of CSU. A short course of prednisone at 20 to 50 mg/d (continued, eg, up to 10 days) can often be quite effective. Due to significant adverse effects, frequent use should be avoided and long-term use is not recommended outside of specialty clinics.

2) Montelukast 10 mg in the evening may be effective in treatment of CSU (efficacy data are equivocal).

3) Dapsone has been removed from recent urticaria guidelines but may be considered in addition to H1 antihistamines (efficacy data are equivocal)

4) H2 antihistamines have been removed from recent urticaria guidelines but may be considered in addition to H1 antihistamines (efficacy data are equivocal)

Special ConsiderationsTop

Cold-Induced Urticaria

An epinephrine auto-injector and anaphylaxis action plan should be considered in these patients given their risk of anaphylaxis.

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