Chronic Urticaria: It’s More Than Just Antihistamines!

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The main feature of urticaria is raised skin lesions that appear pale to pink to erythematous and most commonly are intensely pruritic (see Figure 2). These lesions range from a few millimeters to several centimeters in size and may coalesce.

Urticarial Lesions image

Characteristically, evanescent old lesions resolve, and new ones develop over 24 hours, usually without scarring. Scratching generally worsens dermatographism, with new urticaria produced over the scratched area. Any area of the body may be involved.

The lesions of early urticaria may vary in size and blanch when pressure is applied. An individual hive may last minutes or up to 24 hours and may reoccur intermittently on various sites on the body for an unspecified period of time.1,6


Other dermatologic conditions may be mistaken for chronic urticaria. Common rashes that may mimic it include anaphylaxis, atopic dermatitis, medication allergy or fixed drug eruption, ACE inhibitor–related angioedema, mastocytosis, contact dermatitis, autoimmune thyroid disease, bullous pemphigoid, and dermatitis herpetiformis.

Patients should be encouraged to bring pictures of the rash to the office visit, since the rash may have waned at the time of the visit and diagnosis based on the patient’s description alone can be challenging. Most rashes in the differential can be identified or eliminated through a careful history and complete physical exam. When necessary, serologic testing and skin punch biopsies can elucidate and confirm the diagnosis.


History and physical examination

The medical history is the most important part of the evaluation of a patient with urticaria. The information that should be elicited and documented during the history is shown in Table 2.

Key Components of Patient History in the Evaluation of Urticaria image

A general comprehensive physical exam should be undertaken and the findings carefully documented. As noted, it can be helpful for patients to bring in pictures of the rash if the lesions wax and wane. It is also important to assess whether the urticarial lesions blanch when palpated, since this is a characteristic feature of acute and chronic urticarial lesions (but not of those with an autoimmune, cholinergic, or vasculitic cause). Thus, blanching of the wheal is a key finding on physical exam to discriminate between possible causes.8 Lesions pigmented with purpuric areas that scar or last longer than 24 hours suggest urticarial vasculitis; other features that distinguish urticarial vasculitis from chronic urticaria are listed in Table 3.2

Distinguishing Urticarial Vasculitis From Chronic Urticaria image

Laboratory evaluation

Although there is no consensus regarding appropriate laboratory testing, the following tests should be considered for patients with chronic urticaria after completion of a thorough history and physical exam: complete blood count (CBC) with differential; erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP); chemistry panel and hepatic panel; and thyroid-stimulating hormone, antimicrosomal antibodies, and antithyroglobulin antibodies measurements.7

While the CBC is usually within normal limits, if eosinophilia is present, a workup for an atopic disorder or parasitic infection should be considered. If the ESR/CRP results are positive, consider ordering a larger antinuclear antibody (ANA) panel. Note: The utility of performing these tests routinely for chronic urticaria patients is unclear, as studies have demonstrated that results are usually normal. But it is important to order the appropriate tests to help you rule in or out a likely diagnosis.

Additional testing may be indicated by non-IgE or possible autoimmune findings on the history and/or physical exam. This can include a functional autoantibody assay (for autoantibodies to the high-affinity IgE receptor [FcR1]); complement analysis (eg, C3, C4, CH50), especially when concerned about hereditary angioedema; stool analysis for ova and parasites; Helicobacter pylori workup (there is limited experimental evidence to recommend this, however); hepatitis B and C workup; chest radiograph and/or other imaging studies; ANA panel; rheumatoid factor; cryoglobulin levels; skin biopsy; and urinalysis.7

Local urticaria can occur following contact with allergens via an IgE-mediated mechanism. If an allergen is suspected as a possible trigger, serologic testing to assess allergen-specific IgE levels that may be contributing to the urticaria can be performed in a primary care setting. The specific IgE levels most commonly assessed are for the endemic outdoor aeroallergens (eg, pets [cat, dog], dust mites); measurement of food-specific IgE levels can be ordered if a specific allergy is a concern. Allergy skin prick testing for immediate hypersensitivity and a physical challenge test are usually performed in an allergy office by board-certified allergists.

Skin biopsy should be done on all lesions concerning for urticarial vasculitis (see Table 4).2 Biopsy is also important if the hives are painful rather than pruritic, as this may suggest a different cause. The clinician should consider more detailed lab testing and skin biopsy if urticaria does not respond to therapy as anticipated. Also, specific lab testing may be required screening for certain planned medical therapies (eg, glucose-6-phosphate dehydrogenase enzyme deficiency screening before dapsone or hydroxychloroquine therapy).3

Categories of Antihistamines and Approved Dosing for Adults image


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