C hronic spontaneous urticaria (CSU) can be a debilitating condition that significantly affects quality of life (QOL), explain the au- thors of the National Center for Biotechnology Information’s guideline for the diagnosis and treatment of CSU, published as the book Chronic Urticaria. “Characterized by the occurrence of wheals and/or angioedema for a duration of 6 weeks or more, CSU is also referred to as ‘chronic urticaria’ and ‘chronic idiopathic urticaria,’” they write. “Urticaria affects 15%-20% of the population once or more during a lifetime, with females more commonly affected than males.” In the guideline, the authors review the etiology, pathogenesis, and management of CSU and highlight the role of the healthcare professional team in improving care for patients with this condition.

The writing committee recommends that clin- icians treating a patient with CSU perform a thorough examination to identify potential trig- gers and exacerbating factors and exclude differ- ential diagnoses (Table). “This exam should ex- plore time course and clinical features of urticarial rash, associated angioedema, associated systemic and infective symptoms, personal or family his- tory of allergies and autoimmune diseases, social and occupational history, induction by physical factors, recent newly administered medications, relationship to foods, and any exacerbating fac- tors,” they write. “If the patient cannot recall the time course of wheals, drawing around an indi- vidual lesion with a skin marking pen is useful to document resolution within 24 hours. Where history is unrevealing, an external cause is highly unlikely to be identified for patients with CSU.”

Skin Prick Test Not Useful

A routine diagnostic work-up for CSU is limited to blood tests for complete blood count and in- flammatory markers, such as C-reactive protein and/or erythrocyte sedimentation rate, mostly to rule out other potential diseases, according to the authors. “Eosinophilia may be associated with at- opy and parasitic infection,” they write. “Elevated inflammatory markers should prompt consider- ation of associated systemic disease.”

Skin prick testing, typically used to identify spe- cific allergens, is not useful for CSU, as the condi- tion is rarely caused by type 1 allergy, according to the guideline. “However, the utility and interpre- tation of an autologous serum skin test as a screen for autoantibodies to IgE and IgE receptors is an area of active research,” note the authors.

Several diagnostic tools have been developed to assess disease activity (eg, urticaria activity score), disease control (eg, urticaria control test), and impacts on QOL (eg, chronic urticaria QOL in- dex). “Baseline assessments should be performed to help guide treatment decisions and monitor progress,” write the guideline authors.

Treatment Options

The key to management of CSU is to avoid exacerbating factors and to control symptoms, the authors note, adding that several pharmaco- logical treatment options include:

Second-generation H1-antihistamines (eg, cetiri- zine, loratadine, fexofenadine) taken regularly, are first-line pharmacological treatments. However, due to anticholinergic properties and the adverse effect profile on the central nervous system, the routine use of first-generation H1-antihistamines is no longer recommended.

Omalizumab, a monoclonal antibody with a high affinity for free IgE, has been shown to be effica- cious as a second-line adjunct therapy for CSU that is unresponsive to H1-antihistamines. Ad- ministered as a subcutaneous injection, the stan- dard dosing regimen is 300 mg every 4 weeks.

Ciclosporin is recommended as a third-line agent for CSU that remains refractory to the combin- ation of H1-antihistamine and omalizumab. CSU is an off-label indication, and the dose and duration of ciclosporin should be minimized to avoid adverse events, including nephrotoxicity and hypertension.

For acute flares of CSU, short courses only of systemic corticosteroids may help alleviate symp- tom severity and reduce the duration of the flare. Topical corticosteroids are not used for the treat- ment of CSU.

“CSU follows a fluctuant disease course and may resolve spontaneously,” the authors conclude. “Accordingly, efficacy and need for continuation of treatment should be evaluated periodically at 3- to- 6-month intervals. The psychological bur- den of CSU should not be underestimated, and where appropriate, counseling and psychothera- py may enhance overall health outcomes.”