Introduction

Chronic urticaria can be a difficult chief complaint to investigate and the diagnosis is primarily revealed through detailed history taking and physical exam. Patients are often concerned that recurrent hives are due to an acute allergic reaction and when no obvious trigger is found this can present a conundrum to both the patient and physician. The following information may be helpful in the diagnosis and management of patients with chronic urticaria.

  1. Chronic urticaria is defined as the development of relapsing pruritic erythematous raised wheals with or without angioedema occurring most days of the week for at least 6 weeks. Urticaria that resolves before 6 weeks is defined as acute urticaria.1

  2. Chronic urticaria affects about 1% of the general population. It is typically a self-limiting diagnosis, lasting on average between 2-5 years, although symptoms can persist longer in about one-fifth of patients.2 It affects both adults and children, and typically is more common in females and adults.3

  3. The pathogenesis of urticaria is not well established and includes a complex interplay between mast cells, T cells, basophils, eosinophils, and neutrophils. This has been shown in biopsied skin lesions of patients with chronic spontaneous urticaria.4 Although many theories have been proposed, including an autoimmune theory of disease and possible activation of the coagulation cascade, none have been firmly established.1,5

  4. Inducible/Physical triggers of urticaria make up about 20% of cases. Some examples of these include stress (both physical and emotional), heat, pressure, infections, and non-steroidal anti-inflammatory drugs. The most frequent type of inducible urticaria is symptomatic dermographism, followed by pressure and cold urticaria.4 See the Table for more examples of inducible urticarias. It is important to distinguish that these are triggers and not necessarily the underlying cause of the patient’s urticaria.

  5. Chronic spontaneous urticaria is diagnosed after thorough history and physical exam when no identifiable cause is found. Testing for inhalant or food allergens is not indicated in the general workup of chronic spontaneous urticaria. Of note, the presence of painful, palpable, non-blanching lesions or individual lesions that last longer than 24-48 hours and leave hyperpigmentation would suggest a possible urticarial vasculitis in which case further workup would be required.1

  6. Consider obtaining a tryptase level if the history raises concern for anaphylaxis or a mast cell disorder. A baseline tryptase level is not typically recommended in the initial evaluation of patients with chronic urticaria, however if a patient presents with recurrent urticaria in the setting of other systemic symptoms such as wheezing, flushing, vomiting, hypotension, and/or syncope then one should consider possible anaphylaxis or a mast cell disorder. A tryptase level should be obtained during an acute event as well for comparison from baseline.6 Consider referral to an allergist if the tryptase is elevated.

  7. First line therapy for the treatment of chronic spontaneous urticaria includes initiation of second generation H1 antihistamines and avoidance of possible triggers such as non-steroidal anti-inflammatory drugs, heat, and relevant physical factors. These antihistamines can be titrated up to four times the standard daily dose, if needed. About 50% of patients will respond to antihistamines at the approved dosages.7 Systemic steroids can be used for short term therapy to achieve control but are not recommended for long term use due to their side effect profile.1 For non-responders, consider referral to an allergist.

  8. If a patient’s symptoms continue to be refractory to antihistamines and/or require frequent steroid courses, then the addition of Omalizumab can be considered. Omalizumab is a recombinant humanized IgG1 anti-IgE monoclonal antibody and is the only FDA approved biologic for treatment of refractory chronic spontaneous urticaria in patients aged 12 and older that have failed standard or high dose H1 antihistamine therapy. If Omalizumab is determined to be the next step in therapy, then referral to an allergist is recommended to discuss risk/benefit analysis of both the significant cost of biologic therapy and the side effect profile including risk of anaphylaxis.8

  9. Angioedema without a history of hives warrants consideration for further workup. About 40% of patients with chronic spontaneous urticaria report accompanying angioedema and 13% of patients have isolated angioedema without evidence of hives. If a patient has swelling without a history of hives then the physician should ask about a family history of swelling and consider further workup including baseline complement levels to evaluate for hereditary angioedema. If hereditary angioedema is suspected then referral to an allergist is recommended.9

  10. Chronic urticaria has a significant impact on patients’ quality of life with stress and anxiety being a large manifestation and possibly even cause of their disease process. One study found that patients with chronic spontaneous urticaria are 1.89 times more likely to have a current diagnosis of posttraumatic stress disorder in comparison with a control group.10 Assisting the patient with mental health resources should be considered.

Acknowledgements

The authors have nothing to disclose.