What laboratory tests do you investigate in chronic spontaneous urticaria to exclude other diagnoses?

Our expert, Associate Professor Emek Kocatürk, answers the question of what differential diagnoses to consider when confronted with a patient presenting with symptoms of CSU, explaining how to exclude these through a mixture of clinical and laboratory tests.

Answer

Chronic spontaneous urticaria presents with itchy hives which usually last for less than 24 hours and resolve without leaving a mark. The diagnosis of CSU is usually made clinically, however there are other diagnoses to consider in the presence of atypical lesions, accompanying symptoms and resistance to treatment.

The main differential diagnosis is urticarial vasculitis, which presents with hives lasting for more than 24 hours and leaves post-inflammatory hyperpigmentation after resolution. If a patient presents with hives and a sensation of burning or pain rather than itching which resolves in more than 24 hours leaving a mark, then a punch biopsy is warranted. The diagnosis of urticarial vasculitis is made by histopathological examination of the wheal, which shows the presence of leukocytoclastic vasculitis.1

In a patient presenting with wheals without angioedema, and with accompanying fever, joint and muscle pain, auto-inflammatory disorders should be suspected. The lesions typically do not respond to antihistamines and the patient feels unwell. The marked elevation of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and a neutrophilic leukocytosis are characteristic for auto-inflammatory disorders. Histopathological examination of the wheal demonstrates infiltrates rich in neutrophils.

Patients with recurrent angioedema without wheals, who are not on ACE-inhibitors, should be asked for a detailed family history. They should be checked for hereditary bradykinin-mediated angioedema (HAE I-III) and angioedema due to acquired C1-inhibitor (C1-INH) deficiency (AAE).2 Normal C4 complement levels, C1-inhibitor protein and function levels, the absence of C1-INH antibodies, or mutations in the C1-INH or factor XII gene rules out bradykinin-related angioedema.

In some instances, chronic inducible urticaria (CINDU) may be confused with CSU. The discriminating question is: “Can you make your wheals appear?”. The answer will distinguish CINDU (‘yes’) from CSU (‘no’).  Patients suspected to have CINDU should be investigated for specific trigger(s) of wheal induction (e.g., skin contact with cold water in cold urticaria; exercise or sauna/hot bath in cholinergic urticaria), and offered provocation testing if possible.3 

In the presence of ordinary chronic urticaria, without any indication of other diseases, the EAACI guidelines for urticaria (2013) recommend only limited routine diagnostic testing, including differential blood count and ESR or CRP. 4

Diagnostic algorithm for patients presenting with wheals only, wheals and angioedema, and angioedema only.3
  • Emek Kocatürk

    Dr Emek Kocatürk received her MD degree from Hacettepe University School of Medicine, Ankara, Turkey in 1999.

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  • References

    1. Black AK. Urticarial vasculitis. Clin Dermatol 1999;17:565–569.
    2. Magerl M, Brasch J, Forster U, Hauswald B, Mohr B, Prassler J, et al. Diagnostics and exclusion of hereditary angioedema: a standardized approach for the practice. Hautarzt 2012;63:567–572.
    3. Maurer M, Magerl M, Metz M, Siebenhaar F, Weller K, Krause K. Practical algorithm for diagnosing patients with recurrent wheals or angioedema. Allergy. 2013;68:816‒9.
    4. Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica GW,et al. The EAACI/GA2 LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy. 2014;69:868‒87.

     

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