Positive Basophil Tests Are Linked to High Disease Activity and Other Features of Autoimmune Chronic Spontaneous Urticaria: A Systematic Review.

BACKGROUND: Chronic spontaneous urticaria (CSU) is believed to be Autoimmune (aiCSU) (type IIb CSU) in at least 8% of patients, associated with mast cell-activating IgG autoantibodies. Basophil tests such as the basophil activation test (BAT) and basophil histamine release assay (BHRA) are considered the best single tests for an aiCSU diagnosis. To date, the strength of associations among a positive BAT and/or BHRA (BAT/BHRA+) and CSU features, patient demographics, and response to treatment remains poorly characterized. OBJECTIVE: To evaluate the strength of current evidence on basophil tests as parameters for CSU characteristics. METHODS: We performed a systematic literature search and review to assess the relationship between BAT/BHRA+ and clinical and laboratory parameters of CSU. Of 1,058 records found in the search, 94 studies were reviewed by experts in urticaria and 42 were included in the analysis. RESULTS: In CSU patients, BAT/BHRA+ showed a strong level of evidence for an association with high disease activity and low levels of total IgE. A weak level of evidence was shown for the association of BAT/BHRA+ and the presence of angioedema, and basopenia. CONCLUSIONS: Our results suggest that aiCSU defined by BAT/BHRA+ is more active or severe and is linked to other aiCSU markers such as low total IgE/basopenia. Basophil tests should be standardized and implemented in routine clinical care to improve the diagnosis and treatment of patients with aiCSU.

Evidence for histamine release in chronic inducible urticaria - A systematic review.

Background: Chronic inducible urticaria (CIndU) constitutes a group of nine different CIndUs in which pruritic wheals and/or angioedema occur after exposure to specific and definite triggers. Histamine released from activated and degranulating skin mast cells is held to play a key role in the pathogenesis of CIndU, but evidence to support this has, as of yet, not been reviewed systematically or in detail. We aim to characterize the role and relevance of histamine in CIndU. Methods: We systematically searched 3 electronic databases (PubMed, Scopus, and Embase) for studies that reported increased serum or skin histamine concentration (direct evidence) or in vitro or ex vivo histamine release (indirect evidence) following trigger exposure. Results: An initial total of 3,882 articles was narrowed down to 107 relevant studies of which 52 were in cold urticaria, 19 in cholinergic urticaria, 14 in heat urticaria, 10 in contact urticaria, 7 each in solar urticaria and vibratory angioedema, 4 each in symptomatic dermographism and aquagenic urticaria, and 3 in delayed pressure urticaria. The results of our review support that histamine has a key pathogenic role in the pathogenesis of all CIndUs, but it is not the sole mediator as evidenced by the often poor relationship between the level of histamine and severity of symptoms and the variable clinical efficacy of H1-antihistamines. Conclusions: Histamine released from skin mast cells is a key driver of the development of signs and symptoms and a promising therapeutic target in CIndU.