These recommendations for the definition, diagnosis and management of chronic inducible urticaria (CIndU) extend, revise and update our previous consensus report on physical urticarias and cholinergic urticaria (Allergy, 2009). The aim of these recommendations is to improve the diagnosis and management of patients with CIndU. Our recommendations acknowledge the latest changes in our understanding of CIndU, and the available therapeutic options, as well as the development of novel diagnostic tools.

Chronic spontaneous urticaria (csU), which is characterized by recurrent episodes of mast cell-driven wheal and flare-type skin reactions, is often associated with elevated total IgE levels and thyroid autoimmunity. We speculate that some csU patients express IgE autoantibodies against thyroid antigens such as thyroid peroxidase (TPO), which could bind to skin mast cells and induce their activation. We developed and used a site-directed human IgE capture ELISA to quantify IgE-anti-TPO. We used this assay and investigated csU patients (n = 478) and healthy control subjects (n = 127) for IgE-anti-TPO and then assessed IgE-anti-TPO-positive and -negative csU patients for clinical and serological differences. CsU patients were found to express more than 2fold higher IgE-anti-TPO serum levels as compared to healthy control subjects (p<0.001). 54% of csU patients had serum levels higher than the cut off ( = 5 IU/ml). By distribution analyses we identified two distinct subpopulations of csU patients: 1) IgE-anti-TPO^low ( = 39%, IgE-anti-TPO: median 2.17 interquartile range 0.86–5.44, = comparable to healthy controls) and 2) IgE-anti-TPO^high ( = 61%, IgE-anti-TPO: median 6.67, interquartile range 5.39–8.24). IgE-anti-TPO-positive and -negative csU patients had very similar distributions of age and gender as well as disease activity and duration. IgE-anti-TPO-positive csU patients exhibited significantly higher IgG-anti-TPO levels and lymphocyte counts as well as decreased C4 complement levels. Our findings show that a sizeable subgroup of csU patients expresses IgE antibodies against thyroid peroxidase. These autoantibodies could cause “autoallergic” mast cell activation, a novel pathomechanism of chronic spontaneous urticaria.

Altrichter S, et al. Allergy Asthma Immunol Res. 2021 Mar;13(2):206-218. https://doi.org/10.4168/aair.2021.13.2.206

In physical urticaria, exogenous physical factors such as thermal triggers, solar radiation and mechanic triggers including friction or pressure are responsible for the elicitation of symptoms in the skin of patients. Avoidance of the respective stimulus is usually difficult or impossible, and many patients are not sufficiently treated with standard antihistamines. We report that treatment with omalizumab (Xolair®) of 7 patients with physical urticarias [solar urticaria (n = 2), urticaria factitia/symptomatic dermographism (n = 2), cold urticaria, delayed pressure urticaria and localized heat urticaria] resulted in complete symptom control within days after the first injection in 5 patients. In 1 patient, symptoms improved after increasing the dose of omalizumab, and 1 patient with localized heat urticaria did not respond significantly to treatment. Before anti-immunoglobulin E treatment, all patients had suffered from their physical urticaria for years and had had numerous unsuccessful therapies. The overall excellent responses to omalizumab treatment reported here indicate that anti-immunoglobulin E is a safe and effective treatment for recalcitrant physical urticarias.