Chronic spontaneous urticaria – Autoallergic? Autoimmune? Both?

Published: February 15, 2023

Chronic spontaneous urticaria (CSU) is the most common cause of recurrent hives (wheals) and angioedema. In all patients with CSU, hives and angioedema develop because skin mast cells are activated. Two different types of autoantibodies, IgE and IgG, are held to do this. Patients with mast cell-activating IgE autoantibodies have what is called autoallergic CSU (aaCSU), and patients with mast cell-activating IgG autoantibodies have autoimmune CSU (aiCSU). Patients with aaCSU and patients with aiCSU differ in the course and response to treatment of their disease. AaCSU is more common than aiCSU, but surprisingly little is known about how many patients with CSU have aaCSU, how many have aiCSU, how many have both, and how many CSU patients have neither aaCSU nor aiCSU.

In a recent study published in The Journal of Allergy and Clinical Immunology: In Practice, Xiang and coworkers investigated 111 CSU patients for IgE autoantibodies, namely IgE directed against thyroid peroxidase or interleukin (IL)-24, which are markers of aaCSU. The same patients were also investigated for aiCSU, by use of the autologous serum skin test, basophil activation test, and measurements of IgG autoantibodies, specifically IgG directed against IgE or its receptor. They then compared clinical and laboratory features of patients with aaCSU, patients with aiCSU, and patients with both.

As expected, CSU patients more often had aaCSU (58%) than aiCSU (8%). Surprisingly, all but one patient with aiCSU also had aaCSU, whereas only 13% of aaCSU patients also had aiCSU. Four of ten patients (41%) had neither aaCSU nor aiCSU. Interestingly, patients with aaCSU tended to be younger than those without, whereas patients with aiCSU were more often female and had higher levels of thyroid peroxidase autoantibodies and more severely impaired quality of life. In patients who had both aaCSU and aiCSU, disease characteristics and laboratory findings were more similar to standalone aiCSU than aaCSU. The results of this study confirm that most patients with CSU have mast cell-activating autoantibodies, IgE and/or IgG, which is helpful to know for communicating with patients and for providing them with a concept that explains their disease. Importantly, this study, the first to characterize aaCSU and aiCSU, as well as their coexistence and characteristics in detail, demonstrates that most patients with aiCSU also have aaCSU, and that the different subgroups of CSU are linked to differences in laboratory and clinical features.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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