Most Patients With Autoimmune Chronic Spontaneous Urticaria Also Have Autoallergic Urticaria, but Not Vice Versa

Background Two endotypes of chronic spontaneous urticaria (CSU) associated with mast cell–activating autoantibodies are described, namely autoallergic chronic spontaneous urticaria (aaCSU; with immunoglobulin E [IgE]–anti-autoallergens) and autoimmune chronic spontaneous urticaria (aiCSU; with IgG–anti-high-affinity receptor for the Fc region of immunoglobulin E [FcεRI]/IgE). Objective To investigate the rates of CSU patients with aaCSU and aiCSU. Methods We analyzed 111 CSU patients for aaCSU (ie, IgE to thyroid peroxidase, interleukin 24) and for aiCSU (ie, a positive autologous serum skin and Basophil Activation Test plus immunoglobulin G [IgG]–anti-FcεRI/IgE). Clinical and laboratory parameters were compared in patients with aaCSU, aiCSU, and both. Results Across 111 patients with CSU, 64 (58%) had aaCSU and 9 (8%) had aiCSU. Eight of the 9 aiCSU patients had aaCSU, but only 8 of 64 patients with aaCSU had aiCSU. In total, 7% (8 of 111) of patients had both aiCSU and aaCSU, 41% (46 of 111) had neither, and 16% (18 of 111) tested negative for all markers of aaCSU and aiCSU assessed. Patients with aaCSU or aiCSU are different from those without: patients with stand-alone aaCSU tend to be younger than non-aaCSU patients, aiCSU, and aaCSU/aiCSU overlapping subpopulations. In contrast, patients with aiCSU, with or without aaCSU coexistence, are more often female, have higher levels of thyroid peroxidase autoantibodies (both IgG and IgE), and show more severe quality of life impairment. Conclusions Our novel finding that aiCSU coexisting with aaCSU needs to be confirmed in bigger cohorts and multicenter studies. Autoimmunity driven by autoreactive IgE and/or IgG in CSU needs further investigation for better understanding of the pathophysiology. Two endotypes of chronic spontaneous urticaria (CSU) associated with mast cell–activating autoantibodies are described, namely autoallergic chronic spontaneous urticaria (aaCSU; with immunoglobulin E [IgE]–anti-autoallergens) and autoimmune chronic spontaneous urticaria (aiCSU; with IgG–anti-high-affinity receptor for the Fc region of immunoglobulin E [FcεRI]/IgE). To investigate the rates of CSU patients with aaCSU and aiCSU. We analyzed 111 CSU patients for aaCSU (ie, IgE to thyroid peroxidase, interleukin 24) and for aiCSU (ie, a positive autologous serum skin and Basophil Activation Test plus immunoglobulin G [IgG]–anti-FcεRI/IgE). Clinical and laboratory parameters were compared in patients with aaCSU, aiCSU, and both. Across 111 patients with CSU, 64 (58%) had aaCSU and 9 (8%) had aiCSU. Eight of the 9 aiCSU patients had aaCSU, but only 8 of 64 patients with aaCSU had aiCSU. In total, 7% (8 of 111) of patients had both aiCSU and aaCSU, 41% (46 of 111) had neither, and 16% (18 of 111) tested negative for all markers of aaCSU and aiCSU assessed. Patients with aaCSU or aiCSU are different from those without: patients with stand-alone aaCSU tend to be younger than non-aaCSU patients, aiCSU, and aaCSU/aiCSU overlapping subpopulations. In contrast, patients with aiCSU, with or without aaCSU coexistence, are more often female, have higher levels of thyroid peroxidase autoantibodies (both IgG and IgE), and show more severe quality of life impairment. Our novel finding that aiCSU coexisting with aaCSU needs to be confirmed in bigger cohorts and multicenter studies. Autoimmunity driven by autoreactive IgE and/or IgG in CSU needs further investigation for better understanding of the pathophysiology.