Detecting Histaminergic vs Non-Histaminergic Responders in Chronic Spontaneous Urticaria

Introduction to Chronic Spontaneous Urticaria Endotypes

The American Academy of Allergy, Asthma, and Immunology recommends measuring total IgE and IgG-anti-TPO levels to distinguish histaminergic from non-histaminergic CSU, with a high IgG-anti-TPO to total IgE ratio indicating autoimmune CSU 1, 2, 3

Patients who fail to respond to standard or updosed H1-antihistamines are more likely to have non-histaminergic (autoimmune) CSU, as suggested by the European Academy of Allergy and Clinical Immunology 4, 5, 6
The 2022 international urticaria guidelines, supported by the American College of Allergy, Asthma, and Immunology, recommend a basic workup including total IgE level, IgG-anti-TPO, and their ratio to differentiate endotypes 1, 2, 3, 4, 5
Elevated IgG-anti-TPO levels indicate autoimmune CSU, according to the European Academy of Allergy and Clinical Immunology 1, 2, 3, 4, 5, 6
A high IgG-anti-TPO to total IgE ratio is the best surrogate marker for autoimmune CSU, identifying non-histaminergic responders, as recommended by the American Academy of Allergy, Asthma, and Immunology 1, 4

For histaminergic responders, the American College of Allergy, Asthma, and Immunology suggests progressing through antihistamine updosing and potentially advancing to omalizumab if needed 1, 2, 5, 6
The European Academy of Allergy and Clinical Immunology notes that non-histaminergic responders may require earlier advancement to omalizumab or cyclosporine, with cyclosporine being particularly effective in this population 4, 5, 6