INTRODUCTION
An estimated 15-25% of the population has previously experienced urticaria, with the highest prevalence in women and the middle-aged population.1 Chronic urticaria (CU) is defined as wheals, angioedema, or both, that persist for more than 6 weeks.2 CU affects an estimated 0.5 - 2.3% of the population annually and negatively impacts patients’ quality of life.3 The negative impact of CU can be attributed to decreased sleep quality and psychological issues that persist for years with the disease.
Diagnosis
Chronic urticaria is classified into two subgroups: chronic spontaneous urticaria (CSU) and inducible urticaria. Inducible urticaria has an identifiable external trigger, such as temperature, pressure, heat, or vibration. On the other hand, more than 65% of CU is categorized as chronic spontaneous urticaria (CSU).4
CSU is characterized by pathologic mast cell and basophil activation and degranulation, leading to inflammatory mediator release. Mast cells, the primary mediator of CSU, release preformed mediators that increase vascular permeability such as histamine, tryptase, and leukotrienes.5 Mast cell activation also promotes a delayed production of cytokines that attract inflammatory cells like eosinophils and T cells.
The most popular current theory behind CSU pathogenesis is that it is autoimmune. CSU patients may be differentiated into two autoimmune endotypes based on the Gell and Coombs hypersensitivity classification. Type I CSU patients have IgE against self-antigen leading to pathologic mast cell activation.6 Patients with this endotype demonstrate higher levels of IgE against thyroid peroxidase (TPO) than in healthy patients.7 Over 200 additional IgE antibodies against autoantigens have been also identified, such as IL-24 and thyroglobulin.8 CSU patients with IgE anti-TPO experience higher rates of comorbid allergic disease.9
Type IIb CSU patients have IgG against self-antigen, most commonly IgE or FcεRI (the receptor for IgE).10 Antibodies against FcεRI are the more common of the two. Using strict criteria, this endotype (Type IIb) is thought to be less common. However, clinical severity is greater responsiveness to standard treatment (antihistamines and omalizumab) is decreased.6 Type IIb patients also have higher rates of comorbid autoimmune diseases, most commonly Hashimoto thyroiditis (60%) and vitiligo (7%).11,12
Diagnosis
To diagnose chronic spontaneous urticaria, inducible CU must be excluded. At the present time, the European Academy of Allergology and Clinical Immunology (EEACI), and Global Allergy and Asthma European Network (GA2LEN) generally advise against routine utilization of costly screening programs to determine the cause of urticaria. Only a differential blood count, erythrocyte sedimentation rate, and C-reactive protein measurement are recommended.
As diagnostic tests become less costly in the future, there may be utility in determining a CSU patient's endotype, such as for planning a patient's treatment. There is data that Type I CSU patients who have increased IgE against TPO are responsive to omalizumab.13 Patients who have positive BHRA or BAT (tests for Type IIb CSU) have poor response to omalizumab, but good response to cyclosporine.14,15
