Selective IgE Deficiency Predicts Poor or No Response of Chronic Spontaneous Urticaria to Omalizumab

Abstract

Selective immunoglobulin E deficiency (SIgED) has been reported associated with: autoimmunity, airway infections, asthma, enteropathy, chronic spontaneous urticaria (CSU), and malignancy [1][2][3]. CSU is a mast cell-driven disease characterized by itchy hives frequently associated with angioedema [4]. Although the cause is still being debated, some CSU cases have been linked to autoimmune mechanisms either mediated by IgE autoantibodies (Type I), or by IgG antibodies (Type II) [4]. Omalizumab (a recombinant, humanized anti-IgE antibody) binds IgE and reduces levels of both free IgE and FcϵR1 expression on mast cells and basophils [4]. Treatment guidelines recommend a four-step approach for CSU management. Omalizumab is included in the third line as add-on therapy to second-generation H1antihistamines (H1-AHs). In patients who remain inadequately controlled with omalizumab, treatment with immunosuppressive drugs, such as cyclosporine, is recommended as a fourth-line drug. Response to treatment is usually measured with the Urticaria Activity Score (UAS7) [5]. The licensed dose of omalizumab in Europe is 300 mg administered every four weeks. However, augmenting the dose or shortening dose intervals, may provide better symptom control in patients with limited response to the 300 mg dose [6]. It has been shown that low IgE levels, basopenia and eosinopenia prior to initiation of omalizumab therapy are associated with a reduced clinical efficacy [7]. We tested the hypothesis that patients with SIgED would represent the group of patients with the poorest response to omalizumab. We retrospectively evaluated six patients with CSU associated with SIgED (IgE ≤2 kU /L) and treated with omalizumab, from a cohort of patients reported recently [3]. The study was approved by the Ethics Committee . Demographic data, disease features, comorbidities, laboratory results, omalizumab dosage and treatment outcomes were collected. All patients were female with ages ranging from 46 to 66 years. In four patients, CSU was associated with angioedema. Three patients had associated immune diseases. IgG anti-thyroid peroxidase (aTPO) was found elevated in four among five patients tested, while D-Dimer was assessed and found elevated in three. All but one patient were basopenic, while significant eosinopenia was present in two patients (Table 1). None of the patients achieved adequate control with maximum oral H1-AH dose, and they all also required frequent oral corticosteroid treatment to control flares of CSU. Patients were initially treated with a 300 mg monthly dose of omalizumab. When a partial or null response to omalizumab was observed based on the UAS7 score, either