D2.89 - Basophil Testing Beyond Positivity: Are There More Endotypes in Chronic Spontaneous Urticaria?

Background:Chronic spontaneous urticaria (CSU) is a heterogeneous mast cell–driven disease traditionally classified into IgE-mediated and autoimmune type IIb endotypes. Basophil activation testing (BAT) has been increasingly used to identify autoimmune type IIb CSU. However, emerging evidence suggests that basophil phenotype and basal activation status may provide additional pathophysiological information beyond a simple serum-induced activation readout.

Case description: We report a 34-year-old woman with severe CSU characterized by daily wheals and recurrent facial angioedema, refractory to multiple second-generation H1-antihistamines (loratadine, levocetirizine, bilastine and rupatadine) at up to fourfold doses, as well as montelukast 10 mg. Disease onset followed Parvovirus B19 exposure. The patient also reported symptomatic dermographism. Sustained control was only achieved with continuous low-dose oral corticosteroids (prednisolone 5 mg/day), with rapid relapse upon withdrawal. Disease burden was high (Urticaria Control Test = 4; Dermatology Life Quality Index = 18).

She had a history of IgE-mediated anaphylaxis to crustaceans and molluscs, confirmed by elevated specific IgE, requiring strict avoidance and adrenaline autoinjector prescription. Past medical history included well-controlled hypothyroidism under levothyroxine. Extensive laboratory evaluation excluded systemic inflammation, autoimmune disease and mast cell disorders. Thyroid function was normal with negative anti-TPO antibodies. Total IgE was mildly elevated (144 IU/mL).

BAT using donor basophils incubated with patient serum was negative. However, flow cytometric phenotyping of the patient’s own basophils revealed reduced FcεRI expression, increased CD203c expression and a higher proportion of CD69-positive basophils, consistent with chronic basal activation.

Given severe corticosteroid-dependent CSU refractory to high-dose antihistamines, omalizumab was initiated, leading to rapid clinical improvement, complete corticosteroid withdrawal and sustained disease control after one month.

Conclusion: Despite severe, treatment-refractory disease, the absence of serum-induced basophil activation argues against classical type IIb autoimmune CSU. Detailed basophil phenotyping revealed increased basal activation, highlighting the limitations of a binary BAT interpretation and supporting the existence of additional, incompletely characterized CSU endotypes.