D1.231 - When Antihistamines Paradoxically Worsen Chronic Spontaneous Urticaria: Trust Your Patient
Case report
H1-antihistamines are a vital part of treating patients with Chronic spontaneous urticaria (CSU). However, the situation becomes challenging when patients report paradoxical exacerbations after using standard antihistamines. We describe a 10-year history of CSU in a male patient in his 40s who experienced paradoxical worsening of symptoms upon exposure to multiple H1-antihistamines, including fexofenadine and cetirizine, as evidenced by patient-reported and photographic evidence of severe, generalized hives. This phenomenon aligns with recent findings by Soria et al. (2024), who identified a small subset of patients demonstrating “paradoxical urticaria” triggered by H1-antihistamines rather than alleviated by them.
The only reliable co-factor for the patient’s urticarial flare-ups was temperature; Nonsteroidal anti-inflammatory drugs, often contraindicated in urticaria, did not appear to worsen symptoms. Given the patient’s paradoxical worsening to standard therapies, intermittent bursts of oral prednisolone (30–40 mg) were necessary to control acute flares. Unfortunately, the need for frequent steroid use raised concerns for both corticosteroid-related adverse effects and inadequate disease control.
Following assessment, and in line with National Institute for Health and Care Excellence (NICE) guidelines for refractory CSU, a trial of montelukast was initiated to further optimise medical therapy before pursuing omalizumab. A trial of simultaneous H1 and H2 blockade has also been initiated, and a follow-up is due to take place in January 2025.
In conclusion, this case highlights the need for individualised treatment plans for CSU with paradoxical reactions to antihistamines, and vigilance when introducing or escalating doses of H1-antihistamines, in selected cases. Future research should explore the underlying immunologic mechanisms of these reactions, including the possibility of genetic variants leading to compensatory up-regulation of other antihistamine receptor pathways or partial agonist activity due to structural variants of histamine receptors. Such detailed understanding will be helpful to improve therapeutic outcomes for this challenging subset of patients.
