Stepwise Care in Chronic Spontaneous Urticaria

Chronic spontaneous urticaria (CSU) affects up to 1% of the global population, significantly impacting quality of life through itching, sleep disruption, and psychological stress.¹ Recent research offers updated insights into CSU pathophysiology, triggers, and therapeutic strategies, underscoring the importance of timely, individualized management.²

Understanding of Triggers

CSU often follows a relapsing–remitting course, with several factors known to exacerbate disease activity. Reseachers noted recent analyses confirm that nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, stress, and infections are among the most frequent contributors. NSAID hypersensitivity is reported in up to one-third of patients with CSU, although reproducible reactions occur less often. This variability supports a tailored approach, with avoidance recommended only in patients with clear histories of exacerbation. Evidence linking diet to CSU activity remains limited, and systematic reviews show little benefit from restrictive diets. Clinicians are encouraged to guide patients in avoiding unnecessary elimination regimens that could lead to nutritional compromise.

Stepwise Pharmacologic Therapy

The updated review reinforces second-generation H1-antihistamines (sgAHs) as the foundation of CSU treatment. While standard doses achieve symptom control in approximately half of patients, up-dosing up to fourfold has been shown to be safe and more effective. Importantly, researchers stated prolonged ineffective antihistamine use should be avoided to prevent delays in achieving disease control.

Validated tools such as the Urticaria Activity Score (UAS7) and Urticaria Control Test (UCT) remain essential for monitoring disease activity and guiding treatment adjustments. When patients achieve complete control for 3 to 6 months, tapering of antihistamines can be considered, with gradual reductions preferred to minimize relapse.

Advances in Biologic Therapy

Researchers stated omalizumab continues to represent the cornerstone of biologic therapy for CSU unresponsive to antihistamines. Administered at 300 mg every 4 weeks, it achieves control in most patients, with nearly 60% experiencing rapid improvement within the first month. Real-world data suggest response rates of 85%, including complete remission in more than half of patients.

For partial responders, recent studies highlight the benefits of dose escalation or shortened dosing intervals, although these remain off-label. Tapering strategies after remission remain debated, but evidence suggests that gradual spacing of injections reduces relapse risk compared to abrupt discontinuation.

Role of Cyclosporine A

Cyclosporine A (CsA) remains a third-line therapy, particularly useful in autoimmune CSU. Clinical data support effectiveness at low to moderate doses (2–4 mg/kg/day), with improvement often observed within weeks. However, its use requires careful monitoring due to risks of hypertension, nephrotoxicity, and metabolic complications. Research also indicates that relapse after CsA discontinuation can often be managed with retreatment.

Management in Special Populations

Researchers stated recent findings emphasize the need for population-specific approaches:

• Children and Adolescents: Standard-dose sgAHs remain first-line, with up-dosing as needed. Omalizumab is supported for patients aged 12 and older, with emerging data for younger children. CsA is reserved for refractory cases.
• Pregnancy: Loratadine and cetirizine are preferred, with omalizumab considered for severe, antihistamine-refractory disease. CsA is generally avoided due to associations with maternal hypertension and low birth weight.
• Elderly: Treatment mirrors general guidelines but requires caution due to polypharmacy, altered pharmacokinetics, and heightened sensitivity to sedation or adverse events.

Future Directions

Ongoing work highlights gaps in identifying reliable biomarkers to predict treatment response. Although IgE levels, basophil tests, and inflammatory markers show potential, none are yet validated for routine use. The arrival of omalizumab biosimilars, as well as emerging therapies such as dupilumab and Bruton’s tyrosine kinase inhibitors, promises to expand therapeutic options and improve access.

Conclusion

This recent research reinforces a stepwise approach to CSU management, emphasizing prompt escalation when antihistamines are insufficient and tailoring therapy to individual patient needs. Antihistamines remain first-line, omalizumab is central to biologic treatment, and cyclosporine is reserved for refractory cases. Special considerations for children, pregnant individuals, and elderly patients highlight the importance of personalized care. With novel therapies on the horizon and expanded real-world data collection, clinicians are better equipped than ever to improve outcomes for patients living with CSU.

References

1. Zuberbier T, Ensina LF, Giménez-Arnau A, et al. Chronic urticaria: unmet needs, emerging drugs, and new perspectives on personalised treatment. Lancet. 2024;404(10450):393-404. doi:10.1016/S0140-6736(24)00852-3
2. Kocatürk E, Chu DK, Türk M, et al. Management of chronic spontaneous urticaria made practical: What every clinician should know. J Allergy Clin Immunol Pract. Published online July 21, 2025. doi:10.1016/j.jaip.2025.07.021