Chronic Spontaneous Urticaria: Bringing It Back Where It Belongs – A Disease State Update

At the 2026 ODAC Dermatology Conference, we had the privilege of learning about chronic spontaneous urticaria (CSU) from Dr. Adam Friedman, MD, FAAD, Professor and Chair of Dermatology at The George Washington University School of Medicine. CSU can be a maddening, exhausting condition for patients, with a relapsing disease course and without identifiable triggers. Given that symptoms are often absent during clinical visits and regimens are often adjusted for breakthrough symptoms, CSU requires particularly strong patient-provider trust. Dr. Friedman called dermatologists to action to retake ownership of managing patients with CSU, sharing his expertise about clinching the diagnosis and newly approved treatment options.

Diagnosis

Dr. Friedman recommended leaning on the clinical diagnostic criteria to pinpoint CSU. The quality of pruritus can be a burning itch, with each single lesion “moving” to different locations on the body and never persisting in one area for more than 24 hours. Episodes last longer than 6 weeks, typically without identifiable triggers of chronic inducible urticaria, such as heat, cold, exercise, pressure, water, sun exposure, and vibration. However, patients with CSU can still have overlap features with chronic inducible urticaria and angioedema. Because symptoms mostly do not align with the dermatology appointment, Dr. Friedman recommends patients keep a diary and snap photos before every medical visit.

For laboratory workup, he declared “lab less, talk more!” Consensus guidelines advise against a full panel for bloodwork in CSU.^1-3 Use review of systems to guide any targeted initial labs such as thyroid stimulating hormone for a small subset of patients. In the context of only transient active lesions, a skin biopsy is typically not helpful but should be considered if individual lesions are atypical, lasting more than 48 hours, and refractory to therapy.

Management

Analogous to what we see in other inflammatory disease states such as psoriasis, emerging evidence shows increased cardiovascular risk in patients with CSU, amongst other co-morbid (not causal) diseases.⁴ Medical expert groups have published various treatment algorithms, with a common theme of escalating quickly to achieve clearance and normalize quality of life.^1-3 Monotherapy with H1 antihistamines is first-line, with the option to safely escalate to fourfold the standard dose.^1-3 To minimize the risk of drowsiness with increased doses, Dr. Friedman opts for the non-sedating second-generation antihistamines, noting that cetirizine is on-label for children 6-12 years of age and fexofenadine is indicated over-the-counter for children at least 12 years of age. Furthermore, oral vitamin D (4000 IU) can be a low-hanging adjunct to antihistamines.⁵

“The present is flaring” with now multiple targeted options for escalating past antihistamines! Free IgE can be targeted with subcutaneous omalizumab, with pre-treatment IgE level and weight no longer dictating the dosing.^1-3 Although up to 300mg every 4 weeks has been approved by the United States Food and Drug Administration (FDA), beyond-label doses of 450mg or 600mg every 4 weeks can be considered for partial responders.^6-8 Subcutaneous dupilumab was approved by the FDA in April 2025, with the pivotal clinical trials demonstrating at least well-controlled symptoms (Urticaria Activity Score over 7 days ≤6) for about 50% of patients.⁹ Oral remibrutinib, a Bruton’s tyrosine kinase blocker FDA-approved in Sept 2025, works FAST for CSU, showing clinically meaningful improvement in the pivotal clinical trials by 1-2 weeks in about 65% of patients.¹⁰ Mucocutaneous bleeding tends to be petechial, without an association between platelet count and bleeding reactions.¹⁰ Furthermore, patients on aspirin and clopidogrel were included in the clinical trials, reflecting real-world clinical context when considering this safety data. For the inevitable patient question of “when can I stop my medications,” Dr. Friedman recommended clearance of itch and rash for at least 6 months before considering tapering off medical management.

In conclusion, CSU can be a frustrating, debilitating condition, with persistence beyond 5 years for about 20% of patients.¹¹ We now have more options to offer than ever before, including a medication with which dermatologists are already comfortable for other indications. With an increasing number of promising therapies in the pipeline, dermatology is primed to once again embrace managing CSU.

References

1. 1. Zuberbier T, Abdul Latiff AH, Abuzakouk M, et al. The international EACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2022 Mar;77(3):734-766. PMID: 34536239.
   2. Bernstein JA, Lang DM, Khan DA, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol. 2014 May;133(5):1270-7. PMID: 24766875.
   3. Sabroe RA, Lawlor F, Grattan CEH, et al; British Association of Dermatologists’ Clinical Standards Unit. British Association of Dermatologists guidelines for the management of people with chronic urticaria 2021. Br J Dermatol. 2022 Mar;186(3):398-413. Epub 2022 Jan 27. PMID: 34773650.
   4. Curman P, Thaçi D, Ludwig RJ. Increased cardiovascular risk in chronic spontaneous urticaria: a large real-world cohort study. Allergy. 2025 Oct 25. PMID: 41137491.
   5. Rorie A, Poole JA. Vitamin D supplementation: a potential booster for urticaria therapy. Expert Rev Clin Immunol. 2014 Oct;10(10):1269-71. PMID: 25155458.
   6. XOLAIR [prescribing information]. Genentech USA, Inc. and Novartis Pharmaceuticals Corporation; 2021. Accessed Jan 18, 2026.
   7. Al-Shaikhly T, Rosenthal JA, Ayars AG, Petroni DH. Omalizumab for chronic urticaria in children younger than 12 years. Ann Allergy Asthma Immunol. 2019 Aug;123(2):208-210.e2. PMID: 31082483.
   8. Sussman G, Hébert J, Gulliver W, et al. Omalizumab re-treatment and step-up in patients with chronic spontaneous urticaria: OPTIMA trial. J Allergy Clin Immunol Pract. 2020 Jul-Aug;8(7):2372-2378.e5.
   9. Maurer M, Casale TB, Saini SS, et al. Dupilumab in patients with chronic spontaneous urticaria (LIBERTY-CSU CUPID): Two randomized, double-blind, placebo-controlled, phase 3 trials. J Allergy Clin Immunol. 2024 Jul;154(1):184-194. PMID: 38431226.
   10. Metz M, Giménez-Arnau A, Hide M, et al. Remibrutinib in chronic spontaneous urticaria. N Engl J Med. 2025 Mar 6;392(10):984-994. PMID: 40043237.
   11. Weller K, Siebenhaar F, Hawro T, et al. Clinical measures of chronic urticaria. Immunol Allergy Clin North Am. 2017 Feb;37(1):35-49. PMID: 27886909.