SAN DIEGO — New insight into the roots of chronic spontaneous urticaria (CSU) and an expanding toolbox of therapies are transforming the understanding of the disease, a dermatologist told colleagues at the 2025 CalDerm-Pacific Dermatologic Association Joint Meeting.

As the treatment landscape changes, it’s time for dermatologists to play a larger role in CSU management, said April Armstrong, MD, MPH, professor and chief of dermatology at the University of California, Los Angeles. “CSU has long been in the realm of allergy, but it’s time we take it back. With new therapies available and more coming soon, we can really address moderate-to-severe disease and improve outcomes for our patients.”

As Armstrong explained, there are two types of urticaria: acute, with recurrent wheals lasting less than 6 weeks, and chronic, with symptoms lasting more than 6 weeks. “Eighty percent of chronic urticaria is chronic spontaneous urticaria,” she said. “That means 80% of the time, you may not be able to find a cause. Only 20% of cases are inducible.”

Data suggest that CSU affects about 1% of the world’s population, with a 2:1 female-to-male ratio, she said. “About half of your patients will go into remission within the first 12 months, with or without therapy,” she said. However, “roughly 11% of patients will have symptoms for more than 5 years. For those patients, it can be quite debilitating.”

As for pathogenesis, she said that’s only been a focus of research in the past few years. “We know that mast cells are central to the chronic path to the pathogenesis of CSU. In addition to that, we also have basal cells that are important, and even B cells can be involved in chronic spontaneous urticaria.”

In regard to the treatment of CSU, Armstrong highlighted second-generation antihistamines:

Cetirizine and levocetirizine. Both are available over the counter and are “very potent, but there is some price to pay. Overall, second-generation antihistamines are less sedating than the first generation,” but still can cause some sedation.

Desloratadine and loratadine. Both have “good potency with much less sedation. This is where I tend to move if sedation is an issue.”

Fexofenadine. “If your patient is extremely sensitive to sedation, this is a good option. But the trade-off is lower potency and some absorption caveats if taken with juice. You need to wait at least 4 hours before or 2 hours after drinking juice to take it.”

As for biologics, one option is omalizumab, approved for treating CSU in patients aged 12 years or older, which Armstrong said is mainly used by allergists. “About a third of patients will achieve complete clearance of their hives and itch by week 12. That’s quite good efficacy for a condition that can be so resistant.”

She noted that dosage is not dependent on serum immunoglobulin E (IgE) level. “It doesn’t matter if a patient has a low or high serum IgE level. You can still use this. However, subgroup analyses have shown that patients with higher IgE levels tend to actually respond a little bit better, not surprisingly, than those who have normal IgE levels.”

She also highlighted the approval of dupilumab for CSU in April. “By week 24, about 30% of patients will achieve a UAS7 [Weekly Urticaria Activity Score] of zero, meaning no hives and no itch. The safety profile is very consistent with what we’ve already seen in atopic dermatitis.”

As for the future, she said several classes of mediation are under investigation, including mast cell depletion and anti-IgE therapies, JAK inhibitors, Bruton tyrosine kinase (BTK) inhibitors, and other anticytokine therapies. 

Armstrong also referred to remibrutinib, a BTK inhibitor in late-phase development for CSU by Novartis. “In the clinical trials, we see very rapid improvement, decreasing activity in both the hives and the itch over time. About 40% of patients by week 24 achieve complete clearance with this oral, twice-daily medication.”

Armstrong disclosed having relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly and Company, EPI, Incyte, Janssen Pharmaceuticals, Leo Pharma, ModMed, Novartis, Ortho, Pfizer, Regeneron, Sanofi, Sun, and UCB.