Science of Skin Urticaria Discussion Highlights Expanding Treatment Options and Need to Measure Disease Control

The growing treatment armamentarium for chronic spontaneous urticaria (CSU) is giving dermatologists more opportunities to individualize therapy, but effective management begins with fundamentals: selecting and adequately dosing antihistamines, identifying relevant comorbidities, measuring disease activity, and establishing an appropriate therapeutic goal.

During a case-based discussion at the Science of Skin Summit, meeting organizer Ted Lain, MD, MBA, FAAD; Practical Dermatology Chief Medical Editor Neal Bhatia, MD, FAAD; and Michelle Tarbox, MD, presented patients illustrating different challenges encountered in CSU management, from refractory disease and polypharmacy to treatment selection for women considering pregnancy. 

Comorbidities Can Inform Treatment Decisions

Dr. Lain presented a 37-year-old woman with a 2-year history of CSU and nearly daily breakthrough symptoms affecting sleep and quality of life. Despite prolonged treatment with second-generation antihistamines, she continued to experience flares that led to repeated courses of systemic corticosteroids.

After increasing her second-generation antihistamine to 4 times the standard dose failed to achieve control, Lain investigated relevant comorbidities and discovered a history of atopic dermatitis (AD) that had been poorly controlled with topical therapy.

That history influenced his decision to initiate dupilumab. Although the patient's hives decreased by approximately 50%, her response plateaued. Because her AD had improved substantially, Dr. Lain did not want to abandon dupilumab and ultimately added hydroxychloroquine, which he reported provided additional benefit.

The case underscored the potential importance of taking a broad medical history rather than approaching CSU in isolation. Dr. Lain also emphasized that some difficult-to-control patients ultimately require multiple therapies simultaneously. 

A New Option for Refractory CSU

Dr. Bhatia presented a 22-year-old woman with extensive CSU and angioedema who had previously received numerous therapies, including hydroxychloroquine, azathioprine, antihistamines, and dupilumab. Her disease remained severe, and prior treatments complicated efforts to enroll her in clinical trials.

Dr. Bhatia ultimately transitioned the patient to remibrutinib following its US Food and Drug Administration (FDA) approval. He highlighted the rapid responses observed with the Bruton tyrosine kinase inhibitor in clinical studies and contrasted its targeted mechanism with some of the older immunosuppressive approaches historically used for difficult CSU.

Dr. Bhatia said the availability of newer therapies raises questions about where older systemic agents should fit into the modern treatment algorithm, particularly when their toxicity and monitoring requirements are considered.

He also emphasized that previous exposure to a therapy operating through one pathway should not necessarily predict response to a treatment targeting a different mechanism. 

Not All Antihistamine Regimens Are Equal

Dr. Tarbox's case centered on a 26-year-old woman with nearly daily pruritic wheals, intermittent eyelid angioedema, dermatographism, poor sleep, and a Urticaria Activity Score over 7 days (UAS7) of 30, placing her disease in the severe range.

Despite the patient taking 3 antihistamines (loratadine, diphenhydramine, and promethazine), Dr. Tarbox argued that the regimen did not constitute an adequate therapeutic trial.

Dr. Tarbox emphasized choosing a second-generation H1 antihistamine based on its pharmacologic characteristics and the individual patient's needs. She described cetirizine as potent and fast-acting but potentially sedating at higher doses, whereas fexofenadine offers an important nonsedating option for patients whose work requires sustained alertness.

Once an appropriate agent is selected, Dr. Tarbox recommended escalating from the standard dose to 2 times and, when necessary, as much as 4 times the standard daily dose, stopping escalation once control is achieved. She noted that such updosing is off-label but guideline supported.

“Pick one agent,” Dr. Tarbox advised, rather than leaving patients on a “carousel of useless antihistamine shuffling.” 

Dr. Tarbox also questioned several familiar approaches to CSU. She noted that first-generation antihistamines add sedation and anticholinergic burden, while H2 blockers and montelukast no longer have prominent roles in contemporary guideline-based management. Chronic systemic corticosteroids, meanwhile, should not be used as maintenance therapy.

She also stressed an important point for patient counseling: CSU should not automatically be treated as an allergic disorder requiring trigger identification or elimination diets. 

Pregnancy Plans Can Affect Treatment Selection

Dr. Tarbox's patient also hoped to become pregnant within 6 to 12 months, making reproductive considerations particularly important.

Dr. Tarbox noted that CSU disproportionately affects women, many of whom develop disease during their reproductive years. For this patient, she selected omalizumab because of its pregnancy experience.

For CSU, Dr. Tarbox described omalizumab dosing as a fixed 300-mg subcutaneous dose every 4 weeks rather than dosing based on body weight or IgE. Second-generation antihistamine therapy should be continued alongside it.

Some patients may respond quickly, whereas others require substantially more time. Dr. Tarbox recommended reassessing response around 12 weeks and allowing patients with partial responses additional time, potentially extending treatment to approximately 6 months before determining that the therapy has failed.

Once sustained control is achieved, she suggested periodically attempting to extend the dosing interval because CSU can remit over time. 

Measuring CSU Is Part of Treating CSU

Across the cases, the speakers emphasized that impressions such as “better” or “worse” are insufficient for managing a disease whose manifestations fluctuate substantially.

The UAS7 incorporates both hive burden and itch over 7 days, generating a score ranging from 0 to 42. Dr. Tarbox described scores of 1 to 6 as well controlled, 7 to 15 as mild, 16 to 27 as moderate, and 28 to 42 as severe.

The panel noted that measures such as UAS7 and the Urticaria Control Test (UCT) have practical importance beyond clinical trials. They can document disease burden, track therapeutic response, and provide objective evidence when seeking insurance authorization for advanced therapies.

Although complete freedom from hives represents a high therapeutic bar, Dr. Tarbox said it can be achievable for many patients through additional therapies, dose optimization, or changes in dosing intervals.

The broader message from the session was that difficult CSU should prompt clinicians to reassess not only which drug comes next, but whether existing therapy has been optimized, whether comorbidities affect treatment selection, and whether response is being measured adequately enough to guide the next decision.