Guidelines, Testing, and Future Directions in Urticaria

Dermatology Times recently interviewed Jason Hawkes, MD, MS, a medical dermatologist and principal investigator at the Oregon Medical Research Center in Portland, Oregon. Hawkes shared his extensive experience managing urticaria, both from a personal and professional perspective, shedding light on this multifaceted condition and its evolving therapeutic landscape.

Personal Insights and Clinical Understanding

Hawkes’ interest in urticaria began during medical school when he developed chronic cold urticaria. This personal experience led to a formal diagnosis and spurred his curiosity about the condition. Chronic inducible urticaria (CindU), such as cold urticaria, accounts for about 20% of chronic cases and differs significantly from chronic spontaneous urticaria (CSU). CindU is triggered by specific stimuli, like temperature changes, whereas CSU lacks identifiable triggers.

Hawkes emphasized the importance of thorough patient history and diagnostic tests in identifying urticaria subtypes. “One of the nice aspects of inducible urticaria is that we can do what we call provocation testing, or things that can elicit particular symptoms in those patients,” he said. “For example, with cold urticaria, we can put an ice cube on the inner forearm, let it sit for about 5 minutes or so, and then wait 10 or 15 minutes to see if a wheal forms in those sites. These don't always work. In my case, with cold urticaria, I failed the ice cube test, but I had a very consistent exposure and symptom correlation with cold.”

Interestingly, urticaria presentations are often complex, with some patients exhibiting a mix of chronic urticaria subtypes. This underscores the necessity for clinicians to recognize overlapping symptoms and triggers, allowing for tailored treatment approaches.

Treatment Strategies and Guidelines

Managing urticaria effectively requires distinguishing between acute and chronic cases. Hawkes says acute urticaria primarily affects children under 5 and resolves within weeks, often following an infection or allergen exposure. Conversely, chronic urticaria—affecting up to 40% of patients—persists and necessitates a systematic treatment approach.

Hawkes highlighted the use of treatment guidelines, including the American Academy of Allergy, Asthma, and Immunology (AAAAI) guidelines (revised in 2014) and international guidelines (updated in 2021 and under further revision). Both advocate for trigger elimination and second-generation antihistamine monotherapy as first-line treatments. However, international guidelines prioritize systemic biologic therapies, such as omalizumab, more swiftly than the AAAAI guidelines.

“The guidelines will say [to escalate to 4-fold dosing] between 1 to 4 weeks. Actually, I think practically, we can do this much quicker. Most patients already come in on antihistamine. The nice benefit with antihistamines is they're readily accessible and they're inexpensive, and they work quickly if they're going to work,” Hawkes noted.”I typically ask [patients] to add a pill about every 2 to 3 days. If they're still having symptoms, they typically will work pretty quickly. So really, within about 11/2 to 2 weeks, we can usually get up to that 4-fold dosing. In my experience, they're either going to respond to that 4-fold dosing or antihistamines in general, or they're not.”

Emerging Therapies

Luckily, Hawkes says the therapeutic horizon for urticaria is expanding. He discussed promising developments, including dupilumab and remibrutinib. Dupilumab, already widely used in dermatology for conditions like atopic dermatitis, has demonstrated efficacy in late-stage trials for CSU. Its versatility extends to patients with comorbid conditions such as asthma, enhancing its appeal.

Remibrutinib, a Bruton tyrosine kinase inhibitor, offers an oral alternative for patients averse to injections.Unlike other kinase inhibitors, remibrutinib has a favorable safety profile, with minimal concerns like petechiae in a small percentage of patients.

Other investigational therapies targeting mast cell receptors, such as anti-C-kit therapies and antibodies inducing mast cell depletion, hold potential to address the underlying mechanisms of urticaria comprehensively.

Unmet Needs and Future Directions

Despite these advancements, unmet needs persist. Hawkes emphasized the importance of evidence-based testing, noting the limited utility of broad diagnostic panels in urticaria. “[There is] one exception, the IGE levels that are often checked in patients, they do correlate with a better response with anti-IGE therapy, which is omalizumab,” Hawkes noted. “The problem is that we have patients with high IGE levels who don't respond to therapy, and we also have patients who have very low levels of IGE who are responsive to therapy.”

With this in mind, Hawkes says research into biomarkers remains a priority. Understanding why certain patients develop angioedema, or why some respond differently to therapies, could revolutionize treatment strategies.

As clinicians increasingly embrace urticaria management, collaboration with allergists and ongoing research will be pivotal in addressing the complexities of this challenging condition. With emerging therapies and a deeper understanding of underlying mechanisms, the future holds promise for improved patient care.