Chronic spontaneous urticaria (CSU) was once notoriously difficult to manage, with limited options and substantial patient burden. Although new and emerging therapies offer promise in improving outcomes, challenges remain, including those related to improving education about CSU management and treating special populations such as pregnant women and young children.

CSU can present with symptoms that are very disturbing to the patient. For example, patients with CSU may be covered with hives and/or have troubling itching, and 40% can have angioedema of the lips, face, eyes, and even tongue. Moreover, the disability and anxiety that CSU causes are substantial, especially when we did not have effective drugs.

The landscape of CSU is changing as we speak. Historically, CSU has had a reputation of being notoriously difficult to treat because, for years, we did not have good drugs to treat it. When I started practicing, we had antihistamines followed by steroids, and steroids are now considered contraindicated for chronic use because of their systemic side effects. Now, with all the drugs we have, I would no longer characterize CSU as being particularly difficult to treat if the physician is up to date on how to use the available drugs and has experience caring for patients with CSU, although it may take a little while after starting treatment to get things under control.

One of the challenges we have is educating physicians about effective CSU management. Plenty of physicians are still not following the guidelines and are still using corticosteroids in these patients. Typically, who will a patient with CSU see first? Their family medicine or internal medicine physician, and they may not have the same experience with CSU as an allergist or a dermatologist. So, physicians need to be aware of the signs and symptoms of CSU and be comfortable making referrals, as appropriate.

For first-line therapy, nonsedating antihistamines are recommended, and the dose can be increased to up to 4-fold the standard dose. That is often necessary. Approximately 40% to 45% of patients respond. For nonresponders, omalizumab is the next choice. An injection of 300 mg every 4 weeks stops the urticarial process in approximately 40% to 45% of patients, and 65% to 70% still have a satisfactory outcome. While oral daily cyclosporine has been recommended as the next step for nonresponders to both antihistamines and omalizumab, newer drugs (as discussed below) are likely to supplant it. Nevertheless, the success rate with cyclosporine also approaches the 70% mark, but it requires blood pressure and renal function monitoring. The newly US Food and Drug Administration (FDA)–approved drugs for CSU are dupilumab and remibrutinib. The latter is taken orally and suppresses skin mast cell activation.

Unfortunately, we do not have good biomarkers to consistently help us treat patients with CSU. We have learned that if a patient’s IgE level is particularly low, then they may not respond well to omalizumab, since it binds to circulating IgE. Cyclosporine is sort of a paradox because it seems to work better on sicker patients, but the side effects associated with its use still have to be considered. And to monitor the therapeutic efficacy of any drug, the severity of hives, the presence of angioedema, and the severity of itch also have to be clinically monitored. Finally, validated questionnaires such as the Urticaria Control Test (UCT) can help the clinician and patient track whether the patient is responding.

Further, there are still special cases of CSU that require additional care, including CSU in women who are breastfeeding or pregnant, as well as CSU in children. If one of the drugs passes into breast milk, it might be contraindicated during breastfeeding. Additionally, you would never use cyclosporine during pregnancy. There are some data on the use of omalizumab during pregnancy, but less is known about remibrutinib and dupilumab. Omalizumab has been studied in young children. There are also data with dupilumab in children, and remibrutinib has ongoing trials in pediatric patients. However, you need data in these subpopulations to say with certainty whether it should be used, so that is still an open question.