New consensus guidelines for the diagnosis and treatment of chronic spontaneous urticaria (CSU) mark an advance in evidence-based care. The 2026 published update to the international guideline and the forthcoming US American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters (AAAAI/ACAAI JTFPP) recommendations emphasize the up-dosing of antihistamines, the use of newer advanced therapies as next-step therapy, and the downgrading of higher-risk therapies. However, despite this progress, limited information on biomarkers and empiric treatment sequencing highlight ongoing gaps in CSU management.

This is a big year for patients with CSU because the new international guideline came out in print in February 2026, and the AAAAI/ACAAI JTFPP is slated to publish the new US guidelines later this year. The AAAAI/ACAAI JTFPP released the US guidelines for public comment just recently. This is a complete first draft, which I have read through, and it looks fantastic. After we incorporate the public comments, we can get it into publication. This is so important because many clinicians are using the current US guidelines, which are quite out of date, and, as a result, they are using therapies that may not have as much benefit as some of the newer therapies we have available now.

Personally, I have been using the international guidelines because they are published on a more frequent basis and are therefore more up to date. Hopefully, the US guidelines will be “living guidelines” and will be continuously reviewed and updated as new evidence becomes available, and I can use both. The updated international guideline specifically recommends starting with the licensed dose of a second-generation H₁ antihistamine; if that does not work, the guideline recommends increasing up to 4 times the licensed dose of that same second-generation H₁ antihistamine. Patients are sometimes skeptical of up-dosing, so I really have to explain to them that this is included in the guideline as the next step. Also, I stay with the same second-generation H₁ antihistamine. The guideline recommends up-dosing the same second-generation H₁ antihistamine instead of mixing antihistamines.

If antihistamines do not work, the international guideline says that we should add on an advanced therapy such as omalizumab, dupilumab, or remibrutinib. If this does not work, we can add cyclosporine to the up-dosed antihistamine. And if adding cyclosporine does not work, we can add experimental therapies to the antihistamine.

The older US guidelines state that if a patient fails second-generation H₁ antihistamines, you can add antihistamines that address the H2 receptor, a sedating or first-generation H₁ antihistamine before bed, and a leukotriene receptor antagonist before considering omalizumab or cyclosporine. Thus, the international guideline represents a shift in the way we take care of patients with CSU.

I am also in the midst of reviewing the latest US recommendations. I think that this updated approach, taking all the new data that we have available into account, is very good and eliminates some of the things to which Dr Mosnaim alluded, such as drugs that might help a little but not very much. We can thereby simplify treatment to only include drugs that we know have good efficacy, and patients can come under clinical control more quickly, so I agree with those changes. For example, I stopped using leukotriene receptor antagonists as an add on to antihistamine therapy long ago because we now have so many options. There is no reason to use a leukotriene receptor antagonist in a patient with CSU because it adds so little. The same is true of H2 receptor antagonists, which also have a limited role. So, I agree with Dr Mosnaim.

It will not be long before the new modern US guidelines are published, and I think that they will be very helpful. We have come a long way to where CSU can now be effectively treated in the vast majority of patients, which previously was not the case. However, we need to promulgate the most modern approach to CSU so that everyone—from primary care providers to specialists—knows about it. The primary care providers who see patients initially then might be more comfortable using a higher-than-usual antihistamine dose, which is a valid first step. However, after failing that, providers need to know that we have a lot of other therapeutic options, and it may be a good idea to make a referral to a specialist.

However, although we now have a lot of treatment choices, we still do not have good, really solid guidance on the drugs in terms of the order in which to try them. What would make you go one way or the other in treatment selection currently is often personal preference and empirical.

Now, once a patient is unresponsive to antihistamines, we have 3 advanced treatments (ie, remibrutinib, dupilumab, and omalizumab) that the international guideline suggests can be a next step. With remibrutinib, patients can take it orally twice daily, which is an advantage for those who do not like injections. With dupilumab, patients can inject themselves at home every 2 weeks. With omalizumab, after the first 3 doses, they too can inject themselves at home, but it is every 4 weeks. So, there are pros and cons with each advanced treatment.

However, we do not have definitive data or guideline recommendations on which therapy to use in a specific patient, and that has been the big problem with CSU. There are many different new agents in clinical development for CSU, and the problem is that we do not have good biomarkers. We are way behind the precision medicine that is used in oncology. It is almost an empiric choice as to which agent to use, and that is where we need help. And if there are another 20 new biologics, for example, that are US Food and Drug Administration (FDA) approved for CSU but there still are not good biomarkers, it is really going to be a decision that you need to make with the patient based on their comfort level with a particular treatment and on the efficacy and side effects data that you can glean from the literature and present to them. We are just too far behind oncology to be able to say to a patient, “Look, you are probably going to respond to this drug.”

The routine laboratory testing that is discussed in the 2026 international guideline is not very helpful in choosing an individual advanced therapy or in letting the patient know how long they are going to have the condition. So, while we have some biomarkers in asthma, in CSU, the blood test results do not really help me in guiding therapy. This is when shared decision making becomes important to determine which advanced treatment strategy best fits a patient’s lifestyle and comfort level.