Rethinking CSU as a Mast Cell Problem
In this special conference coverage from the 2026 Elevate-Derm RAPIDS Conference, host Victoria Garcia-Albea, NP, sits down with allergist Payel Gupta, MD, to unpack the interplay between allergy and dermatology. Gupta opens with her lecture on chronic spontaneous urticaria (CSU), emphasizing that mast cells are the major drivers of the pathophysiology, and that clinicians need to think about the multiple pathways that lead to their degranulation.
Gupta walks through the high-affinity FcεR1 receptor on mast cells and how cross-linking of that receptor causes degranulation — cross-linking that can happen in different ways. In CSU patients there are autoimmune and autoallergen components at play, which she frames as the type 1 (autoallergic) and type 2B (autoimmune) endotypes. She notes these endotypes can coexist in the same patient, and that some patients may have neither, which matters as clinicians treat and consider future therapies.
She also points to internal targets like BTK phosphorylation inside the mast cell and how it propagates activation, as well as the IL-4/IL-13 pathway and how blocking it affects downstream effects of degranulation. Her broader message: the CSU therapeutic landscape is changing quickly, and that's a good thing for patients because every body is different and what works for one may not work for another.
Give Patients All Their Options — Even in a Short Visit
One of Gupta's strongest practical points is about how clinicians communicate. CSU patients have often been on a long journey through multiple subspecialists, and she stresses the value of making sure they leave the visit feeling hopeful. Garcia-Albea highlights Gupta's use of shared decision-making — laying out that if one option doesn't work, there are others to come back for.
Importantly, Gupta clarifies that this doesn't require a lengthy speech. If a patient is only on a once-daily second-generation antihistamine and will likely respond to up-titrating to four times daily, providers don't need to detail every medication or side effect. But they should mention that more advanced therapies exist if the antihistamine approach fails, so patients know the road doesn't end there.
Gupta describes herself as a low-paper clinician and, rather than handouts, refers patients (and interested providers) to her podcast, The Itch, which is aimed at patients and caregivers. Her point applies broadly: medical education trains us in a new language, and it's easy to forget patients may not understand terms like prognosis or diagnosis and can leave a visit confused.
The Hidden Risk of Food Avoidance
Turning to allergy testing, Gupta tackles a problem she sees across CSU and atopic dermatitis: patients restricting their diets to chase a trigger. This can create real anxiety around mealtime and lead to nutritional deficiencies. She's seen patients with 10-to-20-pound weight loss and patients eating only one or two foods because everything seems to trigger their hives — when in CSU the driver is actually an internal pathway, not an external food.
Garcia-Albea points out the clinical trap: a patient reporting hives plus significant weight loss can send a clinician down a workup for systemic disease like lymphoma if the food history isn't elicited. Gupta agrees weight loss is always a red flag, but notes that restrictive one-or-two-food diets are common in these shared patients, so asking about food behavior is essential.
Gupta's approach to unwinding food restriction is education: she explains how important food is, that restriction causes real harm, and that CSU is an intrinsic process happening inside the body — not something the external environment or a specific food is causing. She emphasizes that this is best done in coordination with an allergist, who is accustomed to interpreting testing and performing oral food challenges to give patients confidence.
Testing Nuances: Baked Allergens and Aeroallergens
Gupta explains why some patients with a known food allergy tolerate a baked version — seen especially with milk and egg. Heating food at high temperatures changes the protein so the body sees it differently. For egg, component testing looks at proteins like ovalbumin and ovomucoid; an ovomucoid-positive patient likely won't tolerate baked egg, while a negative result opens the possibility, which can be confirmed with a baked egg challenge. Tolerating a baked version can be a sign a child is progressing out of the allergy. This is a blood test.
On aeroallergen testing (dust mite, trees, grasses, weeds, pets), Gupta reserves it for patients with a clear one-to-one clinical correlation — for example, hives or worsening eczema after cat exposure — and for urticaria (not CSU) or atopic dermatitis flares. She's less worried about panel testing for aeroallergens than for foods, because a false-positive grass result won't drive a harmful behavior change. Food panels, by contrast, can generate false positives that patients then act on with restrictive diets, especially when they order testing themselves. Her rule: clinical history has to match the testing.
The Atopic March, Biomarkers, and When to Refer
In her atopic case discussions, Gupta reinforces that atopic multimorbidity is common — atopic dermatitis and asthma frequently coexist through shared type 2 inflammatory pathways. The atopic march typically begins with atopic dermatitis in an infant with a compromised skin barrier, progressing to asthma and then allergic rhinitis (which usually presents after age two). She notes it isn't always in that order, but this is the common infancy pattern.
Gupta highlights type 2 biomarkers — elevated IgE, eosinophils, and FeNO (fractional exhaled nitric oxide) — as tools that can predict biologic response and support phenotyping and treatment selection. This feeds the move toward personalized medicine: matching therapy to a patient's phenotype and comorbidities can improve compliance, sometimes with a single drug addressing shared conditions rather than two.
She urges clinicians not to undermine allergic disease. While these conditions may not carry high mortality, she cites that asthma still causes about 11 deaths a day in this country, and that atopic conditions carry significant quality-of-life burden tied to anxiety and depression. On collaboration, Gupta frames allergists as the de facto primary care physicians for atopic patients. Refer when a patient has multiple atopic comorbidities that aren't well managed, when you need help unwinding food restriction, or when you're not comfortable using biologics — she notes some derm colleagues never got comfortable with omalizumab because of anaphylaxis risk.