Why Dermatologists Should Add Serum Tryptase to the Workup for Chronic Itch

Mast cell disorders have historically landed in the hands of hematology, but newer targeted therapies and a growing recognition of their cutaneous presentations are creating an opening for dermatologists to play a more active role in both diagnosis and treatment. That was the central argument Stefan Weiss, MD, a dermatologist at Trillium Clinic and adjunct professor of dermatology at Brown University School of Medicine, made during his session at Maui Derm NP+PA Summer 2026 in Colorado Springs.1

“It's one of those diseases that if we don't look for it, we don't see it," Weiss said, "and now there's an opportunity to really begin to consider a mast cell disorder as the cause of the itching before we jump necessarily to one of the new great anti-itch therapeutics that we have."

Itch as the Entry Point

Weiss framed chronic itch as the most underutilized clinical cue for suspecting mast cell disease. As itch becomes an increasingly prominent presenting complaint in dermatology, he argued that the workup should routinely include a serum tryptase level before defaulting to atopic dermatitis, pruritus of unknown origin, or other diagnoses.

“You have some skin findings, you have the sensation of itch, and now we really want to add tryptase into the mix of our laboratory evaluation,” he said.

Systemic and cutaneous mastocytosis remain rare conditions, Weiss acknowledged, but they may be more prevalent than current diagnosis rates suggest, particularly in adult and geriatric patients where the disorder is less commonly considered. He noted that dermatology training has historically emphasized mastocytosis as a predominantly pediatric and cutaneous condition, which contributes to underrecognition in older adults who more often present with systemic involvement.

“It's not something that's going to present every day, like psoriasis or atopic dermatitis, but we do want to keep it on our differential,” he said.

Sorting the Diagnostic Categories

Weiss described mast cell activation disorder as an umbrella encompassing a spectrum from IgE-mediated allergic disease to clonal disorders such as systemic mastocytosis to mast cell activation syndrome. When patients present with overlapping features, he emphasized that history, physical exam findings, and laboratory results, including genetic testing, are what allow clinicians to sort between categories.

If an elevated tryptase is identified and the clinical picture is consistent with mast cell disease, both in skin and non-skin findings, he recommends proceeding to genetic blood testing through a reference laboratory such as LabCorp to evaluate for the KIT D816V mutation.

For patients with a confirmed KIT D816V mutation and both cutaneous and non-cutaneous findings consistent with systemic mast cell disease, Weiss pointed to avapritinib as a targeted option now available to dermatologists to consider.

In the PIONEER trial, patients with moderate to severe indolent systemic mastocytosis randomized to avapritinib 25 mg once daily achieved a decrease of 15.6 points in total symptom score from baseline to week 24, compared to 9.2 points in the placebo group.2 Significantly more avapritinib-treated patients also achieved ≥ 50% reductions in serum tryptase, bone marrow mast cell aggregates, and KIT D816V variant allele fraction compared with placebo.

For patients who do not qualify for targeted therapy or for whom access is a barrier, Weiss noted that supportive care options include antihistamines and omalizumab, which he described as older but potentially more accessible given insurance approval rates.1

"By ordering that tryptase level, if you do identify one of these individuals to have mast cell disease, then that's the individual who is now being helped based on [this] lecture," he said.

Editor’s note: Reported disclosures for Weiss include Galderma Laboratories, ABBVIE, Arcutis Biotherapeutics, Incyte Corporation, SUN PHARMACEUTICAL INDUSTRIES, LEO Pharma, Novartis Pharmaceuticals Corporation, and more.

References

1. Weiss S. A New Tack on Mast Cell Disorders. Session presented at Maui Derm NP+PA Summer 2026 in Colorado Springs on June 26.

2. Gotlib J, Castells M, Elberink HO, et al. Avapritinib versus Placebo in Indolent Systemic Mastocytosis. NEJM Evid. 2023;2(6):EVIDoa2200339. doi:10.1056/EVIDoa2200339