Systemic Mastocytosis in Dermatology: Diagnosis and Targeted Therapy

David E. Sloane, MD, EdM, delivered a clinically focused update on systemic mastocytosis (SM) during his Masterclasses in Dermatology session, “Recognizing and Managing Systemic Mastocytosis: The Dermatologist's Role in Early Diagnosis, Treatment, and Collaborative Care,” underscoring the dermatologist’s pivotal role in early recognition and referral. His central message was clear: Dermatologists are often the first to encounter mastocytosis, and early action matters.

“Mastocytosis is a clonal mast cell disease,” Dr Sloane reminded attendees, driven in most patients by activating mutations in the KIT gene, most commonly KIT D816V. Dr Sloane mentioned, “Mast cells like to move around. You can find them in bone marrow, skin, the GI tract, liver, and spleen.”

Cutaneous mastocytosis may present as maculopapular lesions (formerly urticaria pigmentosa) with a positive Darier sign, diffuse erythroderma, or mastocytoma. However, systemic features are the red flags. Patients may report flushing, urticaria, angioedema, tachycardia, hypotension, wheezing, abdominal pain, diarrhea, osteoporosis, or waxing-and-waning “brain fog.”

Dr Sloane emphasized a practical takeaway: If cutaneous findings are accompanied by systemic symptoms, check a serum tryptase and refer for hematology or allergy evaluation if elevated. Early diagnosis can improve quality of life and allow preparation for surgery, pregnancy, or vaccination to reduce the risk of acute reactions. He shared key takeaways: “We now have harmonized diagnostic criteria and definitions. B-findings and C-findings affect diagnosis, prognosis, and workup/treatment. There are multiple prognostic tools. There is a range of dermatologic manifestations in children and adults.”

Symptom control remains foundational. For chronic mediator-related symptoms, therapy includes H1 and H2 antihistamines, leukotriene receptor antagonists, cromolyn sodium, ketotifen, and omalizumab. Acute flares require epinephrine when indicated. Cytoreductive therapy is reserved for advanced SM with organ dysfunction.

Targeted therapy has transformed the treatment landscape. Avapritinib, a KIT D816V inhibitor, is approved for indolent SM and demonstrated sustained and durable improvements in skin manifestations after a median follow up of 3 years in the phase 2 PIONEER study. The agent was generally well tolerated.

Additional investigational tyrosine kinase inhibitors, including elenestinib, bezuclastinib, ripretinib, and BLU-808, are advancing through phase 1 and 2 trials. “All of them are showing promise,” Dr Sloane noted.

Dr Sloane closed with a call to collaboration. Mastocytosis spans dermatology, hematology, allergy/immunology, primary care, psychiatry, and maternal-fetal medicine. “It’s reasonable to coordinate efforts among specialists and other caregivers,” concluded Dr Sloane. “It’s, therefore, a team effort.”

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Reference

Sloane DE. Masterclass: recognizing and managing systemic mastocytosis: the dermatologist's role in early diagnosis, treatment, and collaborative care. Presented at: Masterclasses in Dermatology; February 19–22, 2026; Sarasota, FL.