Indolent Systemic Mastocytosis (ISM) is a rare but often underrecognized clonal mast cell disorder. From random hives to gut pain and brain fog, ISM can feel like a medical mystery. We continue our review of “Management of indolent mastocytosis and mast cell activation syndrome - A clinical yardstick,” published in June 2025 in The Annals of Allergy, Asthma & Immunology. This is Part 2 of our discussion, with a focus on indolent systemic mastocytosis. We look at what causes it, how it’s diagnosed, and how to manage symptoms and improve quality of life. In this episode, we break down this complex mast cell disease and how doctors use baseline serum tryptase, KIT D816V testing, and HaT screening to find answers. Plus, we explain how treatments like antihistamines, mast cell stabilizers, and avapritinib can help people live better with ISM. 📌 INFOGRAPHIC to follow along What we cover in our episode about indolent systemic mastocytosis (ISM): Yardsticks explained: Why the ACAAI uses yardsticks as practical, interim guidelines before full consensus statements are available. Understanding mast cell diseases: The difference between primary (clonal), secondary (allergic), and idiopathic mast cell disorders. Diagnosing ISM: KIT D816V mutation, WHO/ICC criteria, baseline serum tryptase, and when to test for hereditary alpha-tryptasemia (HaT). Symptoms of ISM: Why symptoms vary and how they can involve multiple systems, including skin, GI tract, cardiovascular, and even neuropsychiatric. Management strategies: Trigger avoidance, antihistamines, leukotriene blockers, sodium cromolyn, aspirin therapy, and, when venom immunotherapy is appropriate. Targeted treatment: How avapritinib works and what the PIONEER study shows about its role in ISM. The Itch Review, hosted by Dr. Gupta, Kortney, and Dr. Blaiss, explores allergy and immunology studies, breaking down complex research in conversations accessible to clinicians, patients, and caregivers. Each episode provides key insights from journal articles and includes a one-page infographic in the show notes for easy reference. ___ Made in partnership with The Allergy & Asthma Network. Thanks to Blueprint Medicines for sponsoring today’s episode.  This podcast is for informational purposes only and does not substitute professional medical advice. Always consult with your healthcare provider for any medical concerns.