A research review from international mast cell experts published in The Journal of Allergy and Clinical Immunology: In Practice offers clarification on how mast cell activation disorders (MCADs) should be diagnosed, as well as what distinguishes systemic mastocytosis (SM) from mast cell activation syndrome (MCAS).
The paper outlines long-standing confusion around the term “mast cell activation,” which can happen in many common conditions, such as allergic diseases, infections and autoimmune conditions. But the authors stress that not all mast cell activation is evidence of a mast cell disorder. Rather, true mast cell diseases require specific clinical, biochemical and molecular evidence.
The researchers outline established frameworks for classifying mast cell disorders as primary (such as SM), secondary (triggered by allergies or other external factors) or idiopathic (no identified cause).
SM remains the most well-defined primary MCAD, driven in most cases by the KIT D816V mutation and diagnosed via bone marrow findings and high baseline tryptase. Scoring systems such as REMA, Karolinska and NICAS can help identify who is most likely to have SM, particularly when symptoms center on flushing, hypotension or venom-triggered reactions.
Learn more about SM signs and symptoms
For MCAS, the researchers note strict diagnostic criteria, with all three of the following required:
- Symptoms involving at least two organ systems (often anaphylaxis).
- A documented rise in a mast-cell–specific mediator like tryptase during the reaction.
- Clear improvement with mast-cell–targeted therapy.
Tryptase remains the most specific and reliable mediator, though urinary histamine or prostaglandin metabolites may be helpful in certain cases, the study authors say.
The review warns that overdiagnosis is increasingly common, especially when vague symptoms or nonspecific lab markers are used. Many people referred for MCAS evaluation ultimately do not meet consensus criteria, which can delay correct diagnosis and expose patients to unnecessary treatments.
Ultimately, the authors urge clinicians to apply consensus diagnostic criteria rigorously to prevent delayed diagnosis or misdiagnosis. As referrals for suspected MCADS rise, they argue, careful evaluation is essential to ensure patients get the appropriate care.
Sign up here to get the latest news, perspectives, and information about SM sent directly to your inbox. Registration is free and only takes a minute.
