Can Mast Cell Activation Syndrome (MCAS) present with mild nausea, upset stomach, and a general feeling of being unwell between flares?

MCAS Presentation Between Flares

MCAS is fundamentally defined by episodic, not chronic, symptoms—mild persistent nausea, upset stomach, and general malaise between flares do not align with the diagnostic criteria for MCAS and should prompt evaluation for alternative diagnoses. 1

Core Diagnostic Principle

The American Academy of Allergy, Asthma, and Immunology (AAAAI) explicitly states that persistent symptoms should direct clinicians to a different underlying diagnosis, as MCAS requires recurrent episodic symptoms affecting 2 or more organ systems concurrently. 1 Chronic increases in mediator levels or continuous symptoms are inconsistent with MCAS and may instead reflect other conditions such as systemic mastocytosis, functional gastrointestinal disorders, or unrelated pathology. 1

What MCAS Actually Looks Like

True MCAS presents with acute, recurrent episodes involving at least 2 organ systems simultaneously, such as: 1

• Cardiovascular: hypotension, tachycardia, syncope or near-syncope
• Dermatologic: urticaria, pruritus, flushing, angioedema (particularly eyelids, lips, tongue)
• Respiratory: wheezing, shortness of breath, inspiratory stridor
• Gastrointestinal: crampy abdominal pain, diarrhea, nausea, vomiting

The key distinguishing feature is that these symptoms occur in discrete episodes consistent with systemic anaphylaxis, not as continuous low-grade complaints. 1

Diagnostic Requirements

The 2025 AGA guidelines emphasize that MCAS testing should only be considered when patients present with episodic symptoms suggesting a generalized mast cell disorder involving 2 or more physiological systems (cutaneous, GI, cardiac, respiratory, neuropsychiatric). 1

All three criteria must be met for MCAS diagnosis: 1

1. Episodic symptoms affecting ≥2 organ systems concurrently
2. Documented acute increases in mast cell mediators (serum tryptase increase of 20% above baseline plus 2 ng/mL during flares, measured 1-4 hours after symptom onset) 1
3. Clinical response to mast cell-targeted therapies (histamine blockers, mast cell stabilizers, leukotriene antagonists) 1

What Your Patient's Symptoms Likely Represent

Mild persistent GI symptoms between flares are more consistent with: 1, 2

• Disorders of gut-brain interaction (DGBI) such as functional dyspepsia or IBS
• Comorbid conditions like POTS (which can cause chronic nausea, abdominal pain, and early satiety independent of MCAS) 1
• Gastroparesis or other motility disorders (particularly if there's associated hypermobility spectrum disorder) 1
• Other inflammatory or infectious conditions that require thorough evaluation 3, 4

The 2025 AGA guidelines specifically note that GI symptoms alone in patients without clinical or laboratory evidence of mast cell disorders do not warrant MCAS testing. 1

Clinical Pitfall to Avoid

Do not diagnose MCAS based on chronic symptoms without documented episodic multi-system involvement and laboratory confirmation during acute episodes. 1, 5 Many patients are incorrectly informed they have MCAS without completing thorough medical evaluation, leading to missed alternative diagnoses and inappropriate management. 3, 4

If your patient has only mild persistent GI symptoms between discrete flares, evaluate them according to standard DGBI diagnostic approaches, consider autonomic testing if orthostatic symptoms are present, and reserve MCAS workup for when they experience acute multi-system episodes. 1, 2