Can a patient with nocturnal diarrhea, acid reflux, nasal regurgitation, intermittent rash, orthostatic dizziness, lower leg swelling with pitting edema, and night sweats, whose symptoms worsen with diarrhea flares, meet the criteria for Mast Cell Activation Syndrome (MCAS)?

Could This Patient Meet MCAS Criteria?

This patient's presentation is unlikely to meet formal MCAS diagnostic criteria because the symptoms appear to be chronic and persistent rather than acute, recurrent, episodic events affecting multiple organ systems simultaneously. 1, 2

Critical Diagnostic Gap: Episodic vs. Chronic Symptoms

The most important distinction here is that MCAS requires acute, recurrent episodes with concurrent multi-system involvement, not chronic or persistent symptoms. 1, 2, 3

• The American Academy of Allergy, Asthma, and Immunology explicitly states that persistent symptoms should direct clinicians to a different underlying diagnosis, as chronic increases in mediator levels or continuous symptoms are inconsistent with MCAS. 2
• Your patient describes nocturnal diarrhea occurring 1-3 times per week with 1-7 episodes per night, acid reflux, and intermittent symptoms that "worsen with flares" but without clear discrete episodes where multiple systems are simultaneously affected. 2
• The pattern described sounds more like chronic GI symptoms with variable severity rather than the discrete anaphylaxis-like episodes that characterize true MCAS. 1, 3

What True MCAS Episodes Look Like

True MCAS presents with acute attacks where at least 2 organ systems are affected simultaneously during discrete episodes, typically including: 1, 3

• Cardiovascular: Hypotension, tachycardia, syncope or near-syncope occurring during the acute episode 3
• Dermatologic: Urticaria, flushing, pruritus, angioedema appearing acutely 3
• Respiratory: Wheezing, shortness of breath, stridor during the attack 3
• Gastrointestinal: Crampy abdominal pain, diarrhea, nausea with vomiting occurring together 3

The key is that these symptoms occur together during discrete episodes, not as chronic ongoing problems that wax and wane. 1, 2

Your Patient's Symptoms Suggest Alternative Diagnoses

The chronic nocturnal diarrhea, persistent acid reflux with nasal regurgitation, and intermittent symptoms between episodes are more consistent with other conditions: 2

• Disorders of gut-brain interaction (IBS, functional dyspepsia): Mild persistent GI symptoms between flares fit this pattern better than MCAS. 2
• POTS (Postural Orthostatic Tachycardia Syndrome): The orthostatic dizziness, lower leg edema, and chronic nausea could indicate autonomic dysfunction. 1, 2
• Gastroparesis or other motility disorders: Nocturnal reflux with nasal regurgitation suggests significant esophageal/gastric dysmotility. 2
• Hypermobility spectrum disorders: These commonly present with GI symptoms, autonomic dysfunction, and can coexist with the symptoms described. 1

Diagnostic Testing If You Still Suspect MCAS

If you genuinely suspect MCAS despite the chronic symptom pattern, you must document acute mediator elevation during symptomatic episodes: 1

• Obtain a baseline serum tryptase when the patient is asymptomatic. 1
• During a symptomatic "flare," collect serum tryptase 1-4 hours after symptom onset. 1
• A 20% increase above baseline PLUS an absolute increase of 2 ng/mL is required to demonstrate mast cell activation. 1
• Consider 24-hour urine collection for N-methylhistamine, 11β-PGF2α, or LTE4 during symptomatic periods. 1

The Three Required Criteria for MCAS Diagnosis

All three criteria must be met—not just one or two: 1, 2, 3

1. Episodic symptoms affecting ≥2 organ systems concurrently (not chronic symptoms with variable severity) 1, 2
2. Documented acute increases in mast cell mediators during symptomatic episodes (tryptase increase of 20% + 2 ng/mL) 1
3. Clinical response to mast cell-targeted therapies (H1/H2 antihistamines, leukotriene antagonists, mast cell stabilizers) 1, 3

Common Pitfall to Avoid

The biggest pitfall is overdiagnosing MCAS in patients with chronic multi-system symptoms who do not have true episodic anaphylaxis-like events. 2, 4

• Many patients are incorrectly told they have MCAS without completing a thorough medical evaluation for more common conditions. 4
• The number of inappropriate MCAS referrals is increasing, leading to missed diagnoses of treatable conditions like celiac disease, inflammatory bowel disease, or autonomic disorders. 1, 4

Recommended Diagnostic Approach for This Patient

Given the chronic nature of symptoms, pursue these evaluations first: 1, 2

• Autonomic function testing (tilt table testing) for suspected POTS given orthostatic dizziness and lower extremity edema. 1
• Celiac disease testing should be considered earlier in patients with varied GI symptoms, not just diarrhea. 1
• Gastric emptying study and assessment of gastric accommodation for chronic upper GI symptoms and nocturnal reflux. 1
• Anorectal manometry and balloon expulsion testing if there are any lower GI symptoms suggesting pelvic floor dysfunction. 1
• Consider evaluation for hypermobility spectrum disorders given the constellation of GI, autonomic, and systemic symptoms. 1

Only after excluding these more common conditions should you pursue MCAS testing with baseline and episodic tryptase measurements. 1, 2 If MCAS is ultimately supported by clinical and laboratory findings, refer to an allergy specialist or mast cell disease research center for additional evaluation. 1