What are the symptoms of Mast Cell Activation Syndrome (MCAS)?

Symptoms of Mast Cell Activation Syndrome (MCAS)

MCAS presents with acute, recurrent episodes involving at least 2 organ systems simultaneously—not chronic continuous symptoms—with the most diagnostically valuable manifestations being cardiovascular (hypotension, tachycardia, syncope), dermatologic (urticaria, flushing, angioedema), respiratory (wheezing, shortness of breath), and gastrointestinal (crampy abdominal pain, diarrhea, nausea with vomiting) symptoms occurring together during discrete episodes. 1, 2

Core Symptom Pattern

The defining characteristic of MCAS is episodic, not continuous symptoms. 2 Persistent or chronic symptoms should direct you toward alternative diagnoses such as functional gastrointestinal disorders, systemic mastocytosis, or unrelated pathology. 2 This distinction is critical and frequently missed in clinical practice.

Organ System Involvement

Cardiovascular Symptoms

• Hypotension 1, 2
• Tachycardia 1, 2
• Syncope or near-syncope 1, 2

Dermatologic Symptoms

• Flushing 1, 2
• Urticaria 1, 2
• Pruritus 1, 2
• Angioedema, particularly affecting eyelids, lips, and tongue 1, 2
• Dermatographism 1

Respiratory Symptoms

• Wheezing (inspiratory or expiratory) 1, 2
• Shortness of breath 1, 2
• Inspiratory stridor 1, 2

Gastrointestinal Symptoms

• Crampy abdominal pain 1, 2
• Diarrhea 1, 2
• Nausea with vomiting 1, 2
• Abdominal cramping 1

Neurologic Symptoms

• Headache 1
• Poor concentration and memory 1
• "Brain fog" 1

Naso-Ocular Symptoms

• Nasal stuffiness 1
• Nasal pruritus 1
• Conjunctival injection 1

Critical Diagnostic Requirements

All three criteria must be met for MCAS diagnosis: episodic symptoms affecting ≥2 organ systems concurrently, documented acute increases in mast cell mediators during symptomatic episodes, and clinical response to mast cell-targeted therapies. 2 The requirement for concurrent multi-system involvement during discrete episodes distinguishes true MCAS from other conditions.

Common Pitfalls and Misdiagnoses

Chronic increases in mediator levels or continuous symptoms are inconsistent with MCAS. 2 Many patients are incorrectly labeled with MCAS when they actually have:

• Functional gastrointestinal disorders (IBS, functional dyspepsia) if they have mild persistent GI symptoms between flares 2
• Postural orthostatic tachycardia syndrome (POTS), which causes chronic nausea, abdominal pain, and early satiety independent of MCAS 2
• Gastroparesis or other motility disorders, particularly with comorbid hypermobility spectrum disorder 2
• Ehlers-Danlos syndrome, which can coexist with hereditary alpha-tryptasemia but is not caused by MCAS 1

Symptoms that lack precision for MCAS diagnosis and should not be used as primary diagnostic criteria include: fatigue, fibromyalgia-like pain, tired appearance, chronically ill appearance, edema, tinnitus, adenopathy, constipation, chronic low back pain, mood disturbances, anxiety, weight change, thyroid dysfunction, and various psychiatric or neurologic disorders. 1 These may be present but are not specific enough to establish the diagnosis.

Life-Threatening Manifestations

Anaphylaxis represents the most severe form of mast cell activation and requires immediate medical attention with epinephrine and supportive care measures. 1 The risk of perioperative anaphylaxis is estimated to be higher in patients with systemic mastocytosis relative to the general population. 1

Symptom Triggers

Common triggers that can precipitate episodes include: hot water, alcohol, certain drugs, stress, exercise, infection, physical stimuli, and hormonal fluctuations. 3 Temperature extremes (hypothermia or hyperthermia) and unnecessary trauma should be avoided. 1