Recognizing Mast Cell Activation Syndrome (MCAS)

Mast cell activation syndrome (MCAS) is a condition where mast cells in the body release too many chemicals, leading to a range of symptoms like flushing, low blood pressure, and gastrointestinal issues.

To be diagnosed with MCAS, a patient must have a significant increase in serum tryptase levels during an attack, symptoms that improve with medication targeting mast cells, and symptoms involving at least two organ systems.

However, there's been confusion and misdiagnosis due to alternative, less strict criteria that lack validation. It's important to use specific criteria, like the Vienna consensus criteria, to diagnose MCAS correctly and avoid missing other underlying conditions. More research is needed to develop reliable biomarkers to help distinguish MCAS from other conditions.

The definition of MCAS after the Vienna consensus is based on three diagnostic criteria that have to be fulfilled before the diagnosis of MCAS can be established:

1. Typical (MCA-related) clinical symptoms
2. An event-related increase in serum tryptase above the individual's baseline tryptase (sBT), according to the formula: sBT + 20% of sBT (= 120% of sBT = sBT × 1.2) plus 2 ng/mL
3. Response to drugs directed against MCA or the production or effects of MC mediators.

Mast cell mediators and common clinical symptoms attributable to severe mast cell activation

Clinical criterion of mast cell activation syndrome (MCAS)

Features that qualify as MCAS criteria are shown in the left box and those that do not justify MCAS in the right box.

• Severe, episodic, and recurrent symptoms induced by MC mediators with concurrent involvement of at least two organ systems are required to meet the clinical consensus criterion of MCAS.
• The most frequently reported symptoms of MCAS encompass cardiovascular, cutaneous, gastrointestinal, respiratory, and naso-ocular symptoms.
• Mast cell activation syndrome events usually satisfy the clinical criteria of anaphylaxis. For instance, concurrently occurring symptoms such as flushing and hypotensive syncope are highly suggestive for MCAS.
• Conversely, less severe (often chronic) symptoms or localized forms of MCA (ie, limited to skin or respiratory tract, such as chronic urticaria or uncontrolled asthma) do not qualify as diagnostic criteria of MCAS.
• Serum tryptase levels serve as the most specific marker and gold standard for measuring the MC burden
• The tryptase level usually increases during substantial systemic MCA/degranulation, peaks in serum about 1 hour after clinical onset of the event, and then declines with a half-life of about 2 hours, and may remain elevated 4 hours or longer, depending on the magnitude of the initial elevation.

Overview of differential diagnoses mimicking mast cell activation and mast cell activation syndrome

Optimal Takeaways

Severe mast cell activation can cause an array of symptoms, including:

• Skin flushing, pruritis, urticaria, and angioedema
• Gastrointestinal cramping, diarrhea, and vomiting
• Respiratory nasal congestion, sneezing, shortness of breath, wheezing, stridor, and hypoxia

Mast Cell Activation Syndrome (MCAS) may be present if:

• At least 2 organ systems are involved, e.g., concurrently occurring symptoms such as flushing and hypotensive syncope are highly suggestive for MCAS
• Significant serum tryptase elevation above baseline
• Response to therapy that reduces mast cell mediator activity

Differential diagnoses should be ruled out prior to MCAS determination, including:

• Adrenal insufficiency
• Allergic episodes involving basophils but not mast cells
• Arrythmias
• Atopic or contact dermatitis
• Dysautonomia
• Food poisoning or acute GI infection
• Hypopituitarism
• IBD, IBS
• Myocardial infarction
• Panic attacks and anxiety conditions
• Rosacea
• Seizures
• Stroke
• Systemic capillary leak syndrome
• Thyroid disease
• Vasculitis
• Vasovagal syncope

Reference

Gülen, Theo et al. “Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review.” The journal of allergy and clinical immunology. In practice vol. 9,11 (2021): 3918-3928. doi:10.1016/j.jaip.2021.06.011 Creative Commons Attribution (CC BY 4.0)