From the Guidelines
Mast cell activation syndrome (MCAS) is diagnosed based on three major criteria: recurrent symptoms consistent with mast cell activation affecting at least two organ systems, laboratory evidence of mast cell activation, and a response to medications that target mast cell mediators or their receptors. The diagnostic criteria for MCAS include symptoms such as skin (flushing, itching), gastrointestinal (abdominal pain, diarrhea), cardiovascular (tachycardia, hypotension), respiratory (wheezing, shortness of breath), or neurological (headache, brain fog) systems, as well as laboratory evidence of mast cell activation, including elevated levels of mast cell mediators like serum tryptase, N-methylhistamine, prostaglandin D2, or leukotriene E4 during symptomatic periods 1.
Key Diagnostic Criteria
- Recurrent symptoms consistent with mast cell activation affecting at least two organ systems
- Laboratory evidence of mast cell activation, including elevated levels of mast cell mediators
- Response to medications that target mast cell mediators or their receptors, such as H1 antihistamines (like cetirizine or fexofenadine), H2 antihistamines (like famotidine), mast cell stabilizers (like cromolyn sodium), or leukotriene modifiers (like montelukast) 1.
Recent Updates
The most recent guidelines, published in 2024, emphasize the importance of a comprehensive diagnostic approach, including clinical evaluation, laboratory testing, and response to treatment 1.
Clinical Considerations
The diagnosis of MCAS can be challenging due to the nonspecific nature of symptoms and the transient nature of laboratory findings, requiring samples to be collected during acute episodes. Proper diagnosis is crucial for developing an effective treatment plan to manage this chronic condition. Other conditions that could explain the symptoms must be ruled out, and a thorough evaluation should be conducted to determine the underlying cause of symptoms.
From the Research
Diagnostic Criteria for Mast Cell Activation Syndrome
The diagnostic criteria for Mast Cell Activation Syndrome (MCAS) involve a combination of clinical symptoms and laboratory tests. Some of the key criteria include:
- Episodic symptoms affecting two or more organ systems, such as the skin, gastrointestinal, cardiovascular, respiratory, and neurologic systems 2
- Symptoms such as urticaria, angioedema, flushing, nausea, vomiting, diarrhea, abdominal cramping, hypotensive syncope, tachycardia, wheezing, conjunctival injection, pruritus, nasal stuffiness, and decrease in frequency, severity, or resolution of symptoms with anti-mediator therapy 2
- Laboratory data, including increased validated urinary or serum markers of MCAS, documentation of an increase of the marker above the patient's baseline value during symptomatic periods on more than two occasions, or baseline serum tryptase levels that are persistently above 15 ng/mL 2
- Other assays, such as 24-h urine histamine metabolites, PGD2 or its metabolite, and 11-β-prostaglandin F2 alpha 2
Classification and Diagnosis
MCAS can be classified into primary, secondary, and idiopathic forms, with primary forms including systemic mastocytosis and other clonal mast cell disorders, and secondary forms characterized by normal mast cells activated by external triggers 3
- Diagnosis is established after exclusion of other possible clinical entities, and laboratory tools are limited, making it challenging for clinicians to identify and confirm MCAS 3
- A recent global classification proposes a response of clinical symptoms, a substantial transient increase in serum total tryptase or increase in other mast cell-derived mediators, histamine or PGD2 or urinary metabolites, and agents that attenuate production or mast cell mediator activities 2
Clinical Manifestations and Treatment
Clinical manifestations of MCAS can include abdominal pain, diarrhea, flushing, dermatographism, memory and concentration difficulties, and headache 4