From the Guidelines
Diagnosing mast cell activation syndrome (MCAS) requires a comprehensive approach focusing on symptoms, laboratory tests, and response to treatment, as outlined in the 2019 report by the AAAAI Mast Cell Disorders Committee Work Group 1. To diagnose MCAS, patients should present with recurrent episodes affecting multiple organ systems, including:
- Skin symptoms such as flushing, hives, and itching
- Gastrointestinal symptoms like nausea, diarrhea, and abdominal pain
- Respiratory symptoms including wheezing and shortness of breath
- Cardiovascular symptoms such as tachycardia and hypotension
- Neurological symptoms like brain fog and headaches Diagnosis involves documenting elevated mast cell mediators during symptomatic episodes, particularly:
- Tryptase
- Histamine
- Prostaglandin D2
- Leukotriene metabolites in blood or urine A 20% increase in serum tryptase during an attack compared to baseline is considered significant, as noted in the studies 1. A therapeutic trial is often part of diagnosis, with improvement on medications like H1 antihistamines (cetirizine 10mg daily or loratadine 10mg daily), H2 blockers (famotidine 20mg twice daily), mast cell stabilizers (cromolyn sodium 200mg four times daily), or leukotriene inhibitors (montelukast 10mg daily) 1. The diagnosis of MCAS should be entertained in patients with an appropriate clinical and laboratory profile when other conditions have been excluded, and a specialist in allergy/immunology or hematology with experience in mast cell disorders should ideally manage the diagnostic process, as proper diagnosis enables targeted treatment to improve quality of life 1. Key considerations in the diagnosis include:
- Recurrent symptoms consistent with mast cell activation with involvement of two organs
- Elevation of one or more validated Mast Cell Mediators in association with the symptoms
- Response to targeted therapeutic interventions The algorithm for diagnosing MCAS, as outlined in the studies 1, involves assessing for primary MCAS with somatic or germ line mutation, and considering a bone marrow study for a GOF KIT mutation if necessary.
From the Research
Mast Cell Activation Symptoms Diagnosis
- Mast cell activation syndrome (MCAS) involves multiple organ systems, including the skin, gastrointestinal, cardiovascular, respiratory, and neurologic systems 2.
- Symptoms of MCAS can include:
- Urticaria
- Angioedema
- Flushing
- Nausea
- Vomiting
- Diarrhea
- Abdominal cramping
- Hypotensive syncope
- Tachycardia
- Wheezing
- Conjunctival injection
- Pruritus
- Nasal stuffiness
- Diagnosis of MCAS can be made based on:
- Episodic symptoms affecting two or more organ systems
- 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
- Baseline serum tryptase levels that are persistently above 15 ng/mL
- Increase of the tryptase level above baseline value on one occasion
- 24-h urine histamine metabolites, PGD2 or its metabolite, and 11-β-prostaglandin F2 alpha
- A recent global classification of MCAS includes:
- Response of clinical symptoms
- Substantial transient increase in serum total tryptase or increase in other mast cell-derived mediators, histamine or PGD2 or urinary metabolites
- Agents that attenuate production or mast cell mediator activities 2
- Gastrointestinal symptoms of MCAS can be mistaken for functional gastrointestinal disorders, but can be diagnosed and managed by gastroenterologists 3
- Diagnosis and management of MCAS can improve the quality of life for patients who have been mislabeled with a functional gastrointestinal disorder 3