From the Guidelines
Mast Cell Activation Syndrome (MCAS) is a primary clinical condition characterized by spontaneous episodic signs and symptoms of systemic anaphylaxis concurrently affecting at least 2 organ systems, resulting from secreted mast cell mediators.
Key Features of MCAS
- Recurrent episodes of systemic anaphylaxis with concurrent involvement of at least 2 of the 4 organ systems:
- Cardiovascular: hypotension, tachycardia, and syncope or near-syncope
- Dermatologic: urticaria, pruritus, and flushing
- Respiratory: wheezing, shortness of breath, and inspiratory stridor
- Gastrointestinal: crampy abdominal pain, diarrhea, nausea, and vomiting
- Symptoms associated with acute increases in levels of mast cell mediators, such as tryptase, histamine, prostaglandin D2, and leukotriene C4
- Response to therapy with mast cell mediator blocking agents, mast cell stabilizers, or both, such as H1 and H2 histamine receptor antihistamines, type 1 cysteinyl leukotriene receptor antagonists, and inhibitors of COX for PGD2 or 5-lipoxygenase for LTC4 1
Diagnosis of MCAS
- Diagnosis should be entertained in patients with an appropriate clinical and laboratory profile when other conditions have been excluded
- Evaluation should include measuring mediator levels at baseline and during an acute episode
- Symptoms should resolve with therapies directed at the increased mediator 1
Classification and Unmet Needs
- Current classification of MCAS is based on the latest studies and consensus guidelines for clinically diagnosing systemic anaphylaxis in real time
- Further research is needed to understand the relationship between hereditary a-tryptasemia and MCAS, as well as the role of other mediators, such as platelet-activating factor, heparin, chymase, or carboxypeptidase A3 1
From the Research
Definition and Characteristics of Mast Cell Activation Syndrome (MCAS)
- Mast Cell Activation Syndrome (MCAS) is a term applied to several clinical entities that have gained increased attention from patients and medical providers 2
- MCAS is a rare condition defined by a severe systemic reaction to mast cell (MC)-derived mediators, often presenting with clinical signs of anaphylaxis and sometimes an underlying IgE-dependent allergy 3
- It is thought to be a common, yet under-recognized, chronic multi-system disorder caused by inappropriate mast cell activation, with gastrointestinal symptoms frequently reported by patients 4
Diagnostic Criteria and Challenges
- Proposed diagnostic criteria for MCAS include episodic symptoms with mast cell mediators affecting two or more organ systems, such as urticaria, angioedema, flushing, nausea, vomiting, diarrhea, abdominal cramping, hypotensive syncope, tachycardia, wheezing, conjunctival injection, pruritus, nasal stuffiness 5, 6
- 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, or baseline serum tryptase levels that are persistently above 15 ng/mL, can aid in diagnosis 6
- However, diagnostic criteria are not yet definitive, and there are many gaps in knowledge, resulting in confusion about this clinical syndrome 2
Classification and Spectrum of MCAS Disorders
- MCAS can be classified as primary, secondary, and idiopathic, involving the skin, gastrointestinal, cardiovascular, respiratory, and neurologic systems 6
- A "spectrum of MCAS disorders" has been proposed, highlighting symptoms, diagnostic tests, and treatments 6
- The diagnosis of MCAS can be challenging, and patients often experience significant delays in diagnosis, with gastrointestinal symptoms often mistaken for functional gastrointestinal disorders 4