A recent review published in Immunology and Allergy Clinics of North America compared mast cell activationMast cell activation Describes when mast cells release histamine and other mediators into the blood stream in response to an allergen or other trigger. This leads to symptoms like fatigue, rash and, in severe cases, anaphylaxis. syndrome (MCAS) with several conditions that have overlapping symptoms, including systemic mastocytosis (SM).
Despite advances in the detection of MCAS, diagnosis continues to be complicated by the fact that conditions like SM, dysautonomia and hereditary alpha tryptasemia can have similar symptoms. Understanding the differences between these conditions may not only improve diagnosis but also promote research to further understand the underlying mechanisms behind them.
A major criterion for diagnosing MCAS is symptoms related to mast cell activation in two or more organ systems. This may include flushing, itching, shortness of breath, fatigue and brain fog. However, all of these symptoms may exist in patients with SM as well.
Read more about SM testing and diagnosis
Individuals with MCAS must have laboratory evidence of the condition as well, which may be marked by increases in serum tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. level at baseline or during a flare. Again, though, this sign overlaps with SM: tryptase levels often fluctuate in patients with SM.
The third major diagnostic criterion for MCAS is symptom improvement with treatment. Because treatment response is subjective and can vary across individuals with MCAS, evaluating this criterion can be challenging.
Hymenoptera venom anaphylaxisAnaphylaxis A severe allergic reaction that can turn fatal without treatment. Patients with SM are at a higher risk of developing anaphylaxis. may help to distinguish MCAS from SM, as this feature is more common among those with SM. Even this is not a perfect distinguisher, however. A subset of individuals with a severe Hymenoptera venom allergy may carry the KIT D816V mutation but have normal baseline tryptase levels and no other symptoms of SM or cutaneous mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults..
What is a KIT gene mutationKIT gene mutation Most SM cases are caused by the KIT D816V mutation. The KIT gene codes for a type of protein called a receptor tyrosine kinase, which signals mast cells to grow, divide and move.?
SM is usually caused by a sporadic mutation in the KIT gene, which codes for a protein called CD117 transmembrane tyrosine kinase. The protein is involved in the growth, survival and migration of mast cells. The most common KIT mutation associated with SM is the D816V mutation, which results in the amino acid aspartic acid being replaced by the amino acid valine in the protein chain.
Bone marrow biopsyBone marrow biopsy A procedure to collect a sample of bone marrow using a needle. Often used to examine the characteristics of mast cells and diagnose SM. remains the gold standard for diagnosing SM. Nevertheless, the combination of clinical symptoms and laboratory findings is necessary for stratifying patients by subtype and risk level.
The study also highlighted the strengths and challenges of social media in improving detection of MCAS and conditions with similar symptoms. While social media has helped to significantly raise awareness, it has also led to the spread of misinformation, exacerbating patient confusion.
“A compassionate approach to these patients using shared decision-making principles is essential for achieving optimal clinical outcomes and minimizing health care burden,” the authors concluded.
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