A recent review published in Immunology and Allergy Clinics of North America compared mast cell activation 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 tryptase 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 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 mastocytosis.
What is a KIT gene mutation?
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 biopsy 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.
Sign up here to get the latest news, perspectives, and information about SM sent directly to your inbox. Registration is free and only takes a minute.
