Differential Diagnosis for Mast Cell Activation Syndrome and Systemic Mastocytosis

When attempting to distinguish between Mast Cell Activation Syndrome (MCAS) and Systemic Mastocytosis (SM), it's crucial to consider a range of potential diagnoses due to the complexity and overlap of symptoms between these two conditions. Here's a structured approach to differential diagnosis:

• Single Most Likely Diagnosis:

  • Systemic Mastocytosis: This is considered the single most likely diagnosis when there's a significant accumulation of mast cells in one or more organs, often accompanied by characteristic morphological changes and/or expression of specific mast cell markers. The presence of the D816V KIT mutation in mast cells is a key diagnostic criterion.

• Other Likely Diagnoses:

  • Mast Cell Activation Syndrome (MCAS): Characterized by the presence of chronic mast cell activation symptoms without the significant accumulation of mast cells seen in systemic mastocytosis. Diagnosis is often based on clinical criteria, including the presence of symptoms in two or more organ systems, a decrease in symptoms with mast cell stabilizers or H1/H2 antihistamines, and an increase in serum tryptase or other mast cell mediators during symptomatic periods.
  • Allergic Disorders: Conditions like atopic dermatitis, asthma, or chronic urticaria can mimic some symptoms of MCAS and SM, making them important to consider in the differential diagnosis.
  • Ehlers-Danlos Syndrome (EDS): Some patients with EDS may exhibit symptoms overlapping with MCAS, such as gastrointestinal issues, orthostatic intolerance, and easy bruising, due to the potential for mast cell activation in EDS.

• Do Not Miss Diagnoses:

  • Pheochromocytoma: Although rare, pheochromocytoma can present with episodic hypertension, tachycardia, and flushing, similar to mast cell activation episodes. Missing this diagnosis could be life-threatening due to the risk of hypertensive crises.
  • Carcinoid Syndrome: This condition, caused by a neuroendocrine tumor secreting serotonin, can lead to flushing, diarrhea, wheezing, and heart valve abnormalities, overlapping with symptoms of MCAS and SM.
  • Autoimmune Disorders: Conditions like lupus or rheumatoid arthritis can sometimes present with systemic symptoms that might be confused with MCAS or SM, and are critical not to miss due to their potential for serious organ damage.

• Rare Diagnoses:

  • Hereditary Alpha-Tryptasemia: A recently described condition characterized by an increase in the alpha-tryptase gene copy number, leading to elevated basal serum tryptase levels and symptoms similar to MCAS.
  • Gastrointestinal Mastocytosis: A rare condition where mast cell accumulation is primarily in the gastrointestinal tract, which can cause symptoms like abdominal pain, diarrhea, and flushing.
  • Telangiectasia Macularis Eruptiva Perstans (TMEP): A rare form of cutaneous mastocytosis that can present with skin lesions and systemic symptoms, although it is much less common than other forms of mastocytosis.

Each of these diagnoses requires careful consideration of clinical presentation, laboratory findings, and sometimes specific diagnostic tests to accurately differentiate between Mast Cell Activation Syndrome and Systemic Mastocytosis, as well as to identify other potential causes of the patient's symptoms.