Mast Cell Activation Disorder – Lab Testing and Diagnosis

Diagnosis of Mast Cell Activation Disorder is made by Lab Testing and Review of Symptoms

There are many symptoms attributed to Mast Cell Activation Disorder (MCAD), which is now believed to afflict as many as 5-10% of the population in western Europe. MCAD may underlie such common illnesses as fibromyalgia, irritable bowel syndrome and dermatitis and many more conditions as listed above. The evidence that mast cells and histamine play a role in so many conditions. Because of that, experts in the field, such as Molderings and LB Afrin, propose the criteria for diagnosis for MCAS be expanded. When making a diagnosis, doctors may include a broad range of symptoms related to histamine intolerance and mast cell activation disorder plus one Major Criterion and one Minor Criterion is likely sufficient to make a diagnosis. Tests offered here include Serum Tryptase, Plasma Histamine and Urine N-methyltransferase.

WHO 2008 Diagnostic Criteria for Systemic Mastocytosis

Major Criterion:

  1. Multifocal, dense aggregates of MCs (15 or more) in sections of bone marrow or other extracutaneous tissues and confirmed by tryptase immunohistochemistry or other special stains

Minor Criteria:

  1. Atypical or spindled appearance of at least 25% of the MCs in the diagnostic biopsy
  2. Expression of CD2 and/or CD25 by MCs in marrow, blood, or extracutaneous organs
  3. KIT codon 816 mutation in marrow, blood, or extracutaneous organs
  4. Persistent elevation of serum total tryptase > 20 ng/ml

Diagnosis of SM made by either (1) major criterion + any one or more minor criteria, or (2) any three minor criteria.

Proposed Diagnostic Criteria for MCAD

Valent et al. Criteria

  1. Chronic/recurrent symptoms (flushing, pruritus, urticaria, angioedema, nasal congestion or pruritus, wheezing, throat swelling, headache, hypotension, and/or diarrhea) consistent with aberrant MC mediator release
  2. Absence of any other known disorder that can better account for these symptoms
  3. Increase in serum total tryptase of [20% above baseline, plus another 2 ng/ml] during, or within 4 hours after, a symptomatic period
  4. Response of symptoms to histamine H1 and/or H2 receptor antagonists or other “MC-targeting” agents such as

Molderings et al. Criteria:

Major Criteria:

  1. Multifocal MC aggregates as per WHO major criterion for SM
  2. Clinical history consistent with chronic/recurrent aberrant MC mediator release

Minor Criteria:

  1. Abnormal MC morphology as per WHO SM minor criterion #1
  2. CD2 and/or CD25 expression as per WHO SM minor criterion #2
  3. Detection of known constitutively activating mutations in MCs in blood, marrow, or extracutaneous organs
  4. Elevation in serum tryptase or chromogranin A, plasma heparin or histamine, urinary N-methylhistamine, and/or other MC- specific mediators such as (but not limited to) relevant leuko- trienes (B4, C4, D4, E4) or PGD2 or its metabolite 11-b-PGF2a.

*Diagnosis of MCAS made by either (1) both major criteria, or (2) the second major criterion plus any one of the minor criteria, or (3) any three minor criteria.

Ref:

  1. Afrin LB, Molderings GJ. A concise, practical guide to diagnostic assessment for mast cell activation disease. World J Hematol. 2014;3:1–17.

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