Mast cell activation disorder

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Mast cell activation disorder (MCAD) is a spectrum of disorders that involve an immune response from a source that is not related to a disease. MCAD is characterized by symptoms that result from overactive mast cells, which are a cell in the immune system that produces histamine.[1].

The symptoms of MCAD can also be very similar to that of myalgic encephalomyelitis (ME) and therefore may be confused. It is also possible to have ME and MCAS disorders simultaneously.

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Signs and Symptoms[edit | edit source]

Symptoms of MCAD are generally similar although each disorder can be characterized individually. Primary MCAD is a condition in which too many mast cells are being created by the bone marrow[2]; Secondary MCAD would be that the body's mast cells are being created normally, but are over-responsive to dietary or environmental triggers. Both of these situations might lead an individual to have excess histamine in circulation. Excess histamine can cause severe inflammation and a wide variety of symptoms. Almost any organ system in the body can be affected by MCAD[2]. Because a variety of symptoms can be present MCAD is commonly misdiagnosed.

A confounding element in diagnosing MCAD is that signs and symptoms occur in almost all areas of the body. The symptoms might wax and wane

Most patients experience fatigue, fevers, and sensitivity to individualized environmental "triggers." Other commonly identified signs and symptoms are as follows[3]:

  • hot flashes, irregular heartbeat, high or low blood pressure (hypotension and/or hypertension)
  • vertigo, dizziness, forgetfulness, depression or anxiety, headaches, insomnia, restlessness
  • hives or other visible skin rashes
  • arthritis, muscle pain, bone pain, osteoporosis/osteopenia
  • anaphylaxis (a severe allergic reaction)
  • Malabsorption and gastrointestinal distress leading to low iron and low Vitamin D and low B12

Diagnosis[edit | edit source]

MCAD can be difficult to diagnose as the cause of the syndrome is still considered to be unknown. In 2010, a criteria for diagnosing MCAS was proposed by Dr. Cem Akin and colleagues. These criteria suggest that two or more organ systems must be affected; this can include gastrointestinal, cardiovascular, skin, or respiratory. If given histamine or mast cell therapy, the patient's symptoms must improve. Thirdly, the patient should be tested for serum tryptase an enzyme secreted by mast cells during the peak of a symptomatic episode. If tryptase is >15ng/mL the patient may have MCAD. Urine and blood tests should be collected more than once to confirm a positive diagnosis. Prostaglandin and histamine levels can be also be tested[4].

Comorbidities[edit | edit source]

MCAD is often diagnosed in patients that have been previously diagnosed with Ehlers-Danlos syndrome (EDS), a heritable connective tissue disorder, postural orthostatic tachycardia syndrome (POTS), a form of orthostatic intolerance. Both of these conditions are also commonly co-morbid with ME. The overlap between EDS, POTS, and MCAD is thought to be due to increased tryptase production [5].

An extra copy of the gene TPSAB1 has been noted as a possible cause for increased tryptase production.It has also been implicated in many other immunological diseases including autism, fibromyalgia, and chronic Lyme disease [6][7] .

Common Treatments[edit | edit source]

Vitamin C has been noted to reduce blood histamine levels[8][9]. Magnesium deficiency has been seen to increase mast cell production in some cases; therefore magnesium supplementation may be helpful in controlling mast cell division[10].

Over the counter antihistamines such as Allegra, Zyrtec, or Claritin are a common treatment for MCAD. It is recommended that the patient should consult a physician for secondary symptom treatment or targeted mast cell therapies[11]. Some patients also use herbal antihistamine supplements such as quercetin or diamine oxidase (DAO), an enzyme normally produced by the body that breaks down histamine.

Experimental Treatments[edit | edit source]

There is some limited evidence that sauna may be useful in antihistamine resistant urticaria, an allergic skin condition that involves mast cell activation and the production of excess histamine.[12]

Omalizumab has been proposed as a possible mast cell stabilizer and is used in allergic asthma and chronic urticaria.

Doctors[edit | edit source]

There are a very few mast cell specialists working in the United States. An expert is Dr. Lawrence Afrin formerly at the University of Minnesota now in in Armonk, NY. Drs Clem Akin and Mariana Castells run a mastocytosis clinic at Brigham and Women's in Boston. More integrative doctors are beginning to be aware of mast cell activation syndrome, but it remains elusive in both treatment and diagnosis.

Triggers[edit | edit source]

Emotional or physical stress, many foods, and environmental factors can trigger mast cell degranulation. It is likely that each individual will have his or her personal triggers[1][2].

Learn more[edit | edit source]

Mast cell activation syndrome, Wikipedia

  • Molderings GJ, Brettner S, Homann J, Afrin LB. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. Journal of Hematology & Oncology. 2011;4:10. doi:10.1186/1756-8722-4-10. (

See also[edit | edit source]

References[edit | edit source]

  1. 1.0 1.1 Frieri, Marianne (2015). "Mast Cell Activation Syndrome". Allergy and Immunology. 
  2. 2.0 2.1 2.2 Akim, Cem (August 2017). "Mast Cell Activation Syndromes". The Journal of Allergy and Clinical Immunology. 
  3. Molderings, G (2011). "Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options". J Hematol Oncol. 
  4. Akin, Cem (2010). "Mast Cell Activation Syndrome: Proposed Diagnostic Criteria". J Allergy and Clinical Immuno. 
  5. Milner, Joshua, Dr. "Research Update: POTS, EDS, MCAS Genetics." 2015 Dysautonomia International Conference & CME. Washington DC. Dysautonomia International Research Update: POTS, EDS, MCAS Genetics. Web. <>.
  6. Horowitz, Kate (October 17, 2016). "One Gene Mutation Links Three Mysterious, Debilitating Diseases". Mental Floss. Retrieved April 22, 2018. 
  7. Cheung, Ingrid (February 2015). "A New Disease Cluster: Mast Cell Activation Syndrome, Postural Orthostatic Tachycardia Syndrome, and Ehlers-Danlos Syndrome". The Journal of Allergy and Clinical Immunology. 
  8. Clemetson, C. A. (April 1980), "Histamine and ascorbic acid in human blood", The Journal of Nutrition, 110 (4): 662–668, ISSN 0022-3166, PMID 7365537 
  9. Yazdani, Shaik (2016). "Relationship Between Vitamin C, Mast Cells, and Inflammation". J Nutr Food Sci. 
  10. Takemoto, S. "Magnesium deficiency induces the emergence of mast cells in the liver of rats". J Nutr Sci Vitaminol. 
  11. Molderings, G (2016). "Pharmacological treatment options for mast cell activation disease". Naunyn Schmiedebergs Arch Pharmacol. 
  12. Magen, Eli (2014). "Beneficial Effect of Sauna Therapy on Severe Antihistamine-Resistant Chronic Urticaria" (PDF). Israeli Medical Association Journal. 

The information provided at this site is not intended to diagnose or treat any illness.

From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history