Mast cell activation syndrome
Mast cell activation syndrome (MCAS) is a disorder where mast cells are normal in number, but release excessive amounts of chemicals known as mast cell mediators including histamine. The symptoms of MCAS can be very similar to that of myalgic encephalomyelitis (ME), and therefore may be confused. Moreover, it is also possible to have ME and MCAS simultaneously.
- 1 Signs and Symptoms
- 2 Diagnosis
- 3 Physicians
- 4 Comorbidities
- 5 Myalgic Encephalomyelitis and Chronic Fatigue Syndrome
- 6 Common triggers
- 7 Potential treatments
- 8 Learn more
- 9 See also
- 10 References
Signs and Symptoms[edit | edit source]
In MCAS, the body's mast cells are being created in normal number, 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 MCAS. Because a variety of symptoms can be present, MCAS is commonly misdiagnosed.
A confounding element in diagnosing MCAS is that signs and symptoms occur in almost all areas of the body. The symptoms might wax and wane.
- anaphylaxis (a severe allergic reaction)
- Malabsorption and gastrointestinal distress leading to low iron and low Vitamin D and low Vitamin B12
Diagnosis[edit | edit source]
MCAS 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 anti-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 MCAS. Urine and blood tests should be collected more than once to confirm a positive diagnosis. Prostaglandin and histamine levels can be also be tested.
Physicians[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 Hospital in Boston. More integrative doctors are beginning to be aware of mast cell activation syndrome, but it remains elusive in both treatment and diagnosis.
Comorbidities[edit | edit source]
MCAS is often diagnosed in patients that have been previously diagnosed with Ehlers-Danlos syndrome (EDS), a heritable connective tissue disorder, and with 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 MCAS is thought to be due to increased tryptase production.
An extra copy of the gene TPSAB1 has been noted as a possible cause for increased tryptase production. This gene has also been implicated in many other immunological diseases including fibromyalgia, and chronic Lyme disease.
Myalgic Encephalomyelitis and Chronic Fatigue Syndrome[edit | edit source]
Research on the relationship between mast cells and ME is in its infancy. One study found that individuals diagnosed with moderate to severe ME have been noted to have higher amounts of dysfunctional mast cells in circulation.
At a two-day physician summit in Salt Lake City, Utah in March 2018, physicians discussed the relationship between “Chronic Fatigue Syndrome” and mast cell activation syndrome.
- David Kaufman: "ME/CFS is a descriptive diagnosis of a bunch of symptoms, but it says nothing about what's causing the symptoms, which is probably part of the reason it's so hard for it to get recognition. So, the question becomes, What other pathology is driving this illness and making the person feel so ill? I think mast cell activation is one of those drivers, whether cause, effect, or perpetuator, I don't know."
- Charles Lapp: "I see a lot of this. I think it's one of the many overlap syndromes that we've been missing for years."
- Susan Levine: "I suspect 50% to 60% of ME/CFS patients have it. It's a very new concept."...In Levine's experience, MCAS often manifests in patients being unable to tolerate certain foods or medications. "If we can reduce the mast cell problem, we can facilitate taking other drugs to treat ME/CFS," she said. However, she also cautioned, "It's going to be a subset, not all ME/CFS patients."
Common triggers[edit | edit source]
Mast cell degranulation can be triggered by a wide range of foods absorbed via the alimentary tract; environmental exposures inhaled through the nose such as mold, diesel fuel and chemical fragrances; emotional or physical stress; exercise; direct skin contact with chemicals, and even sunlight. While many lists exist describing the range of possible triggers, many people tolerate triggers others cannot and a person’s list of triggers can be highly individual.
Potential treatments[edit | edit source]
Vitamin C[edit | edit source]
Numerous studies have found Vitamin C to be inversely correlated with histamine and that the administration of Vitamin C reduces blood histamine levels. It does this potentially through several mechanisms: by inhibiting mast cell production; by increasing diamine oxidase (an enzyme that breaks down histamine and is chiefly found in the gut); by inhibiting mast cell degranulation (and the release of histamine in the first place), and by inhibiting histidine decarboxylase (the enzyme that forms histamine).
Magnesium[edit | edit source]
Like Vitamin C, magnesium is a co-factor in the production of diamine oxidase. Magnesium deficiency has been seen to increase mast cell production in some cases; therefore magnesium supplementation may be helpful in controlling mast cell division.
Antihistamines[edit | edit source]
Over-the-counter H1 and H2 antihistamine blockers such as Allegra (Fexofenadine), Zyrtec (Cetirizine), Claritin (Loratadine), and compounded Zaditor/Zaditen (Ketotifen) are common treatments for MCAS. It is recommended that the patient should consult a physician for secondary symptom treatment or targeted mast cell therapies.
Prescription drug treatments include Xolair (Omalizumab), which has been proposed as a possible mast cell stabilizer and is used in allergic asthma and chronic urticaria.
Leukotriene inhibitors[edit | edit source]
Mast cell stabilizers[edit | edit source]
Acetylcholinesterase inhibitors[edit | edit source]
In 2015, a large German study found 29% of ME/CFS patients had elevated autoantibodies to M3 and M4 muscarinic acetylcholine receptors, as well as ß2 adrenergic receptors. A 2016 Australian study found that ME/CFS patients had significantly greater numbers of single nucleotide polymorphisms associated with the gene encoding for M3 muscarinic acetylcholine receptors. One study found that acetylcholine via muscarinic receptors strongly inhibited the release of histamine in mucosal mast cells.Mestinon, an acetylcholinesterase inhibitor, and vagus nerve stimulators can increase the amount of acetylcholine circulating in the peripheral nervous system.
Omalizumab[edit | edit source]
Omalizumab is an anti-IgE monoclonal antibody approved for treating other allergic diseases. In a study of 55 French patients with mast cell disorders, 43 patients achieved a "best response" and 76.7% of the responding patients achieved a persistent response (three months or longer.) Median time to first response was 2 months and median time to best response was 6 months. One severe adverse event occurred, with researchers suggesting this recommends initiating treatment in hospital, but otherwise found the safety profile acceptable.
Sauna[edit | edit source]
|Name||Type||Form||Availability||Mechanism of action||Notes|
|Claritin (Loratadine)||H1 Blocker||OTC||Low anticholinergic activity. Not sedating.|
|Benadryl||H1 Blocker||Oral and IV||OTC, prescription||Sedating.|
|Tagament (Cimetidine)||H2 Blocker|
|Pepcid (Famotidine)||H2 Blocker|
|Axid (Nizatidine)||H2 Blocker|
|Zantac (Ranitidine)||H2 Blocker||Oral, injection, IV||Withdrawn from market in US|
|Zyrtec||H1 blocker||OTC||Not sedating.|
|Allegra||H1 blocker||Not sedating.|
|Zaditor/Zaditen||H1 Blocker; Mast cell stabilizer||Not sedating.|
|Diamine oxidase||Enzyme normally produced by the body||Breaks down histamine. Especially found in gut and placenta.|
|Vitamin C||OTC||Inhibits mast cell production and degranulation; increases diamine oxidase; breaks down histamine.|
|Magnesium||OTC||Co-factor in diamine oxidase|||
Learn more[edit | edit source]
- 2011, Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. Journal of Hematology & Oncology. (Research)
See also[edit | edit source]
References[edit | edit source]
- Akim, Cem (August 2017). "Mast Cell Activation Syndromes". The Journal of Allergy and Clinical Immunology.
- Molderings, G (2011). "Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options". J Hematol Oncol.
- Akin, Cem (2010). "Mast Cell Activation Syndrome: Proposed Diagnostic Criteria". J Allergy and Clinical Immuno.
- 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. <https://vimeo.com/142039306>.
- Horowitz, Kate (October 17, 2016). "One Gene Mutation Links Three Mysterious, Debilitating Diseases". Mental Floss. Retrieved April 22, 2018.
- 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.
- Nguyen, T.; Johnston, S.; Chacko, A.; Gibson, D.; Cepon, J.; Smith, D.; Staines, D.; Marshall-Gradisnik, S. (2017), "Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients", Asian Pac J Allergy Immunol, 35 (2): 75-81, doi:10.12932/AP0771
- "Medscape Log In". www.medscape.com. Retrieved September 25, 2018.
- Frieri, Marianne (2015). "Mast Cell Activation Syndrome". Allergy and Immunology.
- 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
- Johnston, C. S.; Martin, L. J.; Cai, X. (April 1992), "Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis", Journal of the American College of Nutrition, 11 (2): 172–176, ISSN 0731-5724, PMID 1578094
- Johnston, CS (December 1996). "Vitamin C depletion is associated with alterations in blood histamine and plasma free carnitine in adults". J Am Coll Nutr.
- Yazdani, Shaik (2016). "Relationship Between Vitamin C, Mast Cells, and Inflammation". J Nutr Food Sci.
- Mio, M (1999). "Ultraviolet B (UVB) light-induced histamine release from rat peritoneal mast cells and its augmentation by certain phenothiazine compounds". Immunopharmacology.
- Molderings, Gerhard (2016). "Pharmacological treatment options for mast cell activation disease". Naunyn Schmiedebergs Arch Pharmacol.
- Takemoto, S. "Magnesium deficiency induces the emergence of mast cells in the liver of rats". J Nutr Sci Vitaminol.
- "Medications to Treat Mast Cell Diseases". The Mast Cell Disease Society. Retrieved February 16, 2021.
- Klimas, Lisa (October 27, 2014). "MCAS: Treatment". Mast Attack. Retrieved December 8, 2018.
- Molderings, G (July 2016). "Pharmacological treatment options for mast cell activation disease". Naunyn Schmiedebergs Arch Pharmacol. 389 (7): 671–94. doi:10.1007/s00210-016-1247-1. PMC 4903110. PMID 27132234.
- Loebel, Madlen; Grabowski, Patricia; Heidecke, Harald; Bauer, Sandra; Hanitsch, Leif G.; Wittke, Kirsten; Meisel, Christian; Reinke, Petra; Volk, Hans-Dieter (February 2016). "Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome". Brain, Behavior, and Immunity. 52: 32–39. doi:10.1016/j.bbi.2015.09.013. ISSN 1090-2139. PMID 26399744.
- "Autoantibodies found in subset of CFS patients | #MEAction". MEAction. Retrieved August 10, 2018.
- Marshall-Gradisnik, Sonya; Smith, Peter; Nilius, Bernd; Staines, Donald R. (January 1, 2015). "Examination of Single Nucleotide Polymorphisms in Acetylcholine Receptors in Chronic Fatigue Syndrome Patients". Immunology and Immunogenetics Insights. 7: III.S25105. doi:10.4137/III.S25105. ISSN 1178-6345.
- "Acetylcholine via Muscarinic Receptors Inhibits Histamine Release from Human Isolated Bronchi". American Journal of Respiratory and Critical Care Medicine. doi:10.1164/ajrccm.156.2.96-12079#.v7vo-zmrlmv.
- "A new therapy to calm down mast cells". American Academy of Allergy, Asthma & Immunology. April 9, 2019. Retrieved July 28, 2019.
- Magen, Eli (2014). "Beneficial Effect of Sauna Therapy on Severe Antihistamine-Resistant Chronic Urticaria" (PDF). Israeli Medical Association Journal.
- "Zantac". drugs.com. Retrieved February 16, 2021.
- Klimas, Lisa (October 27, 2014). "MCAS: Treatment". Mast Attack. Retrieved February 21, 2019.
- Molderings, Gerhard J; Brettner, Stefan; Homann, Jürgen; Afrin, Lawrence B (March 22, 2011). "Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options". Journal of Hematology & Oncology. 4: 10. doi:10.1186/1756-8722-4-10. ISSN 1756-8722. PMC 3069946. PMID 21418662.
postural orthostatic tachycardia syndrome (POTS) - A form of orthostatic intolerance where the cardinal symptom is excessive tachycardia due to changing position (e.g. from lying down to sitting up).
myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.
autoantibody An antibody that works against the body's own antigens, a hallmark of autoimmune diseases. Autoantibodies are the opposite of an antibodies.
dysautonomia disorders of the autonomic nervous system that cause disturbances in all or some autonomic functions, may cause problems regulating autonomic functions, including heart rate, blood pressure, body temperature, and digestion. Can cause symptoms including lightheadedness, fainting, unstable blood pressure, and orthostatic intolerance.