Mast cell activation syndrome
Mast cell activation syndrome (MCAS) is one type of mast cell activation disorder (MCAD), and is an immunological condition in which mast cells inappropriately and excessively release chemical mediators, resulting in a range of chronic symptoms, sometimes including anaphylaxis or near-anaphylaxis attacks. Primary symptoms include cardiovascular, dermatological, gastrointestinal, neurological and respiratory problems.
Unlike mastocytosis, another type of MCAD, where patients have an abnormally increased number of mast cells, patients with MCAS have a normal number of mast cells that do not function properly and are defined as "hyperresponsive". MCAS is still a poorly understood condition and is a current topic of research.
MCAS is often found in patients with Ehlers–Danlos syndrome (EDS) and postural orthostatic tachycardia syndrome (POTS). It is also found in subset groups of patients with common variable immunodeficiency (CVID).
MCAS is a condition that affects multiple systems, generally in an inflammatory manner. Symptoms typically wax and wane over time, varying in severity and duration. Many signs and symptoms are the same as those for mastocytosis, because both conditions result in too many mediators released by mast cells. It has many overlapping characteristics with recurrent idiopathic anaphylaxis, although there are distinguishing symptoms, specifically hives and angioedema.
- easy bruising
- either a reddish or a pale complexion
- burning feeling
- diarrhea and/or constipation, cramping, intestinal discomfort
- nausea, vomiting
- swallowing difficulty, throat tightness
- Psychological & Neurological
- brain fog, short term memory dysfunction, difficulty with recalling words
- headaches, migraines
- co-morbid psychiatric and behavioral symptoms as a result of mast cell mediators being released in the brain (i.e.: anxiety, depression, mood swings, etc.)
- ocular discomfort, conjunctivitis
- general fatigue and malaise
- food, drug, and chemical allergies or intolerances (especially fragrances)
- Cold and Heat Intolerance
- Anaphylaxis If too many mediators are split into a patient's system, they may also experience anaphylaxis, which primarily includes: difficulty breathing, itchy hives, flushing or pale skin, feeling of warmth, weak and rapid pulse, nausea, vomiting, diarrhea, dizziness and fainting.
Symptoms can be caused or worsened by triggers, which vary widely and are patient-specific. Common triggers include:
- specific foods and drinks (especially alcohol, high-histamine content foods, and histamine releasing additives such as sulfites)
- temperature extremes
- airborne smells including perfumes or smoke
- exercise or exertion
- emotional stress
- hormonal changes, particularly during adolescence, pregnancy and menstruation.
There are no known causes, but the condition appears to be inherited in some patients. Symptoms of MCAS are caused by excessive chemical mediators inappropriately released by mast cells. Mediators include leukotrienes and histamines. The condition may be mild until exacerbated by stressful life events, or symptoms may develop and slowly trend worse with time.
MCAS is often difficult to identify due to the heterogeneity of symptoms and the "lack of flagrant acute presentation." The condition can also be difficult to diagnose, especially since many of the numerous symptoms may be considered "vague". Patients often see many different specialties due to the inherent multisystem nature of the condition, and do not get diagnosed until a holistic view is taken by a diagnostician. Lack of awareness (and even frank refusal to believe in the existence) of MCAS by many medical professionals is currently a hurdle to proper diagnosis. Mast cell activation was assigned an ICD 10 code (D89.40, along with subtype codes D89.41-43 and D89.49) in October 2016.
- "Although different diagnostic criteria are published, a commonly used strategy to diagnose patients is to use all three of the following:
- Symptoms consistent with chronic/recurrent mast cell release:
Recurrent abdominal pain, diarrhea, flushing, itching, nasal congestion, coughing, chest tightness, wheezing, lightheadedness (usually a combination of some of these symptoms is present)
- Laboratory evidence of mast cell mediator (elevated serum tryptase, N-methyl histamine, prostaglandin D2 or 11-beta- prostaglandin F2 alpha, leukotriene E4 and others)
- Improvement in symptoms with the use of medications that block or treat elevations in these mediators"
The World Health Organization has not published diagnostic criteria.
Common pharmacological treatments include:
- Mast cell stabilizers, including cromolyn sodium and natural stabilizers such as quercetin
- H1-antihistamines, such as cetirizine or ketotifen
- H2-antihistamines, such as ranitidine or famotidine
- Antileukotrienes, such as montelukast or zileuton as well as natural products (e.g., curcumin or St. John's wort extracts)
- Nonsteroidal anti-inflammatory drugs, including aspirin can be very helpful in reducing inflammation in some patients, while others can have dangerous reactions
Fillers, binders and dyes in many medications are often the culprit in causing reactions, not necessarily the active agent, so alternative formulations and compounding pharmacies should be considered.
Lifestyle changes may also be needed. Avoidance of triggers is important. It should be emphasized that MCAS patients can potentially react to any new exposure, including food, drink, medication, microbes and smoke via inhalation, ingestion or touch.
A low histamine diet and other elimination diets can be useful in identifying foods that trigger or worsen symptoms. Many MCAS patients already have high histamine levels, so ingesting foods with high histamine or histamine liberators can worsen many symptoms such as vasodilation that causes faintness and palpitations.
There is no cure for MCAS. For most, symptoms wax and wane, but many can experience a general worsening trend over time. Lifespan for those with MCAS appears to be normal, but quality of life can range from mild discomfort to severely impaired. Some patients are impaired enough to be disabled and unable to work.
MCAS is a relatively new diagnosis, being unnamed until 2007, and is believed to be under-diagnosed (Dr. Lawrence Afrin describes it as "likely quite prevalent" and having "increasingly apparent prevalence").
It has been suggested in the literature for decades; however diagnostic criteria have been proposed only in 2010. The condition was hypothesized by the pharmacologists John Oates and Jack Roberts of Vanderbilt University in 1991, and following a build-up of evidence featured in papers by Sonneck et al. and Akin et al., finally named in 2007.
- Valent P (2013). "Mast Cell Activation Syndromes: Definition and Classification". Allergy. 68 (4): 417–24. doi:10.1111/all.12126. PMID 23409940.
- Akin C, Valent P, Metcalfe DD (2010). "Mast cell activation syndrome: Proposed diagnostic criteria". J. Allergy Clin. Immunol. 126: 1099–104.e4. doi:10.1016/j.jaci.2010.08.035. PMC . PMID 21035176.
- Akin C (2015). "Mast Cell Activation Syndromes Presenting as Anaphylaxis". Immunology and Allergy Clinics of North America. 35 (2): 277–85. doi:10.1016/j.iac.2015.01.010.
- White, Andrew, Dr. "A Tale of Two Syndromes – POTS and MCAS". The Dysautonomia Dispatch. Dysautonomia International, 17 Feb. 2015. Web. 12 Oct. 2015, at dysautonomiainternational.org.
- 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, at vimeo.com
- Szczawinska-Poplonyk A. "An Overlapping Syndrome of Allergy and Immune Deficiency in Children". Journal of Allergy. 2012: 1–9. doi:10.1155/2012/658279.
- Afrin, Lawrence B. "A Concise, Practical Guide to Diagnostic Assessment for Mast Cell Activation Disease." WJH World Journal of Hematology 3.1 (2014): 155-232. Accessed 29 January 2018
- Frieri M (2015). "Mast Cell Activation Syndrome". Clin Rev Allergy Immunol. doi:10.1007/s12016-015-8487-6. PMID 25944644.
- Afrin, Lawrence, Dr. "Presentation, Diagnosis, and Management of Mast Cell Activation Syndrome." Mast Cells: Phenotypic Features, Biological Functions and Role in Immunity. Nova Science, 2013. 155-232.
- Ellis AK, Keith PK "Nonallergic rhinitis with eosinophilia syndrome" Curr Allergy Asthma Rep. Accessed 26 Feb 2018
- Finn DF, Walsh JJ (2013). "Twenty-first century mast cell stabilizers". Br. J. Pharmacol. 170 (1): 23–37. doi:10.1111/bph.12138. PMC . PMID 23441583.
A diverse range of mast cell stabilizing compounds have been identified in the last decade from; natural, biological and synthetic sources to drugs already in clinical uses for other indications. Although in many cases, the precise mode of action of these molecules is unclear, all of these substances have demonstrated mast cell stabilization activity and therefore may have potential therapeutic use in the treatment of allergic and related diseases where mast cells are intrinsically involved.Table 1: Naturally occurring mast cell stabilizers
- Weng Z, Zhang B, Asadi S, Sismanopoulos N, Butcher A, Fu X, Katsarou-Katsari A, Antoniou C, Theoharides TC (2012). "Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans". PLoS ONE. 7 (3): e33805. doi:10.1371/journal.pone.0033805. PMC . PMID 22470478.
- Sonneck K, Florian S, Müllauer L, Wimazal F, Födinger M, Sperr WR, Valent P. "Diagnostic and subdiagnostic accumulation of mast cells in the bone marrow of patients with anaphylaxis: Monoclonal mast cell activation syndrome." Int Arch Allergy Immunol. 2007;142(2):158-64. Epub 2006 Oct 20.
- Akin C, Scott LM, Kocabas CN, Kushnir-Sukhov N, Brittain E, Noel P, Metcalfe DD. "Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with "idiopathic" anaphylaxis." Blood. 2007 Oct 1;110(7):2331-3. Epub 2007 Jul 16.
- The role of mast cells in functional GI disorders
- Mast Cell Activation Syndrome – May 2015
- Spectrum of mast cell activation disorders – 2014
- Mast cell activation syndromes: definition and classification – 2013
- Expanding Spectrum of Mast Cell Activation Disorders: Monoclonal and Idiopathic Mast Cell Activation Syndromes – 2013