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'{{distinguish|Mastocytosis}} {{Infobox medical condition (new) | name = Immune Disorder | synonyms = | image = | caption = | pronounce = | field = [[Immunology]] ([[Allergy]]) | symptoms = | complications = | onset = | duration = | types = | causes = | risks = | diagnosis = | differential = | prevention = | treatment = | medication = | prognosis = | frequency = | deaths = }} '''Mast cell activation syndrome''' ('''MCAS''') is one type of [[mast cell activation disorder]] ('''MCAD'''), and is an immunological condition in which [[mast cell]]s inappropriately and excessively release chemical mediators, resulting in a range of chronic symptoms, sometimes including [[anaphylaxis]] or near-anaphylaxis attacks.<ref name="Valent">{{cite journal | author = Valent P | year = 2013 | title = Mast Cell Activation Syndromes: Definition and Classification | url = | journal = Allergy | volume = 68 | issue = 4| pages = 417–24 | pmid = 23409940 | doi=10.1111/all.12126}}</ref><ref name="Cem">{{cite journal | pmc = 3753019 | pmid=21035176 | doi=10.1016/j.jaci.2010.08.035 | volume=126 | title=Mast cell activation syndrome: Proposed diagnostic criteria | year=2010 | journal=J. Allergy Clin. Immunol. | pages=1099–104.e4 | vauthors=Akin C, Valent P, Metcalfe DD}}</ref><ref name="anaph">{{cite journal | author = Akin C | year = 2015 | title = Mast Cell Activation Syndromes Presenting as Anaphylaxis | url = http://www.sciencedirect.com/science/article/pii/S0889856115000119 | journal = Immunology and Allergy Clinics of North America | volume = 35 | issue = 2| pages = 277–85 | doi=10.1016/j.iac.2015.01.010}}</ref> Primary symptoms include cardiovascular, dermatological, gastrointestinal, neurological and respiratory problems.<ref name=Cem /> 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".<ref name=Cem /> MCAS is still a poorly understood condition and is a current topic of research.<ref name="white">[http://www.dysautonomiainternational.org/blog/wordpress/a-tale-of-two-syndromes-pots-and-mcas/ 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].</ref> MCAS is often found in patients with [[Ehlers–Danlos syndrome]] (EDS) and [[postural orthostatic tachycardia syndrome]] (POTS).<ref name="milner">[https://vimeo.com/142039306 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]</ref> It is also found in subset groups of patients with [[common variable immunodeficiency]] (CVID)<ref name="Journal of Allergy">{{cite journal | author = Szczawinska-Poplonyk A | year = | title = An Overlapping Syndrome of Allergy and Immune Deficiency in Children | url = http://www.hindawi.com/journals/ja/2012/658279/ | journal = Journal of Allergy | volume = 2012 | issue = | pages = 1–9| doi = 10.1155/2012/658279 }}</ref> and [[Lyme disease]].<ref name="Lyme">{{cite journal |vauthors=Talkington J, Nickell SP | date = Mar 1999 | title = Borrelia burgdorferi Spirochetes Induce Mast Cell Activation and Cytokine Release | journal = Infect Immun | volume = 67 | issue = 3| pages = 1107–1115 | pmc=96436 | pmid=10024550}}</ref> ==Symptoms == 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.<ref name="guide">[https://www.novapublishers.com/catalog/product_info.php?products_id=42603 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</ref> It has many overlapping characteristics with recurrent idiopathic anaphylaxis, although there are distinguishing symptoms, specifically [[hives]] and [[angioedema]].<ref name=frieri /> '''Common symptoms include:'''<ref name=white /><ref name=presentation /> *''Dermatological'' **flushing **hives **easy bruising **either a reddish or a pale complexion **itchiness **burning feeling **[[dermatographism]] *''Cardiovascular'' **lightheadedness, dizziness, [[presyncope]], [[syncope (medicine)|syncope]], [[arrhythmia]], [[tachycardia]] *''Gastrointestinal'' **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.) *''Respiratory'' **congestion, coughing, wheezing ** [[Nonallergic rhinitis]] with eosinophilia syndrome (NARES) <ref name="NARES">[https://www.ncbi.nlm.nih.gov/pubmed/16579871 Ellis AK, Keith PK "Nonallergic rhinitis with eosinophilia syndrome" Curr Allergy Asthma Rep.] Accessed 26 Feb 2018</ref> **[[Obstructive Sleep Apnea]] *''Vision/Eyes'' **ocular discomfort, [[conjunctivitis]] **redness *''Constitutional'' **general fatigue and malaise **food, drug, and chemical allergies or intolerances (especially fragrances) **Cold and Heat Intolerance *''Musculoskeletal'' **[[osteoporosis]] and [[osteopenia]] (including young patients) *''[[Anaphylaxis]]'' If too many mediators are spilt 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:'''<ref name=presentation /> *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. ==Causes== There are no known causes, but the condition appears to be inherited in some patients.<ref name=milner /> 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.<ref name=white /><ref name=milner /> ==Diagnosis== MCAS is often difficult to identify due to the heterogeneity of symptoms and the "lack of flagrant acute presentation."<ref name="presentation">[https://www.novapublishers.com/catalog/product_info.php?products_id=42603 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.]</ref> 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.<ref name=guide /> 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: <br> 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"<ref name=white /> The [[World Health Organization]] has not published diagnostic criteria. ==Treatment== Common pharmacological treatments include: *[[Mast cell stabilizer]]s,<ref name="frieri">{{cite journal | vauthors = Frieri M | title = Mast Cell Activation Syndrome | journal = Clin Rev Allergy Immunol | volume = | issue = | pages = | year = 2015 | pmid = 25944644 | doi = 10.1007/s12016-015-8487-6 | quote = }}</ref> including [[cromolyn sodium]] and [[natural product|natural]] stabilizers such as [[quercetin]]<ref name="MC stabilizers - review">{{cite journal | vauthors = Finn DF, Walsh JJ | title = Twenty-first century mast cell stabilizers | journal = Br. J. Pharmacol. | volume = 170 | issue = 1 | pages = 23–37 | year = 2013 | pmid = 23441583 | pmc = 3764846 | doi = 10.1111/bph.12138 | quote = 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.}}[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764846/table/tbl1/ Table 1: Naturally occurring mast cell stabilizers]</ref><ref name="Quercetin MC stabilizer - primary supplement">{{cite journal | vauthors = Weng Z, Zhang B, Asadi S, Sismanopoulos N, Butcher A, Fu X, Katsarou-Katsari A, Antoniou C, Theoharides TC | title = Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans | journal = PLoS ONE | volume = 7 | issue = 3 | pages = e33805 | year = 2012 | pmid = 22470478 | pmc = 3314669 | doi = 10.1371/journal.pone.0033805 | url = }}</ref> *[[Antihistamine#H1-antihistamines|H1-antihistamines]],<ref name="frieri" /> such as [[cetirizine]] or [[ketotifen]] *[[Antihistamine#H2-antihistamines|H2-antihistamines]],<ref name="frieri" /> such as [[ranitidine]] or [[famotidine]] *[[Antileukotriene]]s,<ref name="frieri" /> such as [[montelukast]] or [[zileuton]] as well as natural products (e.g., [[curcumin]] or [[St. John's wort]] extracts) *[[Nonsteroidal anti-inflammatory drug]]s,<ref name=guide /> including [[aspirin]] can be very helpful in reducing inflammation in some patients, while others can have dangerous reactions<ref name=guide /> Fillers, [[binder (material)|binders]] and dyes in many medications are often the culprit in causing reactions, not necessarily the [[active ingredient|active agent]], so alternative formulations and [[compounding pharmacies]] should be considered.<ref name=guide /> 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.<ref name=guide /> 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. ==Prognosis== 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.<ref name=guide /> Some patients are impaired enough to be disabled and unable to work. ==Epidemiology== 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").<ref name=guide /> ==History== It has been suggested in the literature for decades; however diagnostic criteria have been proposed only in 2010.<ref name=Cem /> 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.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/17057414 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.]</ref> and Akin et al.,<ref>[https://www.ncbi.nlm.nih.gov/pubmed/17638853 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.]</ref> finally named in 2007.<ref name=guide /> ==See also== * [[FcεRI]] * [[Histamine intolerance]] * [[Immunoglobulin E]] ==References== {{Reflist}} ==Further reading== * [https://www.ncbi.nlm.nih.gov/pubmed/26194403 The role of mast cells in functional GI disorders] * [https://link.springer.com/article/10.1007%2Fs12016-015-8487-6 Mast Cell Activation Syndrome] – May 2015 * [http://www.tandfonline.com/doi/full/10.1586/1744666X.2014.906302#.VhcLJ_lVhBc Spectrum of mast cell activation disorders] – 2014 * {{open access}} [http://onlinelibrary.wiley.com/doi/10.1111/all.12126/epdf Mast cell activation syndromes: definition and classification] – 2013 * {{open access}} [http://www.clinicaltherapeutics.com/article/S0149-2918(13)00171-9/fulltext Expanding Spectrum of Mast Cell Activation Disorders: Monoclonal and Idiopathic Mast Cell Activation Syndromes] – 2013 == External links == {{Medical resources | DiseasesDB = | ICD10 = [http://www.icd10data.com/ICD10CM/Codes/D50-D89/D80-D89/D89-#D89.4 D89.4] | ICD9 = 279.8 | ICDO = | OMIM = | MedlinePlus = | eMedicineSubj = | eMedicineTopic = | MeshID = }} [[Category:Immune system disorders]] [[Category:Syndromes]]'