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Mast cell activation syndrome
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[[File:Example of hives from mast cell activation disorder.jpg|thumb|Hives from mast cell activation disorder]] '''Mast cell activation syndrome''' (MCAS) is a disorder where [[Mast cell|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. ==Signs and Symptoms== In MCAS, the body's [[mast cell]]s 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.<ref name="Akin2017">{{Cite journal | last = Akin | first = Cem | date = Aug 2017 | title = Mast Cell Activation Syndromes|url=https://pubmed.ncbi.nlm.nih.gov/28780942/|journal=The Journal of Allergy and Clinical Immunology|volume=140|issue=2 | pages = 349–355|via=}}</ref> 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. Most patients experience [[fatigue]], [[fever]]s, and sensitivity to individualized environmental "triggers." Other commonly identified signs and symptoms are as follows: *[[Hot flushes|Hot flashes]], [[cardiac arrhythmia|irregular heartbeat]], high or low blood pressure ([[hypotension]] and/or [[hypertension]]) *[[vertigo]], [[dizziness]], [[Memory problems|forgetfulness]], [[depression]] or [[anxiety]], [[headache]]s, [[insomnia]], restlessness *[[hives]] or other visible [[skin rash]]es *[[arthritis]], [[Myalgia|muscle pain]], bone pain, [[osteoporosis]]/osteopenia *[[anaphylaxis]] (a severe allergic reaction) *[[Malabsorption]] and [[Gastrointestinal system|gastrointestinal]] distress leading to low [[iron]] and low [[Vitamin D]] and low [[Cobalamin|Vitamin B12]]<ref name="Molderings2011" /> ==Diagnosis== 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 system|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.<ref name="Akin2010">{{Cite journal | last = Akin | first = Cem | date = 2010 | title=Mast Cell Activation Syndrome: Proposed Diagnostic Criteria|url=https://pubmed.ncbi.nlm.nih.gov/21035176/|journal=J Allergy and Clinical Immuno|volume=126|issue=6|pages=1099-104.e4| doi=10.1016/j.jaci.2010.08.035|via=}}</ref> ==Clinicians== 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, [[United States]]. More integrative doctors are beginning to be aware of mast cell activation syndrome, but it remains elusive in both treatment and diagnosis. ==Comorbidities== Afrin et al. (2016) found the most common comorbities in MCAS, occurring in over 10% of patients, were *[[gastroesophageal reflux disease]] (GERD) 35% *[[hypertension]] 29% *multiple/atypical drug reactions 23% *[[abdominal pain]] not otherwise specified 22% *[[hysterectomy]]/oophorectomy 21% *[[hyperlipidemia]] 20% *[[cholecystectomy]] 20% *[[chemical sensitivities|environmental allergies]] 19% *tobacco abuse 18% *[[asthma]] 18% *[[diabetes|diabetes mellitus]] type 2 17% *[[hypothyroidism]] 17% *[[headache]]s 17% *[[depression]] 16% *[[sinusitis]] 16% *[[fibromyalgia]] 16% *[[anemia]] of chronic [[inflammation]] 15% *[[sleep apnea]] 15% *frequent [[upper respiratory infection|upper respiratory tract infections]] 15% *miscarriage 15% *[[sore throat|pharyngitis]] (sore throat caused by inflammation) or [[tonsillitis]] 14% *[[dysmenorrhea]] 14% *[[thromboembolism]] 13% *[[susceptibility to viruses|frequent or atypical infections]] 13% *[[obesity]] 13% *[[osteoarthritis]] 13% *[[anxiety]]/[[panic attack|panic]] 12% *vertebral disease 12% *cardiovascular malformations 12% *[[dermatitis]] 11 % *presyncope or [[syncope]] 11 % *[[interstitial cystitis]] 11 % *chronic kidney disease 10% *[[postural orthostatic tachycardia syndrome|POTS]] 10%<ref name="Afrin2016" /> 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/CFS|ME]]. The overlap between EDS, POTS, and MCAS is thought to be due to increased tryptase production.<ref name="Milner2015">{{Citation | last = Milner | first =Joshua | title = Research Update: POTS, EDS, MCAS Genetics | date = 2015 |publisher=Dysautonomia International Conference & CME|location=Washington DC|url=https://vimeo.com/142039306}}</ref> An extra copy of the gene [[Tryptase alpha/beta 1|TPSAB1]] has been noted as a possible cause for increased [[tryptase]] production.<ref name="Lyons2016">{{Cite journal | title = Hereditary Alpha Tryptasemia: Genotyping and Associated Clinical Features | date = 2018-08-01|url=https://www.sciencedirect.com/science/article/pii/S0889856118300298|journal=Immunology and Allergy Clinics of North America|volume=38|issue=3 | pages = 483–495 | last = Lyons | first = Jonathan J.|series=Mastocytosis|language=en|doi=10.1016/j.iac.2018.04.003|pmc=PMC6411063|pmid=30007465|issn=0889-8561}}</ref> The TPSAB1 has also been implicated in [[pruritus]], unexplained, [[digestive problems|gastrointestinal symptoms]], and in other diseases including the recently discovered [[Hereditary alpha tryptasemia syndrome|Hereditary Alpha Tryptasemia]].<ref name="Cheung2015">{{Cite journal|url=http://www.jacionline.org/article/S0091-6749(14)02927-3/abstract | title = A New Disease Cluster: Mast Cell Activation Syndrome, Postural Orthostatic Tachycardia Syndrome, and Ehlers-Danlos Syndrome | last = Cheung|first = Ingrid | last2 = Vadas | first2 = Peter | date = Feb 2015 |journal=The Journal of Allergy and Clinical Immunology|volume=135|issue=2|pages=Supp AB65|via=}}</ref><ref name="niaid-FAQ">{{Cite web | title = Hereditary Alpha Tryptasemia Syndrome FAQ|website=[[National Institute of Allergy and Infectious Diseases]] | date = Oct 17, 2016|url=https://www.niaid.nih.gov/research/hereditary-alpha-tryptasemia-faq}}</ref> {{See also|Hereditary alpha tryptasemia syndrome}} A small study by Novak et al. (2022) found [[decreased cerebral blood flow]] and [[small fiber neuropathy]] were very common in MCAS patients.<ref name="Novak2022">{{Cite journal | title = Mast cell disorders are associated with decreased cerebral blood flow and small fiber neuropathy | date = 2022-03-01|url=https://www.sciencedirect.com/science/article/pii/S1081120621011558|journal=Annals of Allergy, Asthma & Immunology|volume=128|issue=3|pages=299–306.e1 | last = Novak|first = Peter | last2 = Giannetti | first2 = Matthew P. | last3 = Weller | first3 = Emily | last4 = Hamilton | first4 = Matthew J. | last5 = Castells | first5 = Mariana|language=en|doi=10.1016/j.anai.2021.10.006|issn=1081-1206}}</ref> ==Myalgic Encephalomyelitis and Chronic Fatigue Syndrome == Most MCAS pstients have [[fatigue]], and approximately half have [[cognitive dysfunction]], and many symptoms of ME/CFS are also found; this may result in other a [[misdiagnosis of myalgic encephalomyelitis and chronic fatigue syndrome|misdiagnosis of chronic fatigue syndrome]] or be the result of having both illnesses.<ref name="Afrin2016" /> The rate of [[post-exertional malaise]], which is now considered the hallmark of ME/CFS, is unknown in MCAS patients. Research on the relationship between mast cells and ME is in its infancy. One study found that individuals diagnosed with [[Moderate myalgic encephalomyelitis or chronic fatigue syndrome|moderate]] to [[severe and very severe ME|severe ME]] have been noted to have higher amounts of dysfunctional mast cells in circulation.<ref name="Nguyen, et al, 2017">{{Cite journal | last = Nguyen | first1 = T. | authorlink1 = | last2 = Johnston | first2 = S. | authorlink2 = | last3 = Chacko | first3 = A. | authorlink3 = | last4 = Gibson | first4 = D. | authorlink4= | last5 = Cepon | first5 = J. | authorlink5 = | last6 = Smith | first6 = D. | authorlink6 = | last7 = Staines | first7 = D. | authorlink7 = Donald Staines | last8 =Marshall-Gradisnik | first8 = S. | authorlink8 = Sonya Marshall-Gradisnik | url = https://pubmed.ncbi.nlm.nih.gov/27362406/ | title = Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients | journal = Asian Pac J Allergy Immunol | volume = 35 | issue = 2 | page = 75-81 | date = 2017| doi = 10.12932/AP0771}}</ref> 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.<ref name="medscapeCFS">{{Cite web|url=https://www.medscape.com/viewarticle/893858 | title = Mast Cell Activation May Underlie 'Chronic Fatigue Syndrome' | date = Mar 13, 2018 | website = Medscape | last = Tucker | first = Miriam IE.|access-date=2018-09-25}}</ref> *[[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== 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 [[Chemical sensitivities|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.<ref name="Frieri2015">{{Cite journal | last = Frieri|first = Marianne | date = 2015 | title=Mast Cell Activation Syndrome|url=https://link.springer.com/article/10.1007%2Fs12016-015-8487-6|journal=Allergy and Immunology|volume=|pages=|via=}}</ref><ref name="Akin2017" /> == Potential treatments == ===Summary=== {| class="wikitable" !Name !Type !Form !Availability !Mechanism of action !Notes |- |[[Loratadine|Claritin (Loratadine)]] |H1 Blocker | |OTC | |Low anticholinergic activity. Not sedating. |- |[[Diphenhydramine|Benadryl]] |H1 Blocker |Oral and IV |OTC, prescription | |Sedating. |- |[[Cimetidine|Tagament]] (Cimetidine) |H2 Blocker | | | | |- |[[Famotidine|Pepcid]] (Famotidine) |H2 Blocker | | | | |- |[[Nizatidine|Axid]] (Nizatidine) |H2 Blocker | | | | |- |[[Ranitidine|Zantac]] (Ranitidine) |H2 Blocker |Oral, injection, IV |Withdrawn from market in US<ref name="zantac">{{Cite web|url=https://www.drugs.com/zantac.html | title = Zantac | last = | first = | date = |website=drugs.com|language=en-US|access-date=2021-02-16}}</ref> | | |- |[[Cetirizine|Zyrtec]] |H1 blocker | |OTC | |Not sedating. |- |[[Fexofenadine|Allegra]] (Fexofenadine) |H1 blocker | | | |Not sedating. |- |[[Ketotifen]] (Zaditor/Zaditen, Zyrtec Itchy Eye Drops) |H1 Blocker, mast cell stabilizer<ref name="k-eyedrops" /><ref name="k-oral" /> |Oral, eye drops.<ref name="k-eyedrops">{{Cite web|url=https://www.drugs.com/monograph/ketotifen.html | title = Ketotifen Monograph for Professionals|website=Drugs.com | date = |access-date=2022-04-05}}</ref><ref name="k-oral" /> |Perscription or OTC.<ref name="k-oral">{{Cite web|url=https://www.drugs.com/cons/ketotifen.html | title = Ketotifen (Oral)|website=Drugs.com | date = Oct 26, 2021|access-date=2022-04-05}}</ref><ref name="k-eyedrops" /> | |Not sedating. |- |[[Quercetin]] | | |OTC | | |- |[[Diamine oxidase]] |Enzyme normally produced by the body | | |Breaks down histamine. Especially found in gut and placenta. | |- |[[Omalizumab]] (Xolair) |Antibody and mast cell stabilizer.<ref name="OmalizumabSP">{{Cite book | title = Omalizumab | date = Feb 20, 2022|publisher=StatPearls Publishing|location=Treasure Island (FL)|first = Calvin | last = Kumar | first2 = Patrick M. | last2 = Zito|url=https://www.ncbi.nlm.nih.gov/books/NBK545183/|access-date=2022-04-05}}</ref> | |Prescription<ref name="Xolairdrugs">{{Cite web | title = Omalizumab|url=https://www.drugs.com/omalizumab.html | date = Feb 20, 2022 | website = drugs.com|access-date=2022-04-05}}</ref> | | |- |[[Vitamin C]] | | |OTC |Inhibits mast cell production and degranulation; increases diamine oxidase; breaks down histamine. |Sustained release version is recommended<ref name="Primer2021">{{Cite journal | title = Mast Cell Activation Syndrome: A Primer for the Gastroenterologist | date = Apr 2021|url=https://link.springer.com/10.1007/s10620-020-06264-9|journal=Digestive Diseases and Sciences|volume=66|issue=4 | pages = 965–982 | last = Weinstock|first = Leonard B. | last2 = Pace | first2 = Laura A. | last3 = Rezaie | first3 = Ali | last4 = Afrin | first4 = Lawrence B. | last5 = Molderings | first5 = Gerhard J.|language=en|doi=10.1007/s10620-020-06264-9|issn=0163-2116}}</ref> |- |[[Magnesium]] | | |OTC |Co-factor in diamine oxidase |<ref name="TMS-meds" /> |- |[[Prednisone]] |Corticosteroid |Oral, injection |Prescription | | |} === Elimination diet === Treatment of MCAS invariably involves trigger identifcation and avoidance<ref name="Primer2021" />. The Royal Prince Alfred Hospital in NSW, Australia has developed an [[RPAH elimination diet|elimination diet]] that focuses on reducing common food chemical triggers such as salicylates, amines, glutamates and particular additives. === Vitamin C === Numerous studies have found [[Vitamin C]] to be inversely correlated with histamine and that the administration of Vitamin C reduces blood [[histamine]] levels.<ref name="clemetson19802">{{Cite journal| issn = 0022-3166| volume = 110 | issue = 4| pages = 662–668| last = Clemetson | first = C.A. | title = Histamine and ascorbic acid in human blood| journal = The Journal of Nutrition | date = April 1980 | pmid = 7365537}}</ref><ref name="johnston1992">{{Cite journal| issn = 0731-5724| volume = 11 | issue = 2| pages = 172–176| last1 = Johnston | first1 = C.S. | last2 = Martin | first2 = L.J. | last3 = Cai | first3 = X.| title = Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis| journal = Journal of the American College of Nutrition | date = April 1992 | pmid = 1578094}}</ref><ref>{{Cite journal | last= Johnston | first = CS | date = December 1996 | title = Vitamin C depletion is associated with alterations in blood histamine and plasma free carnitine in adults|url=https://www.ncbi.nlm.nih.gov/pubmed/8951736|journal=J Am Coll Nutr.|volume=|pages=|via=}}</ref><ref name="Yazdani">{{Cite journal | last = Yazdani|first = Shaik | date = 2016 | title=Relationship Between Vitamin C, Mast Cells, and Inflammation | url =https://www.omicsonline.org/open-access/relationship-between-vitamin-c-mast-cells-and-inflammation-2155-9600-1000456.php?aid=66895|journal=J Nutr Food Sci.|volume=|pages=|via=}}</ref> 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),<ref name="Mio1999">{{Cite journal | last = Mio|first = M | date = 1999 | title = Ultraviolet B (UVB) light-induced histamine release from rat peritoneal mast cells and its augmentation by certain phenothiazine compounds|url=https://www.sciencedirect.com/science/article/pii/S0162310998000538|journal=Immunopharmacology|volume=|pages=|via=}}</ref> and by inhibiting [[histidine decarboxylase]] (the enzyme that forms histamine).<ref name="Molderings2016" /> === Magnesium === 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.<ref name="Takemoto2013">{{Cite journal | last = Takemoto|first = S| date = 2013 | title = Magnesium deficiency induces the emergence of mast cells in the liver of rats|url=https://pubmed.ncbi.nlm.nih.gov/24477254/|journal=J Nutr Sci Vitaminol|volume=59|issue=6 | pages = 560-3| doi= 10.3177/jnsv.59.560|via=}}</ref> === Antihistamines === Over-the-counter [[:Category:H1 antihistamines|H1]] and [[:Category:H2 antihistamines|H2 antihistamine]] blockers such as [[Fexofenadine|Allegra]] (Fexofenadine), [[Cetirizine|Zyrtec]] (Cetirizine), [[Loratadine|Claritin]] (Loratadine), and compounded [[Ketotifen|Zaditor/Zaditen]] (Ketotifen) are common treatments for MCAS.<ref name="TMS-meds">{{Cite web|url=https://tmsforacure.org/treatments-2/medications-treat-mast-cell-diseases/ | title = Medications to Treat Mast Cell Diseases | last = | first = | authorlink = | date = | website = The Mast Cell Disease Society|language=en-US|archive-url=|archive-date=|url-status=|access-date=2021-02-16}}</ref><ref name="Klimas2014">{{Cite web|url=https://www.mastattack.org/2014/10/mcas-treatment/ | title = MCAS: Treatment | last = Klimas | first = Lisa | date = 2014-10-27 | website = Mast Attack|language=en-US|access-date=2018-12-08}}</ref> It is recommended that the patient should consult a physician for secondary symptom treatment or targeted mast cell therapies.<ref name="Molderings2016">{{Cite journal | last = Molderings | first = G | date = Jul 2016 | title = Pharmacological treatment options for mast cell activation disease|url=https://pubmed.ncbi.nlm.nih.gov/27132234/|volume =389|issue=7 | pages = 671-94|doi=10.1007/s00210-016-1247-1|journal=Naunyn Schmiedebergs Arch Pharmacol|via=|pmid=27132234|pmc = 4903110}}</ref> Some patients also use herbal antihistamine supplements such as [[quercetin]] or take [[diamine oxidase]] (DAO), an enzyme normally produced by the body that breaks down histamine, as a supplement. Prescription drug treatments include [[Omalizumba|Xolair]] (Omalizumab), which has been proposed as a possible mast cell stabilizer and is used in allergic asthma and chronic urticaria. ===Leukotriene inhibitors === These include [[Montelukast]] and [[Zafirlukast]].<ref name="TMS-meds" /> Montelukast and zafirlukast block the effects of leukotriene C4 (LTC4) and zileuton blocks LTC4 production, so these reduce wheezing and abdominal cramping.<ref>{{Cite web|url=https://www.aaaai.org/conditions-treatments/related-conditions/mcas|title=Mast Cell Activation Syndrome (MCAS)|website=www.aaaai.org|access-date=2023-04-11}}</ref> Montelukast carries a black box label warning for possibly serious psychiatric adverse effects including psychosis and suicidal ideation.<ref>{{Cite web|url=https://medlineplus.gov/druginfo/meds/a600014.html|title=Montelukast: MedlinePlus Drug Information|website=medlineplus.gov|language=en|access-date=2023-04-11}}</ref> ===Mast cell stabilizers === These include oral [[cromolyn sodium]] (Gastrocrom) and [[Ketotifen]] (Zaditor/Zaditen).<ref name="TMS-meds" /> === Acetylcholinesterase inhibitors === In 2015, a large German study found 29% of [[ME/CFS]] patients had elevated autoantibodies to M3 and M4 [[muscarinic acetylcholine receptor]]s, as well as ß2 [[adrenergic receptor]]s.<ref name="Cromolyn2016">{{Cite journal | last = Loebel|first = Madlen | last2 = Grabowski | first2 = Patricia | last3 = Heidecke | first3 = Harald | last4 = Bauer | first4 = Sandra | last5 = Hanitsch | first5 = Leif G. | last6 = Wittke | first6 = Kirsten | last7 = Meisel | first7 = Christian | last8 = Reinke | first8 = Petra | last9 = Volk | first9 = Hans-Dieter | date = Feb 2016 | title = Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52 | pages = 32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref><ref>{{Cite web|url=http://www.meaction.net/2015/09/26/antibodies-found-in-subset-of-cfs-patients/ | title = Autoantibodies found in subset of CFS patients|website = [[The MEAction Network]]|language=en-US|access-date=2018-08-10}}</ref> A 2016 Australian study found that ME/CFS patients had significantly greater numbers of [[single nucleotide polymorphism]]s associated with the gene encoding for M3 muscarinic acetylcholine receptors.<ref name="Marshall2015">{{Cite journal | last = Marshall-Gradisnik|first = Sonya | last2 = Smith | first2 = Peter | last3 = Nilius | first3 = Bernd | last4 = Staines | first4 = Donald R. | date = 2015-01-01 | title = Examination of Single Nucleotide Polymorphisms in Acetylcholine Receptors in Chronic Fatigue Syndrome Patients|url=https://doi.org/10.4137/III.S25105|journal=Immunology and Immunogenetics Insights|language=en|volume=7|pages=III.S25105|doi=10.4137/III.S25105|issn=1178-6345}}</ref> One study found that [[acetylcholine]] via muscarinic receptors strongly inhibited the release of [[histamine]] in [[mucosal]] mast cells.<ref>{{Cite journal | title = Acetylcholine via Muscarinic Receptors Inhibits Histamine Release from Human Isolated Bronchi|url=http://www.atsjournals.org/doi/full/10.1164/ajrccm.156.2.96-12079#.V7vo-ZMrLMV|journal =American Journal of Respiratory and Critical Care Medicine|language=en|doi=10.1164/ajrccm.156.2.96-12079#.v7vo-zmrlmv}}</ref> [[Mestinon]], an [[acetylcholinesterase]] inhibitor, and [[Vagus nerve stimulator|vagus nerve stimulators]] can increase the amount of acetylcholine circulating in the peripheral nervous system. ===Omalizumab=== [[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.)<ref name="aaaai2019">{{Cite web|url=https://www.aaaai.org/global/latest-research-summaries/New-Research-from-JACI-In-Practice/mast-cells | title = A new therapy to calm down mast cells | last = | first = | authorlink = | date = April 9, 2019 | website = American Academy of Allergy, Asthma & Immunology|archive-url=|archive-date=|url-status=|access-date=July 28, 2019}}</ref> 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.<ref name="aaaai2019" /> === Sauna === 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.<ref name="Magen2014">{{Cite journal | last = Magen | first = Eli | date = 2014 | title = Beneficial Effect of Sauna Therapy on Severe Antihistamine-Resistant Chronic Urticaria|url=http://www.espalibrary.eu/media/filer_public/5e/18/5e180886-9aa4-4d26-9ff2-158689f0fbcc/38034.pdf | journal=Israeli Medical Association Journal|volume=|pages=|via=}}</ref> ==Notable studies == *2016, Characterization of Mast Cell Activation Syndrome<ref name="Afrin2016">https://doi.org/10.1182/blood.V128.22.3683.3683</ref> - [https://www.sciencedirect.com/science/article/pii/S0006497119336845 (Full text)] *2011, Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. Journal of Hematology & Oncology<ref name="Molderings2011">{{Cite journal | last = Molderings | first = Gerhard J | last2 = Brettner | first2 = Stefan | last3 = Homann | first3 = Jürgen | last4 = Afrin | first4 = Lawrence B | authorlink4 = Lawrence Afrin | date = 2011-03-22 | title = Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069946/|journal=Journal of Hematology & Oncology|volume=4|issue=|pages=10|doi=10.1186/1756-8722-4-10|issn=1756-8722|pmc=3069946|pmid=21418662}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069946/ (Full text)] *2020, Diagnosis of mast cell activation syndrome: a global "consensus-2"<ref name="Afrin2020">{{Cite journal | title = Diagnosis of mast cell activation syndrome: a global “consensus-2” | date = 2021-05-01|url=https://www.degruyter.com/document/doi/10.1515/dx-2020-0005/html?lang=en|journal=Diagnosis|volume=8|issue=2|pages=137–152 | last = Afrin | first = Lawrence B. | authorlink = Lawrence Afrin | last2 = Ackerley | first2 = Mary B. | authorlink2 = | last3 = Bluestein | first3 = Linda S. | authorlink3 = | last4 = Brewer | first4 = Joseph H. | authorlink4 = Joseph Brewer | last5 = Brook | first5 = Jill B. | authorlink5 = | last6 = Buchanan | first6 = Ariana D. | authorlink6 = | last7 = Cuni | first7 = Jill R. | last8 = Davey | first8 = William P. | last9 = Dempsey | first9 = Tania T. | last10 = Dorff | first10 = Shanda R. | last11 = Dubravec | first11 = Martin S.|language=en|doi=10.1515/dx-2020-0005|pmc=|pmid=|access-date=|issn=2194-802X|quote=|via=}}</ref> - [https://www.degruyter.com/document/doi/10.1515/dx-2020-0005/html?lang=en (Full text)] *2019, Doctor, I Think I Am Suffering from MCAS: Differential Diagnosis and Separating Facts from Fiction<ref name="Valent2019">{{Cite journal | title = Doctor, I Think I Am Suffering from MCAS: Differential Diagnosis and Separating Facts from Fiction | date = 2019-04-01|url=https://www.jaci-inpractice.org/article/S2213-2198(18)30819-5/abstract|journal=The Journal of Allergy and Clinical Immunology: In Practice|volume=7|issue=4|pages=1109–1114 | last = Valent | first = Peter | last2 = Akin | first2 = Cem|language=English|doi=10.1016/j.jaip.2018.11.045|pmid=30961836|issn=2213-2198}}</ref> - [https://linkinghub.elsevier.com/retrieve/pii/S2213-2198(18)30819-5 (Full text)] ==Learn more== * [https://www.mastattack.org/2014/10/mcas-treatment/ MCAS: Treatment] - Mast Attack ==See also== *[[Lawrence Afrin]] *[[Mast cell]] *[[Hereditary alpha tryptasemia syndrome]] (HATS) *[[Theoharis Theoharides]] ==References== {{Reflist}} [[Category:Diagnoses]] [[Category:Potential comorbidities]]
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