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Mast cell activation syndrome
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== 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(Nizatidine) |H2 Blocker | | | | |- |[[Ranitidine|Zantac]] (Ranitidine) |H2 Blocker |Oral, injection, IV |Withdrawn from market in US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>
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