Treatment Options for Mast Cell Disease

Similar to many other conditions like asthma and allergies, there is currently no cure for mast cell disease. Treatment is aimed at reducing the severity of symptoms and occurrence of flares. Treatment protocol includes lifestyle changes as well as medication-based interventions. Some examples of Mast Cell Disease include Systemic Mastocytosis (SM), Mast Cell Activation Syndrome (MCAS), and Hereditary alpha-tryptasemia (HaT), but it is important to note that the diagnosis and treatment of each of these is unique.

This is provided for informational purposes only, and should not be treated as medical advice. For diagnosis and treatment of MCAD, please speak with your doctor.

‍

Prophylactic Avoidance of Identified Triggers

Both diet and environment can trigger symptoms so an important first step in managing mast cell diseases (MCAD) including Mast Cell Activation Syndrome (MCAS) is to adopt a prophylactic approach to all identified known and likely triggers.¹

‍

Prophylactic Treatment with Medication

Antihistamine Medications (Histamine Blockers)

H1 Blocker Antihistamines

H1 antihistamines can help to improve a wide variety of symptoms associated with mast cell instability (degranulation) including treating pruritus (itchy skin), flushing of the skin, headaches, and brain fog. Although typically used for typical allergies, antihistamines are known to treat a wide range of symptoms associated with the mast cell instability typical Mast Cell Disease (MCAD).^2,3

Second and third generation antihistamines should be trialed before 1st generation as they tend to be better tolerated by patients. Typically, it takes a few weeks of trial and error with each medication to identify which treatment option is most effective at controlling symptoms while minimizing side effects. Zyrtec is typically the first-line therapy, and it is frequently most effective when used every 12 hours (instead of every 24 hours) in dosages that are 2 to 3 times higher than the typical dose. Patients should consult with their doctor to identify the best treatment protocol.

Benadryl® (Diphenhydramine) should not be used unless the patient has failed all other H1 blockers. It can quickly suppress mast cell activation, but it not a preferred treatment option because it often causes undesirable drowsiness and its half-life is as short as one hour. Patients typically use Benadryl as a rescue medication during emergencies or flares.  For the most severe cases, especially during an emergency or surgery, continuous diphenhydramine infusion has been reported to be effective.³²

1st Generation H1 Blockers

• Chlorpheniramine (Chlortrimeton®)
• Diphenhydramine (Benadryl®)
• Doxepin hydrochloride (Doxepin®, Sinequan®)
• Hydroxyzine hydrochloride (Atarax®)
• Oral ketotifen

2nd Generation H1 Blockers

• Cetirizine (Zyrtec®)
• Loratadine (Claritin®)

3rd Generation H1 Blockers

• Levocetirizine (Xyzal®)
• Fexofenadine (Allegra®)
• Desloratadine (Clarinex®)

H2 Blocker Antihistamines

H2 blocker antihistamines help manage systemic symptoms as well as symptoms in the gastrointestinal tract such as cramps, constipation, and diarrhea.²

• Cimetidine (Tagamet®)
• Famotidine (Pepcid®)
• Ranitidine (no longer available over the counter in the US)

Mast Cell Stabilizers

Mast cell stabilizers are most often prescribed in combination with histamine blockers and help treat a wide range of symptoms. Patients may sometimes need to take more than one mast cell stabilizer, depending on their symptoms. For example, oral cromolyn sodium is used to treat gastrointestinal issues, while ketotifen is used to treat general mast cell symptoms.4,5

• Bioflavonoids such as quercetin and luteolin^6,7
• Oral cromolyn sodium (Gastrocrom®)^4,8
• Topical cromolyn sodium⁹
• Oral ketotifen^5,10
• Vitamin C11
• Vitamin D12

Leukotriene Inhibitors

Leukotriene inhibitors are most often prescribed in combination with histamine blockers. Leukotriene inhibitors help treat asthma and respiratory symptoms in addition to psoriasis and dermatitis.¹³

• Montelukast (Singulair ®)
• Zafirlukast (Accolate®)
• Zileuton (Zyflo®/Zyflo CR®)

Aspirin Therapy

Aspirin may be prescribed in small doses in combination with histamine blockers to help manage symptoms, such as flushing of the skin and symptoms associated with the excess release of prostaglandin (PG) D2.14,15 e This is not a first-line therapy, and should only be added to the regimen after trialing H1 and H2 blockers.  Do not self-treat/medicate with aspirin! Aspirin, while a miracle treatment for some, may cause anaphylaxis for others.

While aspirin is available over-the-counter, aspirin therapy should always be initiated and managed under the direct supervision of a physician. This is especially true for severe cases of MCAD who present with frequent anaphylaxis.

Since long-term use of aspirin is associated with a risk of gastrointestinal bleeding, aspirin therapy is not recommended for patients with conditions of the GI tract or with an increased risk of ulcerative GI conditions.^2,16

Anti-IgE Therapy

Anti-IgE therapy helps with overall mast cell stability and therefore a wide range of symptoms affecting all organ systems.17

• Omalizumab (Xolair®)

PPIs (Proton Pump Inhibitors)

PPIs (proton pump inhibitors) can be used to treat GERD (Gastroesophageal Reflux Disease) that develops as a result of mast cell disease.³⁰

• Exlansoprazol (Dexilant®)
• Esomeprazole (Nexium®)
• Lansoprazole (Prevacid®)
• Omeprazole (Prilosec®)
• Pantoprazole (Protonix®)
• Rabeprazole (Aciphex®)

Chemotherapy

In cases where the patient is diagnosed with an aggressive, systemic variant of mastocytosis (a rare form of cancer), chemotherapy, more specifically D816V KIT Inhibitors, can be prescribed.¹⁸  Note that this should only be used in confirmed cases of mastocytosis, and it is not recommended for MCAS, HAT, or other non-cancerous forms of Mast Cell Disease (MCAD).

FDA-Approved D816V KIT Inhibitors

• Avapritinib (Ayvakit ®)^19,20
• Midostaurin (Rydapt ®)^21,22

D816V KIT Inhibitors Currently in Clinical Trial

• Cladribine (Leustatin®, Leustat®, Litak®)²³
• Dasatinib (Sprycel®)²⁴
• Imatinib (Gleevec®)²⁵
• INF - α 2b (Interferon Alpha 2b)²⁶
• Masitinib (Masivet®)²⁷
• Nilotinib (Tasigna®)²⁸
• Ripretinib (Qinlock®)²⁹

PUVA Phototherapy for the Treatment of Severe Skin Symptoms

PUVA combination therapy using oral psoralen plus ultraviolet-A light can be used in cases of severe skin symptoms to help treat skin lesions.³¹

Emergency Treatment

Emergency treatment for mast cell disease is administered in the case of anaphylactic shock. All patients should create an emergency treatment plan with their physician that includes:

• Increasing dosage of H1 and H2 blockers
• Taking Benadryl®
• Using an inhaler
• Using a self-injectable Epi-Pen®

‍

FAQ:

Which antihistamine is best for MCAS?‍

Both H1 blockers like Zyrtec and H2 blockers such as famotidine are commonly recommended. Combination therapy, using both H1 and H2 antihistamines, is often more effective for MCAS symptom control as it covers a broader range of histamine receptors.

How much Zyrtec should I take for MCAS?‍

The typical dose for Zyrtec to manage MCAS symptoms in adults is usually 10 mg once daily, but some patients may require up to twice daily under medical supervision. It’s important to consult with a healthcare provider before adjusting your dosage to ensure it aligns with your specific needs and any other medications.

Is Zyrtec effective for managing mast cell activity?‍

Yes, Zyrtec, an antihistamine, is often used to help control symptoms of MCAS. It works by blocking histamine receptors, reducing histamine-driven symptoms like itching, swelling, and gastrointestinal distress that can be triggered by mast cell activation.

Does Zyrtec contain a histamine blocker?‍

Yes, Zyrtec is an H1 antihistamine that blocks histamine receptors in the body, specifically targeting H1 receptors to prevent symptoms related to allergic reactions and mast cell activation.

Does Zyrtec reduce inflammation?‍

Zyrtec primarily blocks histamine and does not directly reduce inflammation. However, by managing histamine responses, it can help alleviate inflammation-related symptoms like itching and swelling that result from mast cell activation.

Can I take two Zyrtec tablets a day for severe allergies?‍

Taking more than the recommended dose of Zyrtec should only be done under a healthcare provider’s guidance. For severe symptoms, doubling the dose may sometimes be allowed, but it's important to verify with a doctor to avoid potential side effects.

‍

References:

‍

This article draws heavily from the work of Mast Cell Hope which can be viewed at https://www.mastcellhope.org/education/common-treatments

1. Maintz L and Novak N. Histamine and histamine intolerance. The American Journal of Clinical Nutrition. 2007:85(5);1185–1196. https://doi.org/10.1093/ajcn/85.5.1185
2. Valent P, Akin C, Gleixner KV, et al. Multidisciplinary Challenges in Mastocytosis and How to Address with Personalized Medicine Approaches. Int J Mol Sci. 2019;20(12):2976. https://doi:10.3390/ijms20122976
3. Criado PR, Criado RF, Maruta CW, Machado Filho Cd. Histamine, histamine receptors and antihistamines: new concepts. An Bras Dermatol. 2010;85(2):195-210. https://pubmed.ncbi.nlm.nih.gov/20520935/
4. Stefanini GF, Saggioro A, Alvisi V, Angelini G, Capurso L, di Lorenzo G, Dobrilla G, Dodero M, Galimberti M, Gasbarrini G, et al. Oral cromolyn sodium in comparison with elimination diet in the irritable bowel syndrome, diarrheic type. Multicenter study of 428 patients. Scand J Gastroenterol. 1995 Jun;30(6):535-41. https://pubmed.ncbi.nlm.nih.gov/7569760/
5. Sokol KC, Amar NK, Starkey J, Grant JA. Ketotifen in the management of chronic urticaria: resurrection of an old drug. Ann Allergy Asthma Immunol. 2013;111(6):433-436. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309375/
6. Shaik Y, Caraffa A, Ronconi G, Lessiani G, Conti P. Impact of polyphenols on mast cells with special emphasis on the effect of quercetin and luteolin. Cent Eur J Immunol. 2018;43(4):476-481. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384425/
7. Weng Z, Zhang B, Asadi S, Sismanopoulos N, Butcher A, Fu X, Katsarou-Katsari A, Antoniou C, Theoharides TC. Quercetin Is More Effective than Cromolyn in Blocking Human Mast Cell Cytokine Release and Inhibits Contact Dermatitis and Photosensitivity in Humans. PLoS One. 2012;7(3):e33805. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0033805
8. Minutello K, Gupta V. Cromolyn Sodium. [Updated 2022 Jan 8]. In: StatPearls (Internet). Treasure Island (FL): StatPearls Publishing; 2022 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK557473/.
9. Edwards AM, Capková S. Oral and topical sodium cromoglicate in the treatment of diffuse cutaneous mastocytosis in an infant. BMJ Case Rep. 2011;2011. https://pubmed.ncbi.nlm.nih.gov/7569760/
10. Ang DC, Hilligoss J, Stump T. Mast Cell Stabilizer (Ketotifen) in Fibromyalgia: Phase 1 Randomized Controlled Clinical Trial. Clin J Pain. 2015;31(9):836-842. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417653/#:~:text=Ketotifen%20is%20a%20mast%20cell,%2Dstabilizing%20properties%20(25)
11. Shaik-Dasthagirisaheb, Yazdani. Relationship between Vitamin C, Mast Cells and Inflammation. Journal of Nutrition & Food Sciences. 06. https://www.researchgate.net/publication/293799498_Relationship_between_Vitamin_C_Mast_Cells_and_Inflammation
12. Liu ZQ, Li XX, Qiu SQ, Yu Y, Li MG, Yang LT, Li LJ, Wang S, Zheng PY, Liu ZG, Yang PC. Vitamin D contributes to mast cell stabilization. Allergy. 2017;72(8):1184-1192. https://pubmed.ncbi.nlm.nih.gov/27998003/
13. Cikler E, Ersoy Y, Cetinel S, Ercan F. The leukotriene d4 receptor antagonist, montelukast, inhibits mast cell degranulation in the dermis induced by water avoidance stress. Acta Histochem. 2009;111(2):112-8. https://pubmed.ncbi.nlm.nih.gov/18617226/
14. Cefali EA, Simmons PD, Stanek EJ, McGovern ME, Kissling CJ. Aspirin reduces cutaneous flushing after administration of an optimized extended-release niacin formulation. Int J Clin Pharmacol Ther. 2007;45(2):78-88. https://pubmed.ncbi.nlm.nih.gov/17323787/#:~:text=Aspirin%20also%20significantly%20reduced%20intensity,flushing%20incidence%2C%20intensity%20and%20duration
15. Butterfield JH, Weiler CR. Prevention of mast cell activation disorder-associated clinical sequelae of excessive prostaglandin D(2) production. Int Arch Allergy Immunol. 2008;147(4):338-43. https://pubmed.ncbi.nlm.nih.gov/18622141/
16. Huang ES, Strate LL, Ho WW, Lee SS, Chan AT. Long-term use of aspirin and the risk of gastrointestinal bleeding. Am J Med. 2011;124(5):426-433. https://pubmed.ncbi.nlm.nih.gov/21531232/#:~:text=Conclusion%3A%20Regular%20aspirin%20use%20is,%2D%20and%20long%2Dterm%20users
17. Weiss SL, Hyman JB, Carlson GS, Coop CA. Long-Term Successful Treatment of Indolent Systemic Mastocytosis With Omalizumab. Fed Pract. 2021;38(1):44-48. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870274/
18. Gilreath JA, Tchertanov L, Deininger MW. Novel approaches to treating advanced systemic mastocytosis. Clin Pharmacol. 2019 Jul 10;11:77-92. https://pubmed.ncbi.nlm.nih.gov/31372066/
19. US Food and Drug Administration. FDA approves avapritinib for advanced systemic mastocytosis. Published June 16, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-avapritinib-advanced-systemic-mastocytosis
20. DeAngelo DJ, Radia DH, George TI, Robinson WA, Quiery AT, Drummond MW, Bose P, Hexner EO, Winton EF, Horny HP, Tugnait M, Schmidt-Kittler O, Evans EK, Lin HM, Mar BG, Verstovsek S, Deininger MW, Gotlib J. Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial. Nat Med. 2021;27(12):2183-2191. https://pubmed.ncbi.nlm.nih.gov/34873347/
21. Kasamon YL, Ko CW, Subramaniam S, Ma L, Yang Y, Nie L, Shord S, Przepiorka D, Farrell AT, McKee AE, Pazdur R. FDA Approval Summary: Midostaurin for the Treatment of Advanced Systemic Mastocytosis. Oncologist. 2018;23(12):1511-1519. https://pubmed.ncbi.nlm.nih.gov/30115735/#:~:text=In%20April%202017%2C%20the%20U.S.,mast%20cell%20leukemia%20(MCL)
22. Valent P, Akin C, Hartmann K, George TI, Sotlar K, Peter B, Gleixner KV, Blatt K, Sperr WR, Manley PW, Hermine O, Kluin-Nelemans HC, Arock M, Horny HP, Reiter A, Gotlib J. Midostaurin: a magic bullet that blocks mast cell expansion and activation. Ann Oncol. 2017;28(10):2367-2376. https://pubmed.ncbi.nlm.nih.gov/28945834/#:~:text=Midostaurin%2C%20also%20known%20as%20PKC412,inhibits%20IgE%2Ddependent%20mediator%20secretion.&text=Keywords%3A%20IgE%3B%20mast%20cell%20activation,%3B%20mast%20cells%3B%20targeted%20drugs
23. Akin C. Cladribine for mastocytosis: benefits and risks. Blood. 2015 Aug;126(8):931-2. https://pubmed.ncbi.nlm.nih.gov/26294717/
24. Verstovsek S, Tefferi A, Cortes J, et al. Phase II study of dasatinib in Philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis. Clin Cancer Res. 2008;14(12):3906-3915. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018899/
25. Alvarez-Twose I, Matito A, Morgado JM, et al. Imatinib in systemic mastocytosis: a phase IV clinical trial in patients lacking exon 17 KIT mutations and review of the literature. Oncotarget. 2016;8(40):68950-68963. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620310/
26. Butterfield JH, Tefferi A, Kozuh GF. Successful treatment of systemic mastocytosis with high-dose interferon-alfa: long-term follow-up of a case. Leuk Res. 2005 Feb;29(2):131-4. https://pubmed.ncbi.nlm.nih.gov/15607359/
27. Lortholary O, Chandesris MO, Bulai Livideanu C, et al. Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study. Lancet. 2017;389(10069):612-620. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985971/
28. Blay JY, von Mehren M. Nilotinib: a novel, selective tyrosine kinase inhibitor [published correction appears in Semin Oncol. 2011 Jun;38(3):467]. Semin Oncol. 2011;38 Suppl 1(0 1):S3-S9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004101/#:~:text=Activity%20against%20KIT%20and%20mutant,cell%20lines%20(Table%201)
29. Gupta A, Singh J, García-Valverde A, Serrano C, Flynn DL, Smith BD. Ripretinib and MEK Inhibitors Synergize to Induce Apoptosis in Preclinical Models of GIST and Systemic Mastocytosis. Molecular Cancer Therapeutics. 2021:20(7). https://mct.aacrjournals.org/content/20/7/1234
30. Wauters L, Ceulemans M, Frings D, Lambaerts M, Accarie A, Toth J, Mols R, Augustijns P, De Hertogh G, Van Oudenhove L, Tack J, Vanuytsel T. Proton Pump Inhibitors Reduce Duodenal Eosinophilia, Mast Cells, and Permeability in Patients With Functional Dyspepsia. Gastroenterology. 2021 Apr;160(5):1521-1531.e9. https://pubmed.ncbi.nlm.nih.gov/33346007/
31. Pyatilova P, Teplyuk N, Olisova O, Kovrigina A, Gadaev I, Kolkhir P. Efficacy of PUVA in Russian patients with mastocytosis: a case series and review of literature. Int J Dermatol. 2018 Sep;57(9):e59-e64. https://pubmed.ncbi.nlm.nih.gov/30133755/
32. Molderings GJ, Haenisch B, Brettner S, Homann J, Menzen M, Dumoulin FL, Panse J, Butterfield J, Afrin LB. Pharmacological treatment options for mast cell activation disease. Naunyn Schmiedebergs Arch Pharmacol. 2016 Jul;389(7):671-94. doi: https://doi.org/10.1007/s00210-016-1247-1 . Epub 2016 Apr 30. PMID: 27132234; PMCID: PMC4903110.

‍