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.

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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

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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®

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References:

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

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