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MCAS: Treatment

This post discusses medications used to treat MCAS. Doses listed are taken directly from “Presentation, diagnosis and management of mast cell activation syndrome” by Lawrence B. Afrin. These doses are general recommendations. Medication should always be taken under the direction of a provider who knows you and your case personally.

MCAS is generally treated identically to ISM, with the medications that block the action of released mediators, that prevent the release of mediators or that prevent the production of mediators. As a reminder, any medication that causes a reaction should be evaluated to see if it is truly caused by the drug or by a dye or inert ingredient. Medications compounded without dyes or noxious fillers can be truly life changing for mast cell patients. Generally, new medications for be trialed for 1-2 months to determine if they are effective.

Antihistamines are first line medications for both acute and chronic management of MCAS (but not for anaphylaxis – epinephrine is first line medication for anaphylaxis.) Most currently available antihistamines either block the histamine 1 (H1) receptor or the histamine 2 (H2) receptor and are referred to by the receptors they block. It is generally recommended for MCAS patients to take medication to block H1 and H2 receptors daily as baseline medications.

Loratadine is a common H1 starting medication. It has low anticholinergic activity and is not sedating. Dosing usually starts at 10mg daily and may be increased to 10mg 2-3 times a day. Fexofenadine starting dose in MCAS is usually 180mg every 12 hours; cetirizine 10mg every 12 hours; levocetirizine 5mg every 12 hours. Loratadine, fexofenadine and cetirizine are all available without prescription in the US. Of note, none of these medications are available for IV administration, so Benadryl should be used for emergency management of severe MCAS symptoms.

There are several H2 blockers available in the US, most over the counter. Cimetidine and ranitidine have more drug-drug interactions than famotidine and nizatadine. Famotidine, which is also readily sourced for IV administration, is usually dosed at 20-40mg every 12 hours, though in severe cases, doses of 80mg every 12 hours may be used. (This dosing is also seen in Zollinger-Ellison Syndrome patients.) Ranitidine starts at 75mg every 12 hours, increasing to 300mg every 12 hours. Nizatadine (Axid) is dosed at 150-300mg every 12 hours, and cimetidine at 400mg every 12 hours.

There are several other medications with H1 antihistamine effect. Tricyclic antidepressants, phenothiazine antiemetics (like promethazine) and quetiapine, an antipsychotic, are all H1 blockers. Addition of these medications often helps even when another H1 blocker is being taken by the patient. In particular, use of doxepin has been well described. It is usually started at 10mg twice daily and can be increased by 10mg twice daily to doses of 40-50mg twice daily. Beyond this, exhaustion and grogginess are often intolerable.

Ketotifen is a medication with both antihistamine and mast cell stabilizing properties, meaning it interferes with the release of mediators. The oral use of this medication for mast cell disease management is not well described, in part due to the oral formulation not being available in the US. Dosing is usually started at 1mg twice daily and increased in increments of 1mg twice daily until desired effects are noted and balanced with an acceptable side effect profile. As described by Afrin, single dosing is usually 6mg or less, and can be taken up to four times a day.

Benzodiazepines are often helpful in MCAS, due both to its action on mast cells and also directly on organs, particularly GI organs. Lorazepam, clonazepam and alprazolam are preferred due to their shorter window of action. All can be dosed beginning at 0.25mg every 12 hours, increasing by 0.25mg twice daily every week. Flunitrazepam has been described in treatment of mast cell disease. This medication has a longer halflife and is generally dosed at 0.5-2mg once a day.

Imidazopyridine medications like zolpidem (Ambien) also act on the benzodiazepine receptors of the body. Though usually taken for insomnia, some MCAS patients report relief of other symptoms. Whether or not these medications work in a patient seems independent of whether benzodiazepines are currently being taken by the patient or have worked or failed in the past.

Non-steroidal anti-inflammatory drugs (NSAIDS) can be helpful in MCAS patients who tolerate them. In particular, use of aspirin to bind prostaglandins has been very well described. A common starting dose is 325mg twice daily, with dosing up to 650-1300mg twice daily seen. Some patients take as much as 1300mg four times a day, but doses higher than 2600mg/day are unhelpful in most patients. Non enteric coated aspirin seems to be better tolerated and more effective at relieving symptoms in MCAS than enteric coated. In MCAS patients for whom aspirin is inappropriate (such as those with low platelets or decreased kidney function), COX2 inhibitors like Celebrex are sometimes used. Celebrex dosing in these patients usually begins at 100mg twice daily and increases up to 400mg twice daily.

Leukotriene inhibitors are frequently used in MCAS patients. Montelukast is the most common, being dosed as 10mg once to twice a day. Zafirlukast is dosed at 20mg twice daily. Doses should be decreased appropriately if liver dysfunction is also present.

Cromolyn is the most well known mast cell stabilizer, despite the fact that the mechanism by which it acts is still unclear. More recently, it has been noted to block mast cell receptor 35, which is increased when IgE is present. Cromolyn has extremely poor absorption, with 98% of oral doses being excreted unchanged. When inhaled, absorption increases to around 5%. Oral dosing is from 100-200mg 2-4 times daily. When nebulized, dosing is usually 20mg 2-4 times daily. Of note, patients usually experience a resurgence of symptoms when first starting the medication that may last 3-4 days. In my experience, this symptom increase is sometimes observed when increasing the dose. It can take several weeks to determine if cromolyn is truly effective in patient, with some people only seeing serious gains after four months.

Pentosan is less well known mast cell stabilizer whose mechanism is likewise unknown. This medication is commonly used in interstitial cystitis, a mast cell disorder that affects the genitourinary tract. Though Pentosan seems to be most effective in the GU tract, some patients report decrease in other symptoms while on this medication. It is usually dosed at 100mg every 8-12 hours.

Quercetin is commonly mentioned as a natural/homeopathic mast cell stabilizer. After much research on the topic, I have to say that I agree. It has been found to inhibit lipoxygenase and cyclooxygenase, which in turn decreases production of leukotrienes and histamine. It is usually dosed starting at 500-2000mg per day, divided up into 2-4 doses. For example, a daily dose of 500mg may be taken as 125mg four times a day. A newer form, quercetin chalcone, is usually taken at 250mg three times a day.

Pancreatic enzymes, like Creon, are sometimes helpful in MCAS patients who have pancreatitis symptoms, even if they are not having pancreatic type pain. It sometimes helps with chronic diarrhea, weight loss and malabsorption.

Corticosteroids like prednisone are sometimes used to manage MCAS symptoms.  These medications can prevent mast cells from producing mediators and as such can be very effective.  However, long term use can have severe side effects and as such is discouraged.

Omaluzimab (Xolair) is an anti-IgE antibody. It is not clear exactly how this stabilizes mast cells reacting by a non-IgE mechanism. Xolair is injected subcutaneously at doses of 150-300mg every 2-4 weeks. It should be trialed for at least 3-4 months before determining if it is effective. Interestingly, whether or not a patient responds and how well seems to be independent of their pretreatment IgE level.

The successful use of chemo medications for severe MCAS cases has been described in literature. In particular, hydroxyurea can be effective, though rapid onset and severe low blood cell counts are a real risk. It is usually started at 500mg daily and increased up to 2000mg daily as needed. Blood counts should be monitored weekly for four weeks at the onset of treatment and after any dosage increase. Tyrosine kinase inhibitors, like imatinib and dasatinib, have also been used as last resorts in MCAS patients. Imatinib is usually dosed at 100-200mg daily and dasatinib at 20-50mg daily. Patients on these medications require careful monitoring for pulmonary and renal issues. All chemo patients are at increased risk of infection.

IV hydration is being used more frequently to manage baseline symptoms of MCAS patients. TNF-alpha inhibitors have been suggested to help mast cell symptoms, but there have been no symptoms. (I take a TNF-alpha inhibitor for autoimmune issues and do find it helps to relieve some of my mast cell symptoms.) Other possible avenues include IL-1 and IL-1b inhibitors and kinin-b2 receptor blockers. Tryptase inhibitors continue to be in development.



Afrin, Lawrence B. Presentation, diagnosis and management of mast cell activation syndrome. 2013. Mast cells.