- MCAS is generally treated identically to ISM.
- Most cell medications act in one of the following ways:
- Block the action of released mediators
- Prevent the release of mediators
- Prevent production of mediators
- Any medication that causes a reaction should be evaluated to determine if the reaction is to the drug, a dye or a filler.
- New medications are usually trialed for 1-2 months to see if they are effective.
- Antihistamines are first line medications for acute and chronic management of symptoms.
- Currently available antihistamines either block the H1 or H2 receptor.
- Most mast cell patients take daily H1 and H2 medications to give baseline coverage.
- Second generation H1 antihistamines are usually used for daily dosing as they are not sedating and have fewer side effects.
- No second generation H1 antihistamines are available in IV or IM form, so Benadryl should be used in emergent situations.
- Tricyclic antidepressants, phenothiazine antiemetics and quetiapine are H1 blockers.
- Ketotifen is both an H1 antihistamine and a mast cell stabilizer.
- Ketotifen is not approved for oral use in the US, but can be obtained through compounding pharmacies.
- Benzodiazepines act on mast cells and GI tract in beneficial ways.
- Imidazopyridine medications like zolpidem (Ambien) also act on benzodiazepine receptors.
- NSAIDs can be helpful if patients tolerate them.
- Aspirin and other NSAIDs interfere with prostaglandin production.
- Non enteric coated aspirin seems to be better tolerated and more effective for mast cell symptom relief than enteric coated.
- Leukotriene inhibitors are often used.
- Cromolyn is the most well known mast cell stabilizer.
- Cromolyn is poorly absorbed.
- Many patients have flare of symptoms when starting cromolyn.
- Pentosan is a mast cell stabilizer that works on the urinary tract.
- Quercetin is a mast cell stabilizer that interferes with mediator production.
- Pancreatic enzymes like Creon can help with chronic diarrhea, weight loss and malabsorption.
- Corticosteroids like prednisone interfere with mediator production but long term use can have severe side effects.
- Omaluzimab is an anti-IgE antibody. It has been reported by some mast cell patients to reduce reactions.
- Use of chemo medications for severe MCAS cases has been described in literature.
- IV hydration is sometimes used to manage baseline MCAS symptoms.
- TNF inhibitors and interleukin blockers have been suggested as possible treatments.
MCAS: Neurologic and psychiatric symptoms
- Headaches, dizziness, lightheadedness, weakness, vertigo and feeling about to faint are all common.
- Sensory and motor nerves may be overactive, causing tingling, numbness, paresthesia and tics.
- Prostaglandin D2 participates in nerve damage and may cause neurologic symptoms in MCAS.
- MCAS patients often have unusually deep sleep, also known as mast cell coma, probably from PGD2.
- Cognitive and mood disturbances can be caused by mast cell degranulation.
- Psychiatric symptoms in mastocytosis first reported as mixed organic brain syndrome.
- These symptoms are often effectively managed with mast cell medications.
- PTSD is not rare in mast cell patients.
- Autism is increased in patients with mastocytosis and similar reports are surfacing from MCAS patients.
MCAS: Kidney, urinary and genital concerns
- The GU tract can become easily inflamed in MCAS patients.
- Vaginal inflammation, painful intercourse and vaginal pain disorders are often found in mast cell patients.
- Mast cells drive fibrosis when present in kidneys.
- Fertility issues not rare in mast cell patients.
- Mast cells are increased and activated in endometrial lesions.
- Interstitial cystitis is driven by mast cell inflammation.
- Interstitial cystitis patients often have very high mast counts on bladder biopsy.
- Anemia is the most common red blood cell issue in MCAS patients.
- If anemia is macrocytic, bone marrow biopsy should be performed to rule out myelodysplastic syndrome.
- Cobalamin is often deficient.
- Folate deficiency is less common and if present may be due to another hematologic condition, such as hemolytic anemia.
- Many MCAS patients have selective iron malabsorption.
MCAS: Blood, bone marrow and clotting
- MCAS does not affect most routine blood tests.
- Hematologic issues are more common in proliferative mast cell disease, like SM.
- In previously diagnosed SM patients, bone marrow biopsies were negative 1/6 of the time.
- When serum tryptase is less than twice the upper limit of normal, BMB is not recommended.
- MCAS patients may have normal tryptase during reactions.
- A tryptase level of 20% + 2 ng/ml above baseline indicates activation.
- MCAS patients may have elevated monocytes, eosinophils and basophils.
- Reactive lymphocytes may be present in MCAS patients.
- White blood cell and platelet counts can be high or low in MCAS.
- Polycythemia vera, a disease characterized by too many red cells, can cause mast cell activation.
- Poor clotting and easy bruising is often found due to heparin release.
- Formation of blood clots is not rare in MCAS.
- Heparin release stimulates formation of bradykinin, which causes angioedema and low blood pressure.
MCAS: Effects on eyes, ears, nose and mouth
- Eye irritation, excessive tearing, redness, tremors and tics are common.
- When treated with Botox, the problem often recurs.
- Difficulty focusing the eyes is common In MCAS.
- 32% of MCAS patients report eye issues.
- Middle ear irritation is common and often mistaken for an infection.
- Hearing abnormalities are common in MCAS and include hearing loss, ringing of the ears and sensitivity to sound.
- Auditory processing issues are also present in MCAS.
- Nose bleeds may occur due to heparin release.
- MCAS patients often have heightened sense of smell.
- Pain in mouth and lips is common.
- Taste of metal is common.
- Ulcerations and sores may look like herpes sores, but when biopsied almost never are.
- MCAS is associated with burning mouth syndrome.
- Dental decay despite excellent dental hygiene is not unusual in MCAS.
- Kounis Syndrome is also called allergic angina or allergic myocardial infarction.
- Patients suffer severe chest pain or heart attack due to allergic reactions.
- Caused by mast cell activation causing spasm of the coronary artery.
- Over 300 cases in literature.
- Can occur due to mediator release, formation of blood clot inside a blood vessel near the heart, or due to formation of a blood clot on a stent.
- Cardiac enzymes and troponins may be normal.
- Tryptase and histamine are often elevated.
- EKG and angiogram are often normal.
- Hypersensitivity myocarditis is a similar phenomenon caused by eosinophils.
- Treatment requires treatment of both cardiac event and anaphylaxis.
Mast cells and cardiac and vascular dysfunction
- Mast cells contribute to rupture of atherosclerotic plaques.
- Histamine is higher in coronary artery of patients who died from coronary heart disease.
- Higher white blood cell count, platelet and plasma histamine is higher in patients with peripheral vascular disease.
- Tryptase level correlates to risk of coronary artery disease.
- Cervistatin and atorvastatin inhibit SCF action on mast cells.
- Lovastatin inhibited IgE degranulation.
Mast cell mediators: Recommended testing for MCAS diagnosis
- Serum tryptase
- Chilled urine for PGD2, PGF2 and n-methylhistamine
- Some doctors use:
- Chilled plasma PGD2
- Plasma histamine
- Serum chromogranin A
- Stat chilled plasma heparin
Cardiovascular symptoms of MCAS
- Heart palpitations and tachycardia are common.
- Blood pressure may be high or low, often with no trigger.
- True fainting is uncommon, but feeling about to faint is not.
- This may be due to POTS or not.
- When treated for POTS, Afrin reports mast cell patients only see mild reduction in presyncope episodes and little improvement of other symptoms.
- Chest pain is common, may or may not show changes on EKG.
- Edema is a common finding.
- Sclerosis and poor healing is seen in many patients.
Mast cells and metabolic syndrome: Hypertension, obesity and atherosclerosis
- Inflammation is known to contribute to obesity.
- Mast cells congregate in larger than normal numbers in fat tissue of obese patients.
- Obese patients may have higher serum tryptase than patients who are not obese.
- TNF is released by mast cells.
- TNF is important in insulin resistance, which contributes to metabolic syndrome.
- Mast cell stabilizers prevent diet induced obesity and diabetes in animal studies.
- Obesity is usually associated with metabolic syndrome, but it is also seen in patients who are not obese.
- Mast cells are involved in obesity, hypertension and atherosclerosis.
Metabolic issues associated with MCAS
- MCAS patients often have metabolic abnormalities.
- Vitamin D deficiency is common in MCAS.
- Hypothyroidism and elevated TSH are often found in MCAS.
- TPO is often elevated, sometimes without clinical thyroid disease.
- Elevated ferritin is not unusual in mast cell disease. 18% of ISM patients have it.
- Elevated ferritin may be confused with hemochromatosis.
- MCAS is associated with obesity and diabetes mellitus, types I and II.
- Elevated triglycerides are common.
Genetics of MCAS: mutations and methylation
- People with MCAS lack the D816V CKIT mutation.
- Other mutations are often present in CKIT gene of MCAS patients.
- These mutations are not known to be heritable.
- Mast cell disease can run in families.
- Mutations in MCAS CKIT genes are usually heterozygous, meaning there is one mutated copy and one correct copy.
- Methylation may affect development of MCAS.
Constitutional symptoms of MCAS
- Fatigue and malaise most common and can be disabling.
- Chronic fatigue syndrome has been tentatively linked to mast cell activation.
- Doctors disagree on whether or not fevers are part of MCAS.
- Excessive sweating is not unusual.
- A minority of MCAS patients lose weight due to the disease, but weight gain is very common.
- Bariatric surgery is not usually successful in MCAS patients.
- Itching is very common.
- Temperature extremes can trigger mast cell activation.
- Sensitivity to “harmless” stimuli is common in MCAS.
MCAS and MMAS: Similarities and differences
- Monoclonal mast cell activation syndrome is marked by presence of 1 or 2 minor criteria for SM.
- Mast cell activation syndrome meets none of the criteria for SM.
- Mast cell activation is diagnosed by mediator release testing, response to mast cell mediators and presence of mediator release symptoms in at least two organ systems.
- 33% of MCAS patients have tryptase >11.4 ng/ml.
- CM is always absent in MCAS.
- 46% of MMAS and 21% of MCAS patients have severe anaphylaxis to bee stings.
- If diagnosed with MCAS or MMAS, bone marrow biopsy is usually recommended if:
- Baseline tryptase >20 ng/ml
- Anaphylaxis requiring epinephrine without known cause
- Abnormal blood counts
- Unexplained osteoporosis
- Swelling of liver or spleen