October 2014: Post summaries and take home points

MCAS: Treatments

  • 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.

MCAS: Anemia and deficiencies

  • 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

  • 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