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

 

 

 

 

3 Responses

  1. Katie July 5, 2015 / 11:25 am

    Jesus H. Lisa. Amazing work here!

  2. K. July 6, 2015 / 6:36 am

    Under the heading MCAS and MMAS: Similarities and differences, you state that 33% of MCAS patients have tryptase ˃11.4 ng/ml. Are you referring to baseline level?
    And, do you know if there is any data about patients with MCAS with little to no increase in tryptase level from baseline?
    Thank you for the concise and orderly presentation of a huge amount of information.

    • Lisa Klimas July 6, 2015 / 11:56 am

      That’s a great question about the tryptase. I don’t know offhand but will check.

      I’m not sure that there are any studies that follow MCAS patients and tryptase over time, but I can take a look. New papers are coming out all the time.

Comments are closed.