Mast cell disease fact sheet

Mast Cell Disease

  • Mast cell disease includes all forms of disease in which your body makes too many mast cells or those mast cells do not function correctly.
  • Mast cell disease is rare, affecting less than 200,000 people in the US.
  • 90% of mast cell disease only affects the skin (edited to add: based upon estimates of mastocytosis population – counts of MCAS/MCAD not yet available).
  • The remaining 10% is systemic disease.
  • Multiple people in a family sometimes have mast cell disease, but the heritable gene has not been identified.
  • Cutaneous and systemic mastocytosis, mast cell sarcoma and mast cell leukemia are proliferative, meaning your body makes too many mast cells.
  • Mast cell activation syndrome/mast cell activation disorder are not proliferative, meaning there is a normal amount of mast cells behaving badly.
  • Monoclonal mast cell activation syndrome is borderline for proliferation, meaning the body is thinking about making too many mast cells or is just starting to.
  • The biggest risk for most mast cell patients is anaphylaxis, a severe, life-threatening allergic reaction that can be triggered by many things.
  • There is no cure for mast cell disease, but children sometimes grow out of it for unknown reasons.

Types of mast cell disease

  • Cutaneous mastocytosis (CM) is too many mast cells in the skin.
    • This causes rashes (sometimes permanent), hiving and blistering.
    • Urticaria pigmentosa (UP), telangiectasia macularis eruptive perstans (TMEP) and diffuse cutaneous mastocytosis (DCM) are the types of cutaneous mastocytosis. (Edited to include DCM.)
    • It is diagnosed by skin biopsy.
    • You can also have mast cell symptoms that aren’t related to the skin, like nausea, vomiting, weakness, headache, palpitations, etc.
    • Solitary mastocytoma is a benign mast cell tumor usually found on the skin, but sometimes elsewhere. It is sometimes included in the cutaneous mastocytosis category.
    • Children sometimes outgrow cutaneous mastocytosis.
    • When adults develop cutaneous mastocytosis, they usually also have systemic mastocytosis.
  • Systemic mastocytosis is too many mast cells in an organ that is not the skin.
    • The bone marrow is usually where too many mast cells are found, but it is sometimes found in other organs.
    • You can have systemic mastocytosis with or without cutaneous mastocytosis.
    • It is diagnosed by biopsy of an organ other than skin. Other testing like scans and organ tests may be necessary.
    • Indolent systemic mastocytosis (ISM) is stable with no organ damage. Life span is normal.
    • Smoldering systemic mastocytosis (SSM) is progressing towards a more damaging form with some signs that organ damage is beginning. Life span may be shortened if progression is not controlled.
    • Aggressive systemic mastocytosis (ASM) is a dangerous form with organ damage that requires chemotherapy to control. Life span is shorter.
    • Mast cell leukemia (MCL) is a malignant form with organ damage that requires chemotherapy. Life span is significantly reduced.
    • Mast cell sarcoma(MCS) is a malignant form with organ damage that requires chemotherapy. Life span is significantly reduced.
  • Mast cell activation syndrome (MCAS)/ Mast cell activation disorder (MCAD) is when a normal amount of mast cells behave badly. (Edited to change mast cell activation disease to mast cell activation disorder.)
    • It is clinically similar to indolent systemic mastocytosis. Life span is normal.
    • Biopsies are negative.
  • Monoclonal mast cell activation syndrome (MMAS) is when a person meets some of the criteria for systemic mastocytosis but not all. It indicates the mast cells are starting to think about abnormal proliferation.
    • It is clinically similar to indolent systemic mastocytosis. Life span is normal.
    • Biopsies are positive for one or two minor criteria for systemic mastocytosis.

Symptoms

  • Anaphylaxis
  • Skin
    • Flushing is one of the hallmark signs of mast cell disease
    • Other skin symptoms include rashes, hives, itching, angioedema, dermatographism
  • Gastrointestinal
    • Abdominal pain, diarrhea, constipation, swelling of GI tract, difficulty swallowing
  • Neurologic
    • Headache, migraine, feeling faint, numbness, pins and needles, tremors, tics, neuropathy
  • Psychiatric
    • Depression, anxiety, memory difficulties, insomnia, sleep disorders*
  • Cardiovascular
    • Weakness, dizziness, high or low blood pressure, slow or rapid heartbeat, abnormal heart rhythm, chest pain, palpitations

*Edited to add: Psychiatric symptoms are organic symptoms of mast cell disease, rather than reactive conditions from chronic illness.

This list is not exhaustive.

Triggers

  • Many things can cause mast cell reactions or anaphylaxis in mast cell patients.
  • Allergy testing (skin prick or blood testing) is inaccurate in mast cell patients as these tests assess IgE allergies and mast cell patients often have non-IgE reactions.
  • Triggers can change over time and can include:
    • Heat, cold, or rapid change in temperature
    • Friction, especially on the skin
    • Sunlight
    • Illness, such as viral or bacterial infection
    • Exercise
    • Many foods, especially high histamine foods
    • Many preservatives and dyes
    • Many medications
    • Scents and fragrances
    • Physical stress, such as surgery
    • Emotional or psychological stress

Diagnosis: Blood and Urine Testing

  • Blood test: Serum tryptase
    • This tests for the total amount of mast cells in the body, the “mast cell burden”
    • Should be tested during a non-reactive period for baseline and during a reaction
    • Time sensitive: should be tested 1-4 hours after start of reaction
    • Normal range for adults is under 11 ng/ml. (Edited to remove out of place words “is abnormal” at the end of this statement)
    • 2 ng/ml + 20% increased from baseline is indicative of mast cell activation
    • Baseline over 20 ng/ml is a minor criteria for diagnosis systemic mastocytosis
  • 24 hour urine tests:
    • N-methylhistamine
      • Breakdown product of histamine
      • Released by mast cells when reacting
      • Very temperature sensitive
      • Sample must be refrigerated and transported on ice (unless preservative is provided)
      • Measured as a ratio of another molecule, creatinine
      • Normal range for adults is 30-200 mcg/g creatinine
      • One study found that if level was 300 mcg/g creatinine, a bone marrow biopsy was likely to be positive for systemic mastocytosis
    • D2 prostaglandin and 9a,11b-F2 prostaglandin
      • Released by mast cells when reacting
      • Very temperature sensitive
      • Sample must be refrigerated and transported on ice (unless preservative is provided)
      • Normal range for both is under 1000 ng
      • 9a,11b-F2 prostaglandin is a breakdown product of D2 prostaglandin
      • 9a,11b-F2 prostaglandin is the marker for which MCAS/MCAD patients are most often positive
      • If taking aspirin or NSAIDs, these may be discontinued five days before the test or as directed by your physician
      • Other tests sometimes done in blood include heparin, histamine, prostaglandin D2 and chromogranin A.
      • Serum tryptase and 24 hour urine n-methylhistamine, D2 prostaglandin and 9a,11b-F2 prostaglandin are the tests considered to be most reliable indicators of mast cell disease.

Diagnosis: Biopsies

  • Bone marrow biopsy
    • Obtained by bone marrow biopsy and aspiration procedure
    • Stained with Giemsa and tryptase stains
    • Tested with antibodies for CD117, CD2, CD25 and CD34
    • Looking for clusters of mast cells in groups of 15 or more
    • Looking for mast cells that are shaped abnormally, like spindles
    • DNA from the biopsy should be tested for the CKIT D816V mutation, a marker for systemic mastocytosis
  • Skin biopsy
    • Obtained by punch biopsy
    • Stained with Giemsa and tryptase stains
    • Tested with antibodies for CD117, CD2, CD25 and CD34
    • Looking for clusters of mast cells in groups of 15 or more
    • Looking for mast cells that are shaped abnormally, like spindles
    • DNA from the biopsy should be tested for the CKIT D816V mutation, a marker for systemic mastocytosis
  • GI biopsies
    • Obtained by scoping procedures
    • Stained with Giemsa and tryptase stains
    • Tested with antibodies for CD117, CD2, CD25 and CD34
    • Looking for clusters of mast cells in groups of 15 or more
    • Looking for mast cells that are shaped abnormally, like spindles
    • DNA from the biopsy should be tested for the CKIT D816V mutation, a marker for systemic mastocytosis (less likely to be positive than bone marrow biopsies)
    • Mast cells should be counted in five high powered (60X or 100X) fields and the count then averaged
    • Some researchers consider an average of more than 20 mast cells in a high powered field to be high, but this is not agreed upon
    • Some researchers consider an average of more than 20 mast cells in a high powered field to be diagnostic for mastocytic enterocolitis

Treatment

  • H1 antihistamines
    • Second generation, longer acting, non-sedating for daily use
    • First generation, shorter acting, sedating, but more potent
    • Other medications with H1 antihistamine properties like tricyclic antidepressants
  • H2 antihistamines
  • Leukotriene inhibitors
  • Aspirin, if tolerated
  • Mast cell stabilizers
    • Cromolyn
    • Ketotifen
    • Quercetin
  • Epinephrine (should be on hand in case of anaphylaxis)
  • These are baseline medications for MCAS/MCAD, MMAS and ISM cell patients. If symptoms are uncontrolled, other medications may be used off label for mast cell disease.
  • Smouldering systemic mastocytosis patients may require chemotherapy.
  • Aggressive systemic mastocytosis, mast cell leukemia and mast cell sarcoma patients require chemotherapy.

Medications to Avoid

  • Medications that cause degranulation
    • Alcohol (ethanol, isopropanol)
    • Amphoteracin B
    • Atracurium
    • Benzocaine
    • Chloroprocaine
    • Colistin
    • Dextran
    • Dextromethorphan
    • Dipyridamole
    • Doxacurium
    • Iodine based radiographic dye
    • Ketorolac
    • Metocurine
    • Mivacurium
    • Polymyxin B
    • Procaine
    • Quinine
    • Succinylcholine
    • Tetracine
    • Tubocurarine
    • Vancomycin (especially when given intravenously)
    • In some patients, aspirin and NSAIDs (please ask if your doctor if these are appropriate for you)

 

  • Medications that interfere with the action of epinephrine
    • Alpha adrenergic blockers
      • Alfuzosin
      • Atipamezole
      • Carvedilol
      • Doxazosin
      • Idazoxan
      • Labetalol
      • Mirtazapine
      • Phenoxybenzamide
      • Phentolamine
      • Prazosin
      • Silodosin
      • Tamsulosin
      • Terazosin
      • Tolazoline
      • Trazodone
      • Yohimbine
    • Beta adrenergic blockers
      • Acebutolol
      • Atenolol
      • Betaxolol
      • Bisoprolol
      • Bucindolol
      • Butaxamine
      • Carteolol
      • Carvedilol
      • Celiprolol
      • Esmolol
      • Metoprolol
      • Nadolol
      • Nebivolol
      • Oxprenolol
      • Penbutolol
      • Pindolol
      • Propranolol
      • Sotalol
      • Timolol

Please note these lists are not exhaustive and you should check with your provider before starting a new medication. A pharmacist can review to determine if a medication causes mast cell degranulation or interferes with epinephrine. This list represents the medications for which I was able to find evidence of degranulation or a-/b-adrenergic activity.

Special Precautions

  • Mast cell patients require special precautions before major and minor procedures, including radiology procedures with and without contrast or dyes
  • They must premedicate using the following procedure:
    • Prednisone 50mg orally (20 mg for children under 12): 24 hours and 1-2 hours before procedure
    • Diphenhydramine 25-50 mg orally (12.5 mg for children under 12) OR hydroxyzine 25 mg orally, 1 hour before procedure
    • Ranitidiine 150 mg orally (20 mg for children under 12): 1 hour before procedure
    • Montelukast 10 mg orally (5 mg for children under 12): 1 hour before procedure
    • This protocol was developed for the Mastocytosis Society by Dr. Mariana Castells and the original can be found at www.tmsforacure.org/documents/ER_Protocol.pdf

Common coincident conditions

  • Ehlers Danlos Syndrome (EDS), especially hypermobility type (Type III)
  • Postural orthostatic tachycardia syndrome (POTS) or other types of dysautonomia
  • Mast cell disease, EDS and POTS are often found together
  • Autoimmune diseases
  • Myeloproliferative diseases, like essential thrombocythemia and polycythemia vera
  • Eosinophilic disorders