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.
- N-methylhistamine
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
- Alpha adrenergic blockers
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