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mast cell disease

Winding in the light

I have a wound on my abdomen, a literal open wound where my stoma was. Every night I undress it, removing long thin strips of gauze before replacing them with clean packing, manipulating the tendrils with sterilized scissors. It is graphic, visceral. But I prefer to do it myself. I prefer this active stewardship of my body.

It is healing, closing up along the seams that have formed on my skin, one on each side. I am participating in the act of healing my body. Soon the line will be continuous, all the tissue underneath knitted together. Just a line that keeps a secret, like lips sewn shut. No one will ever look at this scar and know I had an ostomy until I tell them.

My GI tract is trying to figure out how to work with this new continuity. It hurts. It feels like everything holding my abdomen together on the left side is trying to give out. I am starting the very slow and arduous process of regaining strength and routine. It feels like a lot on some days. Today it feels like a lot.

But two years ago this was unfathomable. Even six months ago, I thought I knew pretty well the path my life would take it, and it was a short road, a straight line to pain and anaphylaxis and liquids and soft solids forever. I still see that road, but it is longer and it winds its way more into the light.

I don’t believe anymore that there is any fear that is so wide and so deep that you cannot meet it. I just don’t believe it.

Deconditioning, orthostatic intolerance, exercise and chronic illness – Part 7

A number of studies have investigated whether loading with intravenous hydration solutions (saline, etc) or with a volume expander such as dextran can ameliorate symptoms associated with deconditioning. These studies have found that volume expansion (also called fluid or volume loading) can improve a number of symptoms in deconditioned patients, but does not improve exercise capacity. Multiple studies have found the best effects from intravenous saline in conjunction with exercise.

Shibata investigated whether orthostatic intolerance could be mitigated following bed rest with exercise and/or fluid loading (Shibata 2010). This study found that OI could be dextran solution (IV fluids) given after twenty days of bed rest was insufficient to control OI symptoms, but that it was successful when used in conjunction with a daily exercise program. This finding was important, as it indicated that low blood volume was not the exclusive factor in orthostatic intolerance.

Figueroa et al looked at the relationship between blood volume and exercise capacity in POTS patients (Figueroa 2014). They found that acute volume loading with IV saline reduces heart rate and improves orthostatic tolerance and other symptoms in POTS patients. Importantly, IV saline significantly increased the stroke volume, cardiac output and reduced systemic vascular resistance. However, IV saline did not affect peak exercise capacity or improve cardiovascular markers during exercise. So while IV saline does help symptoms in these deconditioned patients, it does not improve exercise capacity. The author notes that for this purpose, acute infusion may not be sufficient and may need to undergone chronically to see benefits on exercise physiology.

Whole body heating is known to increase cardiac output, constrict the blood vessels in the abdominal cavities, increase sympathetic nerve activity in the muscles and decrease vascular resistance in the skin. Taken together, these factors stress the regulatory mechanism of the cardiovascular system. One study (Keller 2009) found that acute expansion of blood volume (with dextran) completely mitigated the impact of heat stress on orthostatic tolerance. In short, receiving an infusion that increased the blood volume allowed the cardiovascular system to function properly in the face of a known stressor.

One study looked at the effect of fluid loading on orthostatic intolerance and blood flow in the brain (Jeong 2012). They found that following bed rest, volume loading alone prevented larger reductions in cerebral blood flow, but did not prevent orthostatic intolerance. Exercise and volume loading prevented orthostatic intolerance but did not affect cerebral blood flow. Importantly, aerobic or resistance exercise before bed rest did not prevent development of decompensation.

A 2000 paper notes that POTS symptom scores improved significantly following administration of IV saline (Gordon 2000). Additionally, a 2013 study evaluated the frequency and characterization of “brain fog”, a common term for the cognitive deficits associated with this (and other) conditions (Joyner 2013). 86% (56/66) of patients reported that IV saline was the most effective treatment for brain fog.

In summary, bolus IV fluids or volume expanders have been found to improve a number of symptoms in deconditioned patients, although they have not been found to improve exercise capacity. For this metric, a graded exercise program is recommended. 

(Author’s note: I have recently been made aware that the data supporting use of graded exercise for chronic fatigue patients was hugely flawed. I retract this statement at this time. For details on this topic, please refer to this Lancet article:

A 2008 paper compared POTS and deconditioning (Joyner 2008). The author pointed out that a number of parallels existed between the physiological changes seen in POTS patients and those seen in deconditioned patients. Additionally, he made note of the parallels between POTS, chronic fatigue syndrome and fibromyalgia and the fact that exercise training had seen benefits in all of them. Given the significant relationship between mast cell disease and POTS, and the large overlap in CFS, fibromyalgia and mast cell populations, it is a comfortable assumption that an effective treatment modality for CFS, POTS and fibromyalgia may also be effective for mast cell disease. It is my belief that this is the basis for the frequently discussed finding of mast cell patients that intravenous fluids ameliorate a number of symptoms.

Furthermore, there are special considerations for mast cell disease that make intravenous fluids likely to cause a positive change in symptom profile. The first is that mast cell degranulation can induce systemic effects on arterial tone, hypotension and vasodilation (Willingham 2009). The next is that hypotension is characteristic of systemic mastocytosis, and that hypotension and syncope may occur due to cerebral hypoperfusion (Ozdemir 2010). Lastly, it is well known that mast cell mediators, including histamine, serotonin and tryptase, can induce capillary leakage leading leading to edema, and that they can increase vascular permeability (He 1997). Taken together, these points indicate that a mast cell patient may lose volume from the bloodstream into the surrounding tissues, which can exacerbate an already existing tendency toward hypotension, in turn made worse by orthostatic intolerance.

Fluid loading in the form of intravenous fluids may decrease symptoms in mast cell patients due to deconditioning, orthostatic intolerance and the capillary leakage often seen as a result of mast cell disease, which is especially present following mast cell attacks and anaphylaxis.



Gordon VM., et al. Hemodynamic and symptomatic effects of acute interventions on tilt in patients with postural tachycardia syndrome. Clin Auton Res. 2000 Feb; 10(1): 29-33.

Ross, Amanda J., et al. What is brain fog? An evaluation of the symptom in postural tachycardia syndrome. Clin Auton Res 2013 Dec; 23(6): 305-311.

Raj, Satish R., et al. Postural orthostatic tachycardia syndrome (POTS). Circulation 2013; 127: 2336-2342.

Rocío A. Figueroa, et al. Acute volume loading and exercise capacity in postural tachycardia syndrome. J Appl Physiol 117:663-668, 2014.

He, Shaoheng, Walls, Andrew F. Mast cell activation may be all that is sufficient and necessary for the rapid development of microvascular leakage and tissue edema. European Journal of Pharmacology 1997; 328(1): 89-97.

Ozdemir, D., et al. Hypotension, syncope and fever in systemic mastocytosis without skin infiltration and rapid response to corticosteroid and cyclosporine: a case report. Case Reports in Medicine, Volume 2010 (2010), Article ID 782595.

Willingham DL, et al. Unexplained and prolonged perioperative hypotension after orthotopic liver transplantation: undiagnosed systemic mastocytosis. Liver Transpl 2009 Jul; 15(7): 701-8.

Keller, David M., et al. Acute volume expansion preserves orthostatic tolerance during whole body heat stress in humans. J Physiol 2009 Mar; 587(5): 1131-1139.

Sung-Moon Jeong , Shigeki Shibata , Benjamin D. Levine , Rong Zhang. Exercise plus volume loading prevents orthostatic intolerance but not reduction in cerebral blood flow velocity after bed rest. American Journal of Physiology – Heart and Circulatory Physiology 2012 Vol. 302 no. 2.

Shizue Masuki , John H. Eisenach , William G. Schrage , Christopher P. Johnson , Niki M. Dietz , Brad W. Wilkins , Paola Sandroni , Phillip A. Low , Michael J. Joyner. Reduced stroke volume during exercise in postural tachycardia syndrome. Journal of Applied Physiology 2007 Vol. 103 no. 4, 1128-1135.






Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 6

Exercise can be very effective in treating deconditioning due to orthostatic intolerance or other conditions. Exercise can exacerbate symptoms in deconditioned patients even when it is mild, and this effect will be more pronounced if exercising in hot weather or after eating. Recumbent exercise, rather upright, is ideal for deconditioned patients at the beginning of exercise regimens, as being upright more stress on the body.

There are some physical maneuvers that can be helpful in avoiding OI episodes or in managing them when they do occur.   A sustained hand grip will activate the sympathetic nervous system and raise blood pressure for a short time. This can be helpful when changing position or following triggering activities, such as eating a meal or exercising. Leg crossing while tensing muscles can also prevent blood from pooling in the leg veins. This is recommended when an OI episode first occurs, and for vasovagal syncope patients to prevent fainting.

One study regimen prescribed POTS patients to engage in recumbent exercise 2-4 times a week for 30-45 minute sessions. In this study, they attempted to keep heart rate at 75-85% of maximum heart rate. As patients continued and became more fit, upright exercise was added in slowly in the second or third week. The length of training sessions increased and sessions of maximum intensity was added gradually until there were two maximum sessions per week. Weight lifting started once a week as a 15-20 minute session and increased to twice weekly 30-40 minute sessions. At the end, patients were exercising 5-6 hours/week. The duration of this study was twelve weeks.

Of the 29 patients who completed this study, a number of cardiovascular markers were improved. Blood volume and plasma volume were both expanded. The peak oxygen uptake during exercise, usually low for POTS patients, was increased by 11%. The muscle in the left ventricle of the heart, often smaller than usual in POTS patients, increased by 8%. Both laying down and standing heart rates decreasing significantly. Quality of life improved significantly and at the conclusion, almost half of the patients who completed the training no longer met the criteria for POTS.

Another study had POTS patients begin exercising twice a week in recumbent exercise, such as rowing or swimming, for 30-45 minutes. They increased to four times per week. After three months, plasma and blood volumes were both increased, as well as total hemoglobin mass and red blood cell volume. Systolic and diastolic pressures were lower while standing. Standing heart rate was lower and the amount of blood pumped out of the heart was stable.

Multiple papers have noted that OI patients are motivated to exercise, but often exert themselves too much in the beginning and trigger symptoms that make it difficult to continue. Going slowly and building up your tolerance is critical here. It is the factor that will make this successful. As an example, when I was very POTSy last year after several days of bed rest, I was advised that I could only stand for 10 minutes a day for an entire week. I could increase by ten minutes every week until I got to sixty, at which point I could resume normal activity. It was incredibly frustrating and drove me crazy, but I was able to get my orthostatic symptoms under control. Gradually increasing activity for OI patients is tried and true.

For severely disabled patients, it may not be practical to begin with recumbent aerobic exercises. If this is the case, gentle stretching and very low impact moves are good to start.

Following this, short workouts preceded by 5-10 minutes of stretching can be added. Target heart rate of 75-80% has been cited as desirable in some publications. Of utmost importance is the use of recumbent exercises, like rowing, swimming or recumbent cycling. Start slow. Dysautonomia International has a great breakdown on their site for how long you should workout at this stage.

Following several weeks of success, normal weekends can be introduced. Some patients are able to recover significant capability, running marathons and so on. It is recommended that POTS patients who are significantly conditioned exercise for at least 45 minutes three times a week.

While OI is a prime example of deconditioning as so many of its patients are deconditioned (95% of POTS patients and 91% of OI patients in one study), it is not the only condition associated with deconditioning that can be significantly improved with exercise.

In various studies with chronic fatigue syndrome patients, 60-84% said they felt better or much better after a graded exercise program. A study with fibromyalgia implemented three times a week workouts of sixty minutes, which included 10 minutes of slow walking, 20 minutes of aerobic exercise at 60-70% max heart rate, 20 minutes stretching and strength training, and 10 minutes cooling down. This program was highly successful for a number of patients.

Given the variety of illnesses which produce secondary deconditioning, and the success achieved by their patient populations with graded exercise, it is reasonable to assume that graded exercise may provide conditioning benefits to the mast cell population. Mast cell patients have the addition concerns that mast cells can be mechanically degranulated by the motions associated with vigorous exercise and that heat and sweating may be triggering, so exercise should be undertaken carefully and never alone. Some patients find utility in premedicating with H1 and H2 antihistamines before exercising. Please consult with your healthcare provider prior to beginning an exercise regimen.



De Lorenzo, H. Xiao, M. Mukherjee, J. Harcup, S. Suleiman, Z. Kadziola and V.V. Kakkar. Chronic fatigue syndrome: physical and cardiovascular deconditioning. Q J Med 1998; 91:475–481.

Hasser, E. M. And Moffitt, J. A. (2001), Regulation of Sympathetic Nervous System Function after Cardiovascular Deconditioning. Annals of the New York Academy of Sciences, 940: 454–468.

Mathias, C. J. et al. Postural tachycardia syndrome – current experience and concepts. Nat. Rev. Neurol. 8, 22–34 (2012).

Parsaik A., et al. Deconditioning in patients with orthostatic intolerance. Neurology 2012; 79; 1435.

Benarroch, Eduardo E. Postural tachycardia syndrome: a heterogeneous and multifactorial disorder. Mayo Clin Proc 2012 Dec; 87(12): 1214-1225.

Shizue Masuki , John H. Eisenach , William G. Schrage , Christopher P. Johnson , Niki M. Dietz , Brad W. Wilkins , Paola Sandroni , Phillip A. Low , Michael J. Joyner. Reduced stroke volume during exercise in postural tachycardia syndrome. Journal of Applied Physiology Published 1 October 2007 Vol. 103 no. 4, 1128-1135.

Sung-Moon Jeong , Gyu-Sam Hwang , Seon-Ok Kim , Benjamin D. Levine , Rong Zhang. Dynamic cerebral autoregulation after bed rest: effects of volume loading and exercise countermeasures. Journal of Applied Physiology 2014 Vol. 116 no. 1, 24-31.




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.


  • 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.


  • 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


  • 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

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




Back together

This winter, when my entire city struggled under walls of ice and snow, I found myself dreaming about the beach. In my mind, I stood by the water’s edge, air warm, breeze strong off the ocean, sun warming my skin. I imagined myself looking and seeing the scar where they closed my ostomy site.

It was such an impractical dream that I didn’t really hope for fruition. I am essentially allergic to the beach – sunblock, sunlight, cold water, heat. And of course my ostomy site would never be closed. It was not even an option then. I never thought it was possible.

Three months later, I arrived at the hospital to have surgery that would reverse my ostomy and reconnect the two segments of my GI tract so that stool would pass through the rectum. It felt surreal, like at any time I would find a man behind a curtain, pulling strings.

They took me right in and every person who spoke to me knew that I had mastocytosis and that I needed premeds one hour before the procedure. They went over everything with me again to make sure it was mast cell safe. “You are the boss,” one nurse told me. “You live with this all the time, just tell us what you need.” I have waited years to hear these words, for providers to believe that.

They administered my premeds and the anesthesiologist came to give me an epidural. It was painless. They taped the line with my safe tape and lay me down. They pushed some midazolam and fentanyl and wheeled me into the operating room.

“I need to tell you something about my skin,” I said suddenly, jerking awake from my semi-unconsciousness. “My skin is really reactive and hives easily, so don’t think that it’s a sign of anaphylaxis.”

“We know,” the nurse said, nodding reassuringly. “It’s in the note you gave us for your chart. We know about your disease and we will be careful.”

And the first time in a long time, I believed it. Everyone in that room understood at least the basics of mast cell disease and our special operative concerns.

I lay back and they put a mask on my face. I breathed deeply and woke up a few hours later in the PACU.

I had an epidural with a bupivacaine PCA pump that I could push as needed to numb my abdomen. I had a hydromorphone PCA pump that I could as needed for additional pain management. I couldn’t feel any pain. It was amazing. I still reacted to the anesthesia with my typical nausea/vomiting but they were prepared for it. Frankly, it was so pleasantly different from my last major surgery that it seemed like a small price to pay.

About twelve hours after surgery, my GI tract started moving. Last time, it didn’t move for five days. This time it was moving and pushing things in the right direction. It was the best possible indication that this had worked. I couldn’t believe it.

The following day I was up walking around. (If you are having abdominal surgery and have mast cell disease, ask about an epidural. It honestly was the lynchpin here and made the pain so manageable so my mast cell reactions to pain were really minor.) I was eating the day after that. I had a couple of reactions but they were easy to control because there were orders to administer Benadryl and Pepcid IV as needed, as well as steroids if the reaction was severe.

I felt so safe. The nursing care was so good I wrote a letter detailing how amazing they were. They all asked me about my disease and diluted my Benadryl and they were just generally fantastic. Instead of spending seven days fighting for things I needed, I spent seven days managing my pain and reactions in an environment with many professionals who cared and understood that I was not just a crazy person asking for crazy things.

I came home a few days ago to my kitchen table covered in presents and cards from the mast cell community. It was so humbling. It was like Masto Christmas. There were books and movies, a huge piece of amethyst, stuffed animals, cute like knick knacks, funny cards, touching cards and pictures drawn by the masto kids. It was the perfect punctuation for this experience. I try to hold things together and to be strong at the broken places, and you guys just pulled everything together for me. I will never forget this kindness as long as I live.

One of the very difficult things about mast cell disease is that we so often have to fight for things we need to be safe. We are always ready for a fight, always on edge. We wonder if it we can keep this up. We are so tired. We just want to be safe. We want others to help us be safe.

This experience was the culmination of years of educating medical professionals and of them receiving education on mast cell disease elsewhere. This time when I said I needed Benadryl, they just got it for me. No fighting. I am the boss of my body.

I write a lot about how I see the world and how I interact with it as a mast cell patient. But in my private writings, I write about how I want the world to be, how it should be. Two weeks ago, I went to the hospital for surgery and during my stay, I realized I was living in that world. Maybe it was just for a little while, but I was there. I could hear the universe whispering to me, “You can do this. Look how far you have come.” So I’m ready to fight again if I have to, because I saw this other reality, and it was real and safe and we can make it like that everywhere if we try.

So when time goes by and it gets hard again, and I’m exhausted from advocating, I’m going to remember this. I’m going to remember this win. I’m going to remember that this safe place made it easy for me to heal and rest. I’m going to remember that this fight is how we make the rest of the world safe for all of us, not just for me, at one hospital, one time.

I’m going to remember that this tired, sick body made this incredible thing possible, and when it seems like I can’t do any more incredible things, I’ll remember that I achieved this, and that I can achieve so much more.

And when you guys are tired and sick of fighting, promise me that you’ll remember that this is possible, and that we’re all in this together. When you think you can’t do it anymore, just extend a hand to the void. We will be there to hold it and put you back together.



Chronic urticaria and angioedema: Part 3

There are several pathways that can culminate in angioedema and urticaria.

Activation of mast cells by IgE is the most well known mechanism. When IgE binds to receptors on mast cells, several things happen. The mast cells release histamine. This in turn causes dilation of the nearby vessels and causes fluid to leak from the bloodstream into the tissues. This causes nerve cells to activate and release substance P, which also contributes to vasodilation and causes mast cells to release more histamine. In response to activation by IgE, mast cells will also produce PGD2 and leukotrienes C4 and D4.

The complement system is one of the ways our body identifies infectious agents and triggers the immune system to kill them. Complement proteins are in the blood all the time, and they can be activated by three distinct pathways, all of which are triggered by pathogens: the classical pathway, the alternative pathway and the lectin pathway. Regardless of which pathway activates the complement system, the molecules C3a, C4a and C5a are produced. These molecules bind to receptors on mast cells and induce histamine release.

Following initial dilation of local vessels, proteins that normally are found in the plasma move into the skin. This activates the kinin system, which produces bradykinin through a series of steps. Bradykinin is a very powerful vasodilator and contributes significantly to loss of volume from the blood stream to the tissues.

C3a, C5a, PGD2, and leukotrienes C4 and D4 all draw other inflammatory cells to the site of activated mast cells. These cells release further molecules to stimulate histamine release. This mechanism perpetuates inflammation beyond the original insult.

Bradykinin levels are normally controlled by the enzyme ACE. When patients take ACE inhibitor medications (like Lisinopril, etc), this interferes with bradykinin degradation and cause urticarial and angioedema.

C1 esterase inhibitor regulates complement and kinin pathways. In patients who are deficient in C1 esterase inhibitor, bradykinin may be overproduced.

Many autoimmune conditions cause the formation of IgG1 and IgG3 antibodies. These molecules can interfere with the complement system and cause production of fragments that activate mast cells, like C3a.

NSAIDs are well characterized in their ability to cause angioedema and urticaria. While the mechanism is not fully understood, it is thought that since NSAIDs stop production of prostaglandins, the mast cells overproduce leukotrienes, which contribute to the angioedema and urticaria.

There are several non-immunologic methods that can result in angioedema and urticaria. Heat or pressure on the skin; radiocontrast dyes; alcohol; vancomycin; opioids; and foods like shellfish and strawberries have been linked to these conditions.



Jonathan A. Bernstein, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol Volume 133, Number 5.

Usmani N,Wilkinson SM. Allergic skin disease: investigation of both immediate and delayed-type hypersensitivity is essential. Clin Exp Allergy 2007;37:1541-6.

Zuberbier T, Maurer M. Urticaria: current opinions about etiology, diagnosis and therapy. Acta Derm Venereol 2007;87:196-205.

Ferdman, Ronald M. Urticaria and angioedema. Clin Ped Emerg Med2007; 8:72-80.


Premedication and surgical concerns in mast cell patients

The exact incidence of immediate anaphylaxis from anesthesia or surgery in mastocytosis patients (or mast cell patients, more generally) is not known. Only a handful of these events have been reported in literature; however, it is likely that the majority of uneventful procedures were not tracked, so statistics are unclear. To date, there have been no controlled trials investigating anesthetics in mast cell patients.

In 2014, a paper was published entitled “Perioperative Management of Patients with Mastocytosis.” This paper is excellent and addresses the specific issues that may arise for mast cell patients before, during and after surgery. I recommend you provide this reference to any doctor involved in your surgical/procedural care that is unfamiliar with mast cell disease.

Mastocytosis patients are at risk for activation by a number of triggers, some of which cannot be avoided in the surgical setting. For this reason, suppression of mediator release in advance of surgery is recommended. The following pre-medication protocol is recommended for mast cell patients for all major and minor procedures and for radiology procedures with and without dyes:

  • Prednisone 50mg orally (20mg for children under 12): 24 hours and 1-2 hours before procedure
  • Diphenhydramine 25-50mg orally (12.5 mg for children under 12) OR hydroxyzine 25mg orally, 1 hour before procedure
  • Ranitidine 150mg orally (20mg for children under 12) 1 hour before procedure
  • Montelukast 10mg orally (5mg for children under 5) 1 hour prior to procedure

This protocol was developed for the Mastocytosis Society by Dr. Mariana Castells and the original can be found here:


Common triggers for mast cell patients in this setting include:

  • Anxiety and psychological stress regarding the procedure. Administration of medication to mitigate anxiety (benzodiazepines, etc) is recommended to avoid mast cell degranulation. It is preferable for mast cell patients to be the first surgery of the day if possible, and for a quiet, calm atmosphere to be maintained in the OR.
  • Temperature changes. Either being too cold or too hot can culminate in a mast cell reaction. Constant monitoring of patient’s temperature is required. Additionally, the OR temperature should be monitored. Head coverings, warming mattresses, and forced-air warming systems can be used to prevent hypothermia. Infusion and irrigation solutions should be warmed, and anesthetic gases should be warmed wherever possible.
  • Irritation of the skin (including use of tourniquet). This can cause mast cell degranulation that leads to urticaria, especially in patients with cutaneous mastocytosis. Blisters may form with pressure from tourniquet or face mask. Mast cell degranulation of this type releases chymase which can lead to edema.
  • The inherent physical trauma associated with surgery. This is of specific consideration when operating in the GI tract, which has a significant mast cell population relative to other organs.
  • Musculoskeletal pain from skeletal involvement in SM patients. Patients should be positioned carefully to avoid causing fractures.
  • Pain can cause mast cell degranulation. For this reason, opioid medications should be used for pain relief wherever possible.



Pascale Dewachter, M.D., Ph.D.; Mariana C. Castells, M.D., Ph.D.; David L. Hepner, M.D., M.P.H.; Claudie Mouton-Faivre, M.D. Perioperative Management of Patients with Mastocytosis. Anesthesiology 03 2014, Vol.120, 753-759.

The opposite of being alone

Last Thursday morning, I flew to Los Angeles for the long awaited meeting with my mastsister Addie and her family. I arrived at Logan Airport two hours before my flight. I have flown seven times in the last year so I am overly familiar with the routine. I carry on one suitcase with medical supplies and clothes, a laptop bag with my computer and my backpack that holds my IV supplies and infusion pump. I carry a letter from my doctor stating I need these things when I travel; aside from the fact that the large fluid bags are always swabbed for explosives, it is never a problem.

I was deposited at the gate almost an hour before my flight. Anytime I book a flight, I call the airline to reiterate that I need to infuse while I fly. They always seat me in the first row so there is more room for people to navigate past me when leaving the row. I have been advised that since the IV line is attached to my body, the FAA views it the same way as an insulin pump, and that I just have to hold it in my lap while we take off and land.

The gate agent came over and began asking questions about my backpack and IV fluids. I told him that it is attached to me, showed him the bag and pump, provided my letter. He and his supervisor made several phone calls and peered at me from behind the counter while talking about me in hushed voices.

The man came back over and asked if I had a fit to fly form. Most of the flights I have taken this year were with this same airline; I took two flights with them just over a month ago. I have never been asked to provide this form and would have gotten one had I been told to.

They continued calling people. I was now the only person not boarded and getting pretty irritated. I walked over to the counter and asked them what was going on.

“If you need IV fluids, then our medical team says you can’t fly,” he told me.

I explained that I had done this several times in the last year and had a note from my doctor that says “Lisa needs the following medications on her person when flying” which would obviously not have been proffered if I couldn’t fly. I explained about my disease and that I have lived with it for a long time and was fully capable of handling any symptoms. They decided I could board the plane but stopped me feet from the plane. The pilot came out and asked further invasive questions about my health and about my IV fluids, which had already cleared security. (In case you’re all wondering, the answer is that no, my IV fluids are not explosive.)

They let me board and the entire population of the plane stared at me while the crew discussed whether or not I was, in their estimation, healthy enough to fly. With their exchanged looks, I felt my personhood being stripped away. All that was left was a complication.

I keep thinking about that other life, before I looked sick enough that a gate agent felt entitled to ask me deeply personal questions about the state of my health. I did so many things. I went to a lot of places. I was able, physically and mentally. And now I’m… not able? Unable? I don’t know what I am, but whatever it is, I’m not the same.

It’s hard to live in the present sometimes. It’s hard not to compare everything I do to a previous iteration that came before I got sick. I can feel myself walking backwards, covering every step I took to get here, trying to find the moment when my fate was sealed. I wonder if I had known back then what was wrong if it would have made a difference. I wonder if I would still be this way, if I would still be unable.

I landed in Los Angeles six hours later without so much as a mast cell hiccup, my infusion pump clicking along happily. Addie and I compared ports and medicines and discussed Frozen at length.  We camped at Newport Beach this weekend and met up with some other masto friends. Ten people with mast cell disease on a beach by the bay, looking for dolphins in the evening light. Ten people with mast cell disease swimming and accessing ports and taking Benadryl and listening to coughs and eating smores. It was calm and breezy and safe. It was the opposite of being alone.

Me and Addie


The comedown

Last fall, I talked with my doctors about removing my rectum. I have had colitis for years.  It hurts and bleeds all the time.

In January, my surgeon scheduled surgery to remove it. This would eliminate all possibility of reversing my ostomy. I was fine with that.

In February, my GI specialist told me I could get a subtotal colectomy and reverse the ostomy.

A week later, my surgeon told me he thought it might be better to just remove the entire colon.

Last Thursday was the two year anniversary of placing my colostomy. My surgeon called me that night to tell me that he had run into my GI specialist and they had together decided to reverse the ostomy and not remove all of the colon because if they are wrong “they can’t put it back”. This removes some colon but for complicated reasons I’m too frustrated to explain right now, there is a rock solid chance that I will end up exactly where I was two years ago before I got my ostomy. A place I swore I would never be again. He offered that if it didn’t work, then we would remove the rest in another surgery.

My hospital time after placing my colostomy is pretty hazy. I remember waking up in the recovery room and pulling the blanket, straining my neck to see the stoma. A nurse ran over and pulled the blanket up; she didn’t want me to see it until my surgeon was there. I watched her walk away before I looked again. It protruded about an inch, was pink and puckered, easily visible through the clear ostomy bag. “Like a rosebud,” my surgeon said. Yes, exactly like that.

The first time I stooled with it was a wonder, this painless relief. It didn’t last, but it was wonderful while it lasted. It hurt, but not as bad as my rectum had hurt before. Not as bad as the agony of not being to go to the bathroom, of constant distension, of your insides wrenching to no effect. No, not that bad, not like that.

I chose to get a colostomy. It’s not a choice that all colostomates get; some people suffer a terrible injury and wake up to a bag around a surgical opening into their intestines. I chose to get a colostomy, and I live with that choice every day, and every day I would say to myself, having this is a good thing. I believed it most days, if only to avoid arguing with myself. It is an act of self preservation, this sort of aggressive acceptance of your body.

Right up until the second my doctor told me he felt I could reverse the ostomy, I had never even considered it. How could I have, when before was so bad? No, I never did. This was part of my choice; I understood when I got it that it would be forever.

Right up until the second my doctor told me he felt I could reverse the ostomy, I never wanted to reverse it. But as soon as he said it, I did. I wanted it more than anything I’ve wanted in a long time.

Now I am looking at the very real possibility of ending up in the position of eventually not being able to stool again without serious intervention. At the very least, not without another surgery in the future. And that’s really stupid, it’s really stupid to decide to do this, because I’m so literally tired of surgery and procedures and shots and IV meds and this fucking port and its stupid dressing and I’m so literally tired of being sick right now that all I want is to not do this anymore. I don’t want to do this anymore. Because I have four feet of trigger living inside of my body and now I’ll never be able to stop cleaning up puke from my toilet every day and reacting to the smell of alcohol when I hook up IV fluids every night and taking the mountains of pills I push around every morning in the pillbox with a resigned finger. I am allergic to my own body and how can I ever get better when I’m literally allergic to myself?

I just want to get better and I’m never going to. But I still want it, I want it more than anything and knowing that I’m never going to doesn’t make me want it any less.

Two years ago, I woke up and saw my stoma, and for many days after that, I told myself it was a good thing, if only to avoid arguing with myself.

Four months ago, I was fine with having an ostomy forever and now I’m getting rid of it and I wish they had never told me I could.

All these plans I have made seem farcical now because they depend on me not reacting to being in pain all the time and that is only possible if I’m not in pain all the time.

Dreams are great and all, but the comedown when they are smashed is fucking hell.

Mast cell medications: Antihistamines by receptor activity

The following medications listed are available in oral or intravenous formulation. Not all medications are available in the US or Europe. Topical and inhaled medications are not included in these lists.

H1 antihistamines interfere with the action of histamine at the H1 receptor. This can help with many symptoms, including flushing, itching, hives, burning skin, nasal congestion, sneezing, constriction of airway, shortness of breath, GI cramping, diarrhea, gas, abdominal pain, tachycardia, blood pressure variability or dizziness. What symptoms are best alleviated varies with the medication; they do not all address all symptoms equally.

First generation Second and third generation Atypical antipsychotics
Alimemazine Acrivastine Aripiprazole
Azatadine Astemizole Asenapine
Benztropine Azelastine Clozapine
Bepotastine Bepotastine Iloperidone
Brompheniramine Bilastine Olanzapine
Buclizine Cetirizine Paliperidone
Captodiame Clemastine Quetiapine
Carbinoxamine Clemizole Risperdone
Chlorcyclizine Clobenztropine Ziprasidone
Chloropyramine Desloratadine Zotepine
Chlorpheniramine Ebastine
Chlorphenoxamine Emedastine
Cinnarizine Epinastine Typical antipsychotics
Clemastine Fexofenadine Chlorpromazine
Cyclizine Ketotifen Flupenthixol
Cyproheptadine Latrepirdine Fluphenazine
Dexbrompheniramine Levocabastine Perphenazine
Dexchlorpheniramine Levocetirizine Prochlorperazine
Dimenhydrinate Loratadine Thioridazine
Diphenhydramine Mebhydrolin Thiothixene
Diphenylpyraline Mizolastine
Doxylamine Rupatadine
Embramine Setastine Tetracyclic antidepressants
Etodroxizine Talastine Amoxapine
Ethylbenztropine Terfenadine Loxapine
Etymemazine Maprotiline
Flunarizine Mianserin
Histapyrrodine Tricyclic antidepressants Mirtazapine
Homochlorcyclizine Amitriptyline Oxaprotiline
Hydroxyethylpromethazine Butriptyline
Hydroxyzine Clomipramine
Isopromethazine Desipramine
Meclizine Dosulepin
Mequitazine Doxepin
Methdilazine Imipramine
Moxastine Iprindole
Orphenadrine Lofepramine
Oxatomide Nortriptyline
Oxomemazine Proptriptyline
Phenindamine Trimipramine


H2 antihistamines interfere with the action of histamine at the H2 receptor. This helps mostly with symptoms affecting the GI tract, such as abdominal pain, nausea, and diarrhea. To a lesser extent, H2 antihistamines can decrease vasodilation.

H2 antagonists


There are few H3 antihistamines and for this reason, their exact effects are largely unknown.  However, in research, H3 antihistamines modulate nerve pain and may normalize the release of several neurotransmitters, including serotonin.

The only medication with known H3 activity available for patient use as an antihistamine anywhere in the world is betahistine. It is anti-vertigo drug used mostly in treatment of Meniere’s disease and other balance disorders. Betahistine actually increases release of histamine and for this reason has been associated with the risk of severe allergic events while taking it.

A 2014 paper described for the first time the H3 reverse agonist/ selective antagonist effects of two antiarrhythmic drugs, amiodarone and lorcainide. This is a very new finding and has not been investigated yet in humans; however, this behavior would explain some of the neurologic effects of these two medications.

H3 antihistamines


Thioperamide has shown promise in research as an H3 and H4 antihistamine, but is not available for patient use.

I have seen blurbs on forums and the internet in which people state that amphetamines are H3 antagonists and doxepin is an H4 antihistamine. I cannot find any evidence that this is the case. Amphetamines interact with the transport of histamine in a very complex way, and that can theoretically interfere with the ability of cells to use histamine. However, this is not the same as a true antihistamine, and the effect of amphetamines on histamine has been difficult to quantify.