The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 4

I have answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

8. Why are symptoms not the same for everyone?

  • Bodies are very complex. This sounds silly to say because of course bodies are complex, but the amount of work a body does on a second to second basis is staggering. All of your organs are working all the time. The way they are working depends on hormones, how recently you ate, if you are stressed out, what kind of environment you live in, if you have been or are pregnant, how old you are, if you are sexually active, where you are in your menstrual cycle, what medications you are on, and what things happened to you up to this point in your life. Not everyone’s body does the same things.
  • Mast cells are involved in regulating many processes at the same time that all of these things are happening. It is releasing chemicals to make these things happen and is receiving messages from other cells.
  • Mast cells are key cells in inflammation. Inflammation is when cells from the immune system tell the body that it is under attack. Some of those cells are white blood cels that were already present. Inflammation causes many white blood cells, including mast cells to go to the site of the inflammation. For example, if you break your arm, the cells near the broken bone will send messages that it needs help from immune cells. Those immune cells will then physically move to the place they were called to. Mast cells may move to the site of inflammation in this way.
  • When an area has been inflamed, sometimes white blood cells stick around even when the area is healed or healing. Mast cells can also do this. If an area is inflamed, you may end up with many mast cells in that spot where there had originally only been a few.
  • When an area has been inflamed, the immune cells nearby can be extra easy to activate for a while. They are “primed”. Primed cells are much more likely to start a new inflammatory episode, even for something tiny, because they are easier to activate. They remember that they previously had to call for help so their instinct is to do it again. In this way, old injuries may “act up” easily. This can keep nearby mast cells primed or even activated long term.
  • Mast cells have pockets called granules that store chemicals inside them. These chemicals are called mediators. They perform many of the mast cell’s normal functions.
  • Mast cells have different jobs in different places in the bodies. The mediators stored inside those pockets are not the same in all mast cells. They are full of the mediators that they need most to do specific jobs in that area. Mast cells can also make new mediators to do specific jobs. The mediators they make are also tailored to their specific jobs.
  • Some mediators are very specific and some are not. Think of this like sending an email. You can send an email to a particular person. This is specific. You can also send an email to an address used by many people, like an email account for several people who work in customer service. Any of them might see it and respond but you don’t know which one. This is nonspecific. Mast cell mediators might talk to just one type of cell or to several kinds of cells, either nearby or in other parts of the body. Which mediators are released can also depend on previous inflammation. Which mediators are released, where they are released, and how much is released also vary from person to person.

9. Why do symptoms change over time?

  • Symptoms can change over time for all of the reasons they are not the same from person to person.
  • It is also possible that symptoms can change due to progression of disease from one diagnostic category to another. For example, patients may suddenly notice their abdomen is swollen and hard. That could be because their liver is swollen and not working properly.
  • You CANNOT assume that the disease is progressing because symptoms change. Symptom change is NOT a marker for progression.
  • Mast cell disease is not inherently progressive. Many people never have a change in diagnosis.

For more detailed reading, please visit these posts:

The Provider Primer Series: Management of mast cell mediator symptoms and release

The Provider Primer Series: Mast cell activation syndrome (MCAS)

The Provider Primer Series: Cutaneous Mastocytosis/ Mastocytosis in the Skin

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (ISM, SSM, ASM)

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (SM-AHD, MCL, MCS)

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 3

I have answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

6. What symptoms does mast cell disease cause?

  • Mast cell disease can cause just about any symptom. Seriously.
  • Mast cell disease can cause symptoms in every system of the body. This is because mast cells are found in tissues throughout the body. They are intimately involved in lots of normal functions of the human body. When mast cells are not working correctly, lots of normal functions are not carried out correctly. When this happens, it causes symptoms. In short, mast cells can cause symptoms anywhere in the body because they were there already to help your body work right.
  • Skin symptoms can include flushing, rashes, hives (urticaria), itching, blistering, and swelling under the skin (angioedema).
  • GI symptoms include nausea, vomiting, diarrhea, constipation, problems with the GI not moving correctly in general (GI dysmotility), swelling of the GI tract, chest and abdominal pain, belching, bloating, discolored stool, excessive salivation, dry mouth, and trouble swallowing.
  • Cardiovascular symptoms include high or low blood pressure, fast or slow heart rate, irregular heartbeat, and poor circulation.
  • Neuropsychiatric symptoms include brain fog, difficulty concentrating, difficulty sleeping at night, excessive tiredness during the day, grogginess, anxiety, depression, tremors, numbness, weakness, burning and tingling (pins and needles), hearing loss, and auditory processing (difficulty understanding what was said to you).
  • Genitourinary symptoms include bladder pain, painful urination, painful intercourse/sexual activities, painful or irregular menstrual cycle (periods), and excessive or inadequate urination (too much or too little urine produced).
  • Respiratory symptoms include cough, excessive phlegm, wheezing, runny nose, sinus congestion, sneezing, and swelling of the airway.
  • General symptoms include fatigue, lack of stamina, difficulty exercising, itchy or watery eyes, and bruising easily.
  • There are some additional symptoms that I have observed in a large number of people that are not classically considered mast cell symptoms, but I now firmly believe them to be. One is fever. I think discoloration of the skin may be mast cell related for some people. Another is dystonia, involuntary muscle contraction, which can mimic appearance of a seizure. There are also different seizure-type episodes that may occur due to the nervous system being overactive. I am reluctant to call them pseudoseizures because that term specifically means they are caused as a result of mental illness. I have no evidence that these seizure-type episodes in mast cell patients occur due to mental illness. I personally refer to them as “mast cell derived seizures.” (For people who are wondering, I have been heavily researching this phenomenon and have some theories about why this happens. It’s not fleshed out enough yet to post but it’s on my think list.)
  • Having mast cell disease can make you more likely to have other conditions that cause symptoms.
  • I’m sure there are other symptoms I have forgotten to mention.

7. Why are skin and GI symptoms so common?

  • The skin has a lot of mast cells relative to other tissues. Your skin also comes into contact with lots of things in the environment. Think about the things your skin touches on a daily basis! It makes sense that it would get the exposure so skin symptoms can be common. Additionally, some of the chemicals mast cells release can cause fluid to become trapped in the skin. For these reasons, symptoms affecting the skin are pretty common.
  • The GI tract also has a lot of mast cells relative to other tissues. Your GI tract also comes in contact with lots of things in the environment. Let’s think about this for a minute. Your GI tract is essentially one long tube through your body. You put things from the environment in your GI tract at the top and they come back out the bottom of the tract. In a way, your GI tract is kind of like the outside of the inside of your body.
  • This is the analogy I learned in anatomy and physiology class to visualizing the GI tract as the outside of the inside of the body. Think of the body as a donut. (A low histamine, fully allergy friendly, requires no GI motility, wonderful donut.) Now think of the GI tract as the donut hole. You can put your finger through the hole in the middle of the donut. Only that center part of the donut will touch your finger. This is kind of like putting food throughout the GI tract. That food only touches a very small part of the body as it passes through.
  • Since what we put into our mouths (or other GI openings) is from the outside, your body has many mast cells in the GI tract to protect the body. Some of the chemicals mast cells release can cause fluid to become trapped in the layers of GI tissue. Some of the medications we take for mast cell disease can affect the GI tract. Some of them change how much acid we make in our stomachs. Some of them slow down the GI tract. A few of them speed it up or make the GI tract more fragile. For these reasons, symptoms affecting the GI tract are very common.

For more detailed reading, please visit these posts:

The Provider Primer Series: Management of mast cell mediator symptoms and release

The Provider Primer Series: Mast cell activation syndrome (MCAS)

The Provider Primer Series: Cutaneous Mastocytosis/ Mastocytosis in the Skin

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (ISM, SSM, ASM)

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (SM-AHD, MCL, MCS)

The Provider Primer Series: Management of mast cell mediator symptoms and release

Mast cell disease is largely managed by treatment of symptoms induced by mast cell mediator release or by interfering with mediator release.

The following tables detail treatment recommendations described in literature by mast cell disease key opinion leaders. Please refer to source literature for future details on dosing, duration, and so on. These are not my personal recommendations and any and all treatment decisions must be made by a medical professional familiar with the patient.

Second and third generation H1 antihistamines are preferred to exclude neurologic symptoms accompanying use of first generation H1 antihistamines. However, first generation H1 antihistamines are sometimes used by mast cell patients and in the setting of anaphylaxis.

In advanced and aggressive forms of mast cell disease, use of cytoreductive agents, chemotherapy, and, very rarely, hematopoietic stem cell transplant may be considered.

Table 1: Primary treatment options (consensus) for mast cell mediator symptoms or release described in literature
Class Target Intended actions of target Symptoms associated with target Reference
H1 antihistamines (second or third generation preferred) H1 histamine receptor Promotes GI motility, vasodilatation and production of prostaglandins, leukotrienes and/or thromboxanes (via release of arachidonic acid) and nitric oxide  Hypotension, decreased chronotropy, flushing, angioedema, pruritis, diarrhea, headache, urticaria, pain, swelling and itching of eyes and nose, bronchoconstriction, cough, and airway impingement Valent 2007[i], Picard 2013[ii], Molderings 2016[iii], Hamilton 2011[iv]
H2 antihistamines H2 histamine receptor Release of gastric acid, vasodilation, smooth muscle relaxation, and modulates antibody production and release in various immune cells Increased chronotropy, increased cardiac contractility, hypertensioni, bronchodilation, increased presence of Th2 T cells, increasing IgE production Valent 2007, Picard 2013, Molderings 2016, Hamilton 2011
Mast cell stabilizer (cromolyn) Unknown targets to modulate electrolyte trafficking across the membrane to deter mast cell degranulation 

 

 

 

Unclear. Mast cell mediator release regulates many physiologic functions, including allergy response, immune defense against pathogens, angiogenesis, and tissue remodeling. In theory, all symptoms derived from mast cell mediator release. Research has demonstrated decreased release of mediators including histamine and eicosanoids. Valent 2007, Picard 2013, Molderings 2016, Hamilton 2011

 

Table 2: Primary treatment options (non-consensus) for mast cell mediator symptoms or release described in literature
Class Target Intended actions of target Symptoms associated with target Reference
Leukotriene receptor antagonists Leukotriene receptor Smooth muscle contraction, immune cell infiltration, production of mucus Bronchoconstriction, airway impingement, overproduction of mucus, pruritis, sinus congestion, runny nose Hamilton 2011, Valent 2007
N/A; Vitamin C decreases histamine levels by accelerated degradation and by interfering with production Unknown targets to deter mast cell degranulation  Mast cell mediator release regulates many physiologic functions, including allergy response, immune defense against pathogens, angiogenesis, and tissue remodeling. In theory, all symptoms derived from mast cell mediator release. Research has demonstrated decreased release of mediators including histamine and eicosanoids. Molderings 2016
H1 antihistamine; mast cell stabilizer Histamine H1 receptor and mast cell stabilizer (ketotifen) See above for function of targets for H1 antihistamines and mast cell stabilizer See above for symptoms targets for H1 antihistamines and mast cell stabilizer Molderings 2016

 

Table 3: Secondary options for mast cell mediator symptoms or release described in literature
Symptom Treatment Reference
Abdominal cramping H2 antihistamines, cromolyn, proton pump inhibitors, leukotriene antagonists, ketotifen Picard 2013
Abdominal cramping H1 antihistamines, H2 histamines, oral cromolyn, leukotriene receptor antagonists, short course glucocorticoids Valent 2007
Abdominal pain H1 antihistamines, H2 histamines, oral cromolyn, leukotriene receptor antagonists, short course glucocorticoids Valent 2007
Angioedema H1 antihistamines, H2 antihistamines, leukotriene receptor antagonists, aspirin, ketotifen Picard 2013
Angioedema Medications used for hereditary angioedema, including antifibrinolytic such as tranexamic acid, bradykinin receptor antagonist Molderings 2016
Blistering Local H1 antihistamines, H1 antihistamines, H2 antihistamines, systemic glucocorticoids, topical cromolyn, dressing Valent 2007
Bone pain Analgesics, NSAIDS, opiates and radiation if severe Valent 2007
Bone pain Bisphosphonates, vitamin D, calcium, anti-RANKL therapy Molderings 2016
Colitis Corticosteroids active in GI tract or systemic Molderings 2016
Conjunctival injection H1 antihistamines, topical H1 antihistamines, topical corticosteroids, topical cromolyn Picard 2013
Conjunctivitis Preservative free eye drops with H1 antihistamine, cromolyn, ketotifen or glucocorticoid Molderings 2016
Dermatographism H1 antihistamines, H2 antihistamines, leukotriene receptor antagonists, aspirin, ketotifen Picard 2013
Diarrhea H1 antihistamines, H2 histamines, oral cromolyn, leukotriene receptor antagonists, short course glucocorticoids Valent 2007
Diarrhea H2 antihistamines, cromolyn, proton pump inhibitors, leukotriene antagonists, ketotifen Picard 2013
Diarrhea Bile acid sequestrants, nystatin, leukotriene receptor antagonists, 5-HT3 receptor inhibitors, aspirin Molderings 2016
Flushing H1 antihistamines, leukotriene receptor antagonists, H2 antihistamines, glucocorticoids, topical cromolyn Valent 2007
Flushing H1 antihistamines, H2 antihistamines, leukotriene receptor antagonists, aspirin, ketotifen Picard 2013
Gastric symptoms Proton pump inhibitors Molderings 2016
Headaches H1 antihistamines, H2 histamines, oral cromolyn Valent 2007
Headaches, poor concentration and memory, brain fog H1 antihistamines, H2 antihistamines, cromolyn, ketotifen Picard 2013
Interstitial cystitis Pentosan, amphetamines Molderings 2016
Joint pain COX-2 inhibitors Molderings 2016
Mastocytoma (if symptomatic, growing) Local immunosuppressants, PUVA, removal Valent 2007
Miscellaneous/ overall elevated symptom profile Disease modifying anti-rheumatoid drugs, antineoplastic drugs, kinase inhibitors with appropriate target, anti-IgE, continuous antihistamine infusion Molderings 2016
Nasal pruritis H1 antihistamines, topical H1 antihistamines, topical corticosteroids, topical cromolyn Picard 2013
Nasal stuffiness H1 antihistamines, topical H1 antihistamines, topical corticosteroids, topical cromolyn Picard 2013
Nausea H2 antihistamines, cromolyn, proton pump inhibitors, leukotriene antagonists, ketotifen Picard 2013
Nausea H1 antihistamines, H2 histamines, oral cromolyn, leukotriene receptor antagonists, short course glucocorticoids Valent 2007
Nausea Dimenhydrinate, benzodiazepines, 5-HT3 inhibitors, NK1 antagonists Molderings 2016
Neuropathic pain, paresthesia Alpha lipoic acid Molderings 2016
Non-cardiac chest pain H2 antihistamines, proton pump inhibitors Molderings 2016
Osteopenia, osteoporosis Bisphosphonates, vitamin D, calcium, anti-RANKL therapy Molderings 2016
Peptic ulceration/bleeding H2 antihistamines, proton pump inhibitors, blood products as needed Valent 2007
Pre-syncope/syncope H1 antihistamines, H2 antihistamines, corticosteroids, anti-IgE Picard 2013
Pruritis H1 antihistamines, H2 antihistamines, topical cromolyn, PUVA treatment, leukotriene receptor antagonists, glucocorticoids Valent 2007
Pruritis H1 antihistamines, H2 antihistamines, leukotriene receptor antagonists, aspirin, ketotifen Picard 2013
Pruritis Topical cromolyn, topical palmitoylethanolamine containing preparations Molderings 2016
Recurrent hypotension H1 antihistamines, H2 antihistamines, systemic glucocorticoids, aspirin Valent 2007
Respiratory symptoms Leukotriene receptor antagonists, 5-lipoxygenase inhibitors, short-acting β-sympathomimetic Molderings 2016
Severe osteopenia or osteoporosis Oral bisphosphonates, IV bisphosphonates, interferon alpha Valent 2007
Tachycardia H1 antihistamines, H2 antihistamines, systemic glucocorticoids, aspirin Valent 2007
Tachycardia H1 antihistamines, H2 antihistamines, corticosteroids, anti-IgE Picard 2013
Tachycardia AT1 receptor antagonists, agents that target funny current Molderings 2016
Throat swelling H1 antihistamines, H2 antihistamines, leukotriene antagonists, corticosteroids, anti-IgE Picard 2013
Urticaria H1 antihistamines, H2 antihistamines, leukotriene receptor antagonists, aspirin, ketotifen Picard 2013
Vomiting H1 antihistamines, H2 histamines, oral cromolyn, leukotriene receptor antagonists, short course glucocorticoids Valent 2007
Vomiting H2 antihistamines, cromolyn, proton pump inhibitors, leukotriene antagonists, ketotifen Picard 2013
Wheezing H1 antihistamines, H2 antihistamines, leukotriene antagonists, corticosteroids, anti-IgE Picard 2013

 

[i] Valent P, et al. (2007). Standards and standardization in mastocytosis: Consensus statements on diagnostics, treatment recommendations and response criteria. European Journal of Clinical Investigation, 37(6):435-453.

[ii] Picard M, et al. (2013). Expanding spectrum of mast cell activation disorders: Monoclonal and idiopathic mast cell activation syndromes. Clinical Therapeutics, 35(5):548-562.

[iii] Molderings GJ, et al. (2016). Pharmacological treatment options for mast cell activation disease. Naunyn-Schmiedeberg’s Arch Pharmol, 389:671.

[iv] Hamilton MJ, et al. (2011). Mast cel activation syndrome: a newly recognized disorder with systemic clinical manifestations. Journal of Allergy and Clinical Immunology, 128(1):147-152.e2

Symptoms, mediators and mechanisms: A general review (Part 1 of 2)

Skin symptoms    
Symptom Mediators Mechanism
Flushing Histamine (H1), PGD2 Increased vasodilation and permeability of blood vessels

Blood is closer to the skin and redness is seen

Itching Histamine (H1), leukotrienes LTC4, LTD4, LTE4, PAF Possibly stimulation of itch receptors or interaction with local neurotransmitters
Urticaria Histamine (H1), PAF, heparin, bradykinin Increased vasodilation and permeability of blood vessels and lymphatic vessels

Fluid is trapped inappropriately between layers of skin

Angioedema Histamine (H1), heparin, bradykinin, PAF Increased vasodilation and permeability of blood vessels and lymphatic vessels

Fluid is trapped inappropriately between layers of tissue

 

Respiratory symptoms    
Symptom Mediators Mechanism
Nasal congestion Histamine (H1), histamine (H2), leukotrienes LTC4, LTD4, LTE4 Increased mucus production

Smooth muscle constriction

Sneezing Histamine (H1), histamine (H2), leukotrienes LTC4, LTD4, LTE4 Increased mucus production

Smooth muscle constriction

Airway constriction/ difficulty breathing Histamine (H1), leukotrienes LTC4, LTD4, LTE4, PAF Increased mucus production

Smooth muscle constriction

 

Cardiovascular symptoms    
Symptom Mediators Mechanism
Low blood pressure Histamine (H1), PAF,  PGD2, bradykinin Decreased force of heart contraction

Increased vasodilation and permeability of blood vessels

Impact on norepinephrine signaling

Change in heart rate

Presyncope/syncope (fainting) Histamine (H1), histamine (H3), PAF, bradykinin Increased vasodilation and permeability of blood vessels

Decrease in blood pressure

Dysfunctional release of neurotransmitters

High blood pressure Chymase,  9a,11b-PGF2, renin, thromboxane A, carboxypeptidase A Impact on renin-angiotensin pathway

Impact on norepinephrine signaling

Tightening and decreased permeability of blood vessels

Tachycardia Histamine (H2), PGD2 Increasing heart rate

Increasing force of heart contraction

Impact on norepinephrine signaling

Arrhythmias Chymase, PAF, renin Impact on renin-angiotensin pathway

Impact on norepinephrine signaling

 

Gastrointestinal symptoms    
Symptom Mediators Mechanism
Diarrhea Histamine (H1), histamine (H2), bradykinin, serotonin Smooth muscle constriction

Increased gastric acid secretion

Dysfunctional release of neurotransmitters

Gas Histamine (H1), histamine (H2), bradykinin Smooth muscle constriction

Increased gastric acid secretion

Abdominal pain Histamine (H1), histamine (H2), bradykinin, serotonin Smooth muscle constriction

Increased gastric acid secretion

Dysfunctional release of neurotransmitters

Nausea/vomiting Histamine (H3), serotonin Dysfunctional release of neurotransmitters
Constipation Histamine (H2), histamine (H3), serotonin (low) Dysfunctional release of neurotransmitters

 

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 + 2% 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

 

 

 

Symptoms of mast cell disease

The following is a generalized list of common symptoms associated with mast cell disease. It is not comprehensive and does not include laboratory or associated diagnoses.

General: fatigue, malaise (“being out of it”), weakness, severe unprovoked sweating, weight gain or loss

Skin: Rashes and lesions of any kind, itching, flushing, angioedema, stretch marks, dermatographism, poor wound healing, alopecia, abnormalities of finger or toenails

Eyes: Irritated eyes, red eyes, excessive tearing, dry eyes, difficulty focusing vision, lid tremor, sensitivity to lightness, including sunlight, general inflammation

Ears: Inflammation of the ear, “ear infections,” hearing loss, sensitivity to sound, ringing in the ears

Mouth/throat/sinuses: Generalized pain of several qualities, but often burning, ulceration, “canker” sores, swelling (angioedema), dental decay, abnormalities in taste, taste of metal, throat discomfort or irritation, need to clear throat frequently, post nasal drip, nose bleeds, irritation of sinuses, sinus congestion

Respiratory: laryngitis, bronchitis, pneumonitis (frequently confused with pneumonia), recurrent cough (usually dry), shortness of breath, wheezing

Cardiovascular: lightheadedness, weakness, dizziness, vertigo, fainting, high or low blood pressure, palpitations, rapid heartbeat, abnormalities in heart rhythm, chest pain, hemorrhoids, edema

Gastrointestinal: abdominal pain, diarrhea, constipation, difficulty swallowing, swelling of any part of the GI tract, nausea

Neurologic: Headache, migraine, “about to faint,” fainting, numbness, pins and needles, neuropathy, tics, tremors, seizures

Psychiatric: Anger, depression, PTSD, anxiety, memory difficulties, anxiety, panic disorders, insomnia, sleep disorders

The hallmark of mast cell disease is allergic-type reaction to a variety of stimuli. These can also occur to substances benign to most people, including scents, “hypoallergenic” materials, heat, sunlight and water. Some people experience anaphylactic reactions that require epinephrine.

References:

Afrin, Lawrence B. Presentation, diagnosis and management of mast cell activation syndrome. 2013. Mast cells.

How to get out of a reaction cycle

If you have mast cell disease, your basic arsenal for managing your disease should include elimination of/ avoidance of known triggers, low histamine diet, second generation H1 antihistamines and H2 antihistamines.  Leukotriene inhibitors, aspirin, mast cell stabilizers, steroids and anti-IgE are also possibilities for maintaining a baseline.
As a mast cell patient, a decent baseline is what you are going for.  A reasonable baseline does not always mean that you can live the same way you did before your diagnosis.  It means that you are somewhat functional on a day to day basis.  What this looks for is different for everyone, but I aim for not being in bed for 20 hours a day, not being in 5/10 pain every day, being mentally coherent.  Most importantly, you should not have to take rescue meds frequently.  If you need rescue meds often, then you are not covering your mast cells well enough with your regular meds.  If you have eliminated triggers, then this usually involves tweaking your meds. 
I’m going to give you my insights on what that looks like, but please keep in mind that any med changes should be discussed with your treating physician.  We are all different people and med dosing can be affected by many factors. 
Part of why mast cell patients are prescribed second generation H1 antihistamines is because they are usually not sedating, have little anticholinergic activity and are, to be honest, pretty safe.  Mast cell patients often take several times the recommended daily dose on medications like loratadine and cetirizine.  (Please note: the daily recommended dose for Benadryl, which is a first generation H1, should be respected – overdosing can have serious consequences.)  So while the average person may take one Zyrtec a day for allergies, a mast cell patient may take 3 or 4 a day.  The same is true for the H2 antihistamines, like ranitidine and famotidine.  It’s not unusual to dose very high on those. 
If you have uncontrolled symptoms on second generation H1 and H2, changing the meds to something else in the same class may help.  Sometimes Pepcid works better than Zantac, or whatever.  Some people find that using one Allegra and one Zyrtec works better than two Allegras.  Consider also that inactive ingredients can be triggering and thus decreasing the effectiveness of a med.
If you have screwed around with H1 and H2 meds and have increased doses, adding leukotriene inhibitors, cromolyn or atypical H1 meds, like promethazine or doxepin, may help.  If that fails, ketotifen helps a lot of people, and anti-IgE (Xolair) has benefited some mast cell patients.  Beyond this, you are looking at things like regular IV fluids, steroids, and less palatable choices.
As I mentioned before, having a good baseline means not using rescue meds regularly.  This is really important to feeling as well as possible.  Serious reactions take a while to recover from, even if they don’t need epi.  So if you’re having one every day, it is impossible to get to your baseline without serious intervention.  The meds used to control serious reactions, including Benadryl, can cause rebound reactions that look like anaphylaxis, but are not anaphylaxis.  Let’s talk about this.
Benadryl can cause rebound reactions for two primary reasons.  The first is because it is a very strong antihistamine and it stops histamine release symptoms really well.  One of the things Benadryl does is it stops mast cells from releasing histamine.  So when it wears off, mast cells tend to release a lot of that histamine at once.  Another release is that Benadryl has very strong anticholinergic action.  When your dose wears off, you can have what’s called “cholinergic rebound.”  This can cause headache, nausea, vomiting, diarrhea, brain fog and other symptoms.  Sound familiar?  This is why people feel “hung over” when their Benadryl wears off.  Second generation H1 antihistamines, like cetirizine and fexofenadine, have almost no appreciable anticholinergic activity so they tend to not have this side effect.
Mast cell patients get hit with the double whammy of sizeable histamine release at the same time as they get hit with cholinergic rebound.  So rebound reactions can feel like anaphylaxis, but they’re not the same thing.  If you take Benadryl every day, you are going to have a rebound reaction every day.  It may not be severe, but this is not uncommonly the culprit in patients who say they always get sick around the same time every day. 
Another reason why it is generally not recommended for mast cell patients to take Benadryl every day is because it can stop working.  This is called tachyphylaxis and it basically means your body gets used to it.  When you need to use epinephrine, you are counting on Benadryl and steroids to help control the effects of anaphylaxis on your body.  Patients in whom Benadryl is ineffective get into very dangerous situations when they anaphylax.  I have a few friends like this and it is seriously not pretty. 
It is possible for anaphylaxis to be biphasic or protracted.  Biphasic reactions are not common, but seem to be more common in mast cell patients than the general population.  (This is my personal observation.)  In these reactions, once the reaction is stopped with epi, you can have another anaphylactic episode of the same or worse intensity without a trigger.  This generally happens within 24 hours and is the original reason Epipens were sold in pairs.  In protracted (sometimes called multiphasic) reactions, this can continue to happen for a number of days.  I find in my personal experience that use of epi early is the best way to avoid multiphasic reactions. 
If you absolutely must take a medication that causes a serious reaction (by which I mean not a typical side effect), desensitization is usually recommended for mast cell patients as opposed to taking antihistamines with each dose.  This method really just suppresses the immediate symptoms, not the inflammatory response.  Drug reactions for mast cell patients can be serious and any reaction can escalate even when it has been mild in the past.  For patients who react to salicylates, but need to take aspirin, Dr. Castells has written an aspirin desensitization protocol that is frequently used.
Part of why people get into these cycles with rescue meds is that they often don’t understand why they are having reactions.  Mast cell patients need to keep careful inventory of their daily histamine level because things that may not cause reactions individually can cause a reaction when you have them all together.  For example, if you have a relaxing day with no stress, maybe you can eat a spinach salad.  But if you go for a walk outside in the heat, and you eat that same spinach salad, you may have a reaction.  This doesn’t just happen to mast cell patients – there are plenty of recorded instances of patients having allergic reactions to food ONLY IF THEY EXERCISED THAT SAME DAY.  This is because exercise increases histamine.  Heat increases histamine.  Eating increases histamine. Stress increases histamine.  Sex increases histamine.  So all of this histamine adds up.  So you may be able to drink a beer, or you may be able to walk two miles, but if you try to do both the same day, you may have a reaction. 
Of course, there is also an idiopathic aspect to mast cell reactions, which means that some people have symptoms for truly unexplained reasons.  However, I find these happen a whole lot less when you really track activities/histamine and try to eliminate triggers. 
Part of how I evaluate my “histamine baseline” for any particular day is by certain physical parameters that I refer to as my “mast cell dead giveaways.”  If these are present, I know I am already starting out as reactive and need to lay low and avoid histamine that day.  Allergic shiners, which look like black eyes, or dark circles under the eyes, are one for me.  Swelling in my fingers tells me I’m having some edema from mast cell degranulation.  The taste of metal in my mouth often precedes reactions.  Skin being more reactive than usual is a very clear indicator for me.  On a reactive day, squeezing my arm with my hand will make my entire arm turn red.  I take my blood pressure in the morning and if my whole arm is red or has hives when I take off the cuff, it is a clear sign to me to not take risks that day.  Any type of “cold symptoms” (cough, stuffiness, clearing of the throat, sore throat) and I have to assume infection, which contributes to mast cell activation and thus to your histamine quota. 
I have written before about how to manage mast cell reactions with medication, so please refer to that post for more details.
Keep track of your histamine inventory.  Learn the “dead giveaways” for your body so you can self check.  If you’re taking Benadryl every day for symptoms, it can often be resolved with increasing meds/ adding other meds.  Taking Benadryl every day should be avoided, especially because it causes rebound reactions that can mimic anaphylaxis symptoms. 

MCAS: Kidney, urinary and genital concerns

Like so many other places in the body, the genitourinary tract of MCAS patients can easily become inflamed.  Many patients, especially women, are treated for chronic urinary tract infections despite negative cultures.  Male MCAS patients are often diagnosed with prostatitis.   Vaginal inflammation, painful inflammation, and vulvodynia/ vulvar vestibulitis are also found frequently in mast cell patients.  (Please see previous post on vaginal pain in chronic disease.)
Mast cells are not often found in healthy renal tissue, but they are frequently present in various types of renal disease.  They are most commonly associated with tubulointerstitial nephritis associated with fibrosis and renal failure, including glomerulonephritis, diabetic nephropathy, allograft rejection, amyloid disease, polycystic kidney disease, reflux nephropathy and others.  Mast cells drive fibrosis and their presence correlates with decrease in glomerular filtration and a poor prognosis. 
MCAS patients with urinary pain often suffer from obstructive ureteral angioedema, swelling of the urethra that prevents the urine from passing through it.  Persistent lower back pain is common, with flank pain and lower abdominal quadrant pain being less common.
Fertility issues are not rare in mast cell patients.  Luteinizing hormone activates mast cells, which release histamine to stimulate ovarian contractility, ovulation and progesterone release by follicles.  Histamine is necessary for these functions and antihistamines can prevent ovulation.  Frequent miscarriage should not be readily attributed to mast cell disease.  Antiphospholipid antibodies should be considered. 
Mast cell degranulation has been implicated in testicular sclerosis via production of 15d-prostaglandin J2.  Mast cell stabilizers can help treat oligospermia significantly enough to result in pregnancy.  Decreased libido and erectile dysfunction is common in mast cell disease, including MCAS.
15-20% of women in childbearing years have endometriosis.  Endometriosis is the occurrence of endometrial tissue outside of its normal location.  In these patients, endometrial tissue is often found in the peritoneum.  These ectopic tissues are often fibrosis and cause significant inflammation. 
Mast cells are significantly increased in endometrial lesions, with 89% showing significant activation in regions that stain heavily for CRH and urocortin.  Mast cells in normal and proliferative endometrium are not activated.  Additionally, IL-1a, IL-6 and TNFa, among other inflammatory mast cell mediators, are increased in the tissue and fluids surrounding endometrial lesions.  (A detailed post on this is coming soon.)
Interstitial cystitis is often misdiagnosed as endometriosis.  In IC, urinary urgency, increased urinary frequency, suprapubic and pelvic pain and pain on intercourse are the most common symptoms.  IC is caused by increased mast cells in the bladder.  In IC patients, 146 mast cells were found over 10 high power fields; in patients with bacterial bladder infections, 97 were found; and in health controls, 51 were found.  (A detailed post on this is also coming.)

References:
Sant, Grannum R., Kempuraj , Duraisamy, Marchand , James E., Theoharides, Theoharis C.  The mast cell in interstitial cystitis: role in pathophysiology and pathogenesis.  2007.  Urology 69 (Suppl 4A): 34-40.
Holdsworth SR, Summers SA.  Role of mast cells in progressive renal disease.  J. Am. Soc. Nephrol. 2008 Dec; 19(12):2254-2261.
Kempuraj D, Theoharides TC, et al.  Increased numbers of activated mast cells in endometrial lesions positive for corticotropin-releasing hormone and urocortin.  Am. J. Reprod. Immunol. 2004; 52:267-275.
Afrin, Lawrence B. Presentation, diagnosis and management of mast cell activation syndrome.  2013.  Mast cells.

MCAS: Effects on eyes, ears, nose and mouth

MCAS patients suffer a variety of symptoms in systems localized to the head, often without well characterized explanations.  Eye, ear, sinus, nasal and mouth symptoms are often documented.
Generic irritation of the eyes, including dry eyes and/or itchy eyes, are the most common ophthalmologic complaint.  Excessive tearing is also common.  Like many other symptoms, the tearing can be occasional or chronic.  Redness, irritation of the sclera (the white part of the eye), the eye lid, and conjunctivitis can all affect one or both eyes.  Tremors and tics of the lid are sometimes found.  When particularly bothersome, patients sometimes seek treatment with botulinum toxin (Botox).  This treatment is at first successful, but the issue later resurfaces.
Difficulty in focusing in both eyes is particularly common when suffering other MCAS symptoms.  Despite seeking ophthalmologic explanations for these symptoms, most patients have no obvious cause of their inflammation.  32% of MCAS patients report eye issues. 
Symptoms affecting both anatomy and function of the ears are not atypical.  Irritation of the outer ear is unusual, but middle ear irritation, resembling an infection, is extremely common.  These “infections” often occur frequently and are resistant to antibiotic treatment because they are, in fact, the result of sterile inflammation. 
Hearing abnormalities are often found in MCAS patients.  They include hearing loss, ringing of the ears, and sensitivity to sound.  This is thought to be from sclerosis of the innter ear bones or tympanic membrane, which has been known to occur coincidentally with mast cell disease since the 1960’s.  Deterioration of the canal hairs and auditory nerve is also suspected in some patients.  Tinnitus is likely from mediator release causing overstimulation of the hair cells and auditory nerve fibers.  The most common finding by audiologists is sensorineural hearing loss of unclear origin.
Mast cells are densely concentrated in the cavities and passages of sinuses and in the nose.  Congestion, inflammation, ulceration, sores and pain are all common.  MCAS patients often have a heightened sense of smell with systemic reactions possible from an offending scent.  Unprovoked nose bleeds sometimes occur, which is thought to be from increased local concentration of heparin.
Pain in the mouth and lips is a frequent complaint.  Like so many other MCAS symptoms, it can be focal or diffuse, mild or disabling.  It is often found with leukoplakia, but yeast infection is not found.  Distorted sense of taste, especially where things often taste of metal, is common.  Ulcerations and sores often present.  While on preliminary examination they resemble herpes sores, they almost never are in MCAS patients. 
MCAS is associated with burning mouth syndrome, which is exactly what it sounds like.  The mucosa is normal on biopsy.  Mast cell mediator therapy can relieve pain, sometimes very quickly. 
Evidence of angioedema is often seen in the mucosa of the cheeks, tongue and lips.  Patients often undergo evaluation for hereditary angioedema.  While they are sometimes found to have decreased levels of C1 esterase antigen or function, it is not low enough to account for the angioedema.  This finding is often a red herring. 
Dental decay, often despite excellent dental hygiene, is being reported with increasing frequency.  It can be a lifelong issue or sudden onset.   There are several reasons suggested for this, but none definitive. 

References:
Afrin, Lawrence B. Presentation, diagnosis and management of mast cell activation syndrome.  2013.  Mast cells.

Constitutional symptoms of MCAS


Constitutional symptoms are any symptoms that affect the function of several systems at once.  They are often nonspecific and can be attributed to many causes, complicating diagnosis. For many people with MCAS, the constitutional symptoms present first and with the greatest frequency.

Fatigue and malaise (the feeling of being “out of it”) are the most common symptoms reported in MCAS patients.  While many patients with these symptoms remain functional, for some, it can be truly, severely disabling, with some patients sleeping for the majority of the day.  Dr. Afrin has referred to stories of “patients in their twenties acting like they are in their eighties.”  Chronic fatigue syndrome, in which patients have severe fatigue unrelated to exertion, not relieved by rest and unrelated to other medical conditions, has been tentatively linked to mast cell activation by Dr. Theoharides. 

I see a lot of discussion about whether or not fevers are part of MCAS.  It depends which researcher is reporting information.  Castells feels strongly that fevers are not part of MCAS symptomology, while Afrin and Molderings feel that they are.  They report that intermittent elevated temperatures are not unusual.  These temperatures are low-grade temperatures, with frank fever being quite rare.  MCAS patients often report constantly feeling cold, though chills and shaking is less common.

I know that one of the ways I can tell my mast cell disease is ramping up is by severe night sweats.  This is apparently common in most presentations of mast cell disease.  As such, many MCAS patients have severe, unprovoked sweating, often overnight, sometimes not.  Some patients report a circadian rhythm.  Furthermore, this sweating is often accompanied by swollen or tender lymph nodes.  When these two symptoms are taken together, usually infection or lymphoma is suspected.  Once these are ruled out, patients are often left with no relief for this frustrating symptom.

Some patients report lack of desire to eat.  Some report quickly feeling full (early satiety.)  In some of these patients, the root cause is a swollen spleen.  A minority of MCAS patients lose weight due to their disease.

Weight gain in MCAS patients is far more common than weight loss.  It often begins suddenly and progresses rapidly, in the absence of dietary or activity changes.  This is partially due to the fluid dynamics of edema due to mast cell activation.  Less often, weight gain is from ascites (free fluid in the abdomen) or serositis, inflammation of the serous tissues, including the pleura (tissue lining the lungs), pericardium (the compartment containing the heart and origination of the large vessels connecting to the heart) and the peritoneum (tissue lining the abdomen.) 

However, the gain in adipose (fat) tissue seems to be responsible for most of the persistent weight gain.  Some patients gain more than 50kg in a year despite significant caloric restriction and frequent exercise.  Many people (and their providers) often attribute their worsening symptoms to the gained weight.  Some people undergo bariatric surgery and despite initial losses, regain the weight, with no improvement of other symptoms.

Pruritis (itching) is very common in MCAS.  Its presentation is varied; episodic or constant; local or diffuse; migratory or not; tolerable or disabling.   

The hallmark of MCAS is that patients invariably present with a collection of “sensitivities.”  These include severe or bizarre reactions to virtually anything, including drugs, food and environemental triggers.  Environmental triggers can be due to the presence of common allergens, physical (such as heat), electrical (such as generation of electrical charge when brushing hair) and even osmotic.  Exposure to harmless microorganisms can cause severe reactions.  Summers are often difficult for MCAS patients due to heat and increased UV exposure, while spring and fall are difficult due to pervasive pollen.  Triggers can cause reactions when the patient touches, inhales or ingests them. 

Though less of a problem than heat, exposure to cold can trigger a hyperadrenergic response that will fuel mast cell activation.  Care must be taken to avoid temperature extremes on either end of the spectrum.

Drug sensitivities are often found to be due to an inactive ingredient in the formulation.  Compounding is an important tool for MCAS patients.  Lactose monohydrate and potato are common fillers for MCAS patients.  Reconstitution at time of use with water is also not uncommon.

 

Reference:

Afrin, Lawrence B.  Presentation, Diagnosis and Management of Mast Cell Activation Syndrome.  2013.  Mast Cells.