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October 2014

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.)

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: Anemia and deficiencies

Anemia is the most common issue affecting red blood cells in MCAS patients.  It can be macrocytic (big cells), normocytic (normal size), or microcytic.  Usually mild to moderate, but occasionally the diagnosis is mistaken for pure red cell aplasia on bone marrow examination.  When macrocytosis is predominant, BMB must be performed to rule out myelodysplastic syndrome (MDS.) 
Cobalamin deficiency is common, even when pernicious anemia is ruled out.  Copper deficiency is sometimes the cause for microcytic anemia, although in MCAS, it sometimes causes normocytic or macrocytic anemia.  This may be caused by absorption, but is also a side effect of overdose of zinc, a common ingredient in over the counter medications taken by MCAS patients to reduce symptoms. Folate deficiency is less frequently found in MCAS and is often due to hemolysis from an acquired condition like acquired chronic autoimmune hemolytic anemia, sometimes found to occur secondary to mast cell disease.  Other hemolytic conditions, like paroxysmal nocturnal hematouria, should be ruled out.
Many MCAS patients have selective iron malabsorption, which sometimes resolves with antihistamine treatment.  GI bleeds must be excluded.  Oral iron absorption tests can be done to test iron malabsorption.  A recent procedure calls for a blood sample to establish baseline plasma iron, administration of 100mg dose of oral sodium ferrous citrate, and another blood sample to test plasma iron two hours later.  Increase of less than 50 ug/dl is considered evidence of malabsorption.
Iron malabsorption can happen for several reasons in the context of MCAS.  Iron deficiency can be from MCAS immune dysfunction that leads to generation of antibodies against the acid secreting cells of the stomach.  When the concentration of stomach acid is too low (achlorhydria), the absorption of non heme dietary iron is dramatically reduced.   H2 antihistamines and PPI medications can interfere with iron absorpotion.   Hepcidin, the production of which is stimulated by mast cell mediators like IL-6 and TNFa, slows down the rate with which GI cells transfer the iron into the blood stream for use.
MCAS patients sometimes exhibit low serum iron and ferritin, but have normal MCV and RCDW, which indicates no deficiency is present.  This profile is thought to allude to correct transport of iron to the blood stream but poor utilization in the bone marrow. 

Afrin, Lawrence B. Presentation, diagnosis and management of mast cell activation syndrome.  2013.  Mast cells.
Kobune M, et al.  Establishment of a simple test for iron absorption from the gastrointestinal tract.  Int. J. hematol. 2011; 93:715-719.
Hitchinson C, et al. Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary hemochromatosis.  Gut 2007 Sep; 56(9):1291-1295.

MCAS: Blood, bone marrow and clotting

One of the reasons MCAS is so difficult to diagnose is because it often has no effect on routine blood work.  Mast cells leave the bone marrow early in their lives, circulate in the blood stream very briefly, and then live in peripheral tissues for life spans of several months to about three years.  The reason many MCAS patients have no obvious hematologic abnormalities is that mediator release in these peripheral tissues usually doesn’t affect generation of blood cells or the blood cells already circulating. 
Hematologic issues are more commonly found in proliferative disease, like SM.  Still, one study found that in SM patients, random bone marrow biopsies missed the diagnosis 1/6 of the time.  For patients in whom SM is suspected, a second BMB can be helpful and bilateral biopsies are being ordered more frequently. 
MCAS patients very rarely have increased numbers of mast cells, spindled cells, CD2/25 receptor expression or the CKIT D816V mutation.  On examination of marrow, when irregularities are found, they are off a mild “myeloproliferative/myelodysplastic” nature, which sometimes leads to a diagnosis of MDS.  These patients do not respond to MDS treatments.
When serum tryptase is less than twice the upper limit of normal, BMB is not recommended due to how infrequently abnormalities are found.  Even during reactions, MCAS patients usually have normal tryptase values.  In recent years, a tryptase of 20% + 2 ng/ml above baseline has become regarded as evidence of activation, but this is not universally accepted.
MCAS patients often have normal blood counts, white blood cell differentials and bone marrow findings.  But there is now a growing population of MCAS patients with evident abnormalities.  Elevation of monocytes is the most common irregularity, followed by elevation of eosinophils, and then elevation of basophils.  High reactive lymphocytes are often identified in these patients on manual differential.  White blood counts can be high or low, often for no clear reason, and usually mild, but sometimes severe.  Likewise, platelets can be high or low, which sometimes garners patients a diagnosis of essential thrombocytosis or immune thrombocytopenia. 
Overproduction of red blood cells can occur to excessive release by mast cells or other cells of mediators stimulating production.  Sometimes patients are originally diagnosed with and treated for polycythemia vera, but do not improve. 
Poor clotting and easy bruising is found in a lot of MCAS patients due to activation that releases heparin.  By itself, it does not typically require treatment.  The bleeding is often localized, such as excessive bleeding from a surgical site but clotting correctly elsewhere.  Antihistamines typically help, with protamine being reserved for severe cases and transexamic acid and aminocaproic acid being reserved for the most severe.
Thromboembolism, formation of a clot in one vessel that breaks away and impedes blood flow in another vessel, is not rare in MCAS patients, even those with normal coagulation labs.  Some patients have low or high PT or PTT values.  Antiphospholipid syndrome should be excluded. 
Heparin released by mast cells activates anti-thrombin III and factor XII, which activate the rest of the intrinsic clotting cascade.  Heparin also stimulates the formation of bradykinin, which in turn causes vascular dilation and loss of fluid volume from the vessels into the tissues.  This is notable as a non-histamine route that can cause angioedema, low blood pressure and fainting in MCAS patients.

Afrin, Lawrence B. Presentation, diagnosis and management of mast cell activation syndrome.  2013.  Mast cells.
Sur R. Cavender D. Malaviya R. Different approaches to study mast cell functions. Int. Immunopharmacol. 2007 May; 7(5):555-567.
Butterfield JH, Li C-Y. Bone marrow biopsies for the diagnosis of systemic mastocytosis: is one biopsy sufficient? Am. J. Clin. Pathol. 2004; 121:264-267.

All one

I hug myself a lot.  It looks like I’m crossing my arms, but I’m not.  Sometimes it’s because I’m cold, but mostly it’s to self sooth.  I cross my right arm under my left and tap my fingers along my ribs.

A while back, I was reading something about integrative medicine that talked about your body storing emotion in certain places.  I remember running my fingers along the base of my skull and wondering if it was true.  I read more and it mentioned specific places associated with energy type.  It said that one of the places you store trauma is over your left ribs, right where my fingertips rest when I hug myself.  I immediately hugged myself and tapped there, to release the energy. 
I have become aware of this spot on my body in the years since.  It is a good barometer for my current emotional stability.  When I get upset, it’s like the muscles in this place remember my heaving sobs.  It gets sore, burning under my touch.  One of the ways I calm myself is by massaging this spot.  When I am very sad, I lie on my bed and listen to music and will my body to release its memory of trauma with my fingers. 
Last week, my massage therapist wanted to try myofascial release.  My lower back was really sore and she cupped it from beneath, her other hand on top of my abdomen, both of her hands still. Minutes passed and I could feel the muscles relaxing.  Just by touching, my body corrected itself.
“It reminds your body that it’s one,” she told me and it made sense.  My body does so many different things that it must be hard to remember that it is one unit, working together.  She massaged my head and then cupped her hands on my chin and neck.  After a little while, I started seeing things.  This was much clearer than the typical massage daydream or meditating visualizations.  It was people, places, events, with lines connecting them.  Everything was blue.  Bright blue.
After the appointment, I looked it up and found out that the chakra associated with that region is associated with the color blue.  It is also associated with spiritual drive and the element of ether.  I closed my eyes and everything was still blue. 
I read more about the chakras.  I knew this stuff once, my great aunt was very into this sort of thing.  I read about how the navel is the seat of the chakra associated with willpower and digestion.  I thought that was so interesting.  My willpower is a pretty serious force, even on bad days.  Is it possible to mess up one chakra thing because you overuse it for something else? 
I stopped eating solid food on Friday.  It has been hard mentally, but when I want to grit my teeth, I close my eyes and immerse myself in blue. 
On Sunday, I did yoga.  This was the first time in several months that it wasn’t a struggle to get through my practice.  I did yoga again on Monday.  And today.  It is starting to feel like it used to.  It is starting to feel like I am connecting the physical and mental and spiritual aspects of myself. 
I wasn’t bleeding today.  I am still very sore, but my swelling is starting to go down.  I’m not happy about the fact that the no solids is working.  I wanted something to work, but I didn’t want no solids to be the answer.  It has upsetting implications for the rest of my life.
But I have exercised for three days in a row and I’m tired but not exhausted and I haven’t thrown up in a few days.  That’s a lot of progress for me.  And I sort of feel like the no solids is part of it, but maybe this connecting to my mind and my spirit is part of it, too.  Maybe instead of struggling to fix my body, I need to teach my mind and my spirit that they’re okay living in this vessel.  Maybe if I can remind myself that we’re all one, it can help me heal. 
I hugged myself tonight and when I touched over my ribs, they weren’t sore.  When I prodded further, blue exploded behind my eyes and colored everything.

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. 

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

Get okay

Last week was hard for me.  I’m not entirely sure why it was so hard.  I got bad news, but frankly, I get bad news a lot.  Sometimes it’s harder for me, and I can’t always predict when those times will be.  It’s one of the weird aspects of chronic illness. 

I had a couple days of feeling sorry for myself, which I also need to do occasionally.  Sometimes I need to sleep a lot and complain and wallow in my unfortunateness for a bit.  This invariably leads to getting mad, and that’s just not a place I like to be.  I find that it’s okay to be mad about being sick in an abstract, transient way, but not as a state of being.  I’m not really a person who is angry about being sick, and I think I’m much happier for that fact.
Friday night, I came home from work and was exhausted.  I have been getting really into these MCAS/MMAS papers (which is great – I have learned so much and I’m super excited to share) and I have had a lot of work stuff happening and my brain was fried.  I decided it was time for some self care to head off a mast cell spiral from stress. I put out the (reverse?) bat signal that I wouldn’t be around for the weekend.
I had picked up a bunch of protein drinks and baby food purees to try, so I organized them and tried out a few.  I made some vegetable stock, baked some Red Kori and Carnival squashes and made a sweet Red Kori/ apple soup and a savory Carnival/ caramelized onion soup with a little grated cheese.  I heated up some cranberries and raspberries with sugar and lemon zest and mixed them with milk and yogurt for breakfast drinks.  I did all the dishes while I cooked, tasted everything and sang along to Ingrid Michaelson.  I finished the night with 10 mason jars full of no solids meals for the week.
I woke up Saturday morning to the smell of rain and the chill of autumn blowing into my bedroom.  Me and Story snuggled under my heated blanket and watched American Horror Story for a while.  I cleaned out my closet and cabinets and threw away/ set aside to donate lots of things.  I walked the dogs, did some writing and ate a lot of very buttery, very salty mashed potatoes. 
Today, I woke up really tired and sore, but for the first time in a very long time, I wasn’t nauseous.  I am still very swollen and my GI tract feels like it’s burning, but I am bleeding less.  I’m not enjoying this no solids diet but I have to say that it is helping.  I did some yoga and took Story for a long walk.  I hung out with the family and watched a movie and tried to just relax.
I’m feeling a lot more like myself.  I’d really rather not need biopsies and scopes and surgery, but you get what you get, and it’s easier to just get it over with.  In response to a post last week about how I had gotten bad news, a friend of mine told me to, “Get a plan – and get okay with it.”  It’s great advice and a motto for living with masto if ever I have heard one. 
So I have a plan.  And I’m okay with it.

Mast cells and cardiac and vascular dysfunction

Mast cells have been implicated in several types of cardiac and vascular dysfunction.  Mast cells are thought to contribute to rupture of atherosclerotic plaques by mediator release.  They are found around blood clots in the body.  Mast cells may destabilize them and mature them by releasing heparin and degrading fibrinogen with tryptase. Increased numbers of mast cells are associated with coronary vasospasm. 
Mast cell mediator levels are often higher in vascular and cardiac events.  In patients who die from coronary heart disease, the histamine concentration in the coronary artery than in control subjects.  Higher white blood cell, platelet and plasma histamine levels are found in patients with peripheral vascular disease. Increased histamine levels are found in patients with both stable coronary artery disease and acute coronary syndrome.  Plasma histamine is elevated in the great cardiac vein of 8/11 patients with variant angina. 
One study found that tryptase is higher in patients without acute coronary syndrome undergoing catheterization, compared to patients with and without obstructive coronary disease.  In this study, patients in the highest 25% of tryptase values had 4.3x greater risk for coronary artery disease.  Tryptase is being investigated as a marker to identify asymptomatic patients with coronary artery disease and to track efficacy of treatment. 
Mast cell mediators are also elevated in non-allergic coronary events, indicating that there is a common pathway for both allergic (Kounis syndrome) and non-allergic cardiac episodes.  Two cholesterol lowering medications, cervistatin and atorvastatin, inhibit stem cell factor (SCF) mediated differentiation of mast cells.  Lovastatin inhibited IgE-mediated degranulation.

Ribatti D, Crivellato E. Mast cells, angiogenesis, and tumour growth. Biochim. Biophys. Acta Mol. Basis Dis. 2012 Jan; 1822(1):2-8.
Glowacki J, Mulliken JB. Mast cells in hemangioma and vascular malformations. Pediatrics 1982; 70(1):48-51.
Kolck UW, Alfter K, Homann J, von Kügelgen I, Molderings GJ. Cardiac mast cells: implications for heart failure. JACC 2007 Mar 13; 49(10):1106-1108.
Biteker M.  Current understanding of Kounis Syndrome.  Expert Rev Clin Immunol 2010 Sep;6(5):777-88.

No solids, clear liquids and NPO

I got phone calls from three of my doctors today.  None of them realized the other two also called.  It was a little funny.
One of the doctors told me they were scheduling an endoscopy and a colonoscopy to get a really thorough look at my GI tract.  They will take biopsies from various parts and stain them to see if my mast cells are generally being terrible people (my money is on this) or if it is something else (I’m looking at you, eosinophils.)  So there’s that.
Another one of my doctors said that in light of the swelling and my persistent bleeding, that I should stop eating solid foods and go on a liquid diet as a stop gap measure to try and stem the inflammation.  I was not expecting to hear this today and I’m feeling pretty sorry for myself, which is not really my style, but is my right.
It got me thinking about the fact that I am pretty used to not eating at all (NPO), or to not eating solids, or to only consuming clear liquids.  This is a side effect of being the vessel for a GI tract that feels it is my mortal enemy.  Before my colostomy surgery, I didn’t eat anything but clear liquids for a few days, while at the same time taking impressive measures to clean the surgical area.  And then I didn’t eat anything for several days after due to post-operative ileus (intestines not moving.) 
So here are my tips for not eating solids or not eating anything but clear liquids.
Figure out which meds will make you hungry.  I take high doses of antihistamines and daily steroids.  These medications increase appetite.  Steroids are actually used in elderly patients to stimulate appetite to keep up their energy.  When I have to take my large doses of antihistamines and steroids, I drink at least 240ml of pureed food (squash soup is a mainstay in my house) or drink at least 500ml of clear liquid about thirty minutes before I take them.  If you are on an NPO (nothing by mouth) order, I recommend starting bolus fluids about thirty minutes before you take your meds.
Set a schedule for liquids and keep it.  Even if you third space like me and oral fluids won’t go to where they’re needed, they will make you feel fuller and suppress appetite.  Keep in mind that suddenly consuming huge amounts of water when you don’t usually will skew your electrolytes, so be sure that you alternate with electrolyte solution.  This is especially true if you have POTS.
Learn how your current dosing affects you without food.  Medication is more available to your body the less solid food you are ingesting.  The cultural touchstone most of us are familiar with is drinking alcohol on any empty stomach.  If you drink on an empty stomach, you get drunker much faster because the alcohol is more available. Medication is the same way.  If you eating thick liquids (pureed food, smoothies), the meds will be more available than if you are eating solid food.  If you are drinking clear liquids, the meds will be more available than if you are eating pureed food.  The difference in both efficacy and side effects can be dramatic.  I recommend having someone with you for the first 48 hours or so until you can predict your reaction to meds. 
Get something for nausea.  Sometimes when you just stop eating, your body misinterprets the problem as there not being enough stomach acid, so it makes extra.  This causes “sour belly” and makes you nauseous.  Additionally, long term hunger will make you nauseous generally, so getting a script for Zofran is helpful. 
It’s okay to add flavor.  When I can only do clear liquids, I make flavor rich, brothy soups and then strain all the solids out.  This way it tastes like chicken soup and not like broth, which really turns my stomach.  Some people chew herbs and spit them out before drinking fluids so that it tastes better.
You are going to be more tired than usual until your body acclimates.  Plan for it. 

So when I am on no solid foods, my day generally looks like this:
630am: Wake up, drink coffee and take thyroid med on empty stomach.
700am: Drink morning milkshake of whatever I feel like milkshaking.  Bemoan the lack of solids in the milkshake.
730am: Take morning meds, including antihistamines and steroids.
800am: 500ml of water.
900am: Cromolyn, 500ml of water.
1000am: Smoothie/soup/whatever.
1100am: 500ml of electrolyte solution.
1200n: Cromolyn, 500ml of water, antihistamines.
1230p: Smoothie/soup/whatever.
200p: 500 ml of electrolyte solution.
300p: Cromolyn, 500ml of water, antihistamines, steroids.
530p: 500ml of water.
600p: Smoothie/soup/whatever.
700p: Cromolyn, 500ml of water.
1000p: Hook up overnight IV fluids (2L.)

1030p: Night time meds. 

This is very generic and gets moved around because I often nap in the afternoon.  I generally drink about 4L of water/electrolyte fluids a day when not eating solids and about 3L a day when I am eating solids. Not eating sucks, but being hungry all the time and not being able to eat sucks worse.  This makes the hunger bearable. 

Mast cell mediators: Recommended testing for MCAS diagnosis

Lab tests specific to mast cell activation for suspected MCAS patients should include serum tryptase, serum chromogranin A, plasma histamine, chilled plasma PGD2, stat chilled plasma heparin, chilled urine for PGD2, PGF2a and n-methylhistamine. 
Tryptase is the most famous mast cell mediator.  It is a complex molecule with many functions in the body.  It is easily damaged by heat and has a short half-life in the body (6-8 minutes in health subjects, 1.5-2.3 hours in patients with hypersensitivity reactions.  In separated serum, it can last approximately four days.  Serum tryptase value is usually normal in MCAS patients, but sometimes it is elevated.  Tryptase values that show an increase of 20% + 2 ng/ml above the baseline level are considered diagnostic for MCAS.
Chromogranin A is a heat-stable mast cell mediator.  High levels can suggest MCAS, but other sources must first be ruled out, such as heart failure, renal insufficiency, neuroendocrine tumors and proton pump inhibitor (PPI) use.  Starting or stopping PPI therapy will generally cause a change in value within five days.  Once other causes have been excluded, serum chromogranin A can be considered a reliable marker of mast cell activity. 
Heparin is a very sensitive and specific marker of mast cell activation.  However, due to its quick metabolism in the body, it is very difficult to measure reliably.  It has a very short half life and quickly deteriorates, even when refrigerated.  Values above 0.02 anti-Factor Xa units/ml are abnormal, but many commercial tests cannot test that low.  Elevated plasma heparin is sometimes found in MCAS patients. 
Histamine is also released by basophils, but the majority is released by mast cells.  It is heat stable and has a short half life in the body.  Serum histamine peaks at about 5 minutes after release and returns to baseline within 15-30 minutes in most patients.  In separated plasma, it is stable at room temperature for at least 48 hours.  It is broken down to n-methylhistamine, which is more stable and can be measured accurately longer.  N-methylhistamine is usually measured in a 24 hour urine test to account for the variability in release over the course of the day. 
Prostaglandin D2 is produced by several other cell types, but mast cell release is responsible for the dominant amount found in the body.  MCAS patients typically produce much higher levels of PGD2 than n-methylhistamine.  PGD2 is less stable than histamine, being metabolized completely in an estimated 30 minutes.  Its metabolite, PGF2a, is the preferred compound for detection due to its superior stability.    Accurate prostaglandin testing relies upon refrigeration of the sample from the start of collection through testing.  NSAIDs inhibit prostaglandin production and can lower PGD2 in blood and urine.  Renal insufficiency may produce an inaccurately low test value, but elevated prostaglandins are sometime seen in patients with renal disease.  Prostaglandins D2 and F2a can be tested in serum, but 24 hour urine samples are considered more accurate.

Leukotriene B4 and cysteinyl leukotrienes C4, D4 and E4 have been noted to be elevated in SM patients and during acute asthma attacks.  Though commercial testing for these compounds is not easily accessible, but they may be elevated in MCAS patients as well.  Other less specific mast cell mediators that are sometimes abnormal in MCAS patients include Factor VIII, plasma free norepinephrine, tumor necrosis factor alpha, and interleukin-6.

Sur R, Cavender D, Malaviya R. Different approaches to study mast cell functions.  Int. Immunopharmacol. 2007 May;7(5):555-567.
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Seidel H, Molderings GJ, Oldenburg J, Meis K, Kolck UW, Homann J, Hertfelder HJ. Bleeding diathesis in patients with mast cell activation disease. Thromb. Haemost. 2011 Nov; 106(5):987-989.
Laroche D, Vergnaud MC, Sillard B, Soufarapis H, Bricard H. Biochemical markers of anaphylactoid reactions to drugs: comparison of plasma histamine and tryptase. Anesthesiol. 1991 Dec; 75(6):945-949.

Takeda J, Ueda E, Takahashi J, Fukushima K. Plasma N-methylhistamine concentration as an indicator of histamine release by intravenous d-tubocurarine in humans: preliminary study in five patients by radioimmunoassay kits. Anesth. Analg. 1995; 80:1015-1017.

Maclouf J, Corvazier E, Wang ZY. Development of a radioimmunoassay for prostaglandin D2 using an antiserum against 11-methoxime prostaglandin D2. Prostaglandins 1986 Jan; 31(1):123-132.
Freeman JG, Ryan JJ, Shelburne CP, Bailey DP, Bouton LA, Narasimhachari N, Domen J, Siméon N, Couderc F, Stewart JK. Catecholamines in murine bone marrowderived mast cells. J. Neuroimmunol. 2001 Oct;119(2):231-238.
Gordon JR, Galli SJ. Mast cells as a source of both preformed and immunologically inducible TNF-α/cachectin. Nature 1990 Jul 19; 346:274-276.

Cardiovascular symptoms of MCAS

MCAS patients often have a number of cardiovascular symptoms.  In true mast cell disease fashion, these symptoms often represent both ends of the spectrum.
Heart palpitations are the most common cardiac complaint, with true rhythmic abnormalities being fairly rare.  Tachycardia is also very common, but occasionally slow heart rate (bradycardia) is reported.  In bradycardic patients, no obvious cause for this can be identified.  Both low and high blood pressure can be seen, many times in the same patient, sometimes even following one after the other in a short period of time.  These changes in blood pressure often have no clear trigger.
True syncope (fainting) is uncommon in MCAS, but presyncope (lightheadedness, weakness, dizziness or vertigo) affects the majority of patients.  These presyncope episodes can be distinct from POTS symptoms, and may not be related to position.  Some patients experience as many as several episodes a day.  When tested for POTS with tilt table, MCAS patients may or may not be positive.  However, when treated for POTS, mast cell patients in general only see mild reduction in their presyncope episodes, with little improvement in their other symptoms.
MCAS patients often complain of chest pain, which may or may not reveal ECG abnormalities.  This type of pain is generally localized specifically to the chest and does not radiate down the arm.  Chest pain must be carefully evaluated due to the potential for two rare cardiac syndromes.  Additionally, mast cell disease can indirectly cause congestive heart failure by the long term action of histamine. 
Takotsubo syndrome, or stress-induced cardiomyopathy, is caused by sudden weakening of the myocardium that causes ballooning of the left ventricle.  It can cause acute heart failure, ventricular arrhythmias, and acute heart failure.  Angiography shows that there is no coronary artery defect to explain the left ventricular abnormalities.  If the patient survives, the left ventricle typically returns to normal after about eight weeks.  This does not occur as a result of an allergic reaction, but is sometimes seen in patients with idiopathic anaphylaxis.  In 75% of patients, serum catecholamines are elevated, a finding sometimes seen in MCAS patients.  Due to severe emotional stress frequently being the trigger for the cardiac event, Takotsubo syndrome is also known as broken heart syndrome.
Kounis syndrome is also known as allergic angina or allergic myocardial infarction.  In these patients, there are no obstructive lesions in the coronary artery.  Patients suffer severe chest pain or heart attack as an extension of an allergic reaction.  Kounis syndrome is caused by mast cell activation causing vasospasm of the coronary artery.  It is not known if the mast cells effecting this pathology are normally developed mast cells or improperly developed, such as seen in mastocytosis and MCAS.  This syndrome accounts for about 0.002% of all acute heart attacks.  (An in depth post on Kounis syndrome is on the way.)
MCAS patients often experience coronary and peripheral atherosclerosis.  Some have pain due to narrowing of the vessels.  Sclerosis and poor healing is seen in many MCAS patients.  Due to the importance of mast cells in angiogenesis, long term mast cell activation can contribute to aneurysms, hemorrhoids, varicosities, hemangiomas, arteriovenous malformations and telangiectasias. 
Edema is a common finding.  Most MCAS patients who have edema have no heart abnormalities and do not have pitting edema, indicating that the edema is likely not from heart disease.  MCAS patients often have widespread edema that can shift to different parts of the body.  There is usually no detectable low albumin.  This is thought to be due to third spacing. 

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