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mast cell disease

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.

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. 

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. 

Afrin, Lawrence B. Presentation, diagnosis and management of mast cell activation syndrome.  2013.  Mast cells.
Molderings GJ, Brettner S, Homann J, Afrin LB. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. J. Hematol. Oncol.2011; 4:10-17.
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.
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.

The speed of falling apart

I saw my GI mast cell specialist today.  I have not been looking forward to this appointment.  I find that whenever the shit hits the fan with my health, it is always him telling me things I don’t want to hear in the small exam room at the end of hall. 

I am having major GI issues.  I am nauseous.  I vomit up most of what I eat.  I am reacting not just to food, but to the actual process of eating.  Beyond this, I have had a major change in lower GI symptoms.  I am bleeding from multiple places and spending a lot of time in the bathroom.  My abdomen is swollen and sore again.  If I lay back, I can literally watch myself digesting. 
We went through all my symptoms.  I told him about my endocrinologist appointment and filled him in on some conversations with my immunologist.  He examined me and palpated my sore abdomen, could feel that my colon was swollen. 
“Your problem is proliferation,” he said.  “If you started with two million mast cells, now you’ve got a hundred. Or more.”  I know.  I didn’t have anything helpful to add.  I really hate when I can’t pull useful more information out of my brain because it doesn’t exist. 
I already have a good surgeon, so he agreed to talk to him and get back to me on who wants to order what.  I will definitely need another colonoscopy with biopsies, at the very least, before they decide what to do for surgery.  He called my GI distress “incredible troubles.”  I laughed when he said it.  “Your troubles, they are incredible,” he clarified.  “A lesser person might not do so well.” But I didn’t feel like I was doing well today.  I wanted to go to sleep, quiet and numb, for as long as I could. 
I have said several times that this has been a strange year.  I feel like I can’t express what I mean by that properly.  While I have gotten sicker this year, I have at the same time found an increasing sense of peace.  I feel like I am helping people, and that was only possible because I am sick.  I learned about mast cell disease because I am sick, and I met all these people because I am sick, and I like this life, that I have because I am sick.  All of this is a side product of being sick. 
I skyped with one of my best friends tonight.  “I feel so guilty because I love what I do and I love all these people but it’s all because I’m sick and I don’t want to be sick anymore,” I cried to her.  I had a good long cry.  It was one of those days. 
But in the dark moments, when it feels like my soul is trying to swallow itself whole, I remember this year, and how as time goes on, I somehow feel less and less at odds with my disease.  I somehow feel the anger subsiding, feel this overwhelming calm as I learn how to live in this body each day. 
This year has been weird.  I am self actualizing at the speed of my body falling apart.

Mast cells and metabolic syndrome: Hypertension, obesity and atherosclerosis

Metabolic syndrome is defined as impaired glucose tolerance (IGT) or type 2 diabetes and/or insulin resistance with two or more of the following findings:

1.       Abdominal obesity, defined as a BMI 30; and/or waist to hip ratio >0.90 in men and >0.85 in women
2.       Baseline blood pressure >160/90 mm Hg
3.       Increased plasma triglycerides >1.7 mmol/L; and/or low levels of HDL cholesterol (<0.9 mmol/L in men; <1.0 mmol/L in women
4.       Microalbuminuria (overnight urinary albumin excretion rate > equal to 20 ug/min.)
Inflammation is a known effector of obesity.  Microscopic examination of obese adipose tissue reveals chronic inflammation and excessive amounts of white blood cells, leukocytes.  Macrophages, white cells that are very important in the inflammatory response, are found in adipose tissue in numbers that are directly proportional to the degree of obesity.  T cells, other white cells, also accumulate in adipose tissue. 
Until recently, most of the research on inflammatory cells in adipose tissue focused on macrophages and T cells.  However, we now know that mast cells congregate in larger than normal numbers in white adipose tissue in obese patients.  These patients also demonstrate a higher serum tryptase concentration than in lean individuals.  Mast cells are usually found near microvessels, very small blood vessels, in white adipose tissue.  The number of microvessels correlate with mast cell count in the tissue, implying that a relation between the microvessels and mast cells.
Mast cells release many chemicals, including TNF (tumor necrosis factor.)  TNF is known to mediate insulin resistance, and is overexpressed in white adipose tissue in obese patients.  Treatment with TNF blockers in patients with inflammatory diseases has demonstrated a significant reduction of blood insulin levels as well as the insulin/glucose index.  Several other mast cell mediators contribute to insulin resistance in fat cells, including IL-6, iNOS, MCP-1 and IL-1. 
Research has shown that mast cell stabilizers, cromolyn and ketotifen, can prevent diet induced obesity and diabetes.  In mice, these medications have been able to reverse obesity and diabetes, as well as reducing body weight and glucose intolerance.  These findings have been very exciting for mast cell patients with diabetes.
It is important to know that while metabolic syndrome is usually associated with obesity, patients of normal weight may also be insulin resistant and have metabolic syndrome.
Hypertension (high blood pressure( in mast cell disease is a topic of a lot of recent debate.  In spontaneously hypertensive rats (SHR), the density of cardiac mast cells is significantly higher than normal immediately after birth.  Throughout life, cardiac mast cell density is much higher in these rats than in controls of the same age.  Mast cell chemicals TNF, NF-kB and IL-6 were overexpressed in these rats even before they became hypertensive.  In later stages of hypertension, hearts of these rats showed increased areas of fibrosis in the heart.  These areas of fibrosis were full of activated mast cells.  Expression of two mast cell chemicals, TGF-B1 and bFGF (basic fibroblast growth factor) is much higher than normal in aging and failing hearts in spontaneously hypertensive rats. 
Importantly, mast cell stabilizer nedocromil was able to prevent fibrosis in SHR rats.  Tryptase levels were elevated in SHRs that were not receiving treatment, but returned to normal after treatment with nedocromil.  In untreated SHRs, levels of interferon gamma and IL-4 were elevated, while IL-6 and IL-10 were lower than normal.  All of these levels normalized after treatment with nedocromil.  This medication also prevented macrophage infiltration in the heart ventricle.  This finding indicates that mast cell signaling to macrophages is an important process in fibrosis.
Atherosclerosis is the accumulation of low density lipoprotein (LDL) cholesterol in the arterial wall.  Macrophages eat particles of LDL, and when they do, they turn into weird looking cells called foam cells.  Mast cells often live very close by foam cells, and many researchers think that mast cells help macrophages transform into foam cells. 
When mast cells release chemicals, chymase and carboxypeptidase A are bound to heparin.  After release, these components form insoluble granules called remnants.  When mast cells are activated, LDL uptake by macrophages rises by 7-24X.  Treatment with cromolyn has been shown to block mast cell dependent LDL uptake by macrophages. 
HDL passes from the bloodstream into the arterial wall.  When mast cells degranulate, those remnants degrade HDL components in the blood, peritoneal fluid and maybe also in atherosclerotic lesions.  Mast cell deficient mice have lower serum total cholesterol, triglycerides, phospholipids and a less atherogenic lipoprotein profile in general.
Mast cells are heavily involved in obesity, hypertension and atherosclerosis.  For this reason, many mast cell patients have these problems. 


Zhang J, Shi GP. Mast cells and metabolic syndrome. Biochim. Biophys. Acta 2012 Jan, 822(1):14-20.


I saw a new doctor last week to address some hormone issues.  She had never heard of mast cell disease.  I gave her the run down succinctly: “The hallmark of my disease is anaphylaxis in the absence of IgE stimulation.  We can anaphylax at any time for any reason.  Some things make reactions more likely and we avoid those things when possible.”
Immediately upon hearing these words, she became uncomfortable.  She took some history and asked me what medications I took.  She looked over my test results and told me I should have IM steroids available in case of emergency.  When I told her that injections increase my risk of anaphylaxis and that I use IV meds to avoid that, she literally threw up her hands.  “Well, do you want the shot or not?” she asked crossly.  I told her I didn’t want it. 
She informed me that I needed several blood tests, which needed to be drawn first thing in the morning.  No one at the lab will draw out of my port and getting blood drawn results in several sticks and generally cause a reaction.  I asked her what I should do and she said, “Well, we’ll figure that out later.”  Which means that she doesn’t care enough to help me figure it out.
She had me get up on the exam table.  She listened to my heart.  “When you touch my skin, it may start to welt, that’s normal,” I told her.  “Oh, I’m not going to touch you,” she said dismissively.  I closed my eyes and felt my hands curling into fists.  She put her stethoscope away and ended the appointment.
I left her office upset.  I have been around the block with arrogant doctors.  They don’t really stress me out much anymore.  This was different.  This was not an instance of a doctor thinking they knew better than me how to manage my disease.  This was an instance of a doctor deciding that treating me effectively was more trouble than I was worth.  She decided that I wasn’t worth an examination.  She decided it didn’t matter if I got those tests because she didn’t care anyway.  
I live with this disease every day.  Most of the time, being sick isn’t the hard part.  Waking up every day and trying to believe that I am worth the trouble – that’s the hard part.