Skip to content

Bone manifestations of SM: Part One

Osteoporosis is a progressive condition in which bone mass and density decreases. This leads to a greater risk of fracture, often fragility fractures, in which a bone breaks from normal activities like a small fall. These breaks usually affect the vertebrae, neck of the femur, wrist (Colles fracture) and ribs. Osteoporosis is defined as bone mineral density 2.5X less than the mean peak bone mass. Osteoporosis has no symptoms in and of itself.

Osteopenia is a decrease in bone mass. It is essentially pre-osteoporosis.

Osteosclerosis is an increase in bone density. This can occur when there has been damage to nearby bone and it has been crushed together into one smaller area.

Osteopetrosis is also an increase in bone density. It may lead to osteosclerosis. In osteopetrosis patients, it is due specifically to a rare genetic disorder.

Osteolysis is the active resorption of bone by osteoclasts. This means that the bone cells are essentially eating the bone away.

Osteoblasts are cells that make bone. Osteoclasts are cells that resorb bone. Your body usually resorbs bone and then puts new bone in the place it resorbed. This allows your body to repair bones.

Trabecular bone is found at the ends of long bones and in vertebrae. It is spongier kind of bone with more bone remodeling and turnover. These weaker places break more easily and are commonly affected in osteoporosis.

All of the conditions listed above are basically imbalances in the processes of bone resorption and formation. In osteopetrosis, the body is depositing bone more quickly than it is resorbing it. In osteosclerosis, more mineral is present in the bone than normal. This is usually caused by damage to the bone by trauma, osteoarthritis or other causes. Osteoporosis is usually the result of one of three mechanisms: excessive resorption of bone, deficient deposition of new bone when remodeling, or disuse, in which lack of mechanical stress on the bone causes bone loss (such as in people in bed rest.) Osteolysis is when your body actively and excessively resorbs the bone. It is a marker associated with severity in several blood disorders and cancers.

55% of Americans over the age of 50 have osteoporosis. 80% of those with osteoporosis are women. Osteoporosis can be caused by a variety of factors, including prolonged use of corticosteroids or several other medications, smoking tobacco, and post-menopausal estrogen deficiency. It is also found secondary to a large number of disorders, including mastocytosis.

Systemic mastocytosis patients who have one or more C findings are considered to have aggressive systemic mastocytosis (ASM), a more severe presentation with shorter expected lifespan. One of these C findings is “bone lesions with large sized osteolyses or/and severe osteoporosis with consecutive pathologic fractures.” Pathologic fractures are bone breaks caused by bone changes due to disease that caused weakness in the bone.

Due to the fact that osteoporosis is so common, there are a number of patients with ISM who have osteoporosis. It is only considered a C finding if it is severe, with multiple fractures due to bone damage, and cannot be attributable to any other cause. It is only a C finding if mastocytosis is the reason the bones are damaged to the point of repeat fractures. In particular, prominent mast cell physicians have spoken out against the inclusion of simple osteoporosis as a C finding, particularly because the risk can be modified with therapy and does not indicate poorer prognosis. Osteoporotic vertebral fractures are particularly prevalent in ISM patients. In one study, of 20% of SM patients with osteoporosis, 18.7% had affected spines compared to 2.5% with affected hip bones.

In SM, the presence of extra mast cells in the bone causes an increase in osteoclasts, which contributes to osteopenia and osteoporosis. Histamine, heparin, TNF, IL-1 and IL-6 are all mast cell mediators known to stimulate osteoclast action. In particular, histamine acts directly on osteoclasts and osteoclast precursors.

MCAS: Neurologic and psychiatric symptoms

The neuropsychiatric symptoms associated with MCAS are numerous and are results of the chemicals released by mast cells.

Headaches are a very common complaint. They can sometimes be managed with typical remedies (Excedrin, Tylenol) and antihistamine treatment often helps with this symptom quickly. However, in some patients, headaches can be disabling. Diagnosis of migraine is not unusual, with mast cell degranulation having been tied previously to migraines.

Dizziness, lightheadedness, weakness, vertigo, and the feeling of being about to faint are all typical in MCAS, though true fainting spells are less common than in mastocytosis. These symptoms often cause many MCAS patients to be diagnosed with dysautonomia or POTS.

MCAS patients often experience increased activation of sensory and motor nerves. This manifests as generic neurologic symptoms, sometimes several at once, like tingling, numbness, paresthesia and tics. Tics generally do not spread from the place they initially present. Paresthesias seem to progress for a period of time, then wane and disappear. Extremities are most commonly affected.

EMG and nerve conduction studies are typically normal or abnormal in a way that is not diagnostic. These tests sometimes reflect a possibility of chronic inflammatory demyelinating polyneuropathy (CIDP.) These patients also sometimes are positive for monoclonal gammopathy of unknown significance (MGUS), a blood marker that has been tied to multiple myeloma. However, in these patients, the MGUS is believed to be an effect of the MCAS.

Another subset of patients are diagnosed with subacute combined degeneration (SCD), a deterioration of the spinal cord associated with B12 deficiency. They are sometimes treated for pernicious anemia despite lack of hematologic support for this diagnosis.

Prostaglandin D2 is a known effector of nerve damage and has been blamed for many of the neurologic symptoms seen in MCAS. Astrogliosis, abnormal proliferation of astrocytes (nerve cells in the brain), and demyelination (loss of the insulating cover for nerves that allows the body to send signals) are markers of neurodegeneration. These factors cause scarring and inhibit nerve repair mechanisms. PGD2 is made by an enzyme called hematopoietic PGD synthase. In mice that don’t make this enzyme, these kinds of neuroinflammation are suppressed. Treatment of normal mice with an inhibitor of this enzyme (HQL-72) also decreases these actions. This indicates that PGD2 is critical in causing neuroinflammation including demyelination. PGD2 also activates pain receptors strongly, causing sometimes profound neurologic pain.

PGD2 is also the most potent somnagen known, meaning that it induces sleep more strongly than any other molecule. MCAS patients report inordinately deep sleep, “mast cell coma.” This is likely due to excessive PGD2. Conversely, some MCAS patients also have insomnia, from excessive histamine.

I have written at length before about cognitive and psychiatric manifestations of mastocytosis, which are the same as in MCAS. Cognitive and mood disturbances are all kinds are reported. Brain fog, including short term memory troubles and word finding problems, is the most common symptom. Irritability, anger, depression, bipolar affective disorder, ADD, anxiety, panic disorders and even sometimes frank psychosis can present. Such symptoms in mastocytosis patients were referred to as mixed organic brain syndrome, a term coined in 1986. The important aspect of these symptoms in MCAS is that they are caused by mast cell activation. As such, they are most effectively treated by managing mast cell release symptoms. Some patients do find relief in some psychiatric medications, but the psychiatrist should be aware that these symptoms are part of mast cell pathology.

Additionally, PTSD is not rare in MCAS patients. This is most often due to the trauma from negative interactions with the medical industry.

Autism is significantly increased in patients with mastocytosis. Similar findings are beginning to surface with MCAS patients. Interesting, most autism spectrum disorder patients have food intolerance and general allergic symptoms. A future post will discuss this in more detail.

References:

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.

Ikuko Mohri, Masako Taniike, Hidetoshi Taniguchi, Takahisa Kanekiyo, Kosuke Aritake, Takashi Inui, Noriko Fukumoto, Naomi Eguchi, Atsuko Kushi, Hitoshi. Prostaglandin D2-Mediated Microglia/Astrocyte Interaction Enhances Astrogliosis and Demyelination in twitcher. The Journal of Neuroscience, April 19, 2006 • 26(16):4383– 4393.

Rogers MP, et al. Mixed organic brain syndrome as a manifestation of systemic mastocytosis. Psychosom Med. 1986 Jul-Aug;48(6):437-47.

 

Origins

I was born into a not really practicing Irish Catholic family. My grandmother is very religious. I went to CCD, had an Advent wreath and made the sacraments in time with all my peers. At no point was it ever explained to me who Jesus was or why I should love him. No one participating in my religious education ever had the vaguest interest in answering my questions about Jesus, Catholicism and the Bible. It pretty much just reinforced that it wasn’t something I would ever feel connected to.

When I growing up, my great aunt showed me how to read tarot cards. It was something several women in our family had done. She told me about crystals and herbs and our spiritual connection to the earth. She lent me books about the old Irish religion (Celtic paganism) and showed me how she incorporated some of these beliefs into her life. This felt real to me. This was the connection I had never had with Catholicism.

I grew into a teenager and read more about Paganism and met other people who believed in the same things. The major tenet of Paganism is to do no harm. It is one of the few world religions to accommodate the validity of multiple belief systems. Paganism does not purport to be the only true religion. It purports to be a religion that shares the world with other religions. It preaches good works and that the universe will punish or reward you according to your actions.

A very common misconception about Paganism is that it is Satanism, which it is not. There is no Satan in pagan religions. We do not sacrifice animals.  We do not eat children.  We are just regular people.

I had a really hurtful conversation today about Halloween. I explained the origins of Halloween from Samhain, the Irish end of the year festival. I explained that it had nothing to do with the devil. I was really not expecting the response that all gods other than the Christian God are guises of the devil, which implies that all of us who worship them are worshipping the devil.

Here’s the thing: I’m getting really tired of people judging me because I’m not Christian. I’m not Christian. I’m probably never going to be. Not everyone in the world is Christian. I am okay with not being Christian.

I have MANY close Christian friends. Many. I have no problem with their being Christian. They are respectful of my choice in religion. I participate in the important religious events of their lives. Sometimes we discuss the differences between our beliefs. We can agree to disagree. Neither of us feels superior to the other. Many of my friends post religious quotes or parables online and offer prayers when I am struggling. I have no problem with these things, and think prayer offers are kind and helpful. Crossfaith friendships are a thing. I have many.

This conversation in particular really upset me because of the events of this week. I stood out front of the entire mast cell community and wrote a public statement that has been read over 1000 times since first being posted. I answer hundreds of questions every week from everyone who asks me. I am actively putting together new initiatives to raise awareness and foster patient and provider education about our diseases. Two hours before this interaction, I was giving a presentation on mast cell disease to 40 researchers to spread awareness about our conditions. So when I’m doing all those things to improve the quality of our collective lives, it’s no big deal that I’m a devil worshipper? Just the rest of the time? Are you kidding me?

This post is not about Christianity. It’s about the fact that judgment is ugly and hurtful. I do not believe in helping a select group of people. I believe in offering the same help to everyone equally. But this is getting hard to live with. I shouldn’t be crying on my couch because someone who I help without question is judging me for my spiritual beliefs. And in the larger context of today, I have realized that this sort of thing is a lot more prevalent in my life than I was allowing myself to realize. My willingness to accept people just the way they are looks a lot like tolerance for this sort of thing and that’s my mistake.

I am a good person. I treat people fairly. I help people as much as I can, sometimes to the point of not getting enough sleep or talking to people in the ER in the middle of the night or reading obscure papers in bed with one eye open so I can find the answer someone needs. I am flawed, but I try hard to improve the lives of those around me. And I don’t judge people for their religious beliefs. Not even a little.

I accept your right to worship however you like and don’t make presumptions about the existential consequences of your religious choices. I am just looking for the same respect. You either accept me or you don’t. I am tired of overextending myself to help people who turn around and judge me in this way. It is unbelievably hurtful. I am not easily upset and I am not easily shaken, but this has got me questioning a lot of things.

I’m going to make myself scarce for a bit outside of my own MastAttack forum on Facebook (feel free to join if you haven’t) because frankly my recent experiences with social media are proving to be bad for my health. I feel like I haven’t written about the science of mast cell disease in ages so I’m going to return to doing that for a while.

As always, I’m here if you have questions. I just ask that you leave me alone if you think I’m a bad/ mislead/ confused person because I choose not to follow your faith. I think I deserve that much. No one needs to feel this way.

Sorry not sorry – Why I’m calling out singer Natalie Grant

Saturday afternoon, a masto friend reached out to me.  She was upset about a Facebook post by a prominent Christian singer, Natalie Grant.  Ms. Grant posted the following to her Facebook wall on Saturday:
“Such a sweet time in Minneapolis at Women of Faith.  But now it’s on to LAX to continue filming the next episode of It Takes a Church.  And why yes, that is a battery operated essential oil diffuser that I’m using in my airplane seat.  Rocking the thieves oil and keeping the germs away.  And it’s helping the plane to smell much better #sorrynotsorry”
I groaned when I read it.  I actually groaned out loud.  I opened the thread to find mast cell patients commenting that oil diffusers can be dangerous for people like us, that they could trigger anaphylaxis. Grant’s fans argued that these people were just looking for something to complain about, that oils could never harm anyone, that you have to ingest a protein to have anaphylaxis.  The general spirit of their responses was that mast cell patients were just being oversensitive. 
That’s exactly right – but not the way that they mean.  Our bodies experience severe reactions to pretty much anything – and those reactions aren’t in our heads.  The fact that so many people commented that it was impossible for an oil diffuser to present a real health risk to others represents a serious danger to people like myself.  That is why the mast cell community found this so upsetting.
So let’s discuss why this is dangerous for people with mast cell disease.
Mast cell diseases are a group of disorders in which your body either makes too many mast cells, mast cells do not function correctly, or both.  Mast cells are the cells that are responsible for allergic reactions.  For normal people to have an allergic reaction, their body has to make a molecule called IgE that remembers it is allergic to something.  So people with peanut allergies have peanut IgE, and when they eat peanuts, the peanut IgE tells the mast cells to have an allergic reaction. 
People with mast cell disease pretty much skip this step entirely.  We have severe allergic reactions to things we are not actually allergic to.  This includes lots of foods, materials, environmental factors and others.  For some people with mast cell disease, these reactions include unpleasant symptoms that can be managed at home, like nausea/vomiting, skin reactions, headaches.  But some of us have severe, life threatening anaphylactic reactions based upon even very casual exposure to these substances.  These reactions require use of epinephrine (Epipens), IV antihistamines and steroids, and monitoring at the hospital to ensure that we survive.  People with severe mast cell disease can have several of these episodes in a year.  (I had three in 48 hours in May.)
To be clear: anaphylaxis can be fatal.  Mast cell patients are more likely to experience anaphylaxis and more likely to have severe reactions.  Our best protection is to avoid triggers and medicate appropriately, but this isn’t always possible.  Due to the rare and unusual nature of our diseases, there are few specialists worldwide so the vast majority of patients must fly to see them.  Hiding at home all the time with a mask on is both not practical and not an acceptable way to live. 
Every day, people with mast cell disease seek to minimize the damage to their bodies by avoiding triggers as much as possible.  In enclosed indoor spaces, this can be particularly difficult.  Once triggered, the only option is to medicate and end exposure to the trigger.  When flying, this is obviously impossible. 
While mast cell diseases are rare, fragrance sensitivities and asthma are not.  The CDC has stated that some risks of exposure to scents include asthma attacks, allergic reactions, headaches, migraines, sore throats, coughing, eye irritation, and other medical symptoms.  Asthma attacks can be triggered by fragrances in 72% of asthma patients.  Patients with multiple chemical sensitivity often have severe symptoms similar to those mast cell patients experience.  The fact that workplaces are gradually transitioning to be fragrance free environments is indicative of scent exposures negatively impacting the quality of life for many people. 
In an age of increasing allergies and allergic-type reactions, I find that people like me are often at odds with people who feel their personal liberties should not be curtailed.  Many people see this stand against the use of a personal diffuser as an attempt to impose the will of a suffering minority onto the population at large.  They are entitled to feel however they feel.  But as a mast cell patient, this is about allowing us to move as safely through the world as possible.  Is it worth feeling “infringed upon” to not use an oil diffuser in an airplane when it could kill someone?  Literally kill them?
Natalie Grant put up a follow up to the original post the next day.  While it initially looked promising, I was very disappointed.  It includes such gems as, “I am not here to argue about whether pure Young Living essential oils specifically, can harm those with this disease.” And, “I have a niece that is so allergic to peanuts, she can be in the front row of a plane and the person in the back row can open a bag of peanuts and she can go in to anaphylaxis.  However, EVERY TIME she flies, she has to inform the airline and flight attendents of her life-threatening condition.  May I make a suggestion to those who are suffering: be vigilant with airline employees.  DO not allow the plan to take off until the passengers have been informed there is someone on board who has a specific life threatening disease, so please do not use perfumes, lotions, oils, etc while on board the plane today.  No one will be a better advocate than YOU.”
This statement sums up exactly how much Natalie Grant is missing the point.  If I stood up in front of a plane and told people not to use anything scented, they would snicker and still use them because nobody believes we can actually die from a reaction to a scent.  When mast cell patients spoke up to point out that her use of an oil diffuser could be dangerous to us, we were mocked and shouted down.  We are advocating for ourselves.  The problem is that Natalie Grant, and her fans, just aren’t listening. 
And mast cell disease being dismissed publicly by someone with her sphere of influence?  Well, I’d venture my world is even a little bit more dangerous now than it was before Saturday.  So I’m calling her out.  #sorrynotsorry
A succinct presentation that sums up scent related health issues for the general public (along with list of references for above statistics) can be found here: http://www.slideshare.net/J_A_Miller/fragrance-sensitivity-awareness

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: 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. 

References:
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.

References:
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. 

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