The Cathedral of Belief

I have a GI bleed. This isn’t new or surprising, I have had bleeds off and on for years. But this is worse. Worse enough that I called to ask at what point I should go to the hospital. After some back and forth, we decided I could stay home as long as it wasn’t enough blood loss to significantly drop my BP or to alarm me personally. So home is where I am.

After approximately 4,679 phone calls and emails, a scope was scheduled for me for this week. Similarly, I have previously had 4,679 scopes. I am a frequent user of hyperbole but I honestly can no longer remember how many scopes I have had. I have had several flexible sigmoidoscopies, several full colonoscopies, a few proctoscopies, several endoscopies and the very rare and elusive colonoscopies via stoma. It’s like my own demented version of Pokemon Go except they don’t happen outside and I have to drink two bottles of what smells like lemon Pledge and I never wanted to catch them all and it’s all bullshit.

Despite the general terribleness of my GI tract, which is, as a general rule, quite terrible, things are improving. I’m not sleeping all day. I am getting back into a rhythm of sleeping at night. My cousin found me a protein shake mix that I can drink safely and which tastes good instead of the least bad. I’m not bruising everywhere and haven’t had blistering hives for a while. I have gained back a few pounds which is a good sign.

I also finally feel like I have my mind back. For me, it has never felt that my actions were what anchored me to my place in the world. It is my thoughts that ground me. We are never more wholly ourselves than when we are in the labyrinth of our own thoughts. We are what we think because what we think turns into what we believe.

Belief is a powerful thing. Maybe the most powerful. It is that ether that makes us more than our bodies and that holds us together when those bodies fail us. Believing strongly in a choice you make confers upon you the ability to make the most of that choice. The power of the words swirling around your mind cast a magic upon it that makes that path stronger and you stronger for being on it. It makes it easier to be grateful and to be happy.

I struggle a lot with my personal outlook and how I portray my life to others. Specifically, I struggle with being happy and what that means for me. I am happy, often. But there’s a guilt there, that I know my experience is sometimes dissected and applied to other rare disease patients for whom this may not be their reality. I don’t want people to think this life is easy just because I’m happy. And there’s an anger there too, that I shouldn’t be happy when I am frequently so sick and my friends are so sick or the existence of rare disease patients is so very precarious. There is a sharp side to this happiness.

What if I had chosen this life? What if I had somehow chosen to have these diseases and the broken elegance of this struggling body and everything else that came with it? Would believing in that choice have given me the strength to feel happy without this internal conflict?

I didn’t choose this life. But recognizing that it is still a good life is a choice, too. A powerful one. Maybe the most powerful.

Beta blockers and epinephrine

Beta blockers (often styled β-blockers) are medications used primarily for their impact on blood pressure and heart rhythm. Given their low cost and relative safety, beta blockers are very commonly prescribed for a number of other conditions as well, including anxiety. They work by blocking beta adrenergic receptors found throughout the body and specifically interfere with the action of norepinephrine and epinephrine.

The use of beta blockers in patients with risk of anaphylaxis requires some special consideration. This is because beta blockers directly block many of the places where epinephrine works to mitigate anaphylaxis. This means that using epinephrine to treat the anaphylaxis may be ineffective. This particular topic has been heavily researched and has not always yielded uniform findings.

The largest and most robust study included over 5000 patients with a history of systemic allergic reactions. This study found that patient use of beta blockers increased the risk of severe anaphylaxis. Use of ACE inhibitors, another drug class that impacts blood pressure, also increased the risk of severe anaphylaxis but to a smaller extent.

However, the risk of severe anaphylaxis was most increased in patients who took both beta blockers and ACE inhibitors together. Both beta blockers and ACE inhibitors were found to both decrease the threshold for mast cell activation and to prime mast cells (make them more easily activated).

Ongoing treatment with beta blockers has been found to be a risk factor for fatal anaphylaxis in some studies. It has also been found to be a risk factor for biphasic anaphylaxis, a type of anaphylaxis in which you have a second anaphylactic episode in the hours that follow successfully treated anaphylaxis.

Patients who must take beta blockers may be given a glucagon autoinjector for use prior to using injectable epinephrine. The reason for this is glucagon is the antidote to beta blocker overdose. When epinephrine binds to the beta receptor, it results in the cells making a molecule called cAMP. cAMP is a very important molecule for cells and it sends signals within the cell to regulate bodily processes. When a patient takes beta blockers, epinephrine can’t tell the cell to make cAMP. Glucagon is able to tell the cell to make cAMP even if the beta receptor is blocked. This action effectively counteracts the beta blocker.

Mast cell patients are usually recommended to use other medications to manage blood pressure and arrhythmias, including calcium channel blockers or renin inhibitors.

 

References:

Simons FER, et al. (2015) 2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines. World Allergy Organization Journal, 8(32).

Nassiri M, et al. (2015) Ramipril and metoprolol intake aggravate human and murine anaphylaxis: evidence for direct mast cell priming. J Allergy Clin Immunol, 135: 491-499.

Shephard G. (2006) Treatment of poisoning caused by β-adrenergic and calcium-channel blockers. American Journal of Health-System Pharmacy, 63(19): 1828-1835.

Tole J, Lieberman P. (2007) Biphasic anaphylaxis: review of incidence, clinical predictors, and observation recommendations. Immunol Allergy Clin N Am, 27(2): 309-326.

Kolch UW, et al. (2016) Cardiovascular symptoms in patients with systemic mast cell activation disease. Translation Research, x: 1-10.

Reitter M, et al. (2014) Fatal anaphylaxis with neuromuscular blocking agents: a risk factor and management analysis. Allergy, 69: 954-959.

More; or, Yzzy’s story

I can understand most things if you can drop it into a living system. If a body can do it, I can imagine it. But there is this thing about the inner dynamics of the human organism: that the more you study it, the less obvious causality is. There is no one way to arrive at an end point. There are dozens.

The body is clever. It is redundant. It learns. If it wants to, the body will find a way.

Mast cell disease is largely a consequence of this fact. Every patient has encountered this. If you treat a symptom with a med, it will crop back up a few months later. If you arrest mast cell production, your body finds a way to circumvent it. If you get stable at a certain dosage, you eventually need higher doses to achieve the same effect.

I think about the intricacies of my body and my diseases almost constantly. Every time my body does some new mysterious and irritating thing, I run through the various possible causes. I try to determine which pathways I have blocked and which can still be used to injure me. The body is cunning. It has many tools at its disposal that can be weaponized toward a singular goal.

But there is a flip side to this ingenuity: we are more than just our bodies.

I first met Yssabelle Eddlemon when she was airlifted to Boston from Oklahoma right before Christmas a few years ago. I had spoken with her mother both online and on the phone prior to meeting her. Yzzy and I had a lot in common. We both had major colon involvement, frequent anaphylaxis, persistent anemia, ports, an ever dwindling list of safe foods, and a short supply of treatment options not yet tried. But she also had mastocytosis in her skin, major liver involvement, and such severe airborne reactions that she mostly lived wearing a mask. And she was five years old.

I became friends with Yzzy’s mother in the way that you do when your lives are miserable in similar ways. I became more involved in Yzzy’s care in the way that you do when you don’t want a kid’s life to be miserable in the same way yours is. I spent a lot of time reviewing her labs and pathology reports and learning about her. She became one of my little people.

She was seen by a ton of doctors, all of whom agreed she was very sick but didn’t know what to do about it. Her implanted port remained used for months after it was placed because no one wanted to be responsible for it. She was in and out of the hospital with anaphylaxis that closed her throat in seconds on a weekly basis. It was a struggle to keep her alive.

Eventually, Yzzy was able to get into a pediatric mast cell specialist in California. Things changed a lot, in a good way. Her meds were revised significantly. IV meds were prescribed to help manage anaphylaxis. The difficult decision to completely remove oral nutrition paid off.

After a few months on TPN (nutrition given completely by IV), she stabilized a lot. A scope done before starting TPN showed that she had confluent sheeting of mast cells in her colon – literally wall to wall mast cells in her colon tissue, so many that they couldn’t be counted. After a year on TPN, her colon biopsy was normal. For the first time, Yzzy was stable enough to go to school for half days while her mom stayed close by. She made friends and loved school. Her quality of life improved dramatically.

Then something happened that I did not expect: she started having these bizarre episodes of crazy high fever and hemolysis. The first few times, we thought it might be her central line so it was treated as an infection. But it kept happening and it became pretty obvious that this was not an infection. There are so many ways for the body to arrive at a sudden fever. No one could figure out the cause, including me. There were too many possibilities and not enough evidence to justify any one of them.

Patients with central lines are advised to go to the emergency department if their fever is over 100.5F. Yzzy’s fevers were sometimes over 105F. She would be brought in only to be sent home in the morning with no treatment and no explanation. She was also deteriorating in other ways. She had to stop going to school. Bizarre symptoms and bloodwork abnormalities piled up.

All said, she was brought into the ED 22 times over the span of several months before anyone figured out what was going on. Last fall, Yzzy was diagnosed with another rare blood disorder: hemophagocytic lymphohistiocytosis. Her immune system was eating her blood cells.

Things happened fast after she was diagnosed. She had suffered significant damage because HLH had been untreated for so long. They initially tried biologics and high dose steroids but the episodes continued. Then they started chemo. It was around this time that we started to grasp the eventuality of the situation. HLH can be fatal. Treatment was slowing it down but it wasn’t stopping the attacks enough to protect her life. She was going to need a transplant.

The weeks after the decision to proceed with transplant were tense and grim. She was frail and the chemo was making it worse. She lost all her hair. She swelled badly from the chemo and steroids. She had a recurring upper GI bleed. She was admitted most of the time. Managing both her systemic mastocytosis and HLH was complicated. Coordinating care across specialities was difficult and frustrating.

Yzzy had a rare stroke of good luck then, one so good that I actually cried: the search for bone marrow donors turned up three possibilities, two of them a perfect match. The transplant was scheduled for just after Christmas. She was discharged so she could spend some time at home before being admitted for several weeks for the transplant.

In early January, Yzzy underwent a brutal course of induction chemo. She developed major clotting issues and severe anemia. A second central line had been placed and was constantly problematic. She was miserable. But she made it through. And on January 12, she had the transplant.

Bone marrow transplants are dicey for the simplest patients. Yzzy is not simple. The risk for serious complications and death were significant. But it was the only option to manage her aggressive HLH. There was also a silver lining, a big one. If the transplant worked, it could cure not just the HLH, but her mast cell disease.

It is impossible to overstate how much we expected a disaster. But there wasn’t one. The transplant went perfectly. In under a week, we started seeing signs that her the transplant was making blood cells for her. In under a month, the transplant had engrafted and replaced her old bone marrow. She stopped having mast cell reactions. She was weaned off her continuous benadryl drip. She started taking oral meds instead of IV. She started trialing things for oral feeds. Her TPN infusion time was decreased. For the first time in years, she was not attached to an IV line 24 hours a day. And her HLH was long gone.

Yzzy has never known a life when her body wasn’t trying to kill her. She’s not old enough. Her body has damaged her organs, caused seizures, and repeatedly sent her into shock. For seven years, Yzzy’s body found ways to work around every treatment, every medication, every change that was made to keep her safe.

But we are more than our bodies. When her team discusses her care plan with her parents outside the door to her hospital room, she plays video games. When she isn’t strong enough to walk around, her parents drive her around to catch pokemon. When she is puking constantly, she plans the menu for a day when she can eat. This is her life and she just lives around it.

Yesterday, fifty days after her transplant, Yzzy went home. She joined a Girl Scout troop and is aggressively selling cookies online. She is making plans for her birthday party in May. She is happy to be home and reunited with her little brother. She is having Nerf gun fights. She is strong enough to run around and can laugh without risking anaphylaxis. This is the dream.

Yzzy is more than her body. And her body was no match for her.

The Unholiday; or, Rare Disease Day

I have multiple rare diseases. I have been living as a rare patient since January 2012 when I was initially diagnosed with mast cell disease. I have collected some other rare diseases for my menagerie in the years since: adrenal insufficiency; Ehlers Danlos Syndrome, hypermobility type; Postural Orthostatic Tachycardia Syndrome; and mixed connective tissue disease with features of lupus and rheumatoid arthritis.

February is Rare Disease Month and the last day of February is Rare Disease Day. MastAttack originated as a exercise in educating people about mast cell disease with daily facts for Rare Disease Month. Over time, I moved those facts from my Facebook page to a blog. That blog evolved into the MastAttack you are currently experiencing.

I have planned for the last few years to do a daily posts in February with each post discussing a different rare disease that affects some mast cell patients. The fact that I was only able to get up two posts (and not even on consecutive days) is a pretty good symbol for what it is like to be a rare disease patient.

Despite recognizing its importance, I feel conflicted about Rare Disease Month. It’s not the visibility that bothers me because I committed to living my life very loudly years ago to empower myself and others in the mast cell community. It’s the transience of the focus. In February, people are inundated with stories about living and dying with rare disease. But on March 1, I’m still going to be here, with these diseases, and friends with these diseases, and the fear and uncertainty that goes with them.

This is not a celebration. We are not celebrating rare disease or even rare disease patients. This is a protest. A march. An event to record that we were here. A memorial, to remember those rare disease patients we lost this past year and all the years before. And a prayer, a deep and primal hope given to the universe that there will someday be a world in which there is no need for a Rare Disease Day.

Thank you for reading our stories this month. Thank you for learning about our diseases and our lives.

Remember us after today. Remember us every day.

The silence and the void

I am struggling a lot with grief lately. As it has become increasingly apparent that my life and my body will never be the way they were before, I have thought a lot about what that means. How they are different. If I can live with it. I think few things cause as much personal revelation as grief. Every fear is amplified. Every dream is farther away.

I had such a firm idea of who I wanted to be. I knew exactly. I wanted to be a doctor and travel around the world. I wanted to get married and have kids. I wanted to treat infectious diseases. I wanted to live in twelve countries for a month each to live abroad for a year. I wanted to buy a little house and paint it purple. I wanted to have a home where every shelf was low enough that I could reach it without standing on something. I wanted to be happy. I wanted a quiet little life with a rewarding career and children. I knew the life I wanted. I loved that little life.

You do not naturally love the things that populate the set of your life. You do not love sitting on the couch. You do not love drinking water. You do not love walking your dog. You do not like to breathe. You do not love every moment when your throat isn’t swelling. The moment you begin to love these things marks a fundamental change. It happens when you glimpse a life beyond the veil, a life where you can’t take out your own trash or drive or clean your apartment. Everything you do is imbued with a frantic appreciation. You come to love these things but you wish you didn’t have to.

I really loved my life. It was beautiful. It was warm and full of possibility. I wasn’t grateful for breathing or waking up to an alarm clock because I didn’t have to be. I could never have imagined how bad things would get and how hard it would be to become a different person with different goals and different dreams.

It has taken me years to build a new life. Nothing beautiful is easily repaired. There is beauty still but it is deeper and less obvious. It is not the excitement for the future. It is not the having of things and opportunities. It is the rare moments when you aren’t struggling. When things are wrong but not more than usual. When the pain is managed. It is the kind of beauty you can only find when everything around you is burning. Beauty is nothing. It is a feeling. It is silence and a heartbreaking void where you can rest for a little while.

I am trialing a new biologic tomorrow in the hope that it will help me to eat again. I am scared that it won’t work. I am scared because I don’t think I can live like this. I am tired.

There is still beauty in my life. It is just harder to find it when every minute is a struggle.

Choosing the sun

I don’t handle change well. I have never liked it. A few years ago, I bought a little piece of wall décor that says “Embrace change.” It hangs next to my bathroom sink. Whenever I stand in front of the sink, I catch myself shaking my head as I read it. I keep it up mostly for irony.

My body doesn’t handle change well either. Lately, it is doing things that it has never done for reasons I can’t determine. Last night, my face swelled as I was reading on my couch. I didn’t have any other symptoms and still don’t know why it happened. I sat up for hours, compulsively poking my face and trying to determine if other parts of my body were swelling, while trying not to panic and induce symptoms that could be confused for anaphylaxis.

I’m starting to realize that I’m not having a bad episode that will resolve and return me to my previous baseline. This is different. I am different. My body and my disease are evolving. Whatever baseline I arrive at will be different from before. I can’t wait this out because it’s not going to end. I will stabilize but I will not be the same. My body will not be the same and my life will not be the same.

So it’s time to stop waiting for this to end. I have to learn how to live my life like this. I have to learn how to fit all the things I love and that bring me joy into this smaller space. I have to find a way to get light in here again because this darkness is suffocating. It has swallowed so many things.

I have spent a lot of time staring into this darkness in the last few months. Some of it with an audience, rehashing it for paramedics and ER doctors, mulling it over with my care team. Most of it alone, in moments when I can’t breathe, suddenly struck by the fact that this disease will almost certainly kill me.

But there are bright spots, even if they seem farther away as the arc of my life grows longer. Good days and moments of joy and traveling. Touching the Great Wall of China. Eating Reuben sandwiches. Walking 60 miles in three days. Encouraging words. Hugs. Seattle. Roller coasters. Kindness. Alone these moments are just tiny flecks of light, but you can gather them. If you string them all together, you can make a tiny sun.

It was really warm in Boston this week, almost 70 degrees Thursday and Friday. I packed up my infusion pump and meds and supplies and walked to the beach with Astoria as I infused IV fluids. I sat in the shade at the beach wall as she ran around, flailing around in the sand and playing with her ball. We walked slowly. We didn’t stay very long. But we got there.

The sun only grows if you feed it. Otherwise, those moments are just holes in the dark.

This is my life now. I am learning how to enjoy it. I am choosing the sun.

Wellness

I do yoga everyday. It is the form of exercise most suited to both my limitations and my needs. I suppose also well suited to my personality. On days when I feel strong, it lets me balance on my hands and fly through the air. It lets me draw my legs up from my core and see the world upside down. On days when I don’t feel strong, I lay my weight into various muscles, stretching them back to their right shape. It lets me think it’s exercise even when all I can do is sit on the mat and breathe. An achievement instead of survival.

On Thursday afternoon, while waiting to check in for my appointment with my mast cell GI specialist, I had anaphylaxis. I was standing and wasn’t immediately sure if it was anaphylaxis or POTS because they both start with a fuzzy lightheadedness. I sat down on the floor and within a few minutes, it became obvious that this was definitely anaphylaxis.

I told one of the admins that I was having anaphylaxis, took a few steps into the bathroom, lay down on the floor and used an epipen. They called a code team and very quickly there were a lot of people. I drew up and pushed some IV meds. I was already infusing IV fluids. They took me to the ER where I stayed for several hours to be sure I wouldn’t rebound or have a biphasic reaction.

The resident asked if I knew what the trigger was for the anaphylaxis. “I think standing up,” I said. It was funny in the way that terrifying things are sometimes funny.

My body is so different now. In every way, it seems. I buy new clothes online because everything I own is too loose or ill fitting. As I put them on, I find all these sharp places beneath my skin, angles where there used to be a softness. The layer of fat over my muscles has thinned considerably. It has the strange effect of making me look stronger and more toned when really I am just unhealthy.

I write constantly and so I always have a journal in reach. I was recently looking through previous entries for something. I was struck by how often I speak of my past self in the third person. I talk about myself like a character. Like I’m the narrator in a story that doesn’t involve me.

I say that I am a different person now because it’s easier to believe that the person I was then could never become the one I am now. It is easier to think that this person is entirely separate for a lot of reasons but mostly so that she could never decay like this. It is much harder to accept that I was that person that did all those things and that I am still that person and never will again.

The days are getting longer and warmer. My mind is working better. My body is well enough to be out of the hospital. I can’t keep down much elemental formula but can get down some nutritional drinks and plain potato chips. I am starting to make plans for later this year that I believe could be realistic.

Every day, I roll out my purple mat. Today I can only do a little and tomorrow I will only do a little but one day, I will be strong enough again to fly.

 

Wellness

 

(PS: Hypermobility much?)

Reintroduction of food to a child with SM

I recently put together some recommendations on reintroducing foods to a child with SM who has been exclusively on IV nutrition (TPN) for an extended period of time. I thought you might find some use in it so I have posted it here.

Before people ask, there are no significant publications on children with MCAS because there are not currently unifying diagnostic criteria.

****

Author’s note: I am not a medical doctor. Protocols for reintroducing foods must be developed by the managing care team and tailored to each patient.

There are no large population studies for pediatric systemic mastocytosis. True systemic mastocytosis (in which WHO diagnostic criteria are satisfied) is rare in children. Accordingly, SM in children is generally reported as case reports rather than studies given the population size[i].

Given the lack of in depth literature specifically regarding food challenge in children with SM, I would draw from data in similar situations to identify a safe and appropriate protocol for reintroducing for [name redacted].

There are five scenarios that may contribute insight for food reintroduction in this patient: oral food challenges for FPIES patients; desensitization procedures for delayed hypersensitivity reactions; reintroduction of food after long term parenteral therapy; premedication of patients with mast cell activation disease, including systemic mastocytosis; and mast cell involvement in gastroparesis, ileus and GI dysmotility.

Based upon these scenarios, we can infer the following:

  • Reintroduction of food to this patient should follow a long, repetitive schedule with gradually increasing quantities.
  • Premedication with antihistamines and glucocorticoids to avoid mast cell reaction should be considered.
  • Mast cell activation can directly induce GI dysmotility. Drug management of mast cell activation can suppress impact upon function.
  • Enteral feeds should be gradually increased while parenteral feeds are gradually decreased.
Scenario Application to food reintroduction in a mast cell patient
1 Oral food challenge in setting of FPIES FPIES and food reactions secondary to mast cell disease are both non-IgE mediated and can culminate in shock requiring emergency intervention.
2 Desensitization for delayed drug hypersensitivity reactions Mast cell degranulation and anaphylactic reactions are not type I hypersensitivity reactions. They may also present on a delayed schedule.
3 Reintroduction of food after long term parenteral nutrition Reintroducing food to patients after long term parenteral nutrition may impact GI function. Gradual reintroduction is recommended.
4 Premedication of patients with mast cell activation disease Patients with mast cell activation disease, including systemic mastocytosis, are advised to premedicate prior to all procedures to decrease risk of reaction and anaphylaxis.
5 Mast cell involvement in gastroparesis, ileus, and GI dysmotility Mast cells contribute significantly to GI motility disorders including gastroparesis and ileus.

 

  1. Oral food challenge in patients with food protein induced enterocolitis syndrome (Caubet 2014[ii], Leonard 2011[iii])
  • Food protein induced enterocolitis syndrome (FPIES) is a severe non –IgE mediated GI food hypersensitivity syndrome.  Patients with FPIES are children. The condition is managed by removing the offending food from the diet for extended periods, usually years.
  • Food challenge in FPIES can result in severe, repetitive vomiting; diarrhea; lethargy; pallor; hypothermia; abdominal distension; and low blood pressure. Not all of these features are universally present for all patients.
  • The following procedure is recommended for oral food challenge in FPIES children:
  • All FPIES oral food challenges must be physician supervised with appropriate supportive care available.
  • Over the first hour, 0.06-0.6 g/kg body weight of food protein should be administered in three equal doses. It should not exceed 3g of total protein or 10g of total food or 100ml of liquid for initial feeding.
  • If patient has no reaction, give a full serving of food as determined by their age.
  • Observe patient for several hours afterward.
  • In the event of severe reaction, administer 1mg/kg methylprednisolone intravenously, up to 60-80 mg total; 20 ml/kg boluses of NS; and epinephrine.
  • Food challenge is considered positive for reaction if patient experiences typical symptoms as a direct result of the challenge.

 

  1. Desensitization for delayed hypersensitivity medication reactions (Scherer 2014[iv], Leoung 2001[v])
  • There are no controlled studies available on desensitization for delayed reactions to drugs.
  • Described procedures have timespans ranging from hours to weeks.
  • Patients who initially failed rapid protocols have succeeded using slower procedures.
  • It may take 2-3 days before hypersensitivity symptoms develop in a delayed reaction.
  • Long protocols with repetitive, gradually escalating dosing are recommended.
  • Antihistamine prophylaxis is often recommended. Drug and dosing vary.
  • The following procedure describes an example of a gradually escalating dosing:

Dose escalation for desensitization, adapted from antibiotic desensitization procedure

(Leoung 2001)[v]

Dosing level Drug portion Frequency of daily dosing
1 12.5% QD
2 25% BID
3 37.5% TID
4 50% BID
5 75% TID
6 100% QD

 

  1. Reintroduction of food after long term parenteral nutrition (Hartl 2009[vi], Oley Foundation)
  • Long term TPN may increase intestinal permeability.
  • Long term TPN may result in diminished enzymatic activity in GI mucosa.
  • The Oley Foundation suggests decreasing parenteral nutrition by 25% while increasing enteral feeds by 25% as the patient tolerates.

 

  1. Premedication of patients with mast cell activation disease (Castells 2016[vii])
  • Mast cell patients are recommended to premedicate for all procedures using H1 and H2 antihistamines, glucocorticoids, and leukotriene receptor antagonists.

 

  1. Mast cell involvement in gastroparesis, ileus, and GI dysmotility (Nguyen 2015[viii], de Winter 2012[ix])
  • Mast cells can be activated by a number of pathways which do not involve IgE, including neuropeptides, complement factors, cytokines and hormones.
  • Mast cells in the GI tract are closely associated with afferent nerve endings.
  • Mast cell behavior in the GI tract is largely controlled by the central nervous system.
  • Mast cells are directly involved in GI dysmotility disorders including gastroparesis and ileus.
  • Mast cell activation and population may be upregulated in the setting of GI inflammation.

[i] Lange M, et al. (2012) Mastocytosis in children and adults: clinical disease heterogeneity. Arch med Sci, 8(3): 533-541.

[ii] Caubet JC, et al. (2014) Clinical features and resolution of food protein induced enterocolitis syndrome: 10-year experience. J Allergy Clin Immunol, 134(2): 382-389.

[iii] Leonard S, et al. (2011) Food protein induced enterocolitis syndrome: an update on natural history and review of management. Ann Allergy Asthma Immunol, 107:95-101.

[iv] Scherer K, et al. (2013) Desensitization in delayed drug hypersensitivity reactions – an EAACI position paper of the Drug Allergy Interest Group. European Journal of Allergy and Clinical Immunology, 68(7): 844-852.

[v] Leoung GS, et al. (2011) Trimethoprim-sulfamethoxazole (TMP-SMZ) Dose Escalation versus direct rechallenge for Pneumocystis carinii pneumonia prophylaxis in human immunodeficiency virus-infected patients with previous adverse reaction to TMP-SMZ. Journal of Infectious Diseases, 184:992-997.

[vi] Hartl WH, et al. (2009) Complications and monitoring – Guidelines on Parenteral Nutrition, Chapter 11. Gen Med Sci, 7:Doc17.

[vii] http://www.tmsforacure.org/documents/ER_Protocol.pdf

[viii] Nguyen LA, et al. (2015) Clinical presentation and pathophysiology of gastroparesis. Gastroenterol Clin N Am, 44: 21-30.

[ix] de Winter BY, et al. (2012) Intestinal mast cells in gut inflammation and motility disturbances. Biochimica et Biophysica Act, 1822: 66-73.

An update on my friend, Kristina Brightbill

In early October 2015, I was sending most of my time trying to figure out how to feed some mast cell kids who couldn’t eat anything but breast milk produced on a very, very restricted diet. There were two kids struggling with this seemingly impossible problem. One of those kids was a little boy named Lucas. His mother, Kristina, is my friend. She had been on a single food diet in order to produce breast milk he could safely eat. She herself was a mast cell patient and the combined effects of mast cell disease, malnutrition, and fear for her child ravaged her body.

Lucas had been admitted to a California hospital for months, thousands of miles from home in Florida. After a long series of setbacks, Lucas’ doctors were okay with letting him go home so that their family could rest to try to introduce foods or IV nutrition again at a later time. On the day he was being discharged, a friend called to tell me that Kristina was in the emergency room.

Over the next few hours, our friends and I called each other, talked to Kristina, and later to her mother and husband. Things progressed very quickly and soon Kristina was unresponsive and intubated. It would be days before we knew what had actually happened – Kristina had suffered a catastrophic pontine stroke in her brainstem. The pons is the place where your body integrates sensory and motor information to allow movement. Despite being completely aware and as intelligent as before the stroke, Kristina was unable to move or communicate.

I have written about Kristina and visiting her before: here, here, here, and here. Both she and her son Lucas require ongoing care for mast cell disease. She is home now and requires 24-hour care every day for the rest of her life. Her care is phenomenally expensive. When I visited Kristina in Florida last year, I was immediately struck by how much pressure her family was under to care for her and Lucas.

After several months of managing care for Lucas and Kristina, the Brightbills and Dalys have decided that the best path forward is to live under one roof. This will allow a better, safer environment with a built in support system. As you can imagine, on top of all of their other expenses (to the tune of $8000/month), this construction will be expensive, but necessary.

I have never accepted money for writing this blog or answering questions. I do not believe that people should have to pay for access to information that could affect their health.

But if you have ever wanted to compensate me, or to repay me in some way, please feel free to make a donation to Kristina and her family.

I care for Kristina, Jed, Lucas, Linda, Katie, and the rest of the Brightbill/Daly family deeply. Please help them if you can. Helping them is helping me.

Chromogranin A

Chromogranin A is a protein secreted in several environments. While it is primarily released in the adrenal medulla with catecholamines (norepinephrine, epinephrine, dopamine, and others), CgA is often found stored in the granules of endocrine cells in the GI tract. CgA is the precursor molecule for several active molecules. Vasostatin-1 and -2 are involved in regulation of various effects of the cardiovascular system, including blood pressure and stroke volume, by opposing the action of catecholamines. Catestatin decreases release of catecholamines. Pancreastatin decreases insulin secretion. A number of other molecules are also derived from CgA.

Chromogranin A and its derivatives are biomarkers for several conditions. 60-80% of neuroendocrine tumor patients demonstrated elevated chromogranin A. A connection with Alzheimer’s disease has recently been reported. Rheumatoid arthritis and lupus patients may have elevated CgA as a result of increased tumor necrosis factor. Various forms of cancer, kidney disease, and elevated cortisol can also impact chromogranin A level.

Elevated CgA has also been linked to a number of inflammatory GI conditions. 30-50% of IBD patients with active disease have elevated serum CgA. In ulcerative colitis, fecal chromogranins were elevated but not correlated with disease activity. Conflicting results have been seen in patients with Crohn’s disease. Some studies have reported an increased amount of CgA containing cells in patients with IBS.

There are a number of methods for quantifying chromogranin A. Proton pump inhibitors and H2 antihistamines can yield false positive results. A study compared several commercial kits for measuring chromogranin A and found that the radioimmunoassay (RIA) kit was most likely to be accurate with a sensitivity of 93% and specificity of 85%. This means that 93% of the time, this kit properly identified patients with high CgA as having high CgA, while 85% of the time, it properly identified patients with normal CgA as having normal CgA. Currently, there are multiple test methods for quantifying serum and plasma CgA with no central standardization.

Chromogranin A is a constituent of granules in rat mast cells. Tumor necrosis factor is a mediator released by mast cells and may also influence the levels of chromogranin A in mast cell patients. One study found that 31.5% of patients with mast cell activation disease (in a cohort mostly composed of MCAS patients) demonstrated elevation of serum CgA. This same study concluded that plasma heparin and 24 urine testing for prostaglandin D2 and 9a,11b-prostaglandin F2 were the most sensitive markers for mast cell activation with other mediators being less effective.

References:

Gut P, et al. (2016) Chromogranin A – unspecific neuroendocrine marker. Clinical utility and potential diagnostic pitfalls. Arch Med Sci, 12(1): 1-9.

Wernersson S, Pejler G. (2014). Mast cell secretory granules: armed for battle. Nature Reviews Immunology, 14: 478-494.

D’Amico MA, et al. (2014) Biological function and clinical relevance of chromogranin A and derived peptides. Endocrin Connect, 3(2):R45-54.

Mazzawi T, et al. (2015) Increased chromogranin A cell density in large intestine of patients with irritable bowel syndrome after receiving dietary guidance. Gastroenterology Research and Practice, Article ID 823897.

Zenker N, Afrin LB. (2015) Utilities of various mast cell mediators in diagnosis mast cell activation syndrome. Blood, 126:5174.

Massironi S, et al. (2016). Chromogranin A and other enteroendocrine markers in inflammatory bowel disease. Neuropeptides, xxx, xxx-xxx.