Cataclysm

I have had a central line for four and a half years.  We placed a PICC line in early 2014 to facilitate vascular access in an emergency, to administer rescue meds at home during an anaphylactic event, and to allow me to use IV fluids at home to stabilize my blood pressure.

Shortly after I had my line placed, I was hospitalized for a five day long episode of protracted anaphylaxis. Because I had pretty much already tried every oral medication that could help manage my symptoms, trying IV medications was the obvious next step. I went home from the hospital with a prescription for IV Benadryl.

Speed matters a lot in management of mast cell disease. There is a tiny window of time during which immediate medication can stave off continued reaction or anaphylaxis. I learned how to dilute and push IV Benadryl during mast cell crisis.

Using IV meds was really nerve wracking at first, much more than I expected it to be. I’m an infectious diseases microbiologist by training and used to develop diagnostics for blood stream infections. I don’t think I can overstate how scared I was of getting sepsis. Every time I touched my line to flush or give meds, my hands shook and my heart pounded. But this was tempered by an obvious benefit: use of IV Benadryl as soon as a reaction started often prevented the need for epinephrine.

My health fluctuated over time. Eventually, I started using IV Benadryl as a baseline medication to manage daily reactions. It allowed me to exercise. It allowed me to eat. It allowed me to travel. It allowed me to work. IV Benadryl restored a much improved quality of life. I have used it ever since.

IV Benadryl is an old medication. It is off patent, cheap to produce, and made by multiple manufacturers licensed in the US. Overwhelmingly, it is used to manage anaphylaxis. Regular use as maintenance for patients was unheard of before the mast cell community began using it to manage reactions. Home use of IV Benadryl both for maintenance and for rescue – that is, to manage regular daily symptoms as well as to be lifesaving in the event of anaphylaxis – has become more popular in the mast cell community in recent years. I think I’m probably partly to blame for this – I have openly talked about how much it has helped me. I probably know a hundred mast cell patients who use it regularly.

In mid September, I got a call from my IV pharmacy. They were calling to tell me that vials of IV Benadryl were unable and they were going to dispense IV Benadryl in prefilled syringes. Fine. I didn’t care what package it was in. But I knew multiple organizations made this medication and I found it strange that vials from all of them would be unavailable at the same time. It was odd. But it was also true. Every manufacturer was reporting that it would be several weeks to months before the vials would be again be available.

A week later, my IV pharmacy called to let me know that the prefilled syringes were no longer available either. I found out on a Friday afternoon that come Tuesday, I would be out of medication. No one could get it. All distributors were out. I called over fifty pharmacies in Massachusetts trying to find some. I talked to the FDA. I talked to the manufacturers. I talked to hospitals nearby.

Despite being labeled a “critical backorder”, this phenomenon was something else entirely. It wasn’t “I can’t get enough of it.” It was “There is no IV Benadryl available anywhere in the US.” EMS is out. Hospitals are out. And every pharmacy everywhere is out or dangerously close. With only a few days warning, mast cell patients found themselves unable to get medication that literally kept them alive.

It is not overstating things to say that IV Benadryl is necessary to sustain life in a number of mast cell patients. I am one of them. Many people need it to maintain an airway. Others, like me, need it to recover blood pressure during anaphylactic shock. A lot of patients were only able to live outside of a hospital safely because they had access to this medication. The danger posed to these people is enormous. This is especially true because in an emergency, you can call 911 and have them take you to the hospital but they don’t even have the medication to treat you. This means that unless patients already have some, in a crisis, it is impossible to get more from literally anywhere. If you need this medication to survive, you are in real peril.

Compounding the issue is that IV Benadryl is the only potent H1 antihistamine available in IV form in the US. There are no alternatives for IV H1 antihistamines. It is IV Benadryl or IV nothing. It is also not used much outside of the US so getting it from abroad isn’t really an option.

Mast cell patients have been encouraged to use epinephrine as early as possible without IV Benadryl to potentially stave off a reaction. So we can all just use epipens anytime we react badly, right? Just kidding. Epipens are also on critical backorder. Okay, let’s use IV fluids to recover blood pressure during anaphylaxis and severe allergic symptoms. Haha, no. IV fluids are also on backorder. One of the safe narcotics for mast cell disease is no longer available. Certain benzodiazepines are no longer available. And we have no idea whether or not these medications will be available in the future.

The stress of this situation is paramount. I have patients getting trached to allow them to be hooked up to a ventilator. I have patients who can’t stand up without reacting or passing out. I have patients who are using epi multiple times a week. And I have patients who are scared to use their epipens so they gamble that they can control their reactions with something else. The single greatest risk factor for fatal anaphylaxis is delay in the administration of epinephrine. “Saving” epipens is dangerous.

Those of us who have won some stability through this medication are terrified of going back. I am terrified of going back. It’s already starting. After several months of debilitating symptoms and repeat anaphylaxis, I have been preparing to return to work in November. I love my job. I love my coworkers. I love my company. I can’t safely return to work until I have a guaranteed supply of IV Benadryl. And as of now, that could take months.

I am angry over this situation in a way that borders on holy fury. Mast cell disease is hard on its best day. It doesn’t need to be made even harder. Total loss of access to rescue meds is life threatening for many of us. In a country known for its premier healthcare, essential medications are completely unavailable. Mast cell patients were not even notified of an impending backorder to allow us to identify a source and stockpile. We were ignored entirely. This is the end result.

This is a dark time for our community. It is a time for fear and anxiety. It is a time of uncertainty. It won’t last forever. But that is cold comfort when you are terrified.

It is also a time to stand up and fight. It is a time to be visible. It is a time to be loud. It is a time to shame these organizations for letting this happen to us. Because if I have to suffer, I will damn well make them watch.

I know a lot of us are struggling. Be careful with yourself. Don’t take risks. Wait it out.

Take care of yourselves. Remember: it won’t always be like this. You don’t have to beat it. You just have to outlast it.

MastAttack response to the recent letter from the National Peanut Board

This post was written to directly stand against a letter recently published by the National Peanut Board (a real name that I did not make up). That letter can be viewed below and insists peanuts do not pose the risk many believe they do to allergic persons. I go through it line by line with the text from National Peanut Board prefaced with “Letter” and my thoughts prefaced with “My response.” As usual, sources are always cited.

****

Letter: It’s time to say goodbye to peanut allergies –

My response: Completely agree. Hooray! This guy for everything!

Letter: -not peanuts.

My response: Hmmm. Well, that took a jarring turn pretty quickly. That’s like saying it’s time to say goodbye to lung cancer, not cigarettes.

Letter: Breaking up is never easy. Today, a 50-year relationship comes to an end as Southwest Airlines stops serving complimentary peanuts on its flights. We’ve enjoyed our time together, but we have to tell our friends…it’s not us.

My response: Relationship drama does not belong on social media. Ten points from Slytherin.

Letter: You see, removing or banning peanuts from airplanes – or classrooms, or theaters or any public space – is a solution that is outdated and not rooted in today’s science.

My response: As a scientist, speaking on behalf of science everywhere, this is the stupidest thing I’ve ever heard. As if avoiding a potent allergen will ever be outdated. Give me a break. *rolls eyes*

Letter: Only somebody who unplugs their Walkman to check their beeper still thinks that location bans are the best way to prevent allergic reactions to peanut exposure.

My response: First of all, don’t hate. The 90’s weren’t that bad.

My response: Secondly, location bans are one piece of a complicated system that peanut allergic people utilize to find safe spaces and keep themselves out of danger. Location bans especially make sense in venues where a person can’t just leave if they find themselves confronted by a dangerous allergen. Like, I don’t know, a metal tube hurtling through the sky at warp speed?

Letter: While Southwest can do what they want to do – and we trust they’re doing it with good intentions – our job is to make sure the decision doesn’t cloud the extraordinary work being done by researchers, health professionals and allergy advocates.

My response: The extraordinary work being done is not in any way clouded by the fact that location bans are absolutely necessary in some situations. Although given the doozy that is the next paragraph, I would venture that the “problem” is that the author of this press release fundamentally misunderstands the current research findings. Hold onto your hats! This next paragraph of this press release is going to. Blow. Your. Mind. (And not in a good way)

Letter: Today, we know that peanut bans, while intended to protect those living with peanut allergies, don’t always work and create a false sense of protection.

My response: So because they don’t prevent every instance of peanut triggered anaphylaxis, we should just not have peanut bans anymore? Come on. Even the National Peanut Board has to realize how phenomenally asinine this statement is.

My response: Let’s say you are driving in a car that has four windows. Suddenly, it begins to pour. The rear passenger side window isn’t going up for some reason. Are you not going to close the other three windows to afford yourself some protection from the rain? Because this press release says they would just never even touch a window button again because when three of the windows roll up, the driver feels a false sense of security from the rain. That is how stupid this is.

My response: Anaphylaxis at school has become increasingly common.

  • “Most significant reactions in children are attributable to peanuts, fish, shellfish, egg, soy, wheat, tree nuts [and] milk.” (Sicherer 2010)
  • “Fatalities in school aged children in the United States have primarily been attributed to peanuts, tree nuts, milk, and seafood.” (Sicherer 2010)
  • “The Centers for Disease Control and Prevention recently reported an 18% increase in food allergy among school-aged children from 1997 to 2007; 1 in 25 children are now affected. Results of studies of children with food allergy indicate that 16% to 18% have experienced a reaction in school. Allergic reactions or treatment for anaphylaxis also occur in children whose allergy was previously undiagnosed (25% of cases of anaphylaxis). Fatalities were noted to be overrepresented by children with peanut, tree nut, or milk allergy.” (Sicherer 2010)
  • “In case series of fatalities from food allergy among preschool – and school-aged children in the United States., 9 of 32 fatalities occurred in school and were associated primarily with significant delays in administering epinephrine.” (Sicherer 2010)

Letter: A person will not have a life-threatening reaction by simply being in the same room as peanuts or peanut butter. You have to ingest the allergen.

My response: This is patently, verifiably false, and you should be ashamed of yourselves for saying it. You should be ashamed of OPENLY LYING about whether or not having peanuts nearby can kill someone. You should be ashamed that misinformation like this further endangers the lives of allergy patients around the world. You should be ashamed that an allergy patient might believe the words in this press release and injure themselves or worse. Where’s your false sense of security now?

My response: The American Academy of Asthma, Allergy, and Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) sit on a joint task force together for the purpose of developing a robust set of medical guidelines to protect patients with allergies. AAAAI and ACAAI both acknowledge that anaphylaxis can occur without ingestion of the trigger.

  • “Severe allergic reactions may be seen in some patients who only inhale or come in contact with food allergens.” (Sampson 2014)
  • “Some patients may experience symptoms on inhalation of a food allergen but not experience symptoms after ingestion of the same food allergen (eg, baker’s asthma).” (Sampson 2014)
  • “Therefore, it may be necessary to avoid food exposure by routes other than ingestion.” (Sampson 2014)
  • “In some cases, severe allergic reactions may be seen in patients who only inhale or come in contact with food allergens, thereby making avoidance even more difficult.” (Sampson 2014)
  • “Patients who are extremely allergic to peanuts might have a reaction at a ball game when peanut particles from husking are blown in the wind and inhaled by that individual and in airplanes when another passenger is eating peanuts.” (Sampson 2014)
  • “Transportation by various means also presents a risk of accidental exposure. Air travel has received the most attention, but long rail trips (especially in foreign countries) and cruise ships present their own set of risks that must be anticipated.” (Sampson 2014)

My response: Other groups also reported that anaphylaxis can occur without ingestion of the trigger.

  • “In some cases, severe allergic reactions may be seen in patients who only inhale or come in contact with food allergens, thereby making avoidance even more difficult.” (Chapman 2006)
  • “Allergic reactions that result from direct skin contact with food allergens are generally less severe than reactions due to allergen ingestion. Reactions that result from inhalation of food allergens are generally less frequent and less severe than reactions caused by either direct skin contact or ingestion. Exceptions to these generalizations are more likely in occupational environments and other settings in which food allergen sensitization occurred via either inhalation or skin contact.” (Chapman 2006) Author’s note: Please note that this was not tested on mast cell patients so reaction severity may vary.
  • “Anaphylaxis from non-ingestion exposure, such as contact with intact skin or being close to an allergen, is uncommon [but does sometimes occur].” (Lieberman 2015)
  • “Case reports and controlled studies in which foods are vaporized through heating have shown that reactions, primarily respiratory, can be elicited. These observations support limiting exposure to allergens being cooked.” (Sicherer 2010)

My response: Anaphylaxis to peanut can be life threatening.

  • “Peanut and tree nuts account for most fatal and near-fatal food allergic reactions in the United States.” (Chapman 2006)
  • “Peanut allergy affects approximately 0.6% of the general population and is the most common cause of fatal food induced anaphylaxis.” (Chapman 2006)
  • “In case series of fatalities from food allergy among preschool – and school-aged children in the United States, 9 of 32 fatalities occurred in school and were associated primarily with significant delays in administering epinephrine.” (Sicherer 2010)
  • “IgE-mediated food allergy is associated with an increased risk of death after accidental ingestion.” (Sicherer 2010)
  • “Although subsequent reactions are not necessarily more severe than initial reactions, they may be. For example, initial mild reactions to peanut may be followed by more severe reactions on subsequent exposures.” (Sicherer 2010)
  • “Clinical factors such as a history of asthma, previous reactions to trace exposures, and allergies to foods mentioned previously are potential risk factors for fatal anaphylaxis.” (Sicherer 2010)
  • “Food allergens are a frequent cause of severe anaphylaxis, particularly in patients with concomitant asthma and allergy to peanut, tree nut, or seafood. Such reactions may be biphasic or protracted. Food allergy should be considered in the differential diagnosis of patients who have idiopathic anaphylaxis.” (Sampson 2014)
  • “A study showed that peanut can be cleaned from the hands of adults by using running water and soap or commercial wipes but not antibacterial gels alone.” (Sicherer 2010)

Letter: We also know that introducing peanut foods to an infant as early as 4-6 months can reduce peanut allergy development by up to 86 percent.

My response: YOU GUYS, I FOUND THE ONLY TRUE STATEMENT ABOUT PEANUT ALLERGIES IN THIS ENTIRE PRESS RELEASE. But don’t get too excited because this only pertains to IgE mediated allergies, traditional allergies. There are a number of food allergies that are not mediated by IgE. If you have mast cell disease or eosinophilic GI disease or FPIES, the age when you introduce a food isn’t the driving issue in whether or not you tolerate it.

 

Sources cited

Chapman JA, et al. Food allergy: a practice parameter. Annals of Asthma, Allergy, and Immunology 2006;96:S1-S68.

Lieberman P, et al. Anaphylaxis – a practice parameter update 2015. Ann Allergy Asthma Immunol 2015;115:341-384.

Sampson HA, et al. Food allergy: A practice parameter.  J Allergy Clin Immunol  2014;134:1016-1025.

Sicherer SH, et al. Clinical Report Management of Food Allergy in the School Setting. Pediatrics 2010;126:1232-1239.

 

 

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 84

97. What is the progression of therapies to treat mast cell disease? What are the next steps if I’m not improving?

There are some general rules of thumb when adding new medications to a regimen in a mast cell patient.
Medication changes should be done one at a time. The reason for this is simple: if you get better, or worse, it will be harder to figure out which medication is the cause. Recommendations on how far apart to space changes vary, but most recommend 3-7 days.
Medications often contain dyes and inactive ingredients like lactose and alcohol that can cause reactions. Many patients take compounded medications to avoid these triggers. Bear in mind that compounding medications can be very expensive and many insurances will not cover it. You should also know that not all medications are able to be compounded.
In some instances, the likely benefit of a problem medication is enough that it is worth it to try and force tolerance. This should never be done without the supervision of a provider. Premedicating before taking a dose of the medication can help curb mast cell symptoms. Personally, I will premedicate before taking a new medication for three days. If I take it on the fourth day, when I’m not premedicated, and I react, I know that I’m unlikely to ever tolerate that med. There are also desensitization protocols that involve use of IV antihistamines, steroids, and sometimes, epinephrine.
• It is my experience that often many medications that would not typically warrant a taper down before stopping must be stopped gradually in mast cell patients to prevent reactions. For example, the general population does not need to wean off IV antihistamines. They can just stop taking it without a taper. But if a mast cell patient needed six doses of IV Benadryl, and they stop the medication cold turkey the following day, they usually react. Mast cell patients should change things slowly.
Some medications can take a while to achieve a beneficial effect. It is usually in the patient’s best interest to continue a med for long enough that they can feel confident in their assessment that a medication is or is not helping.

The following describes medication progression for overall management of mast cell disease. Please note that there are other medications that can be added for specific symptoms that are not described here. Please also note that this list is just a general guideline I find helpful.

1. Start baseline meds.

  • Start second generation H1 antihistamine, like cetirizine. Starting dose is usually one tablet 1-2 times a day.
  • Start H2 antihistamine, like famotidine. Starting dose is usually one tablet 1-2 times a day.
  • Start mast cell stabilizer, usually cromolyn. In adults, target dose is typically 200 mg four times a day. First generation H1 antihistamines, like diphenhydramine (Benadryl) are not typically used as baseline medication because they may have significant side effects, cause rebound reactions, or lose effectiveness as a rescue medication.
  • Many patients benefit from gradual dose increase in cromolyn. For reasons that are not clear, patients sometimes react to cromolyn before achieving some benefit. It can take up to four months for cromolyn to achieve full efficacy.

2. Start leukotriene blocker. Starting dose is usually one tablet at bedtime.
3. Start COX inhibitor, like aspirin. Starting dose is usually one baby aspirin (81 mg) daily. COX inhibitors interfere with production of prostaglandins.
4. Increase dose of H1 antihistamine started in step 1.
5. Increase dose of H2 antihistamine started in step 1.
6. Add another second generation H1 antihistamine to be taken along side the H1 antihistamine started in step 1. Loratadine and cetirizine are a common pair.
7. Add additional H1 antihistamine, like doxepin or cyproheptadine.
8. Start ketotifen. Starting dose is usually 1 mg twice a day. Ketotifen is both an H1 antihistamine and mast cell stabilizer. In the US, oral ketotifen must be obtained through a compounding pharmacy or imported from abroad via an FDA guidelines.
9. Increase dose of leukotriene blocker started in step 2.
10. Add first generation H1 antihistamine, hydroxyxine.
11. Start lipoxygenase inhibitor, like zileuton. Lipoxygenase inhibitors interfere with production of leukotrienes.
12. Increase dose of COX inhibitor started in step 3.
13. Increase dose of ketotifen started in step 8.
14. Take a short burst of corticosteroids, like prednisone. Corticosteroids suppress production of inflammatory mediators by mast cells.
15. Take a daily low dose of corticosteroids after a short burst at higher dose in step 14. Corticosteroids suppress production of inflammatory mediators by mast cells.
16. Start a benzodiazepine, like lorazepam.
17. Start Xolair, an anti-IgE biologic. It is unclear why Xolair helps mast cell disease when mast cell reactions typically occur without IgE involvement in this population.
18. Start regular infusion of IV fluids. This can help a lot with third spacing, fluids becoming trapped in places they aren’t supposed to, leading to swelling and functional dehydration.
19. Add therapies to block other inflammatory mast cell mediators, like interleukins or TNF. Enbrel is sometimes used in this capacity.
20. Add regular doses of IV push medications like diphenhydramine and famotidine.
21. Add continuous infusion of diphenhydramine (Benadryl) through IV line.
22. Start a tyrosine kinase inhibitor. Patients should receive regular bloodwork to monitor for organ damage or low blood cell counts.
23. Start untargeted chemo like interferon, cladribine, or hydroxyurea. Patients should receive regular bloodwork to monitor for organ damage or low blood cell counts.
24. Receive HSCT (bone marrow transplant). This option is ONLY available to patients who have malignant forms of mastocytosis and who have failed every other treatment option.

There are also a number of other changes that may help mast cell patients.
Remove obvious triggers.
Consider removing or limiting some foods. This is tricky because there are at least four different lists of low histamine foods and they all conflict. Removing lots of foods at once makes it much likelier than you will lose tolerance to them. I went strictly low histamine in 2014 and it was literally years before I could tolerate even small amounts of most of the foods I removed.
Adapt medication schedule so that triggering activities occur when medications are most available to your body. This includes things like taking antihistamines before eating or exercising.
Supplement things that many mast cell patients are deficient in. This includes vitamin D and magnesium.
• Start quercetin.
• If possible, low impact exercise can be helpful.
Manage your pain aggressively. Pain is a huge mast cell trigger.
• If you have a lot of environmental triggers, wearing a mast like a Vogmask is a good option.
• For patients who have severe GI involvement, bowel rest sometimes helps. Patients on bowel rest stop taking any food or drink by mouth and receive IV nutrition (TPN).
Avoid overtly stressful situations at all costs. I cannot emphasize this enough. Do not engage in upsetting situations if at all possible.

Sent from my iPad

Mastsisters

I love all my masto kids. But there’s something special about this little girl. The week after her second birthday, her mother, a total stranger to me, called me to convince me to be part of Addie’s team in her very complicated, very high stakes, very frightening, very literal fight for her life. I agreed. Addie was my very first case.

When our paths converged four and a half years ago, Addie was living on the edge of disaster every single day. Incidentally, so was I. We got our first PICC lines the same month. I started chemo two weeks after her mom called me. We were both in and out of the hospital with protracted anaphylaxis and scopes and procedures. We both sustained significant organ damage that year. Things were not good. But I always believed that if we could just stay alive that one day we would get better. Maybe not healthy. Maybe not well. But better. Better was the dream.

Today, we walked around Salem on a perfect breezy June day. We breathed in the salty ocean air. We looked for Halloween figurines in the small shops at Pickering Wharf. We squeezed through secret passages in dusty four hundred year old houses. We struggled to read the lettering on the smooth white faces of centuries old tombstones. We talked about school and safe foods and hospitals and ports. We ate things that would have put us in the ground when we first met.

This is not an easy life. It is never going to be easy. But there is something about looking back years later that makes you see this journey as worthwhile. We can eat food now. We aren’t admitted constantly. We are not shocking left and right. We are not always on the brink of anaphylaxis.

We made it. We are still here. We are still living in the happy moments and getting through the hard ones.

We are mastsisters. We are survivors. We are alive.

Me and Addie, Los Angeles, May 2015

Me and Addie, Salem, June 2018

Sensory memory

Sensory memory is the shortest. It lasts less than a second, usually; the memory of things you hear, echoic memory, might last a little bit longer. The things we see, hear, touch, taste, and smell all provoke a response by our nervous system. These tiny events are filtered almost immediately. Noticing everything would overwhelm our brain, both physically and figuratively. We only acknowledge things that are useful to short term memory; everything else is discarded before we even know it was there.

How many things do we see and hear and feel that our brain decides aren’t important? What if we wanted to see and hear and feel those things? What if it robbed us of these memories? I worried about this years before I understood the neurobiology of forgetting. I think that’s partly why I write: I don’t want to regret forgetting something, even if it’s not important.

My father died last month. He was diagnosed in January with a disease that would kill him. Right away, I hunted down memories of him. Hard copy photographs and pictures on our phones. Home videos from when we were growing up. Voicemails with his voice on them. Handwritten notes. Birthday cards. I started making videos of him so I could hear his voice and remember the way he moved. I journaled exhaustively, writing about my days with him in exquisite detail. I knew how easily those little pieces could be discarded and I didn’t want to lose any of it. It was too important.

All of this has had the weird side effect that I now cannot stop triggering sense memories. They just happen now. I can’t control them. I can’t choose not to pay attention. They are all so complete and so vivid. Splinters of moments that got caught in the void between the past and the present. Here but not here. Then but not then. Visible but untouchable.

In particular, I am overcome with memories from my childhood of us camping. From the ages of 4-14, my family camped every weekend from mid April to early October and for several weeks in the summer. I remember the long car rides to New Hampshire on Friday nights. Wearing my father’s blue jacket, standing in front of him around the campfire on a cool summer night. The smell of the damp earth every April on opening weekend. The sting of hitting the water after my father threw me into the air while we swam in the river. Sunny days at the end of summer when my father, my mother, my sister and I were the only people on the tiny beach. Making sand castles with moats around them. Day trips from the campground to Canobie Lake and Salisbury Beach and York Animal Kingdom.

And then the hard stuff, the memories I wish I never had to make: how soft his hair was under my hand when I tried to soothe him, the way his skin smelled at the end, how his chest rose and fell as he breathed. How it felt to wake up in a world where my father was not alive. How it was physically painful. How every day is still harder than the day before it. How it felt like I was suffocating when he died, like I’m dying. How it still feels like that.

How living in these memories is excruciating. But how losing them would be worse.

Riot in my heart

In 1995, my cousins moved in with us. One of my cousins shared a room with me. Every night, she would put on a mixtape of quieter alternative songs from bands like Alice In Chains, Nirvana, Bush, the Cranberries, Pearl Jam, Smashing Pumpkins and Red Hot Chili Peppers. In the daytime, she would blast louder music. It was the first I ever really connected with music. I liked the messy chaos and angst and obscure lyrics of alternative music. I think I burned a hole in Nirvana’s Nevermind album from listening to it so much in my discman.

A year or two later, one of my friends played me a Ramones album and I fell in love. I still love alternative but punk is the music of my soul. I am a punk. It was the first identity I found for myself and still one proudly wear today. I listen to the Misfits every morning and the Pogues, Generation X, Rancid, Bikini Kill, Operation Ivy, NOFX, and the Clash when I shower.

Punk gives me energy and motivates me. It makes me feel braver than I really am. I don’t wear ripped fish net tights under a plaid skirt with a band shirt and Doc Martens anymore. I don’t get in fist fights and go to shows in tiny shady venues or people’s basements. But I still have punk tendencies toward rebellion and dissent. It’s still in there. I still have a riot in my heart.

When life overwhelms, punk rock is the first thing I reach for. In 2013, I got a ton of bad news and was in so much bone pain that I was literally bedridden some days. I was scared and needed to make some very hard decisions about my health and my life. I wasn’t feeling very brave. I needed to reawaken the punk in me.

My hair was bright red for my senior year of high school. I couldn’t find a picture at the time but I wanted my hair to be that red again. A friend from high school is now a stylish. I asked her if she remembered what color my hair was and could she replicate it without a picture. She did and she could. In November 2013, we cut off eight inches of long light brown hair and painted the remaining hair fire engine red. Punk rock. And just like that, I found my courage.

This year has been so, so difficult. I could not have predicted how much energy I would expend taking care of someone who is dying. A lot of things in my life had to be abandoned for the time being so that I could focus on my family and my health, including a lot of my MastAttack responsibilities. I will resume them at some point.

I’m sitting here at 4am with bright red and purple hair, wearing an Operation Ivy shirt, listening to Rancid and the Misfits, hoping that it will give me the courage I need to survive this year.

Tyrosine kinase inhibitors in the treatment of mast cell diseases

Author’s note: The following post is my personal opinion and is based upon publicly available information and not upon any confidential information I have obtained as a result of my job. The ideas described below are directly attributable to me and not to my employer. I am not a medical doctor and this is not medical advice. This information should be used only to better inform yourself prior to speaking with your provider.

Tyrosine kinase inhibitors have been described in literature for over thirty years. The first tyrosine kinase inhibitor, imatinib, was approved by the FDA in 2001. Because it was the first effective therapy known for a fatal disease, chronic myelogenous leukemia, it was fast tracked through the FDA approval process and approved in two and a half months. In the years that followed, newer tyrosine kinase inhibitors were developed by various pharma organizations. The indications for these therapies expanded from CML to include several other diseases, including certain forms of systemic mastocytosis.

Tyrosine kinase inhibitors were developed with the intention of reducing the toxicity seen in older chemotherapy medications. They do this by targeting specific structures on diseased cells. For example, patients with chronic myelogenous leukemia have a genetic abnormality called the Philadelphia chromosome. This is the result of pieces of DNA getting switched around so that genes that aren’t normally next to each other end up stuck together. This forms a gene called BCRABL that tells cells to continually make new cells even when they aren’t needed. Imatinib targets BCRABL. The idea is that only the cancer cells have BCRABL so healthy cells wouldn’t be damaged.

In reality, it’s a lot more complicated than that. The biggest reason for this is that even though healthy cells don’t have BCRABL, they have other things that look like BCRABL. This is actually why imatinib can treat some cases of systemic mastocytosis: CKIT looks like BCRABL. And there are plenty of other proteins on plenty of other cells, some healthy cells, some diseased cells, that look like BCRABL or CKIT. This means that while tyrosine kinase inhibitors are much more targeted than older forms of chemotherapy, they aren’t so targeted that healthy cells don’t incur any damage at all. Sometimes that damage is serious. Sometimes it is irreversible.

In the mast cell sphere, imatinib was originally used for cases of aggressive systemic mastocytosis that did not have the CKIT D816V mutation. Over time, it was also used for other forms of systemic mastocytosis, including mast cell leukemia, systemic mastocytosis with associated hematologic neoplasm, and smoldering systemic mastocytosis. While imatinib was approved for use in people without the CKIT D816V mutation, there were trials on SM patients who did have the mutation. Published reports found it was less effective but did give benefit to some patients with the mutation. To be clear, the published data strongly points to imatinib being more effective in people without the CKIT mutation than in those that do. But there is some evidence that imatinib might have benefit even if you have the mutation.

I sometimes see people telling other patients that it is dangerous to use imatinib if you have the CKIT mutation. The danger for these people is that it might not work well for them. There’s no special risk beyond that. In fact, the current FDA licensing for imatinib is for patients without the CKIT D816V mutation OR patients in whom CKIT status is unknown. This means that sometimes people are put on it without genetic testing so it’s possible that some of the patients have the mutation.

I want to be so, so super clear about the next thing I say because it is so important that people know this. Imatinib, and other tyrosine kinase inhibitors, are chemotherapies. They are licensed as antineoplastic therapies, also known as chemotherapies. When it’s shipped to your house, it arrives there with the label “contains chemotherapy drugs” on the package. Patients taking it are supposed to be consented for chemotherapy so that they fully understand the risks. TKIs are, for sure, kinder, gentler, more targeted chemo drugs. But they are chemo. And they carry a lot of risks associated with chemotherapy.

I have seen patients describe these drugs as “extremely safe”, “harmless”, “unable to damage other cells”, or even “unable to kill cells.” Those ideas are patently false. These medications are not benign. They are serious. They can cause organ damage, especially liver damage. They can suppress bone marrow, resulting in low blood cell counts. They can cause clotting issues. They most certainly can damage other cells and kill cells, targeted and otherwise. There are hundreds of references describing the ways TKIs can do this, mostly by inducing apoptosis, making a cell kill itself. All of this information is publicly available.

The very fact that TKIs are chemo agents and can cause many of the associated issues is the reason why use of TKIs is controversial in the mast cell community. A lot of people believe that use of TKIs is only warranted in the aggressive forms of systemic mastocytosis that can cause organ damage and death. But there is another school of thought that posits that TKIs are appropriate for indolent SM and MCAS, specifically for cases where anaphylaxis is frequent and severe. They argue that these cases present enough risk to life that the benefits outweigh the risks. Still another group feels that TKIs are safe enough to use for control of non life threatening symptoms in patients with indolent SM and MCAS.

It is my personal opinion that there is benefit to trialing TKIs in patients with indolent SM and MCAS for whom disability or risk to life is significant. I think that you have a right to try unproven therapies when your life is at stake. But I also think that because of the risks, they should only be used when more conservative therapies have failed. The sole fact that they are chemo drugs shouldn’t preclude TKIs from consideration for severe cases of MCAS and ISM. Chemo drugs are prescribed in low doses to treat dozens of conditions, especially immune mediated disorders like autoimmune diseases. But I do think they should be a last resort. I do not personally feel that TKIs are appropriate for general symptom management in non life threatening cases.

My opinion can be summed up pretty cleanly as this: these drugs are serious and they should be reserved for serious cases until such time as we have actual data on how TKIs affect these patients. We need studies, not a handful of case reports, to really understand the risks for MCAS and ISM patients using these therapies. But when other treatments fail and there is risk to life, I think it is appropriate to consider TKIs in these populations.

Management of the peripartum period in a mast cell patient

I’ve been getting a lot of questions about pregnancy and delivery in mast cell patients. I had an interesting case a couple of years ago that I thought people might find illuminating. I contacted the patient and she had no problem with me sharing her case.

The case involved a pregnant mast cell patient experiencing both cardiovascular and mast cell driven complications of the pregnancy with significant risk of preterm delivery. I worked with the patient and her care team to develop a plan to minimize the risk of mast cell activation and anaphylaxis both before and after delivery. Mom delivered by Cesarean and had no complications during or after delivery. Baby also suffered no complications associated with birth.

This is some of the material I provided to her team.

Overview:

Mast cell disease is a group of proliferative and non-proliferative conditions that is hallmarked by severe allergic reactions and anaphylaxis to triggers by non-IgE pathways. Due to the the diverse role of mast cells in many processes, including allergy, immune defense, wound healing and reproduction, mast cell degranulation and activation is an ever present threat.

Premedication:

Mast cell patients are recommended to premedicate prior to any procedure, including non-invasive procedures, to suppress mast cell activation.

24 hours before:
50mg prednisone

1-2 hours before:
50mg prednisone
50mg diphenhydramine
150mg ranitidine
10mg montelukast

An IV protocol used by some patients in place of the oral meds at 1-2 hours:
50mg diphenhydramine
40mg famotidine
40mg methylprednisolone

Following procedures/medical events/anaphylaxis, some patients do best with a taper of antihistamines and steroids to suppress rebound reactions and biphasic anaphylaxis in the following days. An example of this regimen is:

Antihistamine support:
-50mg diphenhydramine IV every 4 hours for first 24 hours
-50mg diphenhydramine IV every 6 hours for next 48 hours
-50mg diphenhydramine IV prn thereafter

Corticosteroid coverage:
Corticosteroids play an integral role in modulating mast cell activation. In the days following procedures/medical events/anaphylaxis, some patients do best with a steroid taper. Please note that the reason for the taper is NOT to prevent adrenal insufficiency, but to provide adequate steroid coverage to suppress mast cell reactions at a time when a non-mast cell patient would safely tolerate an abrupt cessation of steroids.

There is no defined protocol, but many patients use a Medrol dosepak or seven day prednisone taper following anaphylaxis and do well with this protocol following other procedures/events.

Cardiovascular concerns:

In cardiac patients with mast cell disease, Kounis Syndrome (allergic angina/MI) is a risk. In this condition, patients experience angina/MI as the result of a histamine driven process. Mast cell rescue medications (diphenhydramine, famotidine, methylprednisolone) should be given along with appropriate management of cardiovascular symptoms (nitroglycerin, calcium channel blockers). Epinephrine can be used if appropriate.

Beta blockers are a hard contraindication for mast cell patients as they interfere with the action of epinephrine. Use of beta blockers is commonly cited as a risk factor for fatal anaphylaxis. ACE inhibitors are often not recommended due to interaction with the angiotensin/renin system in which mast cells actively participate.

Pain management:

Most opiates are not recommended for mast cell patients due to induction of mast cell degranulation. Fentanyl and hydromorphone are the ones most often used successfully and are the drugs of choice for acute pain management.

Literature findings:

Ciach K, et al. Pregnancy and delivery with mastocytosis treated at the Polish Center of the European Competence Network on Mastocytosis (ECNM). PLoS One 2016; 11(1): e0146924

  • Five women delivered via cesarean. In one patient, the cesarean was performed specifically because of concerns about vaginal delivery in a mastocytosis patient. In the other four cases, cesarean was performed because of preeclampsia; improper positioning of the fetus; lack of labor progression; and large size of the fetus’ head relative to the size of the uterus. In all of these cases, spinal anesthesia was used with no complications.
  • Twelve women delivered vaginally without complications. In two patients, an epidural was used for pain management. In three patients, medication (oxytocin) was used to induce uterine contraction.
  • Four patients experienced pregnancy complications in the second trimester. The complications were pregnancy induced hypertension and swelling of the extremities; deep thrombosis (blood clot formation); toxoplasmosis, an infection; preterm labor without delivery; and vaginal bleeding in the first trimester.
  • Four patients delivered early, at 26 weeks, 36 weeks, and 37 weeks. The woman who delivered at 26 weeks had preeclampsia and her baby died less than a month after delivery due to extreme prematurity. Twelve patients delivered full term. Three babies had low birth weight upon delivery.
  • Mastocytosis patients are at higher risk of complications that involve clotting. Mast cell patients often experience coagulation irregularities, such as blood clot formation.
  • There have been three cases reported in literature of mastocytosis patients who developed preeclampsia that required preterm delivery.
    In order to suppress mast cell reactions and anaphylaxis, patients were premedicated before delivery with antihistamines and corticosteroids. Another study on pregnancy in mastocytosis reported that even with premedication, some patients still experienced mast cell activation during or after labor.
  • Epinephrine, antihistamines and glucocorticoids (steroids) should be readily available during and after labor

Matito A, et al. Clinical impact of pregnancy in mastocytosis: A study of the Spanish network on Mastocytosis (REMA) in 45 cases. Int Arch Allergy Immunol 2011; 156: 104-111.

  • 22% (10) of patients delivered via caesarean. 78% (35) delivered vaginally.
    Nine patients required labor induction. Oxytocin was used in eight cases and dinoprostone was used in one case.
  • Premedication for mast cell activation with antihistamines and glucocorticoids was only given to 38% (17) of patients.
  • 82% (37) of patients received anesthesia. 32 patients received epidurals; 3 received local anesthesia; and 2 received general anesthesia.
  • 11% of patients had mast cell activation symptoms, including flushing and itching, during or just following labor.

Dewachter P, et al. Perioperative management of patients with mastocytosis. Anesthesiology 2014, 12): 753-759.

  • Mastocytosis symptoms can improve, worsen, or remain unchanged during pregnancy.
  • Anesthesia management of mastocytosis patients has not been well described, with 13 CM patients and 33 SM patients mentioned in literature since 2000.
  • In one instance, IV epinephrine was necessary following labor to manage low blood pressure and difficulty breathing in an SM patient.
  • Early use of epidural anesthesia is recommended for mastocytosis patients to manage pain as pain triggers mast cell degranulation.
  • Patients should continue their regular medications to manage mast cell disease until the day of surgery.

Find a light

I have been writing stories for a long time. I have been keeping journals since I was six and they are full of them. I always wrote about my actual day to day life in journals but never enjoyed autobiographical writing and didn’t think I was good at it. That’s entertaining now to think about, considering that I have spent the last four years digging out the hardest parts of me to share with the internet. But before I was Lisa from MastAttack, I was Lisa Klimas who wrote fantasy stories full of witches and magic that was intended to be shared with no one.

I don’t write fantasy stories anymore. (Except maybe the ones in my head where I fantasize that I’m not living in this body anymore.) I stopped when I started writing MastAttack; I’m not sure why, exactly. But even though I don’t write in this genre anymore, I am still very prone to seeing my life through the lens of fantasy; particularly, I relate aspects of my life to symbolic elements I used to use in stories. This is pretty obvious for anyone who has been reading for a while; I talk about the sky and stars and the vast endless space beyond this world in a lot of posts. Somehow, despite writing very frankly about my life, in my mind this is still a story about someone else, a fantasy story where anything could be real, and where the protagonist could do anything with the right magic.

The past six weeks have been difficult for me in ways that I could never have imagined. I was hospitalized for CDiff in Florida, and then again for CDiff in Boston shortly after I got home. On the last day of my second admission for CDiff, I found out that someone I love very much is very, very sick. The kind of sick that makes me numb to think about. It seemed like things started to level out with my health. I was pretty beat up but the infection seemed to finally be under control, and I was more available to help out with family things. Things seemed more manageable. Until they weren’t.

Last week, I noticed a very minor skin irritation around my port access site. Very minor. The kind I have had many times before just by virtue of having mast cell disease and having fair skin that marks easily. But I’m very meticulous about my port so I called my home IV nurse to come look at it. She came and agreed that it was probably a mast cell reaction or a very minor skin infection. It wasn’t hot, swollen, or painful. The redness was faint and covered a very small area around the needle site. I had no fever, chills, or other signs of infection. She was so confident that it was just a skin irritation that we accessed the port. I called my PCP for some prophylactic cephalexin in case it was a skin infection and breathed a sigh of relief.

I woke up in the middle of the following night with a fever and a much redder and angrier looking port. I took mast cell premeds and went to the hospital immediately. And even the ER nurses and doctors didn’t think it was a serious infection. It still wasn’t swollen, painful, or hot. (For people wondering why I’m harping on this, the four cardinal signs of infection are tumor (swelling), rubor (redness), calor (heat), and dolor (pain).) But they weren’t taking any chances and we spent an hour finding a peripheral vein to use while we sorted out my port. My white count was elevated but it is always is. They told me that they expected I would be admitted, get a few doses of IV antibiotics through the port, and go home in a day or two with the port.

Things didn’t exactly happen like that. Over the course of the day, I got sicker. I started feeling sicker, and I started having more mast cell activation. My white count went from normal for me level to through the roof in a few hours. I was rushed into an interventional radiology suite where everyone still thought that the port was not really infected. They told me after the first incision that things looked good. Then they took out the port and all hell broke loose.

There was an infection underneath my port, beneath the port and chest wall. One that had been brewing for a while. Suddenly everyone was talking in loud voices and debriding the poorly numbed cavity. I should have asked for anesthesia before the procedure but I had never had an IR procedure that required more than fentanyl and midazolam so it didn’t occur to me until they were literally carving pieces of tissue out of my chest. That is not a mistake I will make again.

I was hospitalized for several more days, including a total of three days without a central line. I blew in the neighborhood of ten peripheral lines and it would have been more if I hadn’t had good nurses who babied them to try and make them last. I get IV benadryl six times a day most of the time and that’s part of why I have a central line. IV Benadryl is really damaging to blood vessels and soft tissue, and my blood vessels are already in pretty rough shape. Getting IV Benadryl through a peripheral vein is miserable. It feels like knives shooting up your arm. I used all my tricks and wrapped my arm up in a hot, wet towel for several minutes before every dose, and we diluted it and pushed it slowly and flushed it slowly, and it was still excruciating every single time.

They put in a PICC line last Monday so I could go home and keep up with my home IV meds and fluids. I came home on IV antibiotics every eight hours for the line infection and oral antibiotics every six hours to hopefully prevent me from getting CDiff again from the other antibiotics.

The catheter tip grew out Staph aureus, meaning I had a staph infection a couple of inches from my heart. I got very lucky that I was treated fast enough that it never become a fulminant bloodstream infection but it came pretty close. Another few hours and this story might have had a very different ending. As it is, I suffered a lot for several days, and left the hospital with a hole in my chest so deep that it is nearly to the chest wall, deep enough that I cannot pack it myself because I cannot see the bottom.

Part of the shock of this situation is that I have had a central line for four years and have never had an infection. I am a maniac about my line and sterilizing it and being meticulous not to contaminate anything. I avoid hospitalization like the plague so that I’m the only one touching my line. When my last port was removed, after three years and three weeks, I was told that it was the longest continually accessed port in a BWH patient never to be infected. In total, I had three central lines (a PICC line and two ports) for three years and eleven months before we found any evidence of infection.

I couldn’t figure out how it got infected, and especially how the infection got behind the port. In retrospect, I think might have been contaminated when it was implanted. I don’t know how else I would have seeded a bacterial infection between the port and chest wall, but not over the port at all. I’ve felt sicker and more activated the last few months and it’s possible I had an infection growing all that time. It’s also possible that this isn’t the case but my instincts feel like this is the explanation. Either way, I’m never going to know for sure.

I came home earlier this week and was very relieved to see my family, my dogs, and my bed. I wasn’t feeling super but I just had a line infection so I wasn’t really expecting to.

Yesterday, I started having a GI bleed bad enough that I called an ambulance. While on the phone with 911, I started having anaphylaxis because that’s just how we do now. I laid down and used an epipen while feeling pretty dejected that I was now going to be admitted to the hospital for the fourth time in six weeks. I have been admitted for a total of 17 days this year. We are only 49 days into 2018.

Last night, I sat in my isolation room and watched it snow from the tenth floor. It was the middle of the night and the world was silent as snow covered every darkness and imperfection below. Not the terrible storm it was rumored to be. Just snow. Snow that is already melting under a clear blue sky and a brilliant and victorious sun. Light always wins.

I know that I am not really the protagonist of a fantasy story and that I’m not really going to slay the dragon that is my poor health. My health is bad. I have largely made peace with that. I want it to be better but I don’t expect it to be. But I also know that for every evil there is a pure good, and that bad things happen to me but the worst things don’t, and that I won’t always feel this way.

I don’t know how I will get through this or how long it will take or what I will lose along the way. I just know that the snow has fled under a brilliant sun and that somewhere, somehow, I will find a light.

Cut out the broken pieces

I was hospitalized for almost a third of January. In the first hours of 2018, I was put into an ambulance and brought to a hospital where I know no one a thousand miles from home. I arrived with a high fever, continuous, forceful vomiting, and colitis symptoms from hell. A couple of days later, I tested positive for CDiff, a severe colon infection that is dangerous and difficult to treat.

Metronidazole calmed the CDiff enough for me to be discharged. I stayed in Florida several more days, unable to get home because of the storm. I was home only a few days before I was once again brought to a hospital by ambulance with severe colitis. The pain was literally blinding. My vision flashed white at the worst points, lightning coming in waves.

I live with serious chronic pain and almost certainly will for the rest of my life. I am not a stranger to pain. This is the worst pain I have ever experienced. I am not a screamer with pain. I was screaming.

The CDiff was no longer being controlled by metronidazole. I was admitted and we started oral vancomycin four times a day.

I have been sick a long time. I think this was the sickest I have ever been.

I also had some strong emotions to contend with, namely that I was angry. This isn’t the first time I’ve had a major problem with my colon. It has been a consistent problem for years and is usually the reason I end up in the hospital. I have had multiple colon surgeries and so many scopes and biopsies that I sincerely can’t remember how many I have had. Lower GI bleeding is part of my baseline. I have to undertake extraordinary interventions to get stool out of my colon. My colon does not work. It performs none of its intended functions.

When I had my last colon surgery, I begged my doctors to take out the whole thing. I begged them because I knew it would never stop being a problem and would never stop sending me to the hospital periodically. They wouldn’t do it. They took some of my colon but they didn’t take all of it and look where we are now. We’re here, in a place that would be impossible to get to but for the fact that my damaged, bleeding, useless colon is still inside my body. A place we could not have gotten to if they had just cut out this broken piece of me. But they didn’t.

The oral vancomycin worked well for me. I medicated heavily to suppress mast cell reactions to the med, which is a known degranulator. After a few days, my symptoms improved significantly, but my pain was still bad. It took another few days to be able to eat anything and to manage my pain without IV meds.

By the end of my hospital stay, I was very ready to go home. I was cautiously optimistic that the oral vancomycin would work well for me and that the worst was behind me. I packed up all my stuff and filled all my prescriptions and waited in my isolation room for my uncle to arrive to pick me up.

A couple of hours before my uncle arrived, I got a phone call. I was walking around the floor and was in a hallway quiet enough that I could hear a conversation on the phone. I had this weird moment of foreboding when I answered the phone. I know it sounds cliché and theatrical but I really did. I sat down in a chair near the elevator bay and answered the phone and my entire life exploded.

As I sat there talking, something inside of me broke. The pain was immediate and crushing. I couldn’t breathe. I couldn’t stand up. I couldn’t think. My entire life changed and it will never change back. The life I had was gone in a moment, ripped away by a dark, whipping current. I blame this broken piece because it started there. Another broken piece that can never be fixed, that will poison me every day of my life. Another broken piece that can never be removed.

There are some realities too horrible to imagine. When you try, your mind just shows the future the way your life is now. Your mind cannot envision a life without certain people because it is so horrible that surely such a life cannot exist.

I have so many things to say but my soul is too tired and worn to speak them. The effort required is too great. Instead I swallow them down. They collect behind my stomach, cleaving to my spine, growing larger and larger with each truth I cannot get out. A broken piece of my own making that can never be cut out.