Roller coaster

I got my first central line in February 2014. At that point I was at the hospital two or three times a week. Being able to manage my needs at home as much as possible was a welcome relief and so I welcomed the line.

I had a PICC line placed in my left arm about three inches above the elbow. The poor PA who placed it was terrified. She called me the day before to go over the procedure in pinched, staccato notes. She casually mentioned that she was considering doing the placement in the ER since they would have a crash cart nearby. The infusion nurses had regaled her with stories of my reactions and anaphylaxis history. I laughed and then felt bad about it. “Whatever you need to feel comfortable is fine,” I told her. It is the first time I remember a provider being scared of my disease.

The second time I remember a provider being scared of my disease was the following day when a home infusion nurse came to change my dressing. She was much more frightened than the PA had been. She made me hold my epipen while she did the dressing change. “You’re doing fine,” I reassured her, hoping that was true. Comforting trained professionals while they treat me is a special sort of pain, like pulling out a thorn. It shouldn’t have happened in the first place and half the pain is disbelief and feeling ridiculous.

That PICC saw a lot of action. But before I was a mast cell patient, I was an infectious diseases microbiologist, and I wanted that PICC line out. PICC lines are basically a straight shot to infections. I managed to keep my line sterile and my site immaculate and lobbied hard for a port to be placed. In September 2014, the PICC was removed from my arm and a port was placed in my chest.

I wanted a port for a few reasons, but the big reason was because I could manage it completely independently. I expend a lot of energy trying to stay infection free and a big part of that is staying out of the hospital. The PICC line allowed me to give myself meds and fluids but I needed someone else to change the dressing and it was harder to troubleshoot outside of a hospital. With a port, I could access and deaccess the line, change the dressing, and give meds on my own. That meant I only needed to have supplies and myself, and I could bring those just about anywhere. I could also shower more easily, take a real bath, and go swimming with the port. It was an all around win.

In the three years and three weeks that I had it, that port lived quite a life. I took it to my parents’ house and on long walks with my dogs. I took it to work on countless days. I took it to the beach and water parks. I took it to my pool on hot summer evenings. I took it to the hospital for appointments and surgeries and procedures. I took it to my niece’s First Communion. I took it wedding dress shopping with my sister. I took it on many long weekends in New Hampshire. I took it apple picking and trick or treating. I took it Christmas shopping. I took it to my girls’ weekend in Maine. I took it to the Garden of the Gods in Colorado Springs. I took it to California. I took it to Disney World. I took it all over Florida. I took it to the blue waters of Tulum and underground rivers and the Mayan Ruins at Coba. I took it on the Star Ferry and on long walks around Hong Kong. I took it to the Forbidden City and the Great Wall of China.

It wasn’t completely without issues. I had some trouble with my port and a line infection abroad is on my top ten list of things I never want to experience.  But the horrors my mind produced in response to my fear never materialized. I am fortunate to be able to say that my panic attacks have been the scariest things I have experienced with a central line.

My port was my security blanket. It still is. I could travel to all these places because I wasn’t terrified of anaphylaxis. I still took extreme measures to prevent anaphylaxis but I wasn’t paralyzed in fear by the thought of traveling. I had the meds and IV access and could keep myself stable. In an emergency, I could get myself to a decent hospital, and from there, I could get home.

I started having trouble with my port in May. My port had a small reservoir and was difficult to access unless you always put the needle through my skin in the same spot. After years of having a needle continuously penetrating the skin in the exact same spot, scar tissue formed around this spot and the site became indurated. Eventually, the skin at that site became ulcerated and millimeters thin. It was almost to the point that you could see the port through the hole. I developed a literal hole in my chest over my port.

I had a huge amount of anxiety over it. My port allowed me to control so many things about my life and I was really scared about losing that control. I spent a few months trying to get the hole to heal. It did not heal. It ulcerated and got larger.

I had the port replaced at the end of September. They were able to put the new port in the same pocket as the old one with the new line ending in the same blood vessel. They did a fantastic job on the ulcer repair and removed some additional dead tissue. All in all, it went as well possible.

It is staggering to think about how much has changed between the placement of my first central line and my most recent one. It never occurred to me that I would need a permanent central line. I figured I would have it to for a few months and I would get better and it would be removed. It obviously didn’t play out like that.

There have been some very low points. I decompensated a lot. I ended up needing more GI surgery. I transitioned to doing IV meds daily. I needed continuous IV fluids for a while. I’ve had a bunch of procedures, scopes, etc. I lost the ability to eat all solids. I needed several months of medical leave from work.

I’ve had plenty of high points, too. And in the past year, I’ve had a lot of them. Most things considered, I have steadily improved since the spring of this year. I am back to work. I am actively working on MastAttack again. I have been able to adjust my meds a lot as some symptoms have improved. I can eat again, and not just eat, but eat real food. It still takes a lot of work to keep this body functioning but it’s not as much of a constant struggle.

I no longer feel like I’m constantly flirting with anaphylaxis. I haven’t used an epipen in several months. It’s a reality for me that I will never be free of the risk of anaphylaxis. I still keep epipens out in every space in my home. I still carry around four epipens and IV rescue meds at all times. But I’m not waiting for it anymore. I’m not always afraid. That in itself has been unbelievably liberating.

I am working on decreasing my IV meds and IV fluids very, very slowly. My long term goal is to get to a place where I do IV fluids overnight three nights a week and only access as needed for IV rescue meds or procedures. It will likely take years to get to this point, even if I continue to improve. It has been hard because these things have kept me safe for a long time. I think I will never be free of them entirely and that’s okay.

But my relationship with my port is changing. I am very slowly trying to transition to a person who uses my line but who is not completely dependent upon it for safely. Part of this is training my body. Part of this is training my mind to stop catastrophizing and to let go of my anxiety. It’s not obvious yet which part which be the hardest.

I get Xolair every four weeks at my immunologist’s office at the hospital. Last week, his nurse and I were chatting about my recent port placement and decreasing my IV meds. I shared that the idea of not having a continuously accessed port and therefore ready IV access was scary. “Imagine that,” she said as she gave me my injections. “Imagine just accessing a few nights a week. Imagine if you could have it removed!”

I can’t though. I can’t imagine it. I think I will always have a port and will always need some IV support. But the idea that I could only need it to be accessed for three nights a week is mind blowing. A year ago I was passing out if I stood up, my stomach was newly paralyzed, and I couldn’t eat at all. Now I’m back to work full time, working on the courses for MastAttack U, planning international travel for next year and eating chicken pot pies for dinner. Bananas.

As I get more comfortable with this process, the fear is still fresh, but there is now an edge of exhilaration. Like an amazing ride from a high height. A long drop with a safe landing.

A roller coaster.

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 71

85. What is the difference between an anaphylactic reaction and an anaphylactoid reaction?

  • Anaphylaxis is an old term. It has been defined in a number of ways over time.
  • From the 1980s-mid 2000s, that term was typically reserved for cases involving an IgE allergy. If a patient had a life threatening, multisystem allergic reaction from an IgE trigger, that event was called anaphylaxis. Similar reactions that were from a trigger that was not an IgE allergy were called anaphylactoid, which literally means “like anaphylaxis.”
  • In the mid 2003, the World Allergy Organization recommended that the term “anaphylactoid” be abanded. Whereas anaphylaxis had been mostly used to describe IgE reactions, their recommendation was to call all of these events anaphylaxis regardless of whether or not they were from IgE triggers. Anaphylaxis from an IgE trigger was called “immunologic anaphylaxis” and anaphylaxis from a non-IgE trigger was called “non-immunologic anaphylaxis.”
  • These terms are still used, but many providers just use the term anaphylaxis without specifying further.
  • Unfortunately, the recommendation to stop using “anaphylactoid” has not been fully adopted, despite repeated statements from professional organizations supporting it.
  • Part of why the definition of anaphylaxis was amended to be inclusive of all triggers was to encourage more effective treatment. A significant number of providers felt that anaphylactoid described a reaction that was self limiting or that was not serious enough to require epinephrine, despite the fact that treatment should have been the same as for anaphylaxis from any trigger. Moving away from the term “anaphylactoid” helped to confer the understanding that all forms of anaphylaxis were serious, that they required adequate treatment, and that there should not be an expectation that the reaction would resolve without treatment.
  • Mast cell patients ask me often if their “anaphylaxis from mast cell disease” is really anaphylaxis or if it is an anaphylactoid reaction. Per the World Allergy Organization, the term “anaphylactoid” is obsolete, so these patients experience anaphylaxis. But some providers do not recognize this as anaphylaxis.
  • The most important thing to impress upon providers is that regardless of the terminology they prefer, mast cell reactions that are anaphylactic/anaphylactoid still require the same, aggressive treatment. Calling a reaction anaphylactoid does not make it less serious or negate the requirement for advanced treatment.
  • This is an excellent resource for anyone wanting to learn more about the treatment recommendations for anaphylaxis. There are notes about the discussion on use of “anaphylactic” and “anaphylactoid” on page 344.

 

For additional reading, please visit the following posts:

The definition of anaphylaxis

Anaphylaxis and mast cell reactions

 

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 73

86. What is the role of the spleen in systemic mastocytosis? (Part Two)

  • The spleen is basically a big filter for the blood. In the previous post, I mentioned one of its functions: to catch certain types of infections in the blood that your immune system has a hard time fighting in other ways.  It does some other things, too. The spleen stores red blood cells and platelets so that your body has a backup supply in case of hemorrhage or trauma.
  • The spleen also looks for something else when it filters the blood: damaged or abnormal blood cells. Damaged or abnormal blood cells get caught in the spleen so that they don’t continue to circulate in the blood. The spleen then breaks down those bad cells and uses materials from them to help make new healthy cells.
  • If there are lots of abnormal cells, then the spleen gets swollen because it is holding many more cells than usual. This is why the spleen swells in diseases where the body has abnormal cells in the blood stream. How much the spleen swells is directly proportional to the amount of abnormal cells in the blood.
  • For example, in acute leukemias, there are tons of abnormal cells circulating in the bloodstream. The spleen catches as many as they can. Because there are a lot, the spleen swells very quickly. In chronic leukemias, there are still abnormal cells, but they are produced at a much slower rate over time. This means that the spleen has more time to break down the broken blood cells it catches before it catches more of them. In these scenarios, the spleen swells more slowly over a longer period of time.
  • You can apply this understanding directly to mastocytosis. Patients with indolent systemic mastocytosis have fewer mast cells than those with smoldering or aggressive systemic mastocytosis, or mast cell leukemia. The patients with indolent systemic mastocytosis make some abnormal mast cells. The spleen will catch the ones it sees and remove them from the bloodstream. But mast cells don’t live in the blood and they only pass through the bloodstream for a short time. So the spleen has time to break down some mast cells before it catches more.
  • When a patient with indolent systemic mastocytosis starts to produce higher numbers of mast cells, that’s when you see the spleen starting to swell. That’s why spleen swelling is a B finding for systemic mastocytosis – it is an indicator that the body is making more mast cells than before, and could be headed toward a more aggressive form.
  • The number getting filtered out by the spleen increases so the spleen swells. The more abnormal mast cells produced, the more the spleen swells.
  • Additionally, when the bone marrow is making lots of aberrant mast cells, they are introduced into the blood stream in much larger numbers than normal. This means that they are more likely to get caught in the spleen than in a person with indolent systemic mastocytosis.
  • In smoldering systemic mastocytosis, the body makes more mast cells than in indolent systemic mastocytosis, so it’s more common for the spleen to swell. In aggressive systemic mastocytosis, the bone marrow is producing a lot of mast cells and many of them are caught in the spleen over a short period of time. In mast cell leukemia, even more are made and caught, so the spleen becomes clogged up very quickly.
  • When the spleen is swollen from catching bad mast cells, the swelling causes it to break or damage other, healthy blood cells, too. This happens because the swelling of the spleen pinches the pathway for cells through the spleen so the other cells have to squeeze through, causing them to break. This is why patients with more advanced forms of systemic mastocytosis like smoldering systemic mastocytosis, aggressive systemic mastocytosis, and mast cell leukemia are more likely to have low blood cell counts than people with indolent systemic mastocytosis.
  • In addition to the risk of low blood cell counts, the swelling and dysfunction of the spleen can also contribute to portal hypertension. This is when there is high pressure in the blood vessel system that connects the GI tract, the pancreas, the spleen and the liver.
  • Portal hypertension is also a C finding for aggressive systemic mastocytosis. This means that a person who has this because of mastocytosis receives a diagnosis of aggressive systemic mastocytosis.
  • Portal hypertension can affect liver function and can cause fluid that should be in the liver to end up in the general abdominal space, a condition called ascites.
  • Splenic swelling often causes no symptoms. It is unusual for it to cause pain in the general area of the spleen. Left shoulder pain sometimes occurs if the spleen is very swollen.
  • The general rule of thumb is that the spleen has to be twice its normal size for it to be felt on a physical exam. The exact amount of swelling is usually measured by an ultrasound.
  • Spleen swelling does not usually require treatment. Generally, unless there is hypersplenism, it is not treated.
  • The treatment for hypersplenism is splenectomy, surgical removal of the spleen. The spleen is removed mainly for two reasons: to decrease portal hypertension, thereby reducing stress on the liver; and to prevent the spleen from rupturing, which can cause fatal hemorrhage.

This question was answered in two parts. Please see the previous post for more information.

For additional reading, please visit the following posts:

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (ISM, SSM, ASM)

The Provider Primer Series: Natural history of SM-AHD, MCL and MCS

Mast cell disease and the spleen

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 72

86. What is the role of the spleen in systemic mastocytosis? (Part One)

  • The spleen is basically a big filter for the blood. It is supposed to catch certain types of infections in the blood that your immune system has a hard time fighting in other ways.
  • When the spleen is swollen but still functions pretty well, it is called splenomegaly.
  • Swelling of the spleen is not uncommon in systemic mastocytosis. Splenomegaly is most often seen in patients with smoldering systemic mastocytosis, aggressive systemic mastocytosis, and mast cell leukemia, but sometimes patients with indolent systemic mastocytosis have swelling of the spleen.
  • When the spleen swells, the pathway for the blood going through the filter gets pinched. Blood goes in but has to pass through a narrow exit route to get out of the spleen. The more swollen the spleen is, the narrower the pathway for the blood to get through the spleen. This means that cells can be damaged or broken open if the spleen is swollen.
  • How much this happens depends upon how swollen the spleen is. If it is only a little swollen, the change in blood cell counts can be minimal.
  • For systemic mastocytosis, a swollen spleen that works well (splenomegaly) is what is called a B finding. A B finding is a way to tell if a patient’s indolent systemic mastocytosis is moving to a more serious form, like smoldering systemic mastocytosis or aggressive systemic mastocytosis. If a patient has a B finding, they are monitored more closely to look for other clues that could mean the disease is progressing.
  • Please note that the B finding MUST be caused by the mastocytosis to count. For example, if an SM patient falls off their bike and injures their spleen, causing it to swell, this is not a B finding. If the mastocytosis didn’t cause the problem, it doesn’t count.
  • Mast cell patients who have a spleen that is swollen but works correctly don’t damage too many blood cells. This means blood counts are often normal in this situation. If blood cell counts are not normal, the spleen is not the cause.
  • Some patients with aggressive systemic mastocytosis and mast cell leukemia develop a condition called hypersplenism. Hypersplenism basically means the spleen is working way too hard. Hypersplenism is a C finding, a marker that indicates that a patient’s mastocytosis has become very aggressive. If a patient has a C finding, they are diagnosed with aggressive systemic mastocytosis (ASM).
  • Sometimes patients with mast cell leukemia have hypersplenism. However, there are stringent criteria for diagnosing mast cell leukemia. Just having a C finding isn’t enough for a diagnosis of mast cell leukemia, while just having a C finding IS enough for a diagnosis of aggressive systemic mastocytosis.
  • Having a C finding is not a defining feature of mast cell leukemia the way it is for aggressive systemic mastocytosis.
  • Some patients with systemic mastocytosis have another blood disorder that causes the bone marrow to make too many cells. This is cleverly named systemic mastocytosis with associated hematologic disorder (SM-AHD). People with SM-AHD can have any stage of systemic mastocytosis. If they have another blood disorder, they are categorized as having SM-AHD even if they have aggressive systemic mastocytosis or smoldering systemic mastocytosis. So a person with SM-AHD can have any type of systemic mastocytosis, including aggressive systemic mastocytosis.
  • Sometimes patients with systemic mastocytosis alongside another blood disorder (called SM-AHD) have hypersplenism. Here, the hypersplenism could be caused by one of two conditions: systemic mastocytosis, or the other blood disorder. If the mastocytosis causes the spleen issue, the patient gets a diagnosis of aggressive systemic mastocytosis just like any systemic mastocytosis patient. If the other blood disorder is what causes the hypersplenism, the patient does not get a diagnosis of aggressive systemic mastocytosis.
  • If the mastocytosis causes the spleen issue, then we know that this is a C finding, a marker for aggressive systemic mastocytosis. If the other blood disorder is what causes the hypersplenism, it is not a C finding and does not indicate aggressive systemic mastocytosis.
  • Please note that having a C finding is not a defining feature of SM-AHD the way it is for aggressive systemic mastocytosis.
  • Hypersplenism sometimes occurs in patients with SM-AHD. It could be caused by either the systemic mastocytosis or the other blood disorder. It can be trickier to figure out exactly what is causing the splenic issues.
  • If the mastocytosis causes the spleen issue, then we know that this is a C finding, a marker for aggressive systemic mastocytosis. If the other blood disorder is what causes the hypersplenism, it is not a C finding and does not indicate aggressive systemic mastocytosis.
  • Please note that having a C finding is not a defining feature of SM-AHD the way it is for aggressive systemic mastocytosis.
  • You can tell that a person has hypersplenism by looking at four things:
    1. Low counts of certain blood cells in the blood. Red blood cells, platelets, and some white blood cells can be low because of hypersplenism. The white blood cells that are low when a person is hypersplenic are eosinophils, neutrophils, and basophils. These cells all have granules full of chemicals like mast cells do.
    2. The bone marrow trying to make extra blood cells to make up for the ones that being destroyed by the spleen.
    3. Swelling of the spleen.
    4. The expectation that if the spleen is removed, the blood cell counts will go up and the bone marrow will start making normal amounts of blood cells again.

This question was answered in two parts. Please see the following post for more information.

For additional reading, please visit the following posts:

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (ISM, SSM, ASM)

The Provider Primer Series: Natural history of SM-AHD, MCL and MCS

Mast cell disease and the spleen

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 70

84. Is the problem for mast cell patients that they can’t break down histamine properly?

  • Not exactly. Mast cells that are overly activated will make and release more histamine but the activation comes before the histamine, not the other way around. There’s no evidence that indicates that in mast cell disease there is something wrong with the way the body breaks down histamine.
  • Histamine intolerance is not a well accepted diagnosis in the general medical establishment. Histamine intolerance is when patients react to foods and activities that contain or cause the production of histamine in the body. The general thinking on why this happens is that the body doesn’t make enough enzyme to break down the histamine at a normal rate. I have not seen convincing data that histamine intolerance is in fact due to the inability of the body to break down histamine fast enough. Regardless, I know a lot of people who feel better when they take DAO supplements or each DAO rich foods. DAO (diamine oxidase) is one of the enzymes your body uses to break down histamine.
  • Please keep in mind that histamine intolerance is a distinct phenomenon from mast cell disease. In mast cell disease, the problem is that the mast cells are too activated so they release excessive histamine into the body. In histamine intolerance, the mast cells are not overly activated, and the body can’t break down histamine fast enough. This means that even if a person with histamine intolerance makes a normal amount of histamine, their body can’t break it down at a normal rate.
  • It is theoretically possible to have both mast cell disease and histamine intolerance. There’s not a reliable way to test for histamine intolerance beyond symptoms, and there aren’t really robust diagnostic criteria. Some people with suspected mast cell disease test negative despite having mast cell symptoms and responding to treatment. This means that there’s no way to definitively know right now if a trigger causes a reaction because of histamine intolerance or a mast cell reaction beyond having a prior, firm diagnosis of mast cell disease.
  • There is something I find intriguing that may be linked to histamine intolerance. I mentioned diamine oxidase (DAO) above. It is one of enzymes your body uses to break down histamine. The other enzyme your body uses for this is called histamine n-methyltransferase. When this enzyme breaks down histamine, it produces n-methylhistamine.
  • N-methylhistamine is the most common breakdown product of histamine. It is also the molecule that we test for as part of the diagnostic workup for mast cell disease. The reason we test for n-methylhistamine instead of histamine is because histamine is broken down so quickly that n-methylhistamine stays in your body much longer than histamine. We use it as a surrogate marker for histamine since it’s easier to measure.
  • I know a lot of mast cell patients who have flagrant histamine symptoms that repeatedly have normal tests for n-methylhistamine both in blood tests and in 24-hour urine tests. There are a few reasons why this could be but I have started to wonder if the reason those tests come back normal is because your body doesn’t make enough of the enzyme that breaks down histamine in this way. As I said above, there is no real evidence to support this, just something I think about sometimes.

 

For additional reading, please visit the following posts:

The Provider Primer Series: Mediator testing

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 69

83. Are there any supplements that help manage mast cell symptoms?

  • Yes.
  • Mast cell patients are often vitamin or mineral deficient.
  • Iron deficiency is extremely common. This is likely due to anemia of chronic inflammation. Basically, if your body is inflamed long enough, your body hoards the iron and stops moving it from your GI tract into your bloodstream where it can be used. Iron supplements are pretty harsh so patients don’t always tolerate oral supplements. IV iron is an option if your iron is low enough. I personally like the Lucky Iron Fish for increasing iron. It’s pretty neat.
  • Many mast cell patients are magnesium deficient. The exact cause of this is unknown. Lots of us take magnesium supplements.
  • For reasons that aren’t clear, a lot of mast cell patients are vitamin D deficient. Vitamin D acts on mast cells. There is some evidence to suggest that vitamin D can decrease mast cell activation. I personally found that effectively supplementing vitamin D has helped me a lot. A lot of symptoms I blamed on mast cell disease were actually vitamin D deficiency.
  • A number of supplements can decrease mast cell activation or block the action of mast cell mediators. There are a ton of natural mast cell stabilizers. They are sometimes used to help patients manage symptoms, especially in Traditional Chinese Medicine, which in recent years has been studied in clinical trials. Quercetin and resveratrol are commonly used by mast cell patients.
  • I take turmeric daily to reduce inflammation. Turmeric or curcumin can decrease prostaglandin production.
  • Holy Basil is a popular supplement in the mast cell community. It also decreases prostaglandin production. It can also block the histamine H2 receptor. While I often see people say that holy basil is as effective as an H2 blocker as H2 antihistamines like ranitidine or famotidine, I have never been able to find any evidence that this is true. But it does definitely have some ability to block the histamine H2 receptor.
  • Vitamin B12 deficiency sometimes occurs in mast cell patients, especially those with mast cell activation syndrome. This can have some interplay with MTHFR mutations, which can affect the form of vitamin B12 best suited to your body.
  • Vitamin C decreases the amount of histamine released by mast cells. It is recommended by some prominent mast cell researchers and many patients respond well.
  • Alpha lipoic acid is sometimes used, particularly for neurologic symptoms and neurologic pain.
  • I’m not sure if CBD oil is considered a supplement but it is widely used with excellent results. Be aware that the popular notion that marijuana derivatives do not interact with any medications is inaccurate. It especially can interact with tricyclic antidepressants to cause dangerous tachycardia.
  • Keep in mind that all supplements have the potential to interact with medications or to affect a person adversely if they have certain diseases. Exactly how much this happens is hard to pinpoint because over the counter supplements are held to a much lower standard for this type of study than FDA approved medications.
  • Always discuss any supplements you plan to try with your managing provider. Vitamins and minerals can cause toxicity and too much can cause very serious side effects and complications.
  • Do not assume that just because something is derived from nature, or because it is available without a prescription, that something is automatically safer for you than medications.
  • This is not really in my wheelhouse so I would encourage you to ask other patients what has helped them or to consult with a nutritionist.

For additional reading, please visit the following posts:

Effect of vitamin D on mast cells
Naturally occurring mast cell stabilizers: Part 1
Naturally occurring mast cell stabilizers: Part 2
Naturally occurring mast cell stabilizers: Part 3
Naturally occurring mast cell stabilizers: Part 4
The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 19
MTHFR, folate metabolism and methylation

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 68

82. Why do mast cell patients react to leftover food?

  • Reacting to leftovers is arguably the strangest thing about mast cell disease. Lots of people tolerate foods that are freshly cooked but react to eating leftovers in the following days.
  • There are multiple ways that food can be broken down but I’m going to focus on how microbes do this, contributing to mast cell symptoms.
  • Microbes start breaking down food basically immediately. Any kind of food.
  • Freezing arrests microbial growth but doesn’t kill the microbes. Refrigeration slows down microbial growth but it doesn’t fully stop it. Cooking at high temperatures kills microbes.
  • Microbes break down food in several ways but the most important ones for this conversation are protein degradation and lipid (fat) degradation.
  • Proteins are composed of building blocks called amino acids. They are essentially long chains of amino acids. One of those building blocks is called histidine. When histidine is broken down, it produces histamine. This will happen when any protein is broken down, animal or plant.
  • However, animal meat contains hemoglobin, a very large protein that contains tons of histidine. Plants do not have this. This is thought to be one of the reasons why patients often do worse with meat leftovers than plant or grain based leftovers. Another reason is that some meats naturally have a high concentration of histamine to start with.
  • Lipids are found in both plants and animals but they are fundamentally different. Lipids in plants are usually oils while lipids in meats are fats. Lipids can be broken down by microbes or just by exposure to oxygen. This is what causes things to go rancid, more common in animal fats than in plant lipids. Acids and alcohols can be produced when lipids are broken down. Alcohols in particular can be triggering to mast cells.

The dying season

Things die in the fall. It is both my favorite and the worst thing about this time. The scientist in me knows that these little deaths nourish the environment so that one day all of this can be born in me. The mast cell part of me is reactive. We don’t call it Shocktober for nothing. And the human part of me is sad. It’s hard to find the same beauty in stark branches and grey skies and I know that is coming.

We are living through a season in the mast cell community, a different kind of dying season. On a weekly basis for the last two months, I have logged onto social media to discover that yet another mast cell patient has died. There are varying causes of death, including complications of anaphylaxis, organ failure, complications of treatment, and suicide. And it has now been a year since my friend, Ginger, died suddenly.

I have gotten messages from several newer patients asking if this frequency of death is common for mast cell patients. It’s not. They are understandably alarmed at the number of people in our community who have died recently. I am alarmed. Watching your friends die never gets easier. There is no amount of expectation that can blunt the pain. There is no way to prepare.

Spending time in this space feels dangerous. It is not safe to linger here.

I have never stopped being affected by the deaths of mast cell patients I only knew casually. Even if you weren’t close to someone who has died, even if the only link you have is that you both have a common rare disease, you still feel it. You are bonded to the people who understand your suffering. We are part of the same whole.

I have seen a few people express concern that over time, these people will be forgotten. They will not. I remember the name of every single mast cell patient that has died since I joined the community several years ago. I remember the shock I suffered when I learned about each of them. So will all of you.

These people are gone now. There will be no vibrant resurgence in the coming spring. But they were people with lives that touched others and living in the love those people carry is a kind of rebirth. Those people will remember the ways they are changed by having known this person. They will remember favorite things and inside jokes. They will remember goals and aspirations and hopes and faith. They will remember better days.

I want you to remember that the people who are gone can never be completely lost to us. That the things they breathed into the air linger still. That when you breathe, you are breathing them in. This world has been marked by their presence, both physically and emotionally. It has literally been changed in a way that is individual to each person. And because of that, they will never be forgotten. How could they be, when they helped to build this world?

There is a poem about death that has always resonated with me. My instructions for my funeral, hopefully many years from now, include this poem being read.

Do not stand at my grave and weep.
I am not there. I do not sleep.
I am a thousand winds that blow.
I am the diamond glints on snow.
I am the sunlight on ripened grain.
I am the gentle autumn rain.
When you awaken in the morning’s hush,
I am the swift uplifting rush
Of quiet birds in circled flight.
I am the soft stars that shine at night.
Do not stand at my grave and cry;
I am not there. I did not die.
-Mary Elizabeth Frye

Be kind to yourselves. Take care. This season will end.

Clinical trials and data for laypeople, Part 3

Initial investigation of a therapy in humans starts with a phase I clinical trial. Phase I is extremely preliminary. Its purpose is really just to verify whether the therapy can be used in humans at all. It identifies the safe range for therapy dosage and any side effects patients may experience. In phase I, a therapy is given to a very small number of people, tens of people as opposed to thousands like clinical trials in later phases.

In phase I studies, you often see many diagnoses being tested at once. For example, it is not unusual for phase I cancer trials to look at solid tumors. There could be dozens of reasons for a patient to have a cancerous solid tumor. Phase I studies are small. But when they look at several different diseases, you get an even smaller number of patients. For example, let’s say a phase I cancer trial is looking at testing New Drug X in patients with solid tumors. A total of twenty patients will participate in this study. Of those twenty patients, five may have non-small cell lung cancer and two may have colorectal cancer. So you are looking at tiny numbers of people. You are trying to prove that this therapy can be used in humans at all rather than looking at how well it works on a particular disease.

Phase II is when you start to get into the real meat of trialing a therapy. In this phase, a few hundred people are recruited. At this point, the targeted diseases are clearly defined. You don’t see tons of diagnoses being trialed like you might see in Phase I. The goals of a phase II trial are to figure out which dose is the best for treating a disease and to identify any side effects or toxicities a patient may experience from taking the therapy.

In phase II trials, trial design is less uniform. This means that not all phase II trials follow the same pattern. They are sometimes divided into two parts, called phase IIa and phase IIb. Phase IIa trials are usually dedicated to figuring out what dosage should be given to patients. In phase IIb, the studies investigate what dosage gives the best result for patients and cause the lowest level of toxicity and complications, called adverse events.

Most people are familiar with the clinical trial format where some patients get the therapy and some patients get a placebo, and neither the patients nor the investigators know who gets what until the end. This doesn’t always happen, especially in oncology and rare disease trials. For very aggressive diseases, the reason is that getting the placebo and therefore not receiving any treatment would be fatal. In such instances, some patients might get the new therapy while others would get an older therapy that is currently used for people with that disease. When a treatment plan is typically prescribed for patients with a particular diagnosis, that treatment is called the standard of care (SoC). When you read through trial data or articles about trials, you might see something like “[drug name] vs SoC”. This means that some patients get the new therapy and some get the old therapy. The patients may or may not know which therapy they are getting. This depends a lot on the disease and how the new therapy and the standard of care are administered. For example, a new therapy might be given intravenously twice a month. The standard of care could be radiation therapy once a month. For obvious reasons, patients and investigators will know what therapy they are getting. But if both treatments are given via IV twice a month, the patients may not know. The investigators may or may not know depending on the trial design.

In certain situations, a phase II trial might be designed not to compare a new therapy to standard of care, but instead to demonstrate that a therapy can be given safely at a particular dose and have the intended effect upon a disease. This might happen if there is no standard therapy available for a disease. It also happens in rare disease studies because they want to get as much data on how a therapy affects patients with the rare disease and, by nature, there aren’t a lot of patients with that rare disease. So in a study for Rare Disease Y, instead of giving 100 patients the new therapy and 100 patients the standard of care, the investigators may choose to give all 200 patients the new therapy so that they can get as much data as possible on how this drug affects patients with this rare disease.

After phase II studies, the data collected and analyzed is submitted to the regulatory body for countries where the investigators want to be able to use the drug. In the US, this is the FDA. The data is reviewed and the regulatory body will decide what the next step is to be able to use the therapy in people.

There are several possible paths from this point. The regulatory agency may decide that the data is not strong enough to show that the drug works at a particular dose safely in patients while helping their disease. They could tell the investigators to extend their phase II trial, or to design a new trial and try again. They could tell the investigators that they feel the therapy is dangerous and not eligible for use in humans. They could agree the data supports the use of the therapy in this patient population, but want to see more data on a larger population. In this instance, the next step is a phase III trial.

In scenarios where the therapy is demonstrably effective against a disease and relatively safe to use in humans, the regulatory body could also elect to approve the therapy for use immediately. In this case, no phase III trial would be needed to approve the therapy for a particular disease indication. This happens mostly in situations where there is no effective therapy currently for a disease. This has happened in rare disease trials.