The use of intravenous fluids for management of mast cell disease

I get frequent consult requests from patients specifically around the use of IV fluids to treat mast cell disease. I am often asked to provide references for papers that show its use and benefit. I am not able to provide any such references because there are none. There has been no organized study for the use of intravenous fluids to manage symptoms from mast cell disease.

Despite this fact, use of intravenous fluids in mast cell disease is increasing in popularity, largely because it works, and word of effective treatments travels fast in a rare disease community. While there is no firm answer for why it helps, there is a reasonable explanation: it treats both deconditioning and POTS and many mast cell patients have one or both.  I wrote a seven part series on why exactly intravenous fluids help in these situations. I have also written in great detail about the way that mast cell disease and POTS interact.

A paper published in early 2017 reestablished the finding that use of intravenous fluids helps POTS. Treatment lengths and infusion volumes varied from person to person. Despite these variations, use of IV fluids decreased symptoms and improved quality of life for POTS patients. The link to the abstract is here.

Many mast cell mediators are vasoactive, affecting the permeability of blood vessels. This means that mast cell activation causes third spacing, the loss of fluid from the bloodstream to the tissues, where the body cannot use it. This functional dehydration can cause a lot of symptoms, not the least of which is exhaustion and difficulty standing or exercising. For obvious reasons, this will be further exacerbated in a patient that is deconditioning or who has also has POTS.

Orthostatic symptoms can be very activating to patients and managing them effectively can help significantly. I have seen IV fluids work where more traditional methods like drinking lots of fluids and consuming lots of salt, or medications like fludrocortisone have not helped. Additionally, the first line tools for managing POTS, beta blockers, are contraindicated in patients at increased risk for anaphylaxis and therefore in people with mast cell disease.

I am a fervent supporter of IV fluids (also called volume loading) in the context of mast cell disease. I have seen it stabilize patients and reduce the frequency of anaphylaxis and severe symptoms, especially orthostatic symptoms and GI symptoms.

I personally use IV fluids. If I don’t receive IV fluids at least three times a week, my orthostatic symptoms become so severe that it is difficult to stand or even move. This in turn triggers mast cell reactions. The benefits of IV fluids to my personal health are significant. Many patients report the same.

While I support the use of IV fluids in the context of mast cell disease, patients should be aware that there are infection risks associated with repeated IV access or placement of a central line. The risks are much lower for repeated IV access as central lines have a host of other risks, including blood clots, and infections have the potential to be much more serious. However, IV access can be difficult for mast cell patients. The treatment value of IV fluids should be weighed on a case by case basis and IV access on a case by case basis.

For additional reading, please visit the following posts:

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 1

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 2

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 3

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 4

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 5

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 6

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 7

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 12

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 31

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 32

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 75

I get asked a lot about how mast cell disease can affect common blood test results. I have broken this question up into several more manageable pieces so I can thoroughly discuss the reasons for this. The next few 107 series posts will cover how mast cell disease can affect red blood cell count; white blood cell count, including the counts of specific types of white blood cells; platelet counts; liver function tests; kidney function tests; electrolytes; clotting tests; and a few miscellaneous tests.

 

88. How does mast cell disease affect white blood cell counts?

Firstly, remember that while mast cells are technically considered white blood cells, they don’t actually live in the blood. That means that except in very severe malignant cases of aggressive systemic mastocytosis and mast cell leukemia, mast cells won’t directly contribute to white blood cell count in a blood test at all. This means that in a regular white blood cell level blood test, none of those cells are mast cells.

There are a couple of ways in which mast cell disease can cause low white blood cell counts. It can also cause low counts of certain types of white blood cells even if it doesn’t cause low white blood cell count overall.

  • Swelling of the spleen. This can happen in some forms of systemic mastocytosis, and may also happen in some patients with mast cell activation syndrome, although the reason why it happens in MCAS is not as clear. Swelling of the spleen can damage blood cells, including white blood cells, causing lower white blood cell counts. If the spleen is very stressed and working much too hard, a condition called hypersplenism, the damage to blood cells is much more pronounced. This may further lower the white blood cell count. Hypersplenism occurs in aggressive systemic mastocytosis or mast cell leukemia. It is not a feature of other forms of systemic mastocytosis and I am not aware of any cases as a result of mast cell activation syndrome.
  • Medications. Some medications for mast cell disease can cause low white blood cell count. These are not common medications, but are sometimes used, especially in patients with long term symptoms that have not responded to other medications, or where organs could potentially be damaged, like in smoldering or aggressive systemic mastocytosis, or severe mast cell activation syndrome. These include medications like cyclosporine and interferon.
  • Chemotherapy. These medications can also decrease white blood cell count. Chemotherapy is used in smoldering systemic mastocytosis, aggressive systemic mastocytosis, and mast cell leukemia. It is sometimes also used in very aggressive presentations of mast cell activation syndrome. Newer chemotherapies are more targeted and can cause fewer side effects. However, all of the chemotherapies used for mast cell disease can cause the side effect of low blood cell counts, including white blood cell count.
  • Myelofibrosis. Myelofibrosis is a myeloproliferative neoplasm that is related to systemic mastocytosis. In myelofibrosis, the bone marrow becomes filled with deposits of scar tissue so that the body cannot make blood cells correctly or in normal numbers. This can decrease white blood cell counts.
  • Excess fluid in the bloodstream (hypervolemia). In this situation, the body doesn’t actually have too few red blood cells, it just looks like it. If your body loses a lot of fluid to swelling (third spacing) and that fluid is mostly reabsorbed at once, the extra fluid in the bloodstream can make it look like there are too few red cells if they do a blood test. This can also happen if a patient receives a lot of IV fluids.

Even if the overall white blood cell count is normal, mast cell patients sometimes have low levels of certain types of white blood cells.

  • Anaphylaxis. Anaphylaxis can cause basophils to be low.
  • Allergic reactions. These can also cause basophils to be low.
  • Chronic urticaria. Chronic hives and rashes can cause basophils to be low.
  • Use of corticosteroids like prednisone elevates certain types of white blood cells while suppressing others. Lymphocytes, monocytes, eosinophils and basophils can also be low from using corticosteroids like prednisone.
  • Prolonged physical stress. Mast cell disease can cause a lot of damage to the body over time, triggering a chronic stress response. This can selectively lower the amount of lymphocytes and the eosinophils in the body.
  • Autoimmune disease. Autoimmune disease often causes one type of white blood cell to be high and another to be low. Many mast cell patients have autoimmune diseases, so while this is not directly caused by mast cell disease, it often occurs in mast cell patients. For example, rheumatoid arthritis can cause low neutrophils.

There are many more ways that mast cell disease can trigger high white blood cell counts, or high amounts of certain types of white blood cells.

  • Inflammation. Any type of chronic inflammation can cause high white blood cell counts and mast cell disease causes a lot of inflammation.
  • Medications. Use of corticosteroids especially can cause high white blood cell counts. Epinephrine and beta-2 agonists like salbutamol/albuterol, used to open the airway, can also cause high white blood cell counts.
  • Autoimmune disease. Many mast cell patients have autoimmune diseases, so while this is not directly caused by mast cell disease, it often occurs in mast cell patients.

There are several instances where mast cell disease can trigger elevated levels of certain subsets of white blood cells.

  • Swelling of the spleen. I mentioned above that spleen swelling can damage blood cells, causing their levels to be low. Paradoxically, sometimes having a swollen spleen can cause lymphocytes to be high. There are several theories about why this may occur but there is no definitive answer currently.
  • GI inflammation. Chronic inflammation in the GI tract can cause the body to overproduce monocytes. Certain types of inflammatory bowel disease, like ulcerative colitis, can cause high basophils.
  • Allergies. Allergic reactions of any kind will elevate both basophils and eosinophils.
  • Mast cell activation of eosinophils. Mast cells activate eosinophils, which activate mast cells. It is a nasty cycle that causes a lot of symptoms and can be very damaging to organs affected. It is not unusual for mast cell patients to have high numbers of circulating eosinophils. It is also not unusual for mast cell patients to have higher than expected numbers of eosinophils in biopsies, especially GI biopsies. Eosinophilic GI disease also has some overlap with mast cell disease so some patients have both.
  • Mast cell activation of basophils. Basophils are closely related to mast cells and also degranulate in response to allergic triggers and during anaphylaxis.
  • Autoimmune disease. Autoimmune disease often causes one type of white blood cell to be high and another to be low. Many mast cell patients have autoimmune diseases, so while this is not directly caused by mast cell disease, it often occurs in mast cell patients. For example, lupus can cause eosinophilia.
  • Anemia. Iron deficiency is common in mast cell disease. Iron deficiency anemia can increase basophil levels.
  • Vascular inflammation. Mast cell activation has been repeatedly linked to inflammation of blood vessels. This can elevate blood monocyte level.
  • Medication. Use of corticosteroids like prednisone directly increase neutrophil levels.
  • Proliferation of myeloid cells. Overproduction of certain types of blood cells by the bone marrow, including mast cells, can elevate basophils.
  • Obesity. Obesity has been linked many times to chronic inflammation. Mast cell disease can directly cause weight gain by causing high levels of the hormone leptin. Obesity may cause high levels of monocytes.
  • Third spacing. If a lot of fluid from the bloodstream becomes trapped in tissues (third spacing), there is less fluid in the bloodstream so it makes it look like there are too many cells. As I mentioned above, this is not really a scenario where you are making too many white blood cells, it just looks like that on a blood test.

For additional reading, please visit the following posts:

Allergic effector unit: The interactions between mast cells and eosinophils

Anemia of chronic inflammation

Effect of anemia on mast cells

Explain the tests: Complete blood cell count (CBC) – White blood cell count

Explain the tests: Complete blood cell count (CBC) – High white blood cell count

Explain the tests: Complete blood cell count (CBC) – Low white blood cell count

Mast cell disease and the spleen

MCAS: Anemia and deficiencies

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

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

Third spacing

 

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 74

I get asked a lot about how mast cell disease can affect common blood test results. I have broken this question up into several more manageable pieces so I can thoroughly discuss the reasons for this. The next few 107 series posts will cover how mast cell disease can affect red blood cell count; white blood cell count, including the counts of specific types of white blood cells; platelet counts; liver function tests; kidney function tests; electrolytes; clotting tests; and a few miscellaneous tests.

  1. How does mast cell disease affect red blood cell counts?

There are several ways in which mast cell disease can make red blood cell count lower.

  • Anemia of chronic inflammation. This is when chronic inflammation in the body affects the way the body absorbs and uses iron. It can result in iron deficiency. Iron is used to make hemoglobin, the molecule used by red blood cells to carry around oxygen to all the places in the body that need it. If there’s not enough iron to make hemoglobin, the body will not make a normal amount of red blood cells.
  • Vitamin and mineral deficiencies. Like I mentioned above, chronic inflammation can affect the way your body absorbs vitamins and minerals through the GI tract, and the way it uses vitamins and minerals that it does absorb. While iron deficiency is the most obvious example of this, deficiency of vitamin B12 or folate can also slow red cell production.
  • Swelling of the spleen. This can happen in some forms of systemic mastocytosis, and may also happen in some patients with mast cell activation syndrome, although the reason why it happens in MCAS is not as clear. Swelling of the spleen can damage blood cells, including red blood cells, causing lower red blood cell counts. If the spleen is very stressed and working much too hard, a condition called hypersplenism, the damage to blood cells is much more pronounced. This may further lower the red blood cell count. Hypersplenism occurs in aggressive systemic mastocytosis or mast cell leukemia. It is not a feature of other forms of systemic mastocytosis and I am not aware of any cases as a result of mast cell activation syndrome.
  • Medications. Some medications that are used to manage mast cell disease can cause low red blood cell count. Chemotherapies, including targeted chemotherapies like tyrosine kinase inhibitors, can cause low red blood cell count. Medications that specifically interfere with the immune system can do the same thing, including medications for autoimmune diseases like mycophenolate. Non steroidal anti-inflammatory drugs (NSAIDs) are used by some mast cell patients to decrease production of prostaglandins. They can interfere with red blood cell production in the bone marrow and also cause hemolytic anemia, when the immune system attacks red blood cells after they are made and damages them.
  • Excessive bleeding. Mast cell disease can cause excessive bleeding in several ways. Mast cells release lots of heparin, a very potent blood thinner that decreases clotting. This makes it easier for the body to bleed. It is not unusual for mast cell patients to have unusual bruising. Bleeding in the GI tract can also occur. Mast cell disease can cause ulceration, fissures, and hemorrhoids, among other things. Mast cell disease can contribute to dysregulation of the menstrual cycle, causing excessive bleeding in this way.
  • Excessive production of other types of blood cells. In very aggressive forms of systemic mastocytosis, aggressive systemic mastocytosis or mast cell leukemia, the bone marrow is making huge amounts of mast cells. As a result, the bone marrow makes fewer cells of other types, including red blood cells. Some medications can also increase production of other blood types, causing less production of red cells. Corticosteroids can do this.
  • Excess fluid in the bloodstream (hypervolemia). In this situation, the body doesn’t actually have too few red blood cells, it just looks like it. If your body loses a lot of fluid to swelling (third spacing) and that fluid is mostly reabsorbed at once, the extra fluid in the bloodstream can make it look like there are too few red cells if they do a blood test. This can also happen if a patient receives a lot of IV fluids.

There are also a couple of scenarios where mast cell disease can make the red blood cell count higher. This is much less common.

  • Chronically low oxygen. If a person is not getting enough oxygen for a long period of time, the body will make more red blood cells in an effort to compensate for the low oxygen. This could happen in mast cell patients with poor oxygenation.
  • Third spacing. If a lot of fluid from the bloodstream becomes trapped in tissues (third spacing), there is less fluid in the bloodstream so it makes it look like there are too many cells. As I mentioned above, this is not really a scenario where you are making too many red blood cells, it just looks like that on a blood test.

For additional reading, please visit the following posts:

Anemia of chronic inflammation

Effect of anemia on mast cells

Effects of estrogen and progesterone and the role of mast cells in pregnancy

Explain the tests: Complete blood cell count (CBC) – Low red cell count

Explain the tests: Complete blood cell count (CBC) – High red cell count

Explain the tests: Complete blood cell count (CBC) – Red cell indices

Gastrointestinal manifestations of SM: Part 1

Gastrointestinal manifestations of SM: Part 2

Mast cell disease and the spleen

Mast cells, heparin and bradykinin: The effects of mast cells on the kinin-kallikrein system

MCAS: Anemia and deficiencies

MCAS: Blood, bone marrow and clotting

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 3

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 12

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 19

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 20

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 45

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

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

Third spacing

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