The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 82

95. How do you take oral cromolyn?

  • Cromolyn is a mast cell stabilizer. Most mast cell patients are on cromolyn. Currently, it is taken orally for use in the GI tract, or it is taken nebulized for use in the lungs.
  • Cromolyn is an incredibly finicky substance. It sticks to everything. Your body barely uses it: only 2% of cromolyn is actually absorbed in the GI tract and only 5% in the lungs. The cromolyn that is absorbed is actually not the cromolyn that helps stabilize mast cells. The rest basically just sits on top of cells in the GI tract or lungs and stabilizes mast cells that way.
  • In order to maximize benefit from cromolyn, it is important that it not be taken when there is food or medications that cromolyn could stick to. This is mostly an issue for oral cromolyn used in the GI tract. You do not want to take other medications too close to taking cromolyn because the cromolyn may stick to the other med and not be available to stabilize mast cells. You do not want to eat too close to taking cromolyn because the food could stick to cromolyn, making it unavailable to stabilize mast cells, or the food could block the cromolyn from getting to the surface of the mast cells, preventing it from stabilizing them.
  • Oral cromolyn is usually taken 30 minutes before meals and at bedtime for a total of four times daily. Cromolyn should not be taken until two hours or more after eating the previous meal as this is about how long it takes for food to move out of the stomach. It is worth noting that many mast cell patients have gastroparesis or impaired GI motility which can cause food to stay in the stomach longer. There is no particular recommendation on what to do in this instance.
  • Ampules of cromolyn need to be stored at room temperature and protected from light. The ampules should not be taken out of the foil packs until you are using them. They should not be mixed ahead of time.
  • The intended dose for oral cromolyn in mast cell patients is usually 200 mg (two ampules) four times a day. Patients usually do better when they gradually increase the amount of cromolyn they are taking rather than starting at that dose. How slowly they increase varies widely. Patients should speak with their providers about an appropriate dosing schedule. There is lots of information about this in patient groups and forums.

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 79

92. Why is ketotifen not FDA approved? How do I get it?

Ketotifen is a mast cell stabilizer that is also an H1 antihistamine. It is regularly cited by mast cell patients as one of the more effective meds for managing mast cell disease, especially food intolerance. But it can be tricky to get ahold of in the US.

Firstly, ketotifen actually is FDA approved. It is FDA approved in eye drops. However, the formulation typically used by mast cell patients is oral. Oral ketotifen has not been approved in the US, but it’s not because it’s dangerous. It’s because it was never submitted to the FDA for approval. And why was it not submitted? Again, not because it’s dangerous. At the time, the manufacturer did not feel that there was enough of a market to justify the time and expense of an FDA submission when there were so many other H1 antihistamines available both over the counter and with prescription. It’s that simple.

So how do you get ketotifen in the US? You can import it from abroad for personal use as a mast cell patient, but there is an easier way: ketotifen capsules can be bought through compounding pharmacies who order the powder and put it in capsules. The most common strength for capsules is 1mg. Your provider just writes a prescription for it and the compounding pharmacy puts it together for you. As a side note, insurance often does not cover compounded medications so be prepared for that.

Because there wasn’t an FDA submission, there is less safety and dosing information available. In adults, dosing typically starts at 2-3mg a day. Some providers use much higher doses, even going upwards of 20mg per day in some instances. Again, we don’t have study data on this drug in mast cell disease, so conservative dosing is common.

Ketotifen is available as a tablet without a prescription in many countries, including Canada.

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 78

91. How long should it take to know if a medication is working?

  • This topic is controversial and how long to trial meds is not agreed upon. It varies by provider. This is because there haven’t been many studies done on how long it takes to see therapeutic effects in mast cell patients.
  • Firstly, this question is not “how long does it take for a medication to become active after I take it.” This question is how long you should keep taking a new medication to see if it helps your disease.
  • Firstly, when you are trialing a new medication, or even a new medication dose, try as hard as possible to not change anything else at the same time. It is easier to do this for medication that has short term benefits. I realize this is not always possible, and when it is, it is still a pain.
  • However, you really do need to be able to tell if any changes that occur are from the medication change or not. For example, if you are trying a new antihistamine, and two days after you start it, you also increase your dose of another med, and two weeks later you feel better, you are going to have no idea if it was the new antihistamine or the dose increase of the other med that helped.
  • In my experience, this leads to people being on a ton of meds that don’t all help. Some of us are on a ton of meds that actually help and that can’t always be prevented, but a lot of people just keeping adding things on top of one other without being sure they help. This can really complicate things down the line.
  • How long I trial meds has always been determined by how long it takes for them to cause notable changes in clinical symptoms. Because there aren’t a lot of studies on this topic in mast cell patients, it is common to use recommended time frames found in literature for other cells or other diseases.
  • If they have immediate short term benefits, I trial them for two weeks. Medications that block mediators from acting, like antihistamines and leukotriene inhibitors, are in this group.
  • If they have moderate term benefits, I trial them for six weeks. Medications that prevent mediators from being made, like COX inhibitors for prostaglandins or 5-lipoxygenase inhibitors like zileuton, are in this group.
  • If they have long term benefits, I trial them for sixteen weeks. Mast cell stabilizers like cromolyn and ketotifen and biologics like anti-IgE therapies are in this group.
  • If meds have mixed term benefits (like short term and long term effects), I trial them for the longer term.
  • Please note that steroids are a special case here because they have so many effects that are short, moderate and long term. People generally see immediate relief from them but they really are not meds that should be taken regularly if it can be avoided due to the slew of dangerous side effects.
  • These time frames have been recommended to me by my care team but you will need to discuss this with your own care team. I have found literature supporting these time frames necessary to produce clinical changes in other cell types or diseases.
  • I would also like to mention that in the past, I thought that four weeks was the appropriate period for trialing meds with short term benefits like antihistamines. I now feel that a two week trial is sufficient to identify benefits from these meds.
  • Please also note that for advanced systemic mastocytosis, including aggressive systemic mastocytosis and mast cell leukemia, there have been studies that have identified optimal duration of therapy to see a response for interferon and chemotherapies.

 

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 76

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.

89. How does mast cell disease affect platelet counts?

Before I continue, I want to explain one basic fact. Even though they are often included in the term “blood cells”, platelets are not actually cells. They are actually pieces of an original large cell called a megakaryocyte that lives in the bone marrow. Even though platelets are not really cells, they more or less act like they are.

An unusual thing about platelets is that sometimes a specific trigger can cause platelets to become lower or higher.

There are several ways in which mast cell disease can make platelet counts lower.

  • 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 and platelets, causing lower platelet counts. If the spleen is very stressed and working much too hard, a condition called hypersplenism, the damage to blood cells and platelets is much more pronounced. This may further lower platelet counts. 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 platelet counts. Non steroidal anti-inflammatory drugs (NSAIDs) are used by some mast cell patients to decrease production of prostaglandins. They can interfere with platelet production in the bone marrow. Proton pump inhibitors, often used by mast cell patients to help with GI symptoms like heart burn, can decrease platelet coun Some H2 antihistamines can also lower platelet production. However, none of these H2 antihistamines are currently used in medicine.
  • Heparin induced thrombocytopenia. Mast cells make and release large amounts of heparin, a powerful blood thinner. When there is an excessive amount of heparin circulating, it can cause your body to incorrectly produce antibodies that cause an immune response to heparin. A side effect of this situation is that platelets are activated incorrectly, which can lead to the formation of blood clots and low platelet counts. Heparin induced thrombocytopenia has only been definitively described in patients who receive medicinal heparin as a blood thinner. However, it is reasonable to assume that this situation can also affect mast cell patients who have higher than normal levels of platelets circulating in the blood.
  • Liver damage. Liver damage is associated with malignant forms of systemic mastocytosis such as aggressive systemic mastocytosis and mast cell leukemia. Liver damage can also occur as the result of IV nutrition, which is sometimes needed by patients with mastocytosis or mast cell activation syndrome. When the liver is damaged enough, it may not make enough of the molecules that tell the bone marrow to make platelets.
  • Excessive production 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 platelets and cells of other types.
  • Vitamin and mineral deficiencies. 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. Deficiency of vitamin B12 or folate can decrease platelet production.
  • Excess fluid in the bloodstream (hypervolemia). In this situation, the body doesn’t actually have too few platelets, 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 platelets if they do a blood test. This can also happen if a patient receives a lot of IV fluids.

There are also reasons why mast cell disease can cause the body to make too many platelets.

  • 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 deficiency can increase platelet counts.
  • Hemolytic anemia. In hemolytic anemia, the body destroys red blood cells. This can happen for several reasons that may be present in mast cell patients. Hemolytic anemia can increase platelet counts.
  • Iron deficiency. Iron deficiency for any reason can elevate platelet counts.
  • 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. It is not unusual for mast cell patients to have GI bleeding, as well as ulceration, fissures, and hemorrhoids.
  • Sustained GI inflammation. Sustained GI inflammatory disease can cause elevated levels of platelets. Given what we know about mast cell driven GI inflammation, it is reasonable to infer that mast cell GI effects and damage may also elevate platelet levels.
  • Clot formation. If a large clot forms, it can affect the amount of platelets circulating in the blood. Some mast cell patients require central lines for regular use of IV therapies or to preserve IV access in the event of an emergency. Blood clots can form on the outside surface of the line, inside the line, or between the line and the wall of the blood vessel it is in.
  • General inflammation. Platelets are activated by a variety of molecules released when the body is inflamed for any reason. This can translate to increased levels of platelet production.
  • Allergic reactions. Platelets can be directly activated by mast cell degranulation through molecules like platelet activating factor (PAF).
  • Heparin. Heparin can cause platelet levels to increase. As I mentioned above, it can also cause platelet levels to decrease.
  • Removal of the spleen. The spleen can become very stressed and work too hard, a condition called This situation is remedied by removing the spleen. 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.
  • Glucocorticoids. In particular, prednisone is known to increase platelet counts. Prednisone and other glucocorticoids can be used for several reasons in mast cell patients.
  • 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

Mast cell disease and the spleen

MCAS: Anemia and deficiencies

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

MCAS: Blood, bone marrow and clotting

Third spacing

Gastrointestinal manifestations of SM: Part 1

Gastrointestinal manifestations of SM: Part 2

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

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 66

80. When is chemotherapy necessary for mast cell disease?

  • For mastocytosis patients, chemotherapy is used for patients with systemic mastocytosis in whom the disease is malignant (aggressive systemic mastocytosis or mast cell leukemia) or seems to be progressing towards a cancerous form of the disease (smoldering systemic mastocytosis). There are very clear cut guidelines for this. Interferon and chemotherapy are used when a patient has smoldering mastocytosis with increasing mast cell counts; aggressive systemic mastocytosis; or mast cell leukemia, in order to kill off mast cells to slow disease progression and extend a patient’s lifespan.
  • A patient who already meets the criteria for systemic mastocytosis, who has two or more B findings, is considered to have smoldering systemic mastocytosis. SSM is a transition state between indolent SM, which has a normal lifespan, and malignant forms of mast cell disease, including ASM and MCL.
  • Having two or more of the following gets you a diagnosis of SSM: mast cell aggregates that take up 30% or more of cells in a bone marrow biopsy, and/or serum tryptase over 200 ng/mL; bone marrow with too many cells in it overall, without evidence of MDS or a myeloproliferative neoplastic disease; or organ swelling that has not yet affected organ function (swelling of the liver without ascites, spleen swelling enough that it can felt by palpation, lymph nodes swollen to 2 cm or larger).
  • Patients with SSM are watched to see if their body is making lots of mast cells quickly, or if their organs are feeling the strain of too many mast cells. One of the way they check this is to see how quickly their tryptase level increases. If their provider feels that their disease is progressing, they receive chemo or interferon to try and knock the disease down enough that they don’t reach the criteria for ASM.
  • Patients are diagnosed with ASM if they meet the criteria for SM and any of the following criteria: the body not making enough blood cells, cytopenia (absolute neutrophil count below 1000/ul, hemoglobin below 10g/dl, or platelets below 100000/ul); swelling of the liver along with free fluid in the abdomen (ascites), elevated liver enzymes, or portal hypertension; swelling of the spleen along with decreased blood cells due to damage in the spleen, excessive production of blood cells by the bone marrow to compensate, and likely resolution if the spleen is removed; malabsorption in the GI tract causing low protein in the blood (albumin) and weight loss; and severe bone dysfunction, causing a series of bone breaks and large osteolytic lesions from mastocytosis.
  • ASM patients are put on chemotherapy or interferon, usually continuously, unless there is evidence that they have killed off enough mast cells to have a less dangerous disease category.
  • Mast cell leukemia patients are on chemotherapy continuously.
  • There is no described use for chemo in cutaneous mastocytosis.
  • There are situations where patients with other disease categories (ISM, MMAS, MCAS) are put on chemo drugs to try and manage symptoms or shock episodes after all other therapies have failed. While this has been mentioned in literature, there have been no studies on it.
  • Chemo drugs should be used as a last resort. They can have significant side effects and complications that cannot always be remedied by stopping the treatment.
  • Please note that while newer, targeted chemos have become more common, they are in fact chemotherapy and carry significant risks despite being more tailored, including the potential for organ damage or failure.

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, MCS 

The Provider Primer Series: Mast cell activation syndrome (MCAS)

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

I answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

28. Why are so many mast cell patients anemic?
• Anemia occurs when a person has too few red blood cells or not enough hemoglobin. Red blood cells are essentially envelopes that serve specifically to hold hemoglobin. Hemoglobin is a molecule made with iron that picks up oxygen. When you have either too few red blood cells or they don’t have enough hemoglobin, not enough oxygen gets to all the parts of the body that need it.
Patients with chronic illness of many kinds often have anemia. This is called anemia of chronic inflammation or anemia of inflammatory response.
• This type of anemia occurs because of the overactivity of a hormone called hepcidin. This hormone tells cells in the GI tract to hold onto any iron they find. This means they do not pass the iron along to the blood so it can make hemoglobin. Since the body isn’t making enough hemoglobin, the body doesn’t get enough oxygen.
• Mast cell patients often have anemia of chronic inflammation so they may be anemic regardless of how much iron they have in their diet. However, increased supplementation sometimes helps.
• There are several forms of iron that can be taken by mouth. IV iron is also an option. Some people have luck cooking in cast iron pans or using the “Lucky Iron Fish” to get even more iron into their diet in hopes that they can take up a little bit more.
Having enough iron available also decreases mast cell activation. Mast cells make smaller amounts of inflammatory molecules when the body has sufficient iron.
• Mast cell patients may also selectively malabsorb iron in their GI tracts. This means that even if they are absorbing enough of other nutrients, they may not absorb enough iron properly due to inflammation. This sometimes improves with antihistamines.
• Mast cell patients usually take histamine H2 blockers. This decreases the strength of stomach acid which can affect absorption of nutrients like iron. Taking PPIs can do the same thing.
• Malabsorption of other nutrients, like copper, can contribute to anemia.
• Insufficient amounts of B12 or folate can cause also contribute to anemia.

For more detailed reading, please visit these posts:
Anemia of chronic inflammation
MCAS: Anemia and deficiencies
Effect of anemia on mast cells

The MastAttack 107: The Layperson’s Guide to Mast Cell Diseases, Part 17

I answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

25. How do I know what I will react to?
There is no way to definitively know what things will make you react. It is difficult to predict. There are some general guidelines many of us use to figure out what may be a problem but the only way to really know is to try something.
• Please note that because mast cell reactions are not known to be triggered by the same mechanisms as traditional allergies, you cannot exclude an entire class of drugs because you react to one in the way that you do for traditional allergies. This is particularly worth noting for opiates: reaction to morphine, for example, does not exclude fentanyl or hydromorphone.
• Mast cell reactions are not inherently triggered by IgE the way that “true” allergies are. This means that blood tests for IgE allergies will not identify triggers accurately for most mast cell patients. (Although some mast cell patients do have some IgE allergies.)
• Additionally, skin testing is wildly inaccurate in mast cell patients because of how reactive our skin is.
Stopping antihistamines is dangerous for mast cell patients.
Allergy testing is not accurate for mast cell patients.
• There are several ways that various things can cause mast cell reactions. Generally, they do it in one of the following ways: they cause mast cells to empty the chemicals in their pockets into the body (degranulation); they cause mast cells to release chemicals in another way; they already contain significant amounts of histamine; or the interfere with the mechanisms for controlling mast cell activation.
There are a number of medications that can cause mast cell degranulation or histamine release. Please note that not all of these medications are problematic for every patient. Only a provider managing your case can determine if these are safe for you or not. The major medications that may cause degranulation or histamine are listed below. This list is not exhaustive.

-Alcohol: Widely used to sterilize body area, surfaces, or tools; also used when preparing many medications that are not soluble in water
-Amphoterecin: Antifungal
-Aspirin: NSAID, for pain, inflammation, to block prostaglandins, to prevent clot formation
-Atracurium, mivacurium, rocuronium: Muscle relaxant
-Caine anesthetics (esters): Anesthetics, to numb
-Codeine, morphine, meperidine: Opiates, for pain or cough
-Colistin: Antibiotic
-Dextran: Volume expander, used in surgical or emergency situations to improve blood pressure
-Dextromethorphan: Cough suppressant
-Miconazole: Antifungal
-Nefopam: For pain
-NSAIDs (non steroidal anti-inflammatory drugs): For pain, inflammation, blocking production of prostaglandin
-Polymyxin B: Antibiotic
-Radioopaque contrast: To visualize structures in medical scanning procedures
-Reserpine: High blood pressure medication and antipsychotic
-Succinylcholine: Paralytic used for surgical procedures
-Thiopental: Anesthesia induction for surgical procedures
-Vancomycin (especially IV): Antibiotic

• There are a number of medications that are known to interfere with the mechanisms for controlling mast cell activation. Adrenaline is naturally made by the body to help control mast cell activation and other activities. When you interfere with the ability of adrenaline to act, it can potentially trigger mast cell activation. Drug classes that do this include beta blockers and alpha adrenergic blockers. This is particularly an issue if there is a history of anaphylaxis because these medications can interfere with Epipens.
Many foods either contain histamine or can trigger mast cell release of histamine. As with medication, you cannot exclude an entire family of foods because you react to one in the way that you do for traditional allergies.
• There are many lists of foods to avoid. They often conflict with each other. There is not yet a definitive list available. Despite this, there are some general rules of thumb that are agreed upon on what to avoid.
• Products that are fermented, contain alcohol, are overly ripe or leftover from previous days (especially meats), or contain dyes or preservatives are generally excluded.
• Beyond this, recommendations vary a lot more. Many diets recommend excluding yeast, citrus fruits, and nightshade vegetables.
Many activities inherently activate mast cells. Being too hot, standing or sitting in direct sunlight, exercise, sexual activities, menstruation, infection, and any type of physical trauma, even minor, can trigger mast cell activation as part of normal mast cell function.
Premedication is recommended for any medical procedure, even minor, as they can trigger mast cell activation.
• Patients may find that premedication prior to other activating activities is helpful for suppressing reactions.
Ultimately, the only way to know what is activating is through trial and error. Patients should consult their care team about what to trial, when, and how to make it as safe as possible.

For more detailed reading, please visit these posts:

Food allergy series: Mast cell reactions and the low histamine diet

The Provider Primer Series: Introduction to Mast Cells

The Provider Primer Series: Medications that impact degranulation and anaphylaxis

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 10

I have answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

17. Does mast cell disease impact mood, anxiety, and depression?
Yes. This has been described in literature for over 30 years. In 1986, a paper described a series of patients with systemic mastocytosis who had severe psychiatric symptoms as a result of their disease. It was called “mixed organic brain syndrome”.
Depression, anger, bipolar disorder, attention deficit disorders, anxiety, irritating, and panic disorders have all been associated with mast cell disease.
• One study found that in a group of patients with cutaneous mastocytosis and systemic mastocytosis, 75% of the patients had symptoms of depression. In another study, 60% had symptoms of depression or anxiety.
• Many patients have been diagnosed with a psychiatric condition before learning that they have mast cell disease. For many mast cell patients, managing their diseases lessens the severity of their psychiatric symptoms. Antihistamines have been reported many times to improve these symptoms.
• Mast cells are often sitting right next to nerve cells throughout the body. Mast cells are found in large numbers in the brain. Chemicals released by mast cells can cause psychiatric symptoms.
• Some of the chemicals released by mast cells are specifically intended to talk to nerve cells. Histamine is one such chemical. When histamine is not released in the right amounts at the right times, it can affect how other chemicals are released. Some of these chemicals are also for cells to talk to nerves, like serotonin and dopamine. Mast cells can also release serotonin.

18. Are medications for depression, anxiety or other psychiatric conditions used in mast cell patients?
Yes. As with every medication, only you and your care team can decide if a medication is safe for you. No medication is universally safe or always dangerous.
Benzodiazepines are usually well tolerated in mast cell patients. Benzodiazepines actually interact with mast cells and can make them release fewer chemicals. (Be aware that the IV forms of these medications sometimes have alcohol in them).
SSRIs are sometimes taken by mast cell patients. Mast cell patients should be cautious because they can increase serotonin levels and mast cells can also release serotonin.
• Tricyclic antidepressants are more commonly used in mast cell patients. Tricyclic antidepressants actually work as antihistamines, too.
• Other drugs that can manage psychiatric symptoms, like mirtazapine, olanzapine, and quetiapine, also have antihistamine properties.
For more detailed reading, please visit these posts:

 

Neuropsychiatric features of mast cell disease: Part 1 of 2

Neuropsychiatric features of mast cell disease: Part 2 of 2

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 9

I have answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

15. How is mast cell disease treated?
• There are a number of medications to treat mast cell disease. Mast cells release so many chemicals, some in a large quantity. We are not able to totally stop mast cells from releasing the chemicals so we need to use many medications to block their effects on the body.
The baseline regimen for mast cell patients include antihistamines and mast cell stabilizers. Specifically, patients are usually prescribed two antihistamines that work two different ways. These are called H1 antihistamines and H2 antihistamines. The H in these meds stand for histamine. There are many antihistamine options. Antihistamines stop the histamine from working in the body. Even still, many patients experience histamine driven symptoms
Mast cell stabilizers work by making mast cells less likely to release chemicals. There are fewer options for mast cell stabilizers. Cromolyn is a very common mast cell stabilizer. Ketotifen is both a mast cell stabilizer and an antihistamine. Ketotifen that you can take as a pill is not approved in the US because there was not a market for it so it was never submitted to the FDA. However, patients can get ketotifen in pill form through compounding pharmacies in the US.
• Other types of medication commonly used for mast cell disease that block the effect of mast cell chemicals include leukotriene inhibitors and PAF blockers.
Some medications can stop mast cells from making specific chemicals. These include COX inhibitors, lipoxygenase inhibitors, and corticosteroids like prednisone.
Many patients are deficient in some vitamins or minerals because they don’t absorb them well in the GI tract. Vitamin D and iron are commonly low. Patients often take supplements to replace these deficiencies.
• Chemo drugs are sometimes used to treat severe mast cell disease. These drugs can kill mast cells and/or decrease the amount of chemicals released.
• IV fluids are reported by patients to help with symptoms such as fatigue and swelling.
• There are many other medications that can be used to treat other symptoms.

16. Do I have to take medication if I feel okay?
Mast cell patients are usually recommended to take baseline medications like antihistamines and mast cell stabilizers even if they feel okay. This is for two main reasons: mast cells can damage your body even if you don’t feel it; and if you do not take baseline medications, you will have less protection from a severe reaction and anaphylaxis.
• Many patients have other medications prescribed to be taken as needed. These medications are given when symptoms are bad and do not necessarily have to be taken daily.
• Please speak with your provider to clarify what meds are taken as needed and what meds are taken every day.
For more detailed reading, please visit these posts:

The Provider Primer Series: Management of mast cell mediator symptoms and release

The Provider Primer Series: Mast cell activation syndrome (MCAS)

The Provider Primer Series: Cutaneous Mastocytosis/ Mastocytosis in the Skin

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

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (SM-AHD, MCL, MCS)

Beta blockers and epinephrine

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

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

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

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

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

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

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

 

References:

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

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