The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 65

79. Do probiotics help GI symptoms from mast cell disease?

  • Some people may not be aware of this, but my first science love was microbiology. I love bacteria. They are my teeny little super guys. Mostly because they make the world go round. <3
  • Yes, probiotics help symptoms from mast cell disease.
  • Your body is populated with millions and millions of microbes in just about every place where your body comes into contact with the outside world. This is mostly skin, GI tract, GU tract, and upper respiratory tract.
  • This is an example of symbiosis: the science term for “everybody wins.” Microbes get a steady source of food and protection from the outside world by living attached to some part of us. In return, they help us to break down molecules, make vitamins for us, and help protect us from infections by taking up all the available microbe real estate. If there’s already friendly bacteria (or yeast) living in every available place where microbes could attach to us, that helps to protect us from not so friendly microbes who need a place to latch on.
  • Antibiotics and antimicrobials are in tons of over the counter of products. We are in an age where antibiotics and antimycotics are being used more than ever, often in situations where they can’t even provide benefit.
  • These have the effect of killing off all the helpful microbes, leaving us in a situation where the ones that are left are the most resistant to treatment. This is a huge problem for a number of reasons, the biggest one being the genesis of super bugs, antibiotic resistant organisms that we can’t kill.
  • But there’s another big reason: when you kill off helpful bacteria, it affects our day to day bodily functions. Our bodies have evolved to have this symbiotic relationship with these organisms for millennia. When we kill all those little super guys off, our body is open to infections and situations that cause inflammation.
  • The population of microbes that normally lives happily inside our healthy bodies is called our commensal. If it’s in the GI tract, it’s called the GI commensal.
  • We know for sure that food allergies is related at least partially to changes in the GI commensal.
  • There are a number of experiments that show that if you take the GI commensal out of a healthy mouse and transplant it into a food allergic mouse, that mouse is no longer food allergic. We also know that if you take the GI commensal out of a food allergic mouse and transplant it into a healthy mouse, now you have two food allergic mice.
  • Probiotics contain microbes that you can use to replace the good ones that have been killed off. Mast cell patients, and patients with other inflammatory GI diseases, report a lot of benefit with using probiotics. Mast cell patients have to be careful and need to be sure to look up the ingredients of every probiotic they try, as many of them contain triggers, like lactose. VSL3 often works pretty well in people who are reactive. Culturelle is used by lots of patients. It depends on a lot. Your mileage may vary.
  • People with central lines should use caution and always be sure to wash hands and sterilize surfaces between taking probiotics and using their lines. These organisms are not supposed to be introduced to the bloodstream and could potentially cause infections, especially in people with depressed immunity.
  • I would to give a shout out to MastAttack admin, Pari, who is the most relentless advocate for probiotics I have ever seen. She cares more about your use of probiotics than I care about most things.

Loud

I am a dramatic person by nature. This is directly at odds with the logical habits and orderly thinking of a scientist. As you might imagine, I am not infrequently conflicted on how to behave or how to react in many situations. I am also bossy. I like to be right. These aren’t good qualities but it’s who I am and I know it.

I’m also loud in just about every way. My hair is fire engine red. I have a violet streak behind my left ear. I wear large colorful glasses. I do unusual and interesting things to my hair and trap it with flower clips or jeweled hairpieces or brightly patterned bobby pins. I dress like a 50’s housewife. I am physically loud, owing largely to my hearing loss and my inability to modulate my own voice level, but I was loud before.

It is a different loudness I’m thinking about tonight. I’m thinking about the loudness of a voice when you scream for help. This is likely the only way in which I am not loud. I used to be. It was never helpful. I am self reliant in large part because I learned early that screaming for help because I was sick or something was wrong with my body was a fruitless endeavor. It never helped and I gained a reputation as being dramatic and attention seeking, a hypochondriac. I learned to swallow those sounds, the ones that signal that I am wounded, that tell the other creatures that I am prey. This unmet need formed the core of my self esteem as a teenager, or lack thereof.

I met up with an old friend this week, a guy I went to high school with. We were friends when I was starting to become aware that something was wrong with my body. I was always having weird health issues and had episodes of inexplicable severe abdominal pain at the most inopportune times. We chatted about my health, then and now.

“So you always had this and just found out about it as an adult?” He asked.

This is more or less what happened. I’m not convinced that everything I had as a teen was related to mast cell disease, but probably a lot of it was. He mentioned that at the time, he wasn’t sure what was going on, if I was sick or just dramatic. This didn’t upset me at all, and was not new information. We have discussed this in the past, some time ago.

“I actually wasn’t sure either,” I admitted. When so many people think you are just inventing these things, it’s hard not to become convinced yourself. Still, I haven’t often said this explicitly. It seems like a betrayal of my deepest self, the one that swallows those sounds, and feels unnecessarily loud.

It has been a long time since those days, when I was 16 and confused about what exactly was happening to me and how much my mental health played a role. But even now it is a reflex to think I am being too direct. I have to remind myself that telling the world what is happening to me is okay and that wanting empathy and help is okay. I’m gaining volume. But I don’t know that I’ll ever be loud.

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 64

78. Are vaccines contraindicated for people with mast cell disease?

  • What I describe here is a summary of the current state of expert recommendations on this topic. These are not the personal opinions of Lisa Klimas.
  • Generally, vaccines are not contraindicated based solely upon having mast cell disease.
  • The big reason for this is that we know for sure that infections are mast cell activating, in addition to the array of other issues caused by having a condition serious enough to require vaccination.
  • The idea is that if you have a mast cell reaction to a vaccine, it may still grant enough protection against a specific condition, or cross coverage for related conditions, that it may be worth it. Of course, whether or not this is the case depends on a LOT of factors.
  • Vaccination will cause some level of mast cell activation in everyone, mast cell patient or otherwise. This is part of the immune response a person generates that gives them immunity from the vaccine. There is no confusion about whether or not vaccines cause mast cell activation. They do. Every time.
  • It is my experience that the patients who react worst to vaccination are patients with mast cell activation syndrome rather than those with systemic or cutaneous mastocytosis. This is my view from 10,000 feet. There are, of course, exceptions.
  • It is also my experience that the patients who react worst to vaccination often do so because they have another condition where vaccination is contraindicated, like a metabolic disorder. Additionally, I find that many of those patients also have primary immunodeficiencies, meaning they may not be able to generate a vaccine response at all, therefore making vaccination a pointless endeavor for those particular people.
  • So there are some mast cell patients who should not receive vaccines. This is not, usually, because of their mast cell disease. For most of my mast cell patienthood, I have been pretty reactive. I am fully vaccinated and continue to receive vaccines as needed.
  • Mast cell patients should be aware that the normal premedication for procedures has to be modified for vaccination. Specifically, you can’t use systemic corticosteroids for two weeks prior to vaccination in order for the vaccination to be effective. (This excludes patients taking the dose equivalent of 6 mg prednisone or less daily.) This means that antihistamines are the primary method of premedication for vaccination.
  • (Author’s note: I have gotten lots of questions about corticosteroids and vaccination. Corticosteroids are immunosuppressive so they suppress your body’s ability to generate immunity to anything, including a vaccine. If a patient receives either continuous or short burst low dose corticosteroids within two weeks before or after vaccination, most providers feel there is still benefit. However, doses above this blunt the immune response and can cause an ineffective vaccine response. As always, please speak with your provider about how this specifically applies to you. It is possible there are scenarios that this does not cover. As always, this is not medical advice.)
  • Also, I am no way diminishing or arguing that vaccines cannot cause injuries. This post is not to address that.

Introducing Mikal

We are in the process of making some changes here at MastAttack, including building a team to help manage the site, the group, and access to me, in general. We recently have begun the process of digging through the huge backlog of email and FB questions for me. This will help to prioritize things that need my attention and allow me to focus more on my health, my job and my family.

I wanted to introduce everyone to Mikal Mowdy, who has come aboard to help with MastAttack. Many of you likely remember her daughter, Yzzy, who was cured of systemic mastocytosis and hemophagocytic lymphohistiocytosis when she received a bone marrow transplant in January. She has a wealth of mast cell knowledge and will help me to respond to questions.

Please join me in welcoming Mikal!

Lisa

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 63

77. Can you have anaphylaxis with high blood pressure?

  • Yes.
  • The misconception that a person with high blood pressure cannot be experiencing anaphylaxis is enduring and dangerous.
  • Author’s note: Thanks to the intrepid reader who caught a big typo right here. When I published the post, it said, “The misconception that a person with high blood pressure can be experiencing anaphylaxis is enduring and dangerous.” This is a whopper mistake. It should say,  “The misconception that a person with high blood pressure canNOT be experiencing anaphylaxis is enduring and dangerous.” You CAN have high blood pressure and anaphylaxis at the same time. Thanks again!
  • Lots of providers (and patients) think that high blood pressure rules out anaphylaxis. This is not true.
  • This misunderstanding comes from confusing two closely related but distinct concepts: anaphylaxis and anaphylactic shock.
  • Anaphylaxis is a severe allergic reaction affecting multiple organ systems.
  • Anaphylactic shock is when anaphylaxis causes such poor blood circulation that the heart cannot pump out enough blood to the body.
  • Anaphylactic shock is a form of circulatory shock, which means exactly what I just described: oxygenated blood is not being pumped out of the heart and through the blood vessels to the tissues that need it.
  • Anaphylactic shock is defined as blood pressure 30% below the patient’s baseline or a systolic blood pressure below 90 mm Hg. The systolic blood pressure is the top number when you get your blood pressure checked. If that top number is below 90 mm Hg, and that is the result of anaphylaxis, you are in anaphylactic shock.
  • Anaphylactic shock is the most serious potential complication of anaphylaxis. Anaphylactic shock happens when the chemicals released by mast cells cause a lot of the fluid in the bloodstream to “fall out” of the bloodstream and get stuck in the tissues.
  • When this happens, that fluid loss causes the blood pressure to drop. In response, the heart beats faster to try and use the blood it still has left to get oxygen to the body. However, at a certain point, even beating really fast is not enough to get enough blood to the tissues. At this point, shock sets in.
  • Anaphylactic shock occurs specifically as a result of low blood pressure. Because of this, providers strongly associate low blood pressure with anaphylaxis. They may not realize that while a person with high blood pressure cannot be having anaphylactic shock, they can be having anaphylaxis.
  • Part of the confusion is that anaphylaxis has been defined lots of different ways by many different groups. I have written a very detailed post about this (see the link below). Even today, exactly what constitutes anaphylaxis not agreed upon by everybody.
  • The most widely used criteria in the US are the criteria published in 2006 by the World Allergy Organization journal. These criteria explicitly state that a person does not need to have low blood pressure to be having anaphylaxis. A person can meet these criteria based upon a variety of combinations of symptom and vital signs that do not include low blood pressure.

2006 WAO Anaphylaxis Criteria

For additional information, 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 49

 

 

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 62

76. Is it true that allergic reactions can cause heart attacks?

  • Yes.
  • Kounis Syndrome is an acute coronary syndrome caused by activated mast cells releasing chemicals. It is sometimes referred to as “allergic heart attack.” In acute coronary syndrome, there is not enough blood being pumped into the heart. It is named for two of the large blood vessels supplying oxygen to the heart, the coronary arteries. When not enough blood is getting to the heart via the coronary arteries, it can damage heart muscle, sometimes permanently. Heart attack and angina are examples of acute coronary syndromes.
  • In Kounis Syndrome, mast cells become activated, releasing lots of chemicals. These chemicals can irritate the coronary artery, causing it to spasm. This spasm reduces the amount of blood getting to the heart. Sometimes, mast cell activation can trigger the formation of a clot. A clot can be the reason not enough blood is passing through the artery.
  • Several of the molecules released by mast cells can affect the cardiovascular system and contribute to causing Kounis Syndrome. Histamine and leukotrienes can cause the coronary artery to narrow. It can also activate platelets, helping a clot to form. Both tryptase and chymase can cause clots formed elsewhere to break off and get stuck in the coronary artery.
  • Mast cells also help regulate an important molecule called angiotensin II. Angiotensin II is a powerful regulator of blood pressure and can cause the coronary artery to narrow and tighten up.
  • People with Kounis Syndrome may have a history of coronary artery disease. Some patients have a stent in the coronary artery from a previous coronary issue. A stent is a tube that helps keep the blood vessel the right size so that the heart gets the blood it needs. However, many patients with Kounis Syndrome do not have any history of problems with their heart or blood vessels.
  • The symptoms of Kounis Syndrome sometimes look just like the symptoms of any other mast cell reaction or anaphylaxis, making it hard to know that a person is having Kounis Syndrome. Chest pain, irregular heart beat, the heart beating too fast or too slow, and palpitations are all common symptoms of Kounis Syndrome.
  • Another tricky thing about Kounis Syndrome is that it doesn’t always show up on the tests we use to look for heart attack or coronary issues. Because of this, doctors don’t always realize what is happening. Some people do have positive results to these tests, things like EKG, echocardiogram, chest x-ray, and bloodwork to look at levels at cardiac enzymes or troponin. Cardiac enzymes and troponins are often high in a person who is having a heart attack but are sometimes normal for patients with Kounis Syndrome.
  • In order to manage Kounis Syndrome, patients may need treatment for both the allergic reaction and the coronary syndrome.
  • Treatment for the allergic reaction is similar to anaphylaxis treatment: an H1 antihistamine like Benadryl, an H2 antihistamine like famotidine, a corticosteroid like methylprednisolone, IV fluids, and sometimes epinephrine, if that’s appropriate. Please note that epinephrine is not always appropriate for patients who have Kounis Syndrome because epinephrine can actually also cause the coronary artery to narrow.
  • Treatment for the cardiovascular aspect of Kounis Syndrome is very dependent upon symptoms and test results. Calcium channel blockers like verapamil, aspirin, and nitroglycerin are commonly used. Importantly, some of the common medications used to manage coronary syndrome are not safe for mast cell patients. These medications include beta blockers like metoprolol or atenolol, and, to a lesser extent, ACE inhibitors like lisinophil. These medications can interfere with epinephrine so epinephrine may not work if a patient needs it for anaphylaxis.
  • Anything that triggers mast cell activation can cause Kounis Syndrome, including emotional stress.

For additional information, please visit the following posts:
Kounis Syndrome: Subtypes and effects of mast cell mediators (Part 1 of 4)
Kounis Syndrome: Diagnosis (Part 2 of 4)
Kounis Syndrome: Treatment (Part 3 of 4)
Kounis Syndrome: Stress (Part 4 of 4)
Beta blockers and epinephrine
Cardiovascular manifestations of mast cell disease: Part 1 of 5
Cardiovascular manifestations of mast cell disease: Part 2 of 5
Cardiovascular manifestations of mast cell disease: Part 3 of 5
Cardiovascular manifestations of mast cell disease: Part 4 of 5
Cardiovascular manifestations of mast cell disease: Part 5 of 5
The Provider Primers Series: Medications that impact mast cell degranulation and anaphylaxis

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 61

75. What other diseases and disorders are commonly associated with mast cell disease?

I often joke that it would be easier to list what conditions are not commonly associated with mast cell disease because so many conditions occur alongside it. However, there are some conditions that you see a lot in the mast cell population relative to others. In every instance, mast cell disease has the potential to irritate the other condition and vice verse.

Clonal hematologic disorders. Systemic mastocytosis is so frequently accompanied by other blood disorders that it has a diagnosis specifically for this phenomenon: systemic mastocytosis with associated hematologic disorder (SM-AHD). It is estimated that up to 40% of patients with SM eventually develop another clonal hematologic disorder. A clonal hematologic disorder is a condition in which your bone marrow makes too many blood cells. Examples include chronic myelogenous leukemia, acute myeloid leukemia, polycythemia vera, myelofibrosis, and essential thrombocythemia.

Unlike mastocytosis, MCAS can occur secondarily to lots of conditions. In some instances, it’s not clear if the MCAS is secondary to a condition or the condition is secondary to MCAS or neither.

Heritable connective tissue diseases. Ehlers Danlos Syndrome (EDS), is the most common connective tissue disease in the mast cell population. There are multiple types of EDS. While hypermobility type EDS (formerly called Type III) is the most common in MCAS patients, other forms occur also. Other connective tissue diseases seen in mast cell patients include Marfan Syndrome and Loeys-Dietz Syndrome.

Dysautonomia. Dysautonomia is a condition in which your body’s autonomic nervous system doesn’t regulate essential bodily functions correctly. POTS is the most common form of dysautonomia found in mast cell patients but other forms occur, too.

Mast cell patients commonly have MCAS, EDS and POTS together. They cooccur so commonly that some experts think that that this presentation is actually one overarching disease rather than three separate ones affecting mast cell patients.

Eosinophilic GI disease. Mast cells are closely related to eosinophils. They activate eosinophils and eosinophils activate them. Mast cell patients sometimes have eosinophil GI disease where eosinophils activate to lots of triggers and damage the GI tract.

Immunodeficiency. Conditions that specifically impair a person’s immunity, especially those that affect T or B cells, like SCID or CVID, are not unusual in mast cell patients.

Gastrointestinal disease. Mast cells normally live in the GI tract so they are very sensitive to GI inflammation. MCAS can occur secondarily to lots of GI diseases. Crohn’s, ulcerative colitis, inflammatory bowel disease, and irritable bowel syndrome are examples. GI disorders that specifically affect motility are also seen in mast cell disease, like gastroparesis and chronic intestinal pseudoobstruction.

Allergies. Some mast cell patients have true IgE allergies or other allergic disorders like atopic dermatitis.

Autoimmune disease. Autoimmune disease is more common in MCAS patients than in SM patients. The specific disorder could be virtually any autoimmune condition, including rheumatoid arthritis, lupus, Hashimoto’s thyroiditis, autoimmune urticaria, and many others.

Adrenal insufficiency. The body’s mechanisms for produce stress hormones like cortisol can become dysregulated in mast cell patients. This results in a situation in which the body does not make enough steroids of its own to take care of the body during periods of stress. Patients with adrenal insufficiency are dependent upon daily steroids to stay safe.

Chiari malformation. This condition affects the space around a person’s brainstem, causing a wide array of symptoms. Some patients have surgery for this condition.

Asthma. It is difficult to draw an exact line where mast cell disease ends and asthma begins in mast cell patients as the symptoms can be virtually identical.

This list is not exhaustive. Many other conditions sometimes occur in mast cell patients.

For additional reading, please visit the following posts:
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

Somebodies

I’ve been trying to get this post out for a few days. I feel like it’s not finished and sharp in the wrong places but I feel like this needs to be said so I’m saying it now.

When I was first diagnosed with mast cell disease, I was pretty relieved. I had been sick a long time and was so tired of being abused by doctors and called a liar. I could have been diagnosed with anything. I could have been diagnosed with weekly limb falling off disease where every week one of my limbs fell off until I had no limbs left. I needed something to hold onto and a diagnosis had that. (I am grateful to announce that I do not have limb falling off disease.)

I do, however, have mast cell disease. It was a few months before it occurred to me that having mast cell disease might be scary. There wasn’t a lot of information available on it and I didn’t have great journal access then, so I wasn’t able to validate those fears. But I was still afraid. Just a little, at first. And then another several months past and I started having major organ involvement. And I started being afraid for real. This time, my fears were validated.

One of the more common questions I get is whether or not people can die from mast cell disease. I get it a lot from people who are newly diagnosed but I get it from people who have been diagnosed a while. I realized recently that people who have been diagnosed a while only ever ask me this question in private message or email. I’ve been thinking about why that is.

The answer is simple: people are afraid to ask if they can die from mast cell disease in a public forum because, overwhelmingly, the responses are not kind. I am guilty of this, too. Those of us who have been in this community a long time have learned to stratify mast cell patients by level of hematologic malignancy – that is, to separate mast cell patients into those who have malignant forms of mast cell disease (aggressive systemic mastocytosis, mast cell leukemia, and mast cell sarcoma) and those who don’t. Because typically the people who lose their lives to mast cell disease are those with those malignant forms, and those who don’t have them don’t die from mast cell disease. The medical institution views malignant mast cell disease as dangerous and the other forms as not dangerous. Specifically, the establishment touts to everyone who will listen that you don’t die from mast cell disease if it’s not malignant.

But the truth is that’s not really the case, if you think about disease and what it does to a person and all the ways it kills them. It’s true that a person with ASM is not likely to die in the same way as an MCAS patient. A patient with ASM will die from mast cell disease if the thousands of extra mast cells burrow into their organ tissue and destroy that tissue so much that the organ stops working. That’s not what happens in a patient with MCAS. But a patient with MCAS can die in other ways. They can die from anaphylaxis and complications of huge steroid doses and side effects from chemo and sepsis and not being able to afford their health care costs and not having insurance and not being able to face one more minute of the humiliation and desperation that is begging for care from people who don’t want to provide it. All of those things can kill a person, too.

Defining death from mast cell disease along by delineating along the lines of organ failure is disrespectful, unfair and missing the point. All of us who have spent years living inside the data of this disease have done it, including me, and we should be sorry. I am. It has never been my intention to characterize MCAS as less serious than other forms of mast cell disease but I think I did anyway, and whether or not I wanted to do it doesn’t change that. I am sorry for doing this. It is not okay. I am committed to doing better in the future.

Fall is a difficult time for mast cell patients. It’s a lot of change at once. It’s new routines and major environmental upheaval. It’s triggers on crack. Season changes are always hard for us but autumn is harder, I’m not sure exactly why. But in the same way that I associate September with ports, I associate fall with mast cell patients crashing and dying. This year has been no different.

In the last several weeks, we have lost a number of mast cell patients across a variety of diagnoses, to the tune of six in six weeks. It’s painful to even type that. One of them was my friend, an SM patient who died of complications of anaphylaxis. Another was a touchstone in the MCAS community, a young woman who did a great deal to comfort others, and who undoubtedly died of complications of MCAS. Still another died of suicide. These last few weeks have been so, so crushing.

There is a very, VERY good chance that you will live a full life with a normal lifespan as a mast cell patient. But it’s not enough to say that people don’t die from non-malignant forms of mast cell disease because “almost nobody does.” Those “almost nobodies” are somebodies, and they are people with lives and dreams and futures they don’t get to experience. They do not deserve to be lost in the data, digits rounded down to zero.

We owe it to them to remember that they were real and that they were here and that they mattered.

I owe it to them. So let’s do that.

Additional posts on prognosis and disease progression:

Progression of mast cell diseases (Part One)

Progression of mast cell diseases (Part Two)

Progression of mast cell diseases (Part Three)

Progression of mast cell diseases (Part Four)

Progression of mast cell diseases (Part Five)

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 15

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 48

On prognosis and dying from mast cell disease

I am not there. I do not sleep.

 

 

 

Clinical trials and data for laypeople, Part 2

The foundation of science is this: that we can determine how adding or removing something changes a scenario by comparing it to what happens when we do not nothing.

Sunblock is a very simple example of this. In order to see what sunblock does, or does not do, we first keep track of what happens when a person doesn’t use sunblock, and then replicate that situation with the only change being that person now using sunblock. It is important to keep everything else the same: if the person we are testing normally drinks three cups of coffee before noon, wears make up, and doesn’t get enough sleep, we want that person to keep doing those things while we study what the sunblock does.

The reason we want this is because if lots of things change at once, how can we know that the sunblock causes any changes we see? For example, let’s say this person often has an upset stomach. If she suddenly stops drinking coffee when she starts using sunblock, and this improves her upset stomach, the data might indicate that wearing sunblock helps with upset stomach even though that’s not really the case.

Most people think that clinical trials do what I just described: that they compare the effect of a therapy to people who think they are getting the therapy but are actually getting the placebo. While this does sometimes happen, that is almost never the case for people with advanced life threatening diseases or rare diseases. This is a complex topic so I’m going to unpack this in a series of posts so that I can answer questions as they come up.

The first thing to understand is that there are phases of clinical trials. Understanding the phases will help you to know what the data means when the results are released.

For trials that are supervised by the American FDA, there are four phases. They are cleverly called Phase I, Phase II, Phase III, and Phase IV.

Phase I is the first and most preliminary. Phase I trials are safety and dosing trials. I have never seen a phase I trial with more than fifty people. Most of the ones I see involve 10-20 people. This is the first real contact a new treatment (drug or biologic) has with patients that the therapy is intended to treat. It is literally to see how the human body reacts when it is given any amount of this substance.

Phase I trials are to see what adverse events present with this therapy. Adverse events are basically side effects and complications. They are the risks you accept when using the therapy. Some are serious, and some are not.

Dosing trials are just what they sound like: they give different people different doses in order to figure out the lowest effective dose. This is because we want to give as little of this substance as possible because this usually gives the lowest risk for complications. So we will split our phase I group into smaller groups called cohorts. Cohort is just the science term for a group of patients that have things in common that we are studying.

For example, let’s say we have a phase I study for Klimasonium, a drug that is taken once daily and cures mast cell disease. (I super wish for Klimasonium.) Let’s say I gather up 30 patients with MCAS for Klimasonium. (Please do not think this is real thing.) In order to determine what doses we should use to treat patients, I would break up my 30 patients into 3 groups, also called cohorts. Cohort 1 would take one tablet a day. Cohort 2 would take two tablets a day. Cohort 3 would take three tablets a day.

At the end of the trial, I would look at what side effects and complications patients had, and if their disease got worse or better, and in what ways. Based upon this information, I will pick a dose that helps the disease while causing the fewest complications. I will also have to report any and all side effects or complications to the FDA so that the risks of this therapy are recorded and patients who take this drug at any time will be made aware.