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February 2015

Live long and prosper

I became interested in science very young. In particular, I found the body fascinating. I thought the ways in which bodies can differ but still function the same was so interesting. I read medical dictionaries and physiology books in droves. I watched science fiction shows and movies like it was my job. I had a little microscope that came with a methylene blue staining kit for making slides. I liked knowing the answers to things, and I liked that science got them for you. My destiny was sealed. I wanted to science.

I am fortunate to have grown up in an environment where science opportunities are accessible to women. I am fortunate that much of the media I consumed depicted women in science roles as smart and capable. I think my life could have been very different were that not the case.

To my generation of women scientists, Star Trek is an iconic touchstone. For many of us, it was the first time we saw women depicted in science roles. This was certainly the case for me. Dr. Beverly Crusher was my hero. I never wanted to be on the away team. I wanted to put everyone together when they came back.

My sister graduated from Boston University a few years ago. Leonard Nimoy was one of the speakers at her graduation. He put his hand up in the Vulcan salute and said, “Live long and prosper.” The entire audience stood up and did it back. It was one of the most iconic moments of my life. A stadium filled with thousands of people from all walks of life understood the cultural significance of this moment. For people like me, Leonard Nimoy represented an ideal – a society that successfully harnesses the power of logic and science.

I feel like right now I am often forced to defend science. People cherry pick data or believe headlines or issue propaganda without any real understanding of the scientific process and how it works. It is heartbreaking for me. It frightens me to think that a mass disregard for regimented science could be coming. It frightens me to think that everything that has been accomplished will be undone.

Leonard Nimoy died yesterday and it feels like a real, actual loss. Not only to me, but to science.

Live long and prosper.


The fullness of time

It is so easy to lose yourself when you are sick. In the beginning, you are two beings, you and your illness. Together but separate. Independent.   Slowly, you bleed together. And then one day you are contained in this diseased vessel and everything is harder and you can’t get out. Every choice you make, every tiny decision, matters. Everything has consequences.

I have been mulling my GI surgery for several weeks. This is such a nuanced situation. Each solution has its own consequences. None of the options are benign. I always made my health decisions right away. Whatever my gut feeling is, that is my decision. Then I spend a few weeks justifying it to myself and making myself feel better about it. It’s sort of a weird quirk of mine.

That didn’t happen this time. I think about it all day, every day. It makes everything else seem more difficult, this looming decision and impending consequences of my choice.

I am terrified that I will choose wrong and the consequences will harm me. I’m also terrified that what I didn’t choose could have helped a lot. It is hard to know, especially for someone like me, with multiple unusual conditions, and big dreams. I count my big dreams as one of my conditions, something that must be accounted for. I have to be able to live with my choice.

After much research and discussion with my relevant specialists, I have decided on a surgical option. I am having some tests repeated in a couple of weeks, but they are merely to confirm what I already know. Almost exactly two years after I had my colostomy placed, I will be having the entirety of my colon removed save for a little bit of salvageable rectum. My small intestine will be connected directly to the rectal tissue and my ostomy will be reversed. If this fails, I will have a permanent ileostomy and accompanying nutrition problems for life, made worse by the fact that I can’t eat many of the foods used to mitigate this issue.

In the fullness of time, all your choices either fade into the ether or are absorbed into your being.   If I choose wrong, it will become a part of me or become insignificant. Nothing is absolute. These choices become part of the constellation of our lives and you can follow the stars all the way through the story.

I wish everything wasn’t so hard right now. I feel like I am in the middle of a raging storm, the kind you get in New England summers, when the humidity is too much and the sky unleashes it. I’m standing in the downpour, lightning whipping and thunder crashing around me. It is awesome and terrifying. It feels like change.

And I’m scared. But I’m still here.

A comprehensive list of antihistamines: H1 receptor (part 1)

Alimemazine, also called trimeprazine, is a phenothiazine derivative, placing it in the same class as the more well known promethazine. It is used for a variety of purposes, including antipruritic (prevents itching), sedative, antiemetic, anxiety disorders, organic mood disorders and sleep disorders. It is a first generation H1 antagonist. It is not available for use in the US, but is available in many other countries, including several European countries, Japan, Taiwan, South Africa, Australia, New Zealand and throughout the Middle East.

Azatadine is a first generation H1 antagonist with structural similarities to loratadine. It is available as Zadine in India (note: Zadine is a brand name used in several countries for multiple drugs). It is used to treat allergic symptoms.

Bamipine is a first generation topical H1 antagonist used for itching and allergic rashes. It is sometimes combined with hydrocortisone and sold as a cream or gel. It is available in Austria, Germany and Poland.

Benztropine, also called benzatropine, is a first generation H1 antagonist. It is most commonly used in the treatment of Parkinson’s disease, and Parkinson-like symptoms, particularly tremors. It can also be used to treat dystonia. Benztropine is a widely acting medication. It also acts as a dopamine reuptake inhibitor, which can be helpful in treating narcolepsy and attention disorders, and a functional inhibitor of acid sphingomyelinase, which is sometimes used to treat depression. One study found that benztropine decreased symptoms and encouraged nerve re-myelination in MS patients.

Bepotastine is a non-sedating, second generation H1 antagonist. It is available as an oral and ophthalamic mediction in several Asian countries under the brand name Talion, with ophthalmic preparation only available in the US as Bepreve. Bepotastine has been well studied. In adult models, it inhibited histamine, antigen and PAF induced skin reactions, systemic shock, airway constriction and maintained appropriate vascular permeability. It may also inhibit leukotriene B4, NO production and substance P.

Brompheniramine is a first generation propylamine H1 antagonist. It is used for general allergic symptoms and is found over the counter in many countries. Additionally, it functions as a serotonin and norepinephrine reuptake inhibitor, giving it antidepressant properties. The first SSRI was derived from brompheniramine. It also potentiates the effects of opioid pain medication so less pain medication can be used.

Buclizine is an H1 antagonist derived from piperazine. It is mostly used for nausea. It is available in several countries, including India, Taiwan, Singapore and multiple European nations. In the UK, buclizine is available in a combination migraine medication, Migraleve.

Captodiame is an H1 antagonist derived from diphenhydramine. It is also a serotonin receptor antagonist and dopamine receptor agonist. It has antidepressant effects via a unique mechanism that raises brain-derived neurotrophic factor in the hypothalamus only. It can also mitigate CRF activity in the hypothalamus.

Carbinoxamine is an H1 antagonist readily available in many countries, including in the US. It is often combined with other medications, such as decongestants. It is used for urticarial, angioedema, dermatographism, hay fever and allergic rhinitis and conjunctivitis.

Chlorcyclizine is a first generation H1 antagonist derived from phenylpiperazine. It is used for general allergic symptoms and as an antiemetic. It also has local anesthetic properties and antagonizes serotonin receptors.

The impossible things

I don’t remember the first time I was amazed at what my body could do, but a few episodes come immediately to mind. In 2007, my friend and I got lost while hiking in Norway near Bergen. We lost the moderate grade trail and instead found ourselves very carefully descending rock faces and hiking for several hours longer than expected. We had adequate food and water, decent weather and the benefit of a very late sunset, but almost twelve hours of physical exertion made for a long day.

When we got back to the hostel, it took almost an hour in a hot shower to get all the dirt off. We were exhausted. I crawled into bed and slept deeply, a narcotic, dreamless rest. Just before I fell asleep, I thought to myself that I couldn’t believe that I hadn’t injured myself.

In 2009, I fell through the floor of my attic, which was the ceiling of my front porch. I grabbed a beam as I fell and pulled myself up without hesitation. As I sat on the beam, remembering the image of my legs in the hole with my porch below, I was pretty impressed that I had managed to catch myself. I hit a different beam as I fell and had lots of bumps and bruises, including a huge one right at the top of my leg. In the bathroom mirror, it looked like a black smile.  I was otherwise fine.

There are other moments. The first time I did crow pose. The day I ran a 5K. The several 3-day walks in which I walked sixty miles in three days. Actual feats of physical prowess.

I can no longer do things like that. Maybe I will again someday, but right now, it would be impossible. Still, there are moments when my body amazes me.

I walked down to the harbor yesterday. After weeks of suffocating greyness, 35°F felt like spring. The world outside was thawing, liquid, burning bright with reflected light. I didn’t care how much pain I would be in tomorrow. I just wanted to be alive in a world that was finally thawing, even for a short time.

Boston Harbor was frozen. There were no waves. The water was motionless. Large white globes of ice hung suspended, a crystalline sheen atop the surface. It was otherworldly, and really very beautiful. By the time I got home, I was in a massive amount of pain from the muscular strain of staying stable on ice and snow. I spent last night in bed on muscle relaxers with my heated blanket gathered against the small of my back.

Today the pain is worse and the world is once again encased in ice. But I am renewed in the knowledge that sometimes, my body is still capable of impossible things. I may never climb a mountain again, but in the brief reprieve from a legendary winter, my body walked to the ocean and saw the world doing impossible things, too.


Boston Harbor


How to activate mast cells: Complement protein C3a

The complement system is part of the innate immune system. It is composed of many small proteins that circulate as inactive precursor molecules. When the immune system is triggered, enzymes cleave these precursors to form activate cytokines. These cytokines then cleave other precursors to form even more cytokines. This is known as a cascade and it amplifies the inflammatory signal to draw other inflammatory cells and molecules.

Mast cells express many receptors on their surfaces. The one people are most familiar with is the IgE receptor, also called FceRI. One of the receptors mast cells express is for C3a, a fragment of complement protein C3. This fragment is produced by the complement activation cascade. C3a is known for inducing smooth muscle contraction, increasing vascular permeability, recruiting white blood cells to the site of skin injection, and attracting macrophages, neutrophils, some lymphocytes, basophils and mast cells.

Something I haven’t touched on much is the fact that there are two major categories of mast cells in the body. Mucosal mast cells live in the GI mucosa. Serosal mast cells live in the skin, peritoneum and respiratory tract. These two populations have different mediators in their granules and respond differently to stimuli like C3a. In mucosal mast cells, C3a actually inhibits histamine and TNF release. In serosal mast cells, C3a increases degranulation of cells stimulated by IgE or IgG.

C3a has also been shown to cause expression of particular genes in mast cells that participate in production of cytokines. This is achieved by multiple pathways, one that works at low concentrations of C3a (cell surface GPCR) and one that works at higher concentrations (activation of G proteins).

In patients with allergic asthma, inhaled allergens like dust, dust mites, Aspergillus and ragweed pollen, activate the complement system in the mucosa of the respiratory tract. This generates the formation of C3a. Cells around mast cells release enzymes that can cleave C3 to form C3a. When mast cells become activated, they release a number of enzymes that may also cleave C3 to form C3a. Tryptase has been shown to do this in vitro, meaning in a reaction outside of the body.

When some receptors are stimulated too often, they become desensitized. This causes a signal to be sent into the cell that makes the cell internalize the receptor, or literally remove it from the surface so it can’t be activated anymore. This is the case for mast cell C3a receptors. I am curious to know if C3a receptors in mast cell patients don’t get desensitized. In theory, this would result in huge, fast allergic reactions without IgE stimulation and chronic activation of the inflammatory response. This has not been investigated to my knowledge.

Several mast cell mediators, including histamine, make blood vessels more permeable. Some researchers hypothesize that this action works to draw C3 to the activated mast cells. C3 can then be cleaved by tryptase, producing C3a, and amplifying the allergic reaction. Due to its well characterized role in anaphylaxis and allergic response, C3a is known as an anaphylatoxin.



Erdei et al. Regulation of mast cell activation by complement-derived peptides. Immunology Letters 92 (2004) 39–42.

Ali H. Regulation of human mast cell and basophil function by anaphylatoxins C3a and C5a. Immunology Letters 128 (2010) 36–45.

M.R. Woolhiser, K. Brockow, D.D. Metcalfe. Activation of human mast cells by aggregated IgG through FcγRI: additive effects of C3a, Clin. Immunol. 110 (2004) 172–180.

T.C. Theoharides et al. Mast cells and inflammation. Biochimica et Biophysica Acta 1822 (2012) 21–33.

The year we got winter all at once

Hello, dear readers. I am reporting to you from the frozen wasteland of Boston. You may have heard that we got some snow. And we have. We have gotten all the snow. All of it. At once.

People seem to be very curious about this, so I’m going to give my version of events. Because before I was a scientist and before I was a mast cell patient, I was a Bostonian. And whether or not I’m happy about it, I am witnessing Boston history being made right now.

I have lived in the Boston area all my life. So have my parents.   For people who aren’t familiar with Boston, we get very hot, very humid summers; pleasant, rainy springs; amazing, colorful, brisk autumns; and Winter.

Boston winters are snowy. They are stormy. Boston is situated in the northeastern US in a region called New England. New England is known for a very specific type of storm, called a Nor’easter. These are serious storms and can be very dangerous. They cause very strong winds (sometimes hurricane force), major coastal flooding, and very heavy rain or snow, which can bring the visibility down to virtually nothing.

Anyone who has spent a reasonable amount of time in Boston has experienced a Nor’easter. We get memorable ones a few times a decade. In February of 1978, Boston was hit by the Blizzard of 78, a catastrophic Nor’easter in which blizzard level snow fell for 33 hours. Snow accumulation in Boston totaled 27.1 inches (69 cm). Over 10,000 people had to evacuate from their homes. 54 people were killed. A ten year old boy walked into the snow outside his house and vanished. His body was found three weeks later, mere feet from his front door.

The Blizzard of 78 is a very important cultural touchstone in Boston. I was not alive for the blizzard, and my friends who were alive were young. However, our parents were the right age to experience the full brunt of the storm. People were forced to abandon their cars on major highways and try to walk to exits. Power lines and phone lines were down in many places. Stores were closed. Public transportation was not running. Gas stations weren’t open. It was impossible to get in touch with friends, family or work for several days.

My parents remember the mayhem of 78 and I grew up hearing about it anytime it snowed. Bostonians have a very specific pattern of preparing for storms. We go to the grocery store (supermarket) and buy milk and bread. I’m not clear on why those are the things we are told from a young age to buy, but that’s what Boston parents do. When you get home, you pull out all your candles and flashlights. If you live directly on the beach, you may have additional preparations, like boarding up windows. And then you wait. You watch the news. Sometimes you lose power. Sometimes you lose heat. It all eventually passes.

This winter we had almost no snow at all before January 26. On January 26, the Blizzard of 2015 (also known as Juno) hit Boston. We had warning, and being a good Bostonian, I went to the grocery store to the day before. In addition to going to get groceries, there also seems to be an unspoken rule among a significant portion of the Boston population that you must also panic and behave irrationally. And that is how, on the day before the Blizzard of 2015, I came to be at a Whole Foods in Charlestown, MA, watching hipsters ram each other with their shopping carts trying to get to the last bunch of organic kale. I got home, pulled out all of my candles, cooked a bunch of safe food, and bunkered down. The state instituted a travel ban that night so there would be no repeat of 78 on the highways.

I live in a basement apartment, so there was a real concern I would not be able to get out of my apartment with the anticipated snowfall. I woke up on the 27th to about two feet of snow against my front door. My stairs were buried. I started pushing the snow around but Astoria just ran right up. My door opens into our fenced yard. The fence is about six feet high. The drifts almost obscured it. The gate couldn’t be opened.

It was overcast and grey. The world seemed sort of muffled. The snowflakes were big and the snow was light and fluffy. It looked like the snow in one of those sparkly Christmas cards. That afternoon, I went to my parents’ house, three doors down. Astoria and I had to leave through our upstairs neighbors’ home because we couldn’t open the gate to the yard. The snow outside was fully up to my waist. It was unreal.

Waist high snow outside of my home.
Waist high snow outside of my home.

A week after the blizzard, on February 2, we got another major winter storm. Snowfall in Boston was 16.2 inches (41.2 cm). Then on February 8, we got another storm with a snowfall of 22 inches (56 cm). There was still 37 inches (94 cm) of snow on the ground.

We were not managing well with the snow. I don’t really think this is the fault of any one thing, but we weren’t. We didn’t have enough plows or enough people to shovel sidewalks or curbs. People were walking in the streets because the alternative was wading through three feet of snow on the sidewalks. And the streets were icy and snowy, too. Drivers couldn’t see around snowbanks. Traffic was unbelievably bad. It took me 2.5 hours to drive to work. I live less than ten miles from work as the crow flies. And it took me 2.5 hours to get home, on the train. On February 10, all train service was suspended. Before this happened, there had been trains disabled on the tracks for hours.

On February 14-15, we got another 12 inches of snow (30 cm). Except this time, we also got an unprecedented cold snap. On February 15, when I let my dog that morning, it was -3°F, and wind chill brought it down to -25°F. It was shockingly cold. The transit system couldn’t cope with cold of that magnitude and public transportation was again shut down. The city was offering people $30/hr to shovel off the train tracks.

That's a six foot fence behind her buried in the snow.
That’s a six foot fence behind her buried in the snow.


No big deal.
No big deal.


-25 with wind chill
-25 with wind chill

There was also another storm in there somewhere that I can’t remember because so much snow and also it has basically snowed at least a little every day since the first blizzard at the end of January. As of yesterday, this winter has seen a total snowfall of 96.3 inches, second only to the 1995-1996 season, a record of 107.6 inches. But in 1995-1996, that snow fell over the whole season. Boston has gotten 96.3 inches in 22 days. And let’s be real, this winter isn’t over. In Boston, it can snow well in “spring”. My freshman year of college, the day I took my last spring semester final exam, it snowed.

This week, the Boston transit organization (MBTA) announced that after weeks of awful commutes, it would take 30 days to fully restore service – and that’s only if it doesn’t snow anymore. It is impossible to get anywhere. I have friends who live ten miles from work who are spending six hours commuting. I can’t drive to work because if I get stuck for two hours and need IV meds, I can’t drive. I’m afraid to take the train because I can’t get stuck standing for two hours. I also don’t want to be the first person to ever give herself IV meds on the MBTA. The situation is pretty untenable. It takes forever to get anywhere. I have never seen anything like this. We are buried in snow and there isn’t even anywhere to put it.

My street after the most blizzard.  Photo credit: Whitney Vieira-Wall
My street after the most blizzard. Photo credit: Whitney Vieira-Wall


Mountains and mountains of snow
Mountains and mountains of snow
Sidewalk roulette: is it safer on the sidewalk or in the street?
Sidewalk roulette: is it safer on the sidewalk or in the street?

It’s really isolating and people are starting to snap. The Boston mayor recently requested that people stop diving out their second story windows into the snow. So things around here have been more difficult than usual.

A couple of days ago, I decided to take Astoria for a walk.  We were both going stir crazy.  So I bundled up and took her to run around in the snow.  On the way back, we walked up a sorta shoveled path that terminated abruptly about ten feet before a plowed parking lot.  I figured I could trudge through the snow to the parking lot rather than go all the way around.

I was about half way to the parking lot when I fell into the snow.  It was up past my waist and I couldn’t get any traction.  I was 30 yards from my apartment in the middle of town.  I was stuck in the snow.  Really stuck.

I struggled for about five minutes before I decided to push the snow back and dig toe holds.  I was able to pull myself out.  II was sweating all over, my hair plastered to my face, my nose running.  lay back on the snow and laughed.  Because what else is there to do?

BUT! BUT! It won’t last forever. Spring will be come. Even if it’s a late Boston spring, it will come. And the snow will melt. We might be walking around in sundresses and sandals, climbing over snow piles, but it will melt. I know it all seems so bleak right now, but historic winters like this don’t happen often. So we just need to get through another few weeks and things will get better.

And I know it seems like the world betrayed us. But it’s still the same world. It’s the same world that brings us gorgeous breezy New England beach days and the way the air smells when you walk through the Public Garden in May. It’s the same world that brings us campfires and cookouts and pool swimming the dark under summer skies. It’s the same world that brings us that first delicious day when you don’t need a winter jacket. It’s the same world that is going to bring us more sunlight tomorrow than it did today, even if it doesn’t feel like it’s the same.

Summer is coming.
Summer is coming.

And besides. This is fucking Boston. We survived 86 years without winning a World Series. We survived the Big Dig. We survived all those awful fucking actors who think they can do our accent. We are not a people who will be defeated by this onslaught of snow.

And there will be grass!  And buildings!  And detail that isn't buried under snow!
And there will be grass! And buildings! And detail that isn’t buried under snow!

This is the 78 of our generation. This too will pass. So when you wake up tomorrow and you have dig out your car again and this bullshit is still real, just remember. It won’t always be this hard.  Soon it will warm and things will be growing and it will be wonderful.

Because it’s the same world. I promise.


Lyme Disease: IDSA, ILADS and my conclusions (Part 9)

As everyone knows, I have spent the last few months putting together posts on Lyme disease. It took me a lot longer to get through than any other topic I can think of. The reason for this is politics. Lyme, and especially chronic Lyme, and especially chronic Lyme in the absence of a known tick bite or EM rash, is very controversial. It makes it really difficult for patients to know what information can be trusted.

The Infectious Diseases Society of America is an organization that represents health care providers and scientists working in the ID field. My research has been presented at IDSA conferences. IDSA publishes position papers and makes recommendations about treatment standards for various infectious diseases.

The International Lyme and Associated Diseases Society (ILADS) was formed to advocate for the existence of chronic Lyme disease. I couldn’t find an exact date, but they were around by the early 2000’s. In particular, they believe that the IDSA guidelines for diagnosis and treatment for Lyme disease are incorrect. They publish, lobby, and host conferences to educate providers and patients on their views of Lyme disease and coinfections. They believe that the IDSA guidelines prevent access to care.

These views lead to the Connecticut Attorney General suing the IDSA under anti-trust law in 2006. I read through a lot of the literature generated by the IDSA antitrust investigation. The legal action was filed based upon the fact that the IDSA was considered a dominant organization that restricted “consumer choice” and excluded ILADS researchers from their decision making processes.

I’m not going to lie: the fact that a state sued the IDSA for making guidelines based on evidence really leaves a bad taste in my mouth. Because in reviewing the ILADS papers and data, they don’t rely on evidence. They rely on the holes in the presented evidence. (Which are real, in fairness. As I stated before, Lyme diagnostics are not good.)

Here’s an example of what I mean. Let’s say there is a sheet of red paper with a hole cut out of it.

IDSA is saying the sheet is red.

ILADS is saying the hole is blue. They’re not saying that they have proof that it’s not red, it’s blue. They’re saying that there’s a hole in the red paper, could it have been blue before they cut it out? And they say they can tell it was blue because they used a special test in special labs that basically say that if the paper has any color, the result is reported as blue. The options are blue or negative. And even if the lab says it’s not blue, the doctors assume it was blue anyway.

My first experience with ILADS was when I went to the 2011 IDSA conference in Boston. It was at the convention center in South Boston. As I walked along the length of the building to get to the main entrance, I saw a person in a tick costume standing in my path. Tick costumed person had signs with the name “ILADS” emblazoned on them. Tick costumed person was being corralled by security (I assume for blocking the general path of traffic, which they were). It was pretty unforgettable.

I noticed a theme pretty early on in my Lyme research – that ILADS researchers and IDSA researchers would often say the same thing, but with different turns of phrase that lent themselves to misinterpretation. Sneaky. I hate that. There were several papers that I just stopped reading because of the cattiness of the language. It is very obvious that these organizations resent each other, and some researchers make no attempt to hide that. Which is unfortunate, because I’m betting a lot of scientists stop reading because of it.

Anyway, here’s an example:

In August 2013, the CDC released a statement that approximately 300,000 Americans are diagnosed with Lyme disease each year.

But if you go on the ILADS website, that’s not what they say the CDC said. Here’s what they say:

“CDC Reports: Lyme disease infects 300,000 people a year.”

See what happened here? Because they’re similar, but not the same. A few years ago, the CDC began a large, three pronged study to better characterize the nature of Lyme disease in the US. Part of that was identifying how many people were told they have Lyme disease. Another part was figuring out how many of those patients met the diagnostic criteria for Lyme as laid out by the CDC. 300,000 people were told they had Lyme disease. 300,000 people did NOT meet the diagnostic criteria for Lyme as laid out by the CDC. This is really important.

Diagnoses are defined by diagnostic criteria. If you don’t meet the criteria, you’re not counted as being affected for statistical purposes. The CDC is NOT saying that there are 300,000 people annually who meet the diagnostic criteria for Lyme. They are not. Whether or not the CDC criteria is effective for identifying all the people who have Lyme disease is a different issue. (I don’t think it is, if you’re wondering.)

Let’s take another example:

Let’s say there is a disease called Orange Disease. When people swallow orange seeds, oranges grow out of their noses. You can only get this disease from eating orange seeds. It is known to affect 50 people a year.

Now let’s say a group of doctors say that if you eat lemon seeds, lemons will grow out of your nose. They see some patients with this problem. They give them a treatment similar to the one for Orange Disease. These doctors say this problem with lemon seeds is Orange Disease, even though you can only get Orange Disease from eating orange seeds and lemon seeds are not orange seeds. But these doctors say because both oranges and lemons are citrus and the treatments are similar, everyone with these issues has Orange Disease. The rest of the doctors will only diagnose you with Orange Disease if you ate orange seeds.

That is what is happening here.

I believe that something is making 300,000 people a year sick. I do. I think that for those who have been bitten by a tick, it is possible that infection can cause long term changes in your body that cause symptoms. I think that the controlled studies have not shown long term antibiotics to be effective in treating this. I also think too many people say long term antibiotics do help to just write it off. I think the antibiotics do something, in some people.

Having worked in infectious diseases for years, it is hard for me to feel like moving a condition from underwhelming diagnostic criteria to a diagnosis of exclusion is a good idea. Diagnoses of exclusion are just so fraught with danger. Because maybe some of these people who don’t remember a tick bite and have these major constitutional symptoms really do have Lyme disease, but maybe they don’t. I feel certain that part of why it took me so long to get diagnosed with mast cell disease was because I was receiving treatment that really confused the issue. And I worry that this is the case for a lot of people.

It is my finding that Lyme diagnostics are not good.

It is my finding that it is possible to have Lyme disease, both acute and long term, and test negative.

It is my finding that Lyme specialty labs use tests that are not FDA validated, that are not considered reliable by many people.

It is my finding that it is possible for viable Borrelia to persist in the body after treatment.

It is my finding that it is not clear if those Borrelia cause an ongoing infection, or if the previous infection causes a permanent immunologic change that manifests as symptoms.

It is my finding that coinfections are possible. The majority of these organisms are treated with the first line treatment for Lyme disease. However, some are not.

It is my finding that long term antibiotic treatment has not been shown scientifically to help with chronic Lyme symptoms.

It is my finding that long term antibiotic treatment could facilitate benefits in some through anti-inflammatory or immune modulating properties, rather than through treatment of ongoing infection.

It is my finding that long term antibiotic treatment can have serious, irrevocable consequences.

It is my finding that 300,000 people being diagnosed annually with Lyme disease is not the same as 300,000 people being infected annually with Lyme disease.

It is my finding that tweaking the language to change the meaning of a previous finding is rampant in Lyme scientific literature.

It is my finding that unless you run down every citation, there is no way to know the truth.

It is my finding that some of the 300,000 people diagnosed annually with Lyme disease probably do really have symptoms from either a current or previous Borrelia infection, even if they have negative tests. But I would venture that a lot of them don’t.

Lyme disease: Coinfections (part 8)

A lot of patients who are being treated for chronic Lyme are also being treated simultaneously for ongoing coinfections. There is a fairly long list of coinfections, most of which are known to be tickborne diseases. I focused on the ones that are thought to be the most common.

Ehrlichiosis, also known as human monocytic ehrlichiosis, is caused primarily by E. chaffeensis and E. ewingii. This organism infects monocytes and lives its life cycle inside them. This organism is transmitted primarily by the Lone Star tick, found mostly in the south east, south central and mid-west US. Well known in other animals, human infection was first described in 1986. Since then, more than 2300 cases have been reported to the CDC. Of cases reported from 2000-2007, 49% required hospitalization. 1.9% of cases were fatal.

Patients with ehrlichiosis often demonstrate low white counts, red counts and platelet counts fairly quickly. Liver function tests may be elevated. Up to 20% have significant neurocognitive effects, including meningitis type symptoms to 10%. Rash is less common in this condition than other tickborne diseases, affecting less than 30% of infected adults. Fever, severe headache, chills, malaise, muscle pain, nausea, vomiting, diarrhea and red eyes are common symptoms.

Ehrlichiosis is diagnosed by blood tests and in particular with a blood smear. However, like Lyme disease, testing can be negative in early infection. The most effective method for diagnosis is comparison of serum samples taken 2-3 weeks apart: a fourfold increase in IgM or IgG specific for this organism in the later sample compared to the earlier is considered diagnostic. A few of the papers I read on this topic commented that smear analysis alone only identifies microcolonies of Ehrlichia in the monocytes 20% of the time. I wasn’t able to find a primary reference for this statistic, and I would suspect it’s not that low, but I can’t find any evidence either way. I also saw the following phrase repeated in a few places: “Demonstrating the organism in tissue by immunohistochemistry or molecular studies in immunocompetent patients may be difficult, as few organisms are present.” I can’t find a primary reference for that either.

If ehrlichiosis is suspected, antibiotic treatment is recommended regardless of test results. Early treatment is key in avoiding severe complications, such as splenic rupture and death. It is treated with doxycycline orally or intravenously for 10-14 days. In children and adults, treatment with sulfonamide antibiotics are associated with increased morbidity.

Because the causative organisms live inside circulating white blood cells, it is possible it could be transmitted by blood transfusion or solid organ transplant. Multiple cases have been investigated, although no instances of ehrlichiosis spread by these methods have been confirmed.

There is also an infectious agent known as the Ehrlichia muria like Organism (EML). It is so called due to the similarity of disease as well as cross reactivity with Ehrlichia chaffeensis antibodies. This agent has been found to cause infections in Wisconsin and Minnesota. It is not yet clear what tick transmits this infection.


Anaplasmosis (formerly human granulocytic ehrlichiosis, now human granulocytic anaplasmosis) is caused by Anaplasmosis phagocytophilum. Very similar to the organism that causes ehrlichiosis, A. phagocytophilum was previously known as Ehrlichia phagocytophilum until it was reclassified. This organism infects neutrophils and lives its life cycle within them. This condition can be very difficult to distinguish from ehrlichiosis, especially during the acute phase. PCR testing can be used to distinguish based upon DNA sequences.

Anaplasmosis causes fever, severe headache, muscle pain, and chills. Presentation can be minor. Skin rash affects less than 10%. Low platelets and red counts, as well as elevated live function tests, are evident fairly early in infection. Like ehrlichiosis, it is treated with doxycycline and treatment should be started if suspected in spite of negative tests. Symptoms respond quickly to doxycycline, an dother antibiotics should be avoided as they are associated with poorer outcomes. Very ill patients may require longer treatment, but it is considered successful once the fever is resolved. Resistance of this organism to doxycycline has not been reported. I was not able to find evidence of relapse following post-treatment recovery.

Anaplasmosis can be transmitted to humans by at least three types of ticks and shares a vector for Lyme disease. One study found that about 10% of patients with serological evidence of anaplasmosis were also serologically positive for Lyme disease or babesiosis. It can theoretically be transmitted through blood transfusion or solid organ transplant.


Babesiosis in humans is primary caused by B. microti. There have been “isolated” cases of infection by other species in unlikely places, including B. divergens in the US and B. venatorum in Europe, among others. Babesiosis has long been known to affect other mammals, including cows and dogs. Unlike the other co-infecting organisms mentioned thusfar, Babesia spp. are not bacteria, but protozoan parasites. Babesia infection is not thought to be rare, and it is thought that up to half of children and a quarter of previously healthy adults have no symptoms when infected.

Symptomatic patients develop a syndrome similar to malaria patients. Symptoms usually start 1-4 weeks after tick bite, or 1-9 weeks after blood transfusion if contaminated. Symptoms are mostly generic: fever, chills, malaise, fatigue, chills, night sweats. However, it also causes low platelet count and hemolytic anemia. Like other infections, it is likely to be worst in those who with compromised immunity, including those who have no spleen.

Babesia infect red blood cells. It is primarily diagnosed by peripheral blood smears stained with Giemsa stain. PCR is also used. Unlike the other organisms mentioned here, doxycycline is not effective. There are two therapies: atovaquone and azithromycin OR clindamycin and quinine. In severe cases, patients may require exchange transfusion, in which their red cells are removed and replaced with healthy ones. Babesia can be life threatening or even fatal. It can cause heart attack, renal failure, and disseminated intravascular coagulation, among other things. Additionally, Babesia can be transmitted via transfusion, solid organ transplantation or in utero (through infection, not through inheritance – the baby does not inherit a “gene” for Babesia, but instead contracts the infection for the mother.)

So how often are B. burgdorferi, B. microti and A. phagocytophilum found in the same tick?

A 2014 paper found that B. burgdorferi and B. microti were found together 5.96%; A. phagocytophilum and B. burgdorferi together were 2.35%; and A. phagocytophilum and B. microti together were 0.53%. Triple infection was found in 0.52% ticks sampled.

Another 2014 paper found that in one location, 6.4% adult ticks were coinfected, and 5.2% nymphs were; in another location 4% of adults and 1% of nymphs were. In the location with the highest level of infection, 2.5% of adult ticks were infected with B. microti; 37.5%, B. burgdorferi; 7.5% with EML; 0.4% coinfected with A. phagocytophilum; 5% A. phagocytophilum and B. burgdorferi; 1% with A. phagocytophilum and EML; 0.4% with B. microti and B. burgdorferi; 3% with B. burgdorferi and EML; and 0.4% triple infected with B. burgdorferi, A. phagocytophilum and B. microti. Incident was less common in nymphs, except for solitary B. microti infection (3.3%), and B. microti and B. burgdorferi coinfection (2%).

So, sometimes, but not often. Also, the fact that they are found together does not mean they are always transmitted together. That needs to be studied.

It is my finding that yes, coinfection with Borrelia and another organism can cause symptomatic disease. But I find this to be true in a much narrower scope than the internet at large may lead you to believe.

Firstly, I want to clarify that the Lone Star tick is not known to carry Borrelia spp. and is not known to cause Lyme disease. It causes a similar illness through an unknown organism, but really, most tick borne diseases cause similar symptoms, at least at first. So if you are bitten by a Lone Star tick, there is no evidence that you can contract Borrelia this way.

Some people have said that they have both Lyme and ehrlichiosis. Because ehrlichiosis in the true sense is transmitted by the Lone Star tick, this is unlikely. It is possible in theory to be bitten by both ticks and to contract both separately. Some people mean they have contracted the EML agent and Borrelia from one bite. This may be possible, but we have no idea if it is. Additionally, the number of cases verified as being caused by the EML agent is extremely low. So even if this were possible, it is not yet widespread enough to be causative in the number of people who suspect they have both.

I cannot find reliably sourced information on a recurring/relapsing presentation of ehrlichiosis or anaplasmosis. By most accounts, they can cause grave illness if not treated promptly. So I find this idea of “dormancy” unlikely. I understand that the idea of living intracellularly lends for some people more plausibility to this idea of dormancy. While infected cells may live longer, they don’t live that much longer. We’re talking weeks/months, not years here. Also, please look further in the ways cells tell immune cells that they are infected. It is incredibly detailed and too much for me to get into.

I also cannot find reliably sourced information on recurring/relapsing presentation of babesiosis. I agree that it might take longer to find, and it will not be treated effectively with doxycycline. However, my gut feeling tells me that if any of the coinfecting organisms mentioned in this post were likely to cause a long term problem, it is probably going to Babesia spp. That does not mean that I think it can cause a remitting/relapsing type of infection. I just think it can take longer to find and effectively treat it.

However, it is important to realize that a fair amount of people test positive for Babesia who have no symptoms of any kind. There are clear demarcations for what populations are most likely to have severe infections and it is people over 50, people who have HIV, people who are being treated with sulfonamides, and people who are immunocompromised, including those who are asplenic.

Diagnostics for Lyme have been well studied. Diagnostics for these organisms have been less well studied and are less well controlled. However, after early infection, I feel like smears are going to telling. Furthermore, all of these organisms can cause major blood count deficits, which is hard to miss. I think the likelihood of being symptomatic with one of these infections for years without ending up in the hospital or at least ending up on an effective antibiotic empirically (Babesia not withstanding) is pretty low.

Something else I haven’t gotten around to is the fact that you can get reinfected Lyme disease by another tick bite after having (and resolving) Lyme disease previously. I’m not sure if this is true for the other organisms due to the much lower rate of infection and the fact that it has not been well researched.

In literature, a unifying characteristic of the bacterial coinfections is that once the fever is gone, treatment is successful. Antibiotic treatment is recommended until a short time after the fever has broken. Given that I can’t find support for “persistent” infection of these coinfectors, I likewise cannot understand why long term antibiotics are helpful, beyond the inherent anti-inflammatory and immune modulating behaviors of antibiotics. (Which I’m not ignoring – I think if you have continuous health issues years after being bitten by a tick, and antibiotics help – that’s an important clue – but does not necessarily mean it helps because it treats an ongoing infection.)

I addressed before the fact that controlled trials of long term antibiotics have not shown gains in the group receiving antibiotics above the placebo group. About 1/3 of the patients in the largest study improved on placebo. But as a scientist, this idea that every person who feels better with antibiotics is experiencing a placebo effect is… unsatisfying. I don’t know how to explain it. It just seems unlikely to me. Which means I think the antibiotics are doing something. But I’m not convinced that what they are doing is treating long term infections. Especially not of these coinfecting organisms.

Furthermore, antibiotics and antimalarials are not benign. I think some people are really playing with fire here. Especially those people who get IV antibiotics long term and who have indwelling lines for that purpose. Like everything else, this is a risk/reward situation, and I’m not judging anyone who is choosing the risk because these drugs make them feel better. I just feel like there is somewhere in this mess an explanation that may allow them to use more benign medications. And I want that.

Tomorrow I’m going to give you the view on IDSA/ILADS from where I’m sitting and then I’ll be calling it a day on Lyme disease and coinfections. Once tomorrow’s post goes up, feel free to ask questions and discuss. Please be civil. I am sensitive to the fact that a significant number of patients are being treated for chronic Lyme and I have tried to be thorough and fair in my assessment of the situation. If you feel that I have gotten something factually wrong, please provide a peer reviewed literature source. If I have read it, it has already factored into my interpretation. If I haven’t, I will read it, and make amendments if I feel appropriate. I make mistakes and have no problem with people fact checking me. Just please remember that I have really tried to get to the best of my ability to get to the bottom of this.



Hersh, Michelle H., et al. Co-infection of blacklegged ticks with Babesia microti and Borrelia burgdorferi is higher than expected and acquired from small mammal hosts. PLOS One 2014.

Stromdahl et al. Comparison of phenology and pathogen prevalence, including infection with the Ehrlichia muris-like (EML) agent, of Ixodes scapularis removed from soldiers in the midwestern and the northeastern United States over a 15 year period (1997-2012). Parasites & Vectors 2014 7:553.

Pritt BS, Sloan LM, Johnson DK, Munderloh UG, Paskewitz SM, McElroy KM, McFadden JD, Binnicker MJ, Neitzel DF, Liu G, Nicholson WL, Nelson CM, Franson JJ, Martin SA, Cunningham SA, Steward CR, Bogumill K, Bjorgaad ME, Davis JP, McQuiston JH, Warshauer DM, Wilhelm MP, Patel R, Trivedi VA, Eremeeva ME: Emergence of a new pathogenic Ehrlichia species, Wisconsin and Minnesota, 2009. New Engl J Med 2011, 365:422-429.

Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, Krause PJ, Bakken JS, Strle F, Stanek G, Bockenstedt L, Fish D, Dumler JS, Nadelman RB: The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006, 43:1089-1134.

Steiner FE, Pinger RR, Vann CN, Grindle N, Civitello D, Clay K, Fuqua C: Infection and co-infection rates of Anaplasma phagocytophilum variants, Babesia spp., Borrelia burgdorferi, and the rickettsial endosymbiont in Ixodes scapularis (Acari : Ixodidae) from sites in Indiana, Maine, Pennsylvania, and Wisconsin. J Med Entomol 2008, 45:289-297.

Nonaka E, Ebel GD, Wearing HJ: Persistence of pathogens with short infectious periods in seasonal tick populations: the relative importance of three transmission routes. PLoS ONE 2010, 5:e11745.

Dahlgren F, Mandel E, Krebs J, Massung R, McQuiston J (2011) Increasing incidence of Ehrlichia chaffeensis and Anaplasma phagocytophilum in the United States, 2000–2007. Am J Trop Med Hyg 85: 124–131 doi:10.4269/ajtmh.2011.10-0613.

Ostfeld RS (2010) Lyme disease: the ecology of a complex system. New York, NY, USA: Oxford University Press. 232 p.

Krause PJ, McKay K, Thompson CA, Sikand VK, Lentz R, et al. (2002) Disease-specific diagnosis of coinfecting tickborne zoonoses: Babesiosis, human granulocytic ehrlichiosis, and Lyme disease. Clin Infect Dis 34: 1184–1191 doi:10.1086/339813.

Robert B. Nadelman, M.D., Klára Hanincová, Ph.D., Priyanka Mukherjee, B.S., Dionysios Liveris, Ph.D.,

John Nowakowski, M.D., Donna McKenna, A.N.P., Dustin Brisson, Ph.D., Denise Cooper, B.S., Susan Bittker, M.S., Gul Madison, M.D., Diane Holmgren, R.N., Ira Schwartz, Ph.D., and Gary P. Wormser, M.D. Differentiation of Reinfection from Relapse in Recurrent Lyme Disease. N Engl J Med 2012. 367; 20.


Lesser known mast cell mediators (Part 6)

Granulocyte macrophage colony-stimulating factor (GM-CSF) is a growth factor for white blood cells. It induces stem cells to make granulocytes (neutrophils, eosinophils, basophils, mast cells) and monocytes. The molecule activates STAT5, a protein that initiates gene expression. It is found at high levels in the joints of rheumatoid arthritis patients.

Fibroblast growth factor 2 (FGF2, also known as basic fibroblast growth factor, bFGF) is involved in angiogenesis, proliferation and wound healing. FGF2 binds heparin. It is thought that during wound healing, heparin degrading enzymes activate FGF2, driving the development of new blood vessels.

Neutrophin 3 is a nerve growth factor that regulates the survival and growth of neurons and synapses.

Nerve growth factor (NGF) regulates neuron survival and axonal growth. In its absence, neurons undergo apoptosis. It has been found to induce ovulation in some mammals. NGF is often elevated in inflammatory conditions as it suppresses inflammation. Children with autism sometimes have high levels of NGF in their cerebral spinal fluid. Low levels of NGF are seen in metabolic syndromes, type 2 diabetes and obesity.

Platelet derived growth factor (PDGF) is a growth factor that participates in blood vessel growth. It is a required factor for the division of fibroblasts, connective tissue cells important in wound healing.

Nitric oxide (NO, also endothelium derived relaxing factor, EDRF) is a cell signaling molecule and potent vasodilator. It is a precursor to nitroglycerin. It is produced by several nitric oxide synthase enzymes. NO maintains blood vessels by preventing vascular muscle contraction and aggregation of cells on the endothelium. NO has a well described variety of activities.

Leukotriene B4 is a cell signaling molecule. It facilitates the transition of white blood cells from the endothelium into tissues. It also forms reactive oxygen species.

Leukotriene C4 is one of the components of the slow reacting substance of anaphylaxis (SRS-A). It is secreted during anaphylaxis and contributes to the inflammatory processes. It causes prolonged, slow contraction of smooth muscle and bronchoconstriction. It is 5000x more potent than histamine in this capacity but acts more slowly and lasts longer.

Platelet activating factor (PAF) mediates a variety of immune activities, including various inflammatory processes and anaphylaxis. It is also a vasodilator and bronchoconstrictor. At high concentrations, PAF can cause severe airway inflammation to such degree as to be life threatening.


All mediators listed here are produced by mast cells upon stimulation and are not stored in granules.

Lesser known mast cell mediators (Part 5)

Interleukin-16 (IL-16) is a cytokine that attracts several types of cells that express the CD-4 receptor on their surfaces, including monocytes, eosinophils and dendritic cells. It acts by binding to the CD-4 receptor. IL-16 was previously known as lymphocyte chemoattractant factor (LCF).

Interleukin-18 (IL-18) is a cytokine with several defined functions. Working with IL-12, it triggers a cell-mediated immune response after infection. It causes natural killer (NK) cells and some types of T cells to release interferon-γ, and for this reason is sometimes called interferon-γ inducing factor. This interferon activates macrophages and other cell types. IL-18 and IL-12 can inhibit production of IgE and IgG1 when mediated by IL-4. IL-18 causes severe inflammatory reactions and has been implicated in various diseases. In adenomyosis patients, more IL-18 receptors are found in the endometrium. It is one of the molecules responsible for Hashimoto’s thyroiditis. It also increases production of amyloid-beta in neuron cells, which is associated with Alzheimer’s disease.

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that stimulates an acute immune response by binding to CD74. MIF level is associated with severity of rheumatoid arthritis. Glucocorticoids (steroids) stimulate white cells to release MIF.

Transforming growth factor beta (TGF-β) is secreted by mast cells and participates in the pathology of many diseases, including bronchial asthma, heart disease, diabetes, lung fibrosis, telangiectasia, Marfan syndrome, vascular Ehlers Danlos syndrome, Parkinson’s disease, chronic kidney disease, multiple sclerosis, AIDS, among others. (Note: I suspect that one of the links between mast cell disease and EDS is this molecule. Its signaling affects differentiation and regulation of vascular tissues and connective tissues. In a mouse model of Marfan syndrome, a connective tissue disorder, the characteristic Marfan features can be alleviated by administering a TGF- β blocker.)

Tumor necrosis factor (TNF-α) is part of a family of cytokines that cause apoptosis, cell death. It is an adipokine that participates in both general inflammation and the acute phase inflammatory response. It is produced by mast cells as well as many other cell types, including neutrophils, eosinophils and neurons, among others. TNF regulates immune cells, causes fever, weight loss, fatigue and tumor destruction. This molecule is dysregulated in several diseases, including several cancers, severe depression, IBD, Alzheimer’s and rheumatoid arthritis.

Macrophage inflammatory protein 1α (MIP-1α, chemokine ligand 3, CCL3) causes acute inflammation and recruitment of other white blood cells.

Stem cell factor (SCF) is a cytokine that binds to the CD117, better known as CKIT, receptor on mast cells. SCF regulates the mast cell life cycle, telling them when to make new cells and when to die. In CKIT+ mast cell patients, the CKIT receptor is misshapen so the cell mistakenly thinks SCF is bound to the receptor all the time. It also induces histamine release.


All mediators listed here are produced by mast cells upon stimulation and are not stored in granules.