Sit Down Before Reading: A Memoir by Dave Bexfield
Rob is a seasoned high school math teacher, an accomplished outdoorsman, and a talented chef. He’s also a world traveler, Peace Corps volunteer, and father of three. We should have never met—and certainly shouldn’t have become dear friends. But like with most of my friendships, luck, fate, and fat chance got together for a late-night poker game and dealt us hands that forged an unlikely bond.
Laura and I were going out to a special, multi-course dinner that fall night in 2015 with another longtime friend and her husband, only instead of sitting at a private table, it was a community affair. And instead of being seated across from one another, we inexplicably were seated in a line shoulder-to-shoulder. As the restaurant filled and boisterous conversation turned more boisterous, talking over heads and around backs became laughably challenging, so we met the tablemates we could most conveniently stab with a bread knife. Rob and Leslie. By the end of the evening, it was clear that we’d be breaking bread together in the future, only there was an issue. They had my business card and we had nothing but assurances they’d certainly, no doubt, without question, reach out to us soon. Weeks passed. Then months. I began questioning their definition of soon. (Were they also practicing physicians on the side?) Then one day we were flying to Chicago for a health advocacy conference… and a familiar woman boarded the plane. “We are going to call, really!” They soon did.
Fast forward nearly eight years. Rob the outdoorsman, now one of our closest friends, had an unusual concern. He confided in us the other day that ever since a hiking trip to England four years ago, he had felt off. Numbness, dizziness, unsteadiness, heat sensitivity. Even cognition problems. His doctors were stumped. Maybe it was psychosomatic. Maybe it was multiple sclerosis. They couldn’t help. Go to Mayo, they said. So, he came by to ask me personally about what I knew about MS.
I told him that I knew enough to skip Mayo and skip the neurologist, at least for the moment. Did he, perchance, have any run-ins with ticks in the past? Well, Rob thought, he never got the classic bullseye rash, but he did pull off ticks one afternoon after tromping through some high grassy fields on that England trek. He felt fine afterward. Until one day he didn’t. I nodded. I recommended he get a standard Lyme disease test, as imperfect as they are. A month later when he got back the results, I got an unambiguous text from the normally staid math teacher.
Band(s) present: 93, 66, 41, 28, 23, 18 kDa
Your Value: Positive
His excitement was, one might say, palpable. “Yeah motherfuckers!” followed by four exclamation points. Then, “Thank you Dave for the advice!” followed by no less than nine exclamation points. “No one would have ever thought to look,” I responded. “You're welcome and woohoo!!”
“You thought to look!!!” he texted back, breathlessly I presume. “My PCP did not believe me even after everything I told him. Your book is so needed!!”
What Rob didn’t know—couldn’t have known, and what I didn’t tell him—was that I knew the odds overwhelmingly favored a diagnosis of Lyme disease. The deck was stacked. It has always been stacked. But I now held all the cards to the greatest and most catastrophic hand ever dealt in the history of medicine.
The epic multiple sclerosis misdiagnosis kerfuffle I’d uncovered wasn’t the end game. No, it was merely the ante needed to sit at the table. It’s time we play no-limit. And to the detractors long skeptical of Lyme disease’s influence on society, folding isn’t an option.
The Misdiagnosis Playbook
Now might be a good time to grab a favorite beverage and scootch a little closer to a loved one.
When I introduced Part III of Sit Down Before Reading, I laid out a “clear, unambiguous warning to my readers: THIS IS GOING TO BE HARD.” If you thought it was challenging before to accept some of my findings despite the preponderance of evidence, this is going to turn it up to 11. For those not familiar with the This is Spinal Tap amplifier reference (shame on you), I’d like to direct your attention to the ubiquitous 1-10 pain scale posters on the walls of doctor offices, where 10 is considered the worst pain possible. Inevitably, some patients will report an 11 (or higher), leaving frustrated medical staff to then quip under their breaths, “So, worse than getting an arm caught in a woodchipper while having your left eye pecked out by a vengeful raven?”
For perspective, what you are about to learn would justify an 11, a level that, theoretically, is impossible to breach.
As a veteran scientist familiar with controversial findings, Laura warned me not to make too bold of claims lest people shut down, close their eyes, cover their ears, and loudly repeat, “LALALALALA.” Wild conclusions that finger Lyme disease as the source of myriad maladies would threaten to join the pantheon of overwrought, tired conspiracy theories that border on lunacy. Proclamations even suggesting that Lyme is the world’s most pressing epidemic will have readers heading to the exit before their eyes finish a single disbelieving roll.
I’ve tried, believe me, I’ve tried. The problem with science, good science, is that it is unbreakable. For the better part of 18 months, I’ve played the precocious role of Bamm-Bamm Rubble trying to club my hypotheses into submission… only to meet abject failure. Wherever it leads, I must trust the science. Without following it, all of it, I’ll leave too many unanswered questions, opening myself up to a rash of predictable whataboutisms.
The magnitude of the forthcoming revelations cannot be overstated. Globally, at least 4.5% of the world's population has one or more autoimmune diseases—more than 350 million. Some estimates run as high as 10%. A June 2023 study in the Lancet laid out in stark terms the devastation that the more than 80 documented autoimmune diseases have wrought on humankind. A team of researchers investigated the electronic health records of 22 million individuals to measure the incidence, prevalence, and co-occurrence of the 19 most common autoimmune conditions just in the United Kingdom. They discovered that autoimmune diseases affect a whopping 10 percent of their population—13% of all women and 7% of all men.
But it was one sentence in their conclusion that set off blaring alarms impossible to ignore. “The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis.” There it is again, environmental factors. Even Dr. Frederick Miller, the now retired former Clinical Director and Chief of the Environmental Autoimmunity Group at the NIH, has been flailing his arms like an air tube dancer on a used car lot about the rising rates, also fingering the environment as a flashpoint. In February of 2023 he wrote that “both autoimmunity and autoimmune diseases are dramatically increasing in many parts of the world, likely as a result of changes in our exposures to environmental factors.”
It couldn’t possibly be from ticks, whose habitat has grown considerably in the past 30 years due in part to climate change, could it? Could it? To begin to comprehend how it could be even remotely conceivable that Lyme disease—which has infected more than 1.2 billion of Earth’s residents—has infiltrated the confines of autoimmune disease, it helps to select a disease and then take lessons from the chapters of this memoir that have systematically stripped down another autoimmune disease, MS, and documented the researchers’ dogeared playbook of painful missteps.
It seems logical to continue breaking down the grandaddy of them all, rheumatoid arthritis. As I reported pages earlier, it’s the most common of all autoimmune diseases, with an estimated 18 million cases. The most common issue facing patients with untreated Lyme disease? Arthritis, affecting an estimated 60% of long sufferers of the tickborne illness. And this Lyme connection is personal, as a relative, then living in the suburbs of Chicago, went through four years of agonizing joint pain and increasing disability before he was finally diagnosed with the infectious disease. He, too, thought he had dispatched a suspected blackhead from his scalp thinking nothing of it. It wasn’t a blackhead.
For starters, let’s first investigate in RA a popular red herring in autoimmune disease research: the so-called “latitude gradient,” the theory that lack of sunlight and/or vitamin D likely plays a role in acquiring the disease—the same flaw-riddled theory in MS that I took down with the efficiency of John Wick. Alas, just as in MS, RA scientists have latched onto this theory like an Amazonian candiru (if you recall from Chapter 5, the small eel-like fish that purportedly swims up and wedges into the urethra of unsuspecting swimmers). Google Scholar search reveals 3,100 RA studies related to the topic of latitude.
“A statistically significant area of increased RA risk was identified in the northeast United States,” reports a comprehensive 2010 nurses’ health study. Except that “statistically significant” tilt to the Northeast, aka Tick Utopia, aka the Arachnoid Arcadia, aka the Garden of Eaten, is more than a mere tilt. The study, mapping cases of RA at diagnosis using red dots to represent them, turned New England so crimson that it one ups the bloody aftermath of a Freddy Krueger visit. The research also confirmed past studies that found RA is especially rampant in the area, along with, of course, the upper Midwest.
"Distribution of cases and controls for RA. Each point represents the residences for cases (red) at diagnosis and controls (blue) at time of censoring. Locations have been geographically altered to preserve confidentiality."
Vieira VM, Hart JE, Webster TF, Weinburg J, Puett R, Laden F, Costenbader KH, Karlson EW. 2010. Association between residences in U.S. Northern latitudes and Rheumatoid Arthritis: A spatial analysis of the Nurses’ Health Study. Environmental Health Perspectives 118(7): 957-961 https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.0901861
With the location box checked, it’s time to investigate treatments, which for RA—other than straight-up surgery—consists of steroids, NSAIDS (Advil, etc.), and anti-inflammatory disease-modifying antirheumatic drugs (DMARDs). The Mayo Clinic reports that conventional DMARDS include methotrexate, while newer biologic agents include drugs like rituximab. This is a notable mix. These same treatments are used in multiple sclerosis and many other autoimmune diseases and, with few exceptions, enjoy, at best, middling success. Antibiotics, however, are another story.
“Tetracyclines, in particular minocycline, were associated with a clinically significant improvement in disease activity in RA with no absolute increased risk of side effects,” found a 2003 meta-analysis. Tetracyclines are the first line of treatment for Lyme disease. Investigating a step further, a 2021 randomized clinical trial with 160 participants trialed spirochete-nemesis doxycycline as an add-on to the gold standard DMARD methotrexate for 3 months. Half got just methotrexate; the other half got both drugs. The results were eye-opening.
“In the group of patients treated with MTX only… a notable number of patients improved achieving remission (13.5%) and low disease activity (4.1%),” reported the authors of the study. Not great, but better than nothing for the gold standard. What about the study’s other arm? “In the patients treated with doxycycline in combination with MTX… a high number of patients reached the target in the form of accomplishing remission (40.5%) or low activity of the disease (29.7%).”
Holy here we go again, Batman! The shocking efficacy of doxycycline when combined with methotrexate—an astonishing 70% saw benefit—should have been groundbreaking, but further research, while encouraged, was unlikely. The reason? Long-held beliefs in the arthritic profession. “Rheumatologists have not embraced minocycline or doxycycline as primary treatment options for RA and reserve their use primarily in patients with long-standing, refractory disease,” stated a 2011 study. The reasons why are illuminating.
Minocycline has proven to be a very safe and moderately effective disease-modifying antirheumatic drug (DMARD) in the treatment of RA, but its efficacy appears to vary greatly depending on the patient population in which it is used. Although an initial open-label study using minocycline in treatment-resistant RA was encouraging, two subsequent double-blind, placebo-controlled studies from the 1990s found only modest, although statistically significant, clinical improvement. The participants in these latter two trials had long-standing, DMARD-refractory disease. In contrast, more recent trials examining minocycline in DMARD-naïve, early RA yielded more impressive results.
Funny, when these antibiotics are used in Lyme disease, patients experience the exact same results. The antibiotics work like gangbusters when used right away and clear up the infection consistently. But if the disease is left to progress unchecked for years, using these same antibiotics to treat established “long Lyme” routinely falls short. I am living proof. The avalanche of gains I experienced in the first months of being on antibiotics have faded like a temporary tattoo, leaving only a faint shadow of what once was. Even the dramatic cardiac gains I enjoyed after IV antibiotics—when my max heart rate jumped from the low 100s in beats per minute into the more expected 150s for an athlete—took flight a few months later. I now struggle to raise my heart rate and have not crested 120 bpm in months.
What about the “traveler” effect witnessed in Puerto Rico and South Africa, where residents of means travel to Lyme endemic areas like the Northeast US and Europe only to return home unknowingly with the disease, and subsequently get misdiagnosed with a Lyme mimic like MS or RA? Although “RA is one of the most prevalent health conditions in Puerto Rico,” says a 2022 study, prevalence rates have not been studied extensively in the territory. That means we need to follow the sound of vuvuzelas to Africa…and, as expected, a study out of the UK confirms suspicions. “Prevalence of RA in [poorer] rural South African populations was noted to be significantly lower than in [wealthier] urban populations (0.87% compared with 3.3%, respectively), suggesting that environmental factors play an important role that would explain such marked differences in genetically closely related communities.” Bingo.
There are many other areas we could explore to further expose cross contamination—for instance, suspicious diagnostic markers for RA that overlap with Lyme. Take CXCL13, the chemokine that appears to be a sign of Borrelia burgdorferi’s presence. If Lyme is being routinely mistaken for RA, one would expect levels of the chemokine to be similar in the rheumatic disease as well. It is, with an asterisk. It’s frustratingly just not that specific of a marker. “Recent studies have found that CXCL13 and its receptor CXCR5 are implicated in the pathogenesis of several autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, primary Sjögren’s syndrome, myasthenia gravis, and inflammatory bowel disease.” As well as type 1 diabetes, psoriasis, systemic sclerosis, and others.
We could analyze and break down a plethora of misdiagnosis red flags to tease out additional similarities between RA and Lyme, but that would threaten to plunge this analysis into the same trap that has ensnared researchers for more than a century—an overreliance on minutiae at the expense of the big picture. The same big picture created by all those seemingly unrelated dots discovered by researchers. The same big picture that sharpens when those dots unexpectedly and seamlessly connect.
Disease Stacking
When I started wooing Laura after that chance meeting in a greeting card store 35 years ago, I did my darndest to impress her, tamping down any noticeable flaws. Chronically late, I arrived for our dates punctually. For a while. Habitually messy, I spit-shined my room and even my car. For a while. I even suppressed my farts in her presence. For a while. Then one afternoon, after the unwise consumption of a chilidog (what was I thinking?), the charade came crashing down in predictable fashion. The romantic gesture of literally sweeping her off her feet was punctuated by a loud rip that almost certainly was detected by USGS seismographs. A startled Laura, still in my arms and therefore still in the odiferous plume, just smiled. “Was that what I think it was?” We’ve been poofering in each other’s presence ever since.
The point is, Lyme disease, like me and passing gas, can’t hide its prodigious propensity for mischief, not forever. It may lurk, cloaked as another health condition, but at some point, those true colors are going to blaze with the right trigger. If Lyme disease is indeed masquerading as rheumatoid arthritis, every common symptom of the tickborne illness eventually is going to surface in the RA patient population, not just those related to joint pain. Every. Single. One. That means that for my hypothesis to be correct, scientists must be seeing an array of disparate symptoms—from extreme fatigue and vision issues to irregular heartbeat and heat sensitivity—in their research of the rheumatic disease. That's an incredibly high bar to Fosbury flop over.
So, let's make it higher.
As non-RA symptoms present, it would then also be expected that puzzled doctors would diagnose additional other autoimmune diseases to fit the new symptoms. After all, people with an autoimmune disease are highly susceptible to acquiring other autoimmune diseases, dontcha know. What’s another one, or two, or three? It’s so common that stories of patients like Fatiha, her story documented in Yale School of Medicine’s magazine, elicit hardly a shrug. “I was never sick before in my life,” the Connecticut resident told the publication. “Then one day everything changed.”
Seven years ago, Fatiha began to experience joint pain and swelling of her hands. A doctor diagnosed her with Sjögren’s syndrome, an autoimmune disease. Three years later, the joint pain flared up and was accompanied by a severe rash and sudden hair loss. Fatiha, 32, … could barely walk. The diagnosis was lupus, another autoimmune disease. Lupus causes inflammation in the skin, joints, and kidneys. Symptoms include fatigue, joint pain, skin rashes, leg swelling, and chest discomfort. Still later, she received yet another diagnosis: rheumatoid arthritis. Rheumatoid arthritis occurs when the body’s immune system attacks the lining of its joints, causing pain, inflammation, and eventually, cartilage and bone damage. This autoimmune disorder can also harm the body’s internal organs such as the heart, lungs, and nervous system.
Again, if rheumatoid arthritis is just a subset of Lyme disease, this type of disease stacking must be occurring regularly in rheumatoid arthritis. And because Lyme mimics so many other conditions, and spirochetes can’t exactly choose which ones to mimic, those conditions must mirror the entire playbook of autoimmune diseases that Lyme is mistaken for. Every. Single. One.
Yikes. To clear that even higher bar, we’re going to need to channel Ukrainian Sergey Bubka, who broke the world record for men’s pole vault an incredible 35 times. Or maybe not. Researchers have already connected those dots. A novel 2017 study compared how often RA paired with other autoimmune diseases. But they didn’t stop there. For a control, they also conducted a side-by-side comparison with how often osteoarthritis (OA)—the most common form of arthritis and, distinctly, not an autoimmune disease—paired with autoimmune diseases.
Oh boy, now the plot thickens like a properly prepared Cajun roux. This study, analyzing more than 1.4 million healthcare claims spanning the two arthritic conditions, confirmed that RA is indeed diagnosed with other autoimmune conditions far more frequently than osteoarthritis. But with the range of these diseases outnumbering an average NFL roster (55) and its practice squad (16), researchers had to limit the guest list to a preselected 37 autoimmune diseases for their analysis. For each of these diseases, researchers calculated not only the prevalence of how frequently they are paired with RA and OA, as a percentage, but also the odds ratio of how likely each disease would be paired with RA as opposed to OA. For instance, for those suffering from rheumatoid arthritis, 2.42% also had a diagnosis of Sjögren’s syndrome. In contrast, only 0.36% of those with osteoarthritis had Sjögren’s, meaning a patient with RA was a disturbing 6.8 times more likely than someone with OA to come down with the glandular disorder.
The results are chilling.
The RA-autoimmune connection was so stunning that a Will Smith smack to face was required for me to get over the shock. Just alopecia—the disease that theoretically caused Mr. Smith’s wife to go bald, ultimately triggering his regrettable Oscar outburst on Chris Rock’s cheek—and MS had remotely similar prevalence rates. The rest diverged, either modestly or wildly, and always in favor of RA. Every. Single. One.
The list reads like a Who’s Who guide of the most celebrated diseases that Lyme mimics. Leading the way: ankylosing spondylitis, a type of arthritis that mainly affects the back. Although only about 1% of those with RA have the disease, those patients are 8 times more likely to have it than OA patients, at a scant 0.15%. Psoriatic arthritis, a form of arthritis with a rash that is a skin and nail disease, checks in next. Over 3% of patients with RA share the disease, and those individuals are 7.8 times more likely to be afflicted than patients with OA are. There are a number of other popular standouts: Sjögren’s (6.8 times), vasculitis (6.7 times), and scleroderma (5.7 times) to name a few.
But the most common autoimmune disease shared with RA is arguably the most predictable of the lot: lupus. Nearly 4% of all rheumatoid arthritis sufferers also have lupus and are 5.7 times more likely to have the condition than OA patients are. Interestingly, another study compared the prevalence of symptoms between the two diseases over time and found that after 25 years, 15.5% of all RA sufferers had four or more symptoms consistent with lupus.
The once-secure footing that props up the theory of autoimmune diseases is going to fully dissolve before your eyes...
Lupus, like many autoimmune diseases, is extremely challenging to diagnose and is known for its legendary ability to mimic other diseases. Just like Lyme disease. In fact, the two diseases are blindingly alike. Fever, joint stiffness and swelling, gastrointestinal issues, fatigue and malaise, depression, and thyroid issues are just a smattering of the crossover symptoms.
Trick question: How can you or a medical professional tell the difference between lupus and Lyme disease? Simple! One has a known cause and often features a rash, while the other is an autoimmune disease of unknown cause that often features a rash. Duh. You can easily differentiate the two by their distinctive rashes, at least when they show up—a bullseye for Lyme and one that resembles a butterfly on the face for lupus. Oh, and the diseases react differently to antibiotics. As many as 40% of people with Lyme experience debilitating Herxheimer reactions when initiating curative antibiotics, but when you give that same class of antibiotics to those with lupus, some 40% of those patients instead suffer what appears to be an allergic reaction.
But like RA, lupus couldn’t be Lyme disease. No way, Jose. Not a chance, Lance. Impossible, Mrs. Krabappel. (Okay that last one might be a bit of a stretch in the rhyming department.) Way back in 1995, scientists from New York and New Jersey sniffed out the problem and snuffed out any concerns the diseases could be conflated with one another. They discovered in their research that the first tier of Lyme disease testing, the ELISA, must be unreliable when used on patients with these diseases. Because it produces positives. Lots and lots of them. An outrageous number of them. It could only mean one thing.
In conclusion: a positive ELISA for Lyme disease was found in up to 40% of patients with established [lupus] and also in other rheumatic diseases. However, specific serum antibodies to Borrelia were not confirmed by the more specific immunoblot technique. We conclude that immunoblot analysis can help differentiate a false from true positive ELISA for Lyme disease.
After I saw that, flooding my spinning brain was an expression I hadn’t heard since 1985, back when my suit-wearing, always professional boss at my first summer job uttered a profane phrase that shocked a 16-year-old: fuck a duck. Forty years ago I had no idea that my boss’s realty company was weeks away from defaulting on over $1 billion in loans. Or, for that matter, that adults spoke aloud of wild fowl and fornication.
That bad feeling I had from pages earlier? It’s now worse. Way, way worse.
The towering stack of poker chips scientists have amassed over the past century from their winning hands in the autoimmune disease game is impossible to overlook. It’s daunting. They’ve always come out on top. These researchers have since become whales in the medical community, chortling with a muddied Jabba the Hut laugh at anyone who questions their findings. But in gambling parlance, a whale is also a high roller who makes outrageously large bets. They are frequently courted by casinos because, while they often win big, they inevitably will lose bigger.
By every measure, it appears Lyme disease has infected the pillars of the autoimmune solar system. And that stack of chips—the evidence scientists have confidently collected for the past century—suddenly doesn’t look quite so imposing. They’ve gone all-in on a hypothesis that they insist is supported by the science, wagering the highest of stakes: human health. Science, though, doesn’t care about allegiances to a theory or the accolades that come with discovery. Its laws only demand accuracy. And like the house in every casino, science always wins.
Over the coming pages, the once-secure footing that props up the theory of autoimmune diseases is going to fully dissolve before your eyes, revealing nothing more than a fraught foundation made up of Jello and quicksand.
Before you insist that I’m wrong, all wrong, know that the wrath of Lyme disease extends far beyond the confines of that finite cluster of 80+ autoimmune diseases. It washes over an entire galaxy of medical conditions. And within each one is conclusive evidence reaffirming a single, inescapable, horrific fact.
Since the dawn of humanity, the long, stealthy fingers of Lyme disease have had an unbreakable chokehold on the health of society. Its secret as an epidemic was secure, allowing it to spread unchecked, teasing scientists with distracting clues and devious smokescreens. The ultimate SQUIRREL! Unbreakable and uncheckable, that is, until now.
For our next astounding twist, I’ll lay down my cards and show you how scientists and reams of their research have unwittingly and repeatedly identified the same lone marauder, inadvertently harpooning their own conclusions again and again.
And again.
And again.
And again.