Controversies in Lyme disease

Outside the exam room, I leaned against the wall and shut my eyes. There was no way forward. At its core, Mr. Jewell has a belief system which is contradictory to mine. We belong to different religions, each hoping to convince the other to convert. I am the establishment, unwilling to adopt the long-term antibiotic approach for Lyme disease he has embraced as an article of faith. ​

An hour earlier, I had asked Joanne, “Any referral notes or laboratory studies for me to review ahead of time on my new patient?”

“No, he’d prefer to tell you the story from the beginning. Fresh.” ​

“Okay,” I said, the inflection in my voice indicating otherwise. Did he fill out the new patient questionnaire?” ​

“No,” Joanne raised an eyebrow. “He has his records organized in a 3-ring binder. Good luck.” ​

“Thanks.” I lingered outside the exam room. When a patient brings their own records, it usually means that multiple consultants have seen the patient. Having it fed to me selectively page by page, makes it clear that the patient disagrees with some or all of the previous opinions. Lab or radiographic studies may be conflicting. Medications have been either ineffective or poorly tolerated. I am about to hear a medical journey from a particular viewpoint. “Did you notice anything when you roomed him?”

“He was limping,” Joanne answered. “Maybe a bad knee?”

“Okay, that’s a start.” I felt at a distinct disadvantage not knowing anything about my next consult, even mildly irritated. Based on my previous experiences, this next hour may not go well for either of us. Careful, I reminded myself. He’s a patient who needs help. Don’t prejudge. Clear your mind; the man is limping.

I extended my hand as I entered the room. “Good morning Mr. Jewell.”

“Good morning. Thank you for seeing me. Let me start at the beginning, two years ago when I first developed Lyme disease.” Mr. Jewell cracked open the notebook as if he were reading a bedtime story. “My property is infested with ticks; it’s over-run with ticks. I’m constantly pulling them off the dogs, but one evening, I found an imbedded tic on my lower leg and it was quite a process to remove it. Well, I went to the doctor and showed her the remains.” With this, Mr. Jewell handed me a test tube as he repositioned his black-framed glasses on the bridge of his nose. “As you can see, it was a deer tick, not the larger, innocuous dog tick.” I held the tube up to the light and identified a mummified, dark spot the size of a grain of rice nestled on a wad of cotton. Mr. Jewell turned to the next page labeled: TREATMENT. “The doctor prescribed doxycycline. That would be August 24th. 200 mg of doxycycline.”

“And did that help?” I asked, before noticing a line of oily grime around the cuff of my trouser leg. That would be when I stepped into my boat an hour ago and water from a recent thunderstorm flooded over my shoe. My left foot still felt uncomfortably cold. On my tie was a gray smudge—probably from when I leaned down to inspect the bilge pump. I tucked the tie into my shirt.

“Evidently not.” Mr. Jewell hiked up his slacks for me to view his swollen knee. “Can you imagine, two pills of 100 mg doxycycline? What was the doctor thinking?”

I recalled that the Center for Disease Control recommendation for prevention of Lyme disease after pulling off an imbedded tick was indeed 200 mg of doxycycline. At a glance, I estimated that Mr. Jewell’s knee held half-a-cup of fluid. No wonder he was limping, an effusion that large must be painful. Above the knee I glimpsed a silvery, quarter-sized rash on the inner thigh, but as I leaned forward to get a better look, Mr. Jewell tugged his pants cuff down several inches. “There’s a large amount of fluid in this knee,” I said. “Has it ever been tapped?”

“Once. But we’re getting ahead of ourselves.” Mr. Jewell grimaced as he shifted the knee and turned the page. “After the tick bite I didn’t notice much. I’d heard about Lyme disease, everyone’s heard about Lyme disease, but it wasn’t until the following spring when the Lyme symptoms began. At first, I thought it was the divorce. I wasn’t sleeping well and I’ve always been prone to headaches, but every day, my head throbbed. I gained weight.” He patted his abdomen as if to emphasize the obvious. “At work, I was so exhausted I could hardly drag myself back to the office after lunch.”

“And when did the knee swelling occur?” I asked.

“Out of nowhere the knee swelled up one month later.”

“And did someone see you for that?”

“An orthopedic surgeon.” Mr. Jewell removed several pages from his records and handed them to me. I scanned through the results: normal x-ray, negative Lyme testing, and handed them back. “At the end of the visit, he injected the knee with cortisone.”

“And did that help?” I asked.

“It was amazing. Complete relief. But in retrospect, that was probably the worst thing he could have done. I’m sure you’re aware that injecting a Lyme infected knee with cortisone allows the infection free reign. When the swelling relapsed several months later, I felt like someone had exploded a bomb inside it. That’s when I heard about Dr. Finegold, a Lyme savvy doctor in Massachusetts. He was a godsend.”

“That would be, what, a year ago?” I asked. “Yes.” Mr. Jewell handed me another two pages. “Here’s his consult. I was a train wreck by then. Although a second Lyme test was negative, Dr. Finegold assured me that the negative Lyme testing represented a false negative, probably related to the inadequate initial treatment of the imbedded tick the previous year. He emphasized that Lyme is a clinical diagnosis. Testing is notoriously iffy. No, I don’t think he used the word iffy, but you know what I mean, the symptoms, the big picture, that’s what he was looking at to make the diagnosis of chronic Lyme disease. Dr. Finegold had me fill out a Lyme disease questionnaire. You’ll notice that I checked off 32 out of 42 symptoms commonly associated with Lyme disease.”

Indeed. Included in the checklist suggesting Lyme disease was #28: Disturbed sleep: too much, too little, and #40: Exaggerated symptoms or worse hangover from alcohol. “Dr. Finegold cautioned me that I was one of the worst cases he’d ever seen and that treatment would require a multi-faceted approach. Even so, he was optimistic that a full recovery was possible, even expected. So, for 3 months I took doxycycline. After that, well, we tried different combinations of oral antibiotics and supplements. The swelling in the knee didn’t budge. The theory, well, I’m sure you already know this, but the Lyme spirochete is capable of evading the immune system. That’s when he arranged for a month of the intravenous antibiotic, let me make sure I say this right, Ceftriaxone.”

My head was spinning. An imbedded tick promptly treated with the appropriate dose of doxycycline, two negative Lyme tests, months of oral antibiotics and now a course of intravenous antibiotics. Lyme arthritis? I don’t think so. Something else must be driving the knee inflammation. “There were times during the first four months of antibiotic treatment that I believed I was turning the corner, but then almost overnight, the pain and swelling in my knee doubled. The tick was fighting back. My short-term memory was shot; my mood swings horrific. And the fatigue…I could barely will myself out of bed each morning. I was losing the battle. When my arm veins could no longer be used, Dr. Finegold recommended that I have a port placed.” Mr. Jewell reached up to his upper left chest where the port was palpable beneath the skin (through the port, medications can be delivered directly into a large vein). “Once the port was in, Dr. Finegold doubled the dose of the IV antibiotics. It was a last-ditch effort, but it wasn’t enough. I lost my job and applied for disability---that would be four months ago.”

“I’m sorry it came to that.”  I forced a tight-lipped half smile, stood and unfolded a cloth gown from the shelf above the sink. “Let me step out for a minute while you change into a gown. I want to do a complete examination. I’ll be back in a few minutes.” Back in my office I slumped into my swivel chair and pulled a review article on Lyme disease from my files. In the mid-1970’s, two young mothers from Lyme, Connecticut, Polly Murray and Judith Mensch, contacted their State Health Department. Both of their children had been diagnosed with JIA (juvenile idiopathic arthritis), and they knew of other children and adults with similar symptoms. Since JIA is an uncommon immune system disease affecting about 1 in 1000 children, and the mother’s story suggested far higher numbers, Dr. Allen Steere, a first-year fellow in rheumatology, and Dr. Stephen Malawista, the head of the rheumatology department at Yale New Haven Hospital, decided to investigate the unusual cluster. With the mother’s assistance, the two physicians eventually identified 39 children with the disorder in the surrounding community. Many of the families recalled that their child developed a flu-like illness and an unusual rash before experiencing joint swelling. Steere and Malawista reported their findings in the Journal of Arthritis and Rheumatism: Lyme arthritis: An Epidemic of Oligoarticular Arthritis in Children and Adults in Three Connecticut Communities.

By the time I arrived at Yale New Haven Medical Center as a visiting internal medicine resident for a six-month elective in 1984, many of the details of Lyme disease had been clarified. A bacterium, Borrelia burgdorferi, transmitted by the bite of the deer tick, was determined to be the cause of Lyme disease. An expanding rash (erythema migrans) occurred in many, but not all patients after the initial tick bite, and represented the leading edge of the infection. In untreated patients, a flu-like illness with fevers, muscle and joint aching, and fatigue developed. In patients promptly treated with antibiotics, the infection usually resolved. And there were other, more serious complications. Unrecognized Lyme infection could lead to heart rhythm disturbances or inflammation within the central nervous system (meningitis) as well as nerve damage. Some patients eventually developed inflammatory arthritis, usually in a solitary joint such as the knee, but occasionally in smaller joints.

Even though Yale was a hotbed of Lyme research, in our rheumatology clinic, we didn’t automatically assume that all of our patients with swollen joints or unexplained symptoms had Lyme arthritis. After all, there are nearly 100 conditions rheumatologists treat, and Lyme disease was only one of many possibilities. Even in challenging cases, however, clues in the history or physical exam and laboratory studies usually led to a specific diagnosis. Sometimes, it was Lyme disease.  Now, decades later, I’m relieved when Lyme testing is positive in my inflammatory arthritis patients. Instead of having a chronic, life-long disease, they have an infection that is usually cured by a month of the oral antibiotic doxycycline, or, in some resistant cases, a month of intravenous Ceftriaxone. Of course, nothing in medicine is simple; there are exceptions. As our understanding of Lyme arthritis has expanded, a number of studies (including papers written by Dr. Steere), have suggested that rarely, the Lyme spirochete may trigger persistent joint inflammation despite appropriate antibiotics, a process called “reactive arthritis.” That is, the original infection has resolved, but swelling and inflammation persist due to activation of the immune system. These patients respond well to medications which reduce inflammation.

Returning to Mr. Jewell’s room, I noticed that three fingernails had distinctive tiny pits and asked, “Have you noticed the changes in your nails?”

“I have,” he replied. “I keep discovering that the Lyme is hanging on in places I wouldn’t dream of. It’s not just the fluid in the knee. Dr. Finegold said that I’d know when the Lyme infection was on the run when the nails began to heal.” I continued my exam. A silvery patch of skin over the back of the right elbow caught my attention. Psoriasis. Above the knee, the silvery patch of skin in the midthigh I’d glimpsed earlier was also definitely psoriasis. On a hunch, I asked him to slip off his shoes and socks, and here was another clue. The third toe on the right foot was reddened and swollen like a sausage. An alternative explanation for his joint symptoms was clearly present. The skin psoriasis and pitted nails, the swollen knee and inflamed toe represented psoriatic arthritis, not Lyme arthritis. Nothing else fit. For more than a year, Mr. Jewell had suffered unnecessarily and was now applying for disability with both the wrong diagnosis and on the wrong treatment. 

“I’ve been off the infusions for several months,” Mr. Jewell interrupted my thoughts, “ever since my insurance company refused to cover them.” Now I understood why Mr. Jewell was in my office selectively feeding me his medical records. In essence, his health insurance company was asking: Do you agree with Mr. Jewell’s treatment with long-term IV antibiotics for Lyme arthritis? Intravenous infusions are not only expensive, running into thousands of dollars per month, but are associated with significant risks, including allergic reactions, systemic infections, and in rare cases, death. After completing my exam, I asked Mr. Jewell to change and slowly walked back to my office. There, I cracked open a pistachio nut and considered my strategy. How do I convince Mr. Jewell that he has psoriatic arthritis, not Lyme arthritis?

Then I sat quietly for a moment, recalling the fractious history of Lyme disease.

Following the development of antibiotic treatment regimens for Lyme disease in the 1980’s, it became clear that while most patients promptly recovered, approximately one in ten experienced persistent, and at times life-altering fatigue, headaches, and migratory muscle and joint pain. The term, post-Lyme disease syndrome, was coined to describe this patient subgroup. Because academic researchers could not identify persistent infection, antibiotics were not recommended for this group of patients. Although most of these patients eventually recovered, a significant number remained unwell. Advocacy and support groups were formed to promote an alternative view: Patient’s symptoms continued because the original infection was present within cells and difficult, if not impossible, to detect. The diagnosis of Chronic Lyme disease came into the popular lexicon. The two sides disagreed on nearly aspect of Lyme disease, including how often Lyme testing was negative in Lyme disease, antibiotic dosing for prevention of Lyme disease after an embedded tic, and duration of antibiotic treatment for chronic Lyme disease.

Eventually, because they remained unwell, patients like Mr. Jewell not uncommonly received long-term IV antibiotics through a port. But does this approach work? To answer this question, researchers have compared placebo infusions with IV antibiotics in patients with persistent symptoms after a diagnosis of Lyme disease. In total, four separate studies failed to show that IV antibiotics were more effective than a placebo infusion. This did not end the controversy. As described in David Grann’s, 2001 article in The New York Times Magazine, Stalking Dr. Steere, “The Lyme movement considered itself a victim of…(the) scientific establishment…It formed its own powerful organizations, such as the Lyme Disease Foundation; created its own scientific publication, the Journal of Spirochetal and Tick-Borne Diseases; organized its own scientific conferences, and trumpeted its own medical experts with their own treatments.” What’s more, the dispute became intensely personal. Dr. Steere—who had originally described the tick born infection and did not recommend long-term antibiotics, at one point required security guards at his scientific lectures. Official complaints were lodged against him at the state medical licensing board. These were found to be without merit. Mr. Jewell’s case was even more mind-boggling. There was no question in my mind that his knee inflammation and rash represented psoriatic arthritis. His Lyme testing had never been positive and the myriad symptoms he had checked off on his Lyme disease questionnaire overlapped with symptoms in patients with a host of other painful medical conditions---including untreated psoriatic arthritis.   

Aware that I was hopelessly behind schedule, I saw no reason to delay or hedge my opinion. From past experience, I suspected this was not going to go well.  “I have some good news for you, Mr. Jewell. It may take a few months, but with some medication adjustments, I believe that the pain and swelling in your knee can be dramatically improved. Instead of Lyme arthritis, you have psoriatic arthritis, a very treatable condition.”

For a moment, stunned silence. Then Mr. Jewell’s face collapsed and he looked like he was on the verge of tears. One would have thought that I had diagnosed him with an incurable malignancy. “I knew it,” he hung his head. “My sister said I should come see you, but this is exactly what I expected.” He gathered his notebook and jacket and stood to leave. I cracked my neck to the right and surreptitiously palpated my pulse. That’s strange. I’m sweating like crazy and about to ignite from stress and my pulse is a rock-steady 60 per minute. Go figure. The human body is a strange mixture of mind-body interactions. Some make sense, some not.

“Here, let me explain.” I pulled a dermatology textbook from the shelf and opened it to photos of skin psoriasis. Mr. Jewell reluctantly sat down for a better look. “I think you can agree that your skin rashes represent psoriasis. Roughly 20% of patients with skin psoriasis also have inflamed joints, what we call psoriatic arthritis. Since there is no specific blood test to confirm a diagnosis of psoriatic arthritis, my job is to weigh the evidence between a diagnosis of psoriatic arthritis and other forms of inflammatory arthritis and recommend a course of treatment.” 

Mr. Jewell considered this. “So, you agree with Dr. Finegold?”

“No. My opinion is that you have psoriatic arthritis and don’t need further antibiotics.” I wasn’t going to leave any wiggle room in our discussion.

“What about the Lyme diagnostic questionnaire?”

“The questionnaire? It’s not specific for Lyme disease. If any of my patients with active psoriatic or rheumatoid arthritis filled out the questionnaire, it’s likely their answers would be similar to yours.” I paused.

Mr. Jewell seemed to be mulling over my logic.  “Then why do I feel better when I’m on IV antibiotics?” he asked finally. ​

“There are many reasons why symptoms of fatigue or concentration or pain may feel better with a treatment you believe in. But remember, I’m saying symptoms. Your knee swelling is a sign, a measurable objective finding. I don’t see where that has improved with intravenous antibiotics. Has it?”

He glumly looked at his knee. “I’m not sure. Sometimes I think it’s getting better. Dr. Finegold has repeatedly told me that treatment of my arthritis is going to take time. If only the diagnosis of Lyme disease hadn’t been delayed so long, I’d probably be back to normal.”

​I was anything if not persistent. “Look at how much you’ve declined during the past year despite antibiotics,” I countered. “A year ago, you didn’t need a cane to walk. Six months ago, you were working. Going forward, if you allow me to treat you for psoriatic arthritis, I’m confident that we can control the inflammation and prevent future damage.” 

Mr. Jewell rubbed his knee and flexed it slowly back and forth. “What type of medication are you suggesting?”

“Okay. In order to achieve our goal of putting your psoriatic arthritis in remission, I want to begin a weekly medication called methotrexate. It’s an older but very effective drug, so we know a lot about how it works, the risks, and the proven benefits.” As I talked, I noticed Mr. Jewell typing on his iPhone. “And although we need to monitor it for side effects with blood counts and liver testing, the knee swelling should respond…”

“It says here,” Mr. Jewell interrupted me, “It says here, that methotrexate is a drug that is used in chemotherapy. It’s an immunosuppressant, a cancer drug.”

“That’s true.” I swallowed and fought back the urge to escalate the conversation. “Yes, its original use was in cancer medicine, but the dose of methotrexate we use in psoriatic arthritis is a fraction of the dose used in chemotherapy. In the proper dose, it’s well tolerated and helps reset an overactive and misdirected immune system without suppressing it. Some of my patients have safely taken methotrexate for decades. If the methotrexate doesn’t fully control the inflammation, a new class of medications, biologic response modifiers such as Enbrel or Remicade—and there are others—are often remarkably effective in the management of psoriatic arthritis.”

Mr. Jewell crossed his arms and looked beyond me at the clock. Both of us needed a time-out. “Hold tight” I said, “I’ll be back in a moment.” I walked slowly down the hallway to the bathroom, poured myself a cup of coffee in the break room, drank half of it, and poured the rest in the sink. Then I returned to Mr. Jewell’s exam room. “Okay, now where were we?”

“We were talking about medications,” Mr. Jewell replied. 

“Right. And I assume you’ve had a chance to read more about methotrexate?”

“I have. And I would never take a drug like methotrexate or any of the other medications you’ve suggested. Dr. Finegold has a plan. He’s explained to me that the Lyme infection hides out inside our cells. It’s constantly changing and evolving. That’s why I need to bathe my system with combinations of antibiotics, to catch it when it emerges. My immune system needs help. We need to build it up with supplements and changes in diet and you’re asking me to ingest a drug which will tear down my immune system and poison my liver.”

Checkmate. There was no room for compromise. “Then I guess we’ll need to agree to disagree. I’m sorry that so far, your inflammatory arthritis, what I’m calling psoriatic arthritis, hasn’t responded to what Dr. Finegold has prescribed for Lyme disease. I’ll summarize my thoughts to your primary care doctor and leave the door open to see you in the future. If you change your mind, I can…”

“That’s fine, except for one thing,” Mr. Jewell leaned forward on his seat. “I need a letter so that I can restart the IV antibiotics through my port. My insurance company is pressuring me to stop the antibiotics, and I need the form filled out and signed by a rheumatologist.”

Stone-faced, I chewed on my inner lip. “No,” I said finally. “I’m not willing to do that. I don’t agree with your treatment plan.” The visit was over. I don’t recall what Mr. Jewell said as he gathered his belongings and stormed out. The limp was real. His disease was real, only it was the wrong disease. Sometimes in life, we pick the wrong door.