Snowball in a Blizzard

by Steven Hatch

  Of pathogens that cause infectious disease in humans, the closest bacteria that resembles Lyme in terms of its structure and clinical behavior is, surprisingly, syphilis, and the longest course of syphilis treatment is two weeks. It’s also worth noting that Lyme is also like syphilis in that it is exquisitely sensitive to drugs. In a test tube, Borrelia burgdorferi is easily killed by antibiotics, making the idea of “antibiotic resistant Lyme” mostly implausible. By contrast, there are bacteria that are genuinely difficult to treat and for which resistance is a major issue: Staphylococcus aureus, more commonly known as “staph” to laypeople, is the most notorious of these. Despite all of this indirect evidence suggesting that months of antibiotics for Lyme was based on somewhat shaky reasoning, and not knowing what else to do for their patients, many mainstream doctors opted in favor of long treatments.

  The alternative Lyme group embraced the concept of prolonged antibiotics to an even further extent, endorsing treatment courses lasting up to several years. While most mainstream doctors never went that far, the question of how long to treat patients with Lyme remained unsettled. When the mainstream medical community finally did arrive at an answer and issued formal recommendations based on that answer, it found itself on the defensive in ways that essentially nobody could have anticipated.

  The evidence about the value of prolonged antibiotics—or more to the point, the lack thereof—had been accumulating with a series of studies in the early 2000s. A typical example can be found in a paper published in the New England Journal of Medicine in 2001. In the study, researchers looked at more than one hundred patients who had persistent symptoms after having been diagnosed with Lyme disease. They gave half of these patients a month of an intravenous antibiotic known as ceftriaxone followed by two additional months of doxycycline; the other half got placebos. Over the course of several months they followed the patients, monitoring their symptoms for signs of effectiveness. In the group receiving actual antibiotics, about a third of patients felt like they improved, about a third felt the same, and the final third actually felt worse. These proportions, however, were the same as those in the placebo group, indicating there was no real value to the antibiotics.

  Not only was there no evidence of benefit from prolonged treatment, such regimens were clearly associated with risks. All antibiotics destroy gut bacteria, which can lead to gastrointestinal problems, as well as the overgrowth of a toxin-producing bacteria called Clostridium difficile that causes intense diarrhea and, in several cases, severe illness, even including death. Antibiotics can lead to interactions with other drugs that patients take, most notoriously coumadin, a blood thinner taken typically by older patients for various cardiovascular problems (in killing gut bacteria, which synthesize the essential clotting protein vitamin K, antibiotics can significantly augment the effect of coumadin and make the blood too thin; David Marsh would be unlikely to take coumadin, but many older patients who have been referred to chronic Lyme clinics do). Oral antibiotics increase the chance of allergic responses as well as damage to the liver and kidneys, while long-term intravenous access for IV antibiotics, which had become favored by the alternative group as “stronger” therapy, could cause bleeding, blood clots, or lead to potentially life-threatening IV line infections—all in addition to the same risks associated with the oral medications.

  The key here is that the risks of antibiotics accumulate over time. A few weeks of antibiotics tend to have a sufficiently small risk such that mainstream doctors are content to overtreat a certain percentage of patients for suspected Lyme disease, as I noted earlier. But months, and indeed years, of antibiotics, present much more significant hazards. By the early 2000s the evidence had filtered in, and the mainstream medical community shifted its position on the spectrum of certainty. Lacking any clear evidence of benefit, and with good evidence that long treatments for Lyme brought real possibility of harm, the stage was set for a direct confrontation between these two opposing approaches to Lyme disease.

  The organizational acronyms in the story can be confusing. The mainstream professional organization of physicians that specialize in the treatment of infectious diseases such as Lyme is IDSA—the Infectious Diseases Society of America. In the case of Lyme, as I’ve noted above, the alternative group goes by the very similar acronym, ILADS, the International Lyme and Associated Diseases Society.* ILADS was founded in 1999 as an organized response to IDSA. Although alternative physicians had been promoting a theory of Lyme disease sharply at odds with the mainstream viewpoint for years before this, ILADS centralized these physicians under one banner. They also became a prime example of how the Internet could be used to further a particular agenda, particularly one opposed to a group like IDSA: they fashioned a website that has all the trappings of a society of academics and clinicians, albeit one with a different approach than the scientific establishment.

  I don’t think it’s merely a coincidence that the name ILADS is a close approximation of the mainstream IDSA, allowing confusion to be sown even in the acronym orthography.

  It is not much of a surprise, then, that the very existence of an alternative organization like ILADS strikes many as the professional equivalent of the mainstream IDSA, and that there must be a legitimate scientific controversy about even the most basic topics in Lyme disease treatment. Take, for instance, an article by that most establishment of periodicals, the New York Times, in which highly respected health columnist Jane Brody wrote the following in a piece on Lyme in 2008: “The treatments recommended by the [mainstream IDSA] . . . are controversial. They have been challenged by a nonprofit medical group [ILADS], which says they are inadequate to combat the infection in a significant number of patients.” Yet the Times does not give the same platform of plausibility to other groups hostile to mainstream science. For instance, within a year of Brody’s column, a piece entitled “Paleontology and Creationism Meet but Don’t Mesh” described the horror of mainstream paleontologists upon learning how evolution was portrayed in a creationist museum in Kentucky. Throughout the article the writer never formally weighed in on the merits of the debate because, we can safely assume, he didn’t really think there was a valid debate to begin with, siding entirely with the paleontologists. Likewise, antivaxxers have generally been treated by the Times with the skepticism they very much deserve. But Lyme was treated differently.

  Despite the airtime the alternative view is given in the mainstream media, even a cursory examination of the alternative ILADS website indicates that there is a thin patina of scholarliness beneath which there’s very little there. For example, of the ten people listed as officers and directors of the ILADS organization in early 2014, none had board certification in infectious diseases, and after excluding the two on the list who were not physicians, the remaining eight were board certified in either general internal medicine or family medicine. Moreover, few of these officers and directors had any history of NIH-funded research of any kind, much less on the science or clinical presentation or treatment of Lyme—an assemblage of doctors that stood in marked contrast to mainstream IDSA Lyme working groups.

  It would seem absurd to have an alternative cardiology group overseen by psychiatrists and obstetricians—almost none with any experience in research—who claimed to be “heart literate,” yet this is roughly analogous to the ILADS leadership who claim to be “Lyme literate.”

  As a final emblem of its complete break with the scientific establishment, ILADS had in the mid-2000s elected Dr. Raphael Stricker as its president, who at the time of this writing serves as one of the organization’s directors. Dr. Stricker’s career began in HIV research in the early 1990s at the prestigious University of California at San Francisco, where as a junior faculty member he authored an article published in the New England Journal of Medicine. It is hard to be off to a better start in the scientific mainstream than that. Unfortunately, the paper was ultimately withdrawn because he withheld data from his colleagues that would have invalidated his scientific claims. Following t
hese revelations, he was cited by the National Institutes of Health for scientific misconduct, and UCSF fired him as a consequence.*

  The very fact of Dr. Stricker’s fall from grace is sometimes cited by chronic Lyme advocates as evidence of his intellectual integrity, because it proves that the mainstream was so bent on suppressing his views that they concocted allegations of misconduct to have him fired. “I wonder just who [sic] he pissed off enough to make them trump up some charges against him,” wrote cave76 to a largely like-minded audience on the website LymeNet Europe when the topic was broached on a discussion thread (which can be found in the bibliography).

  So when in 2006 the mainstream IDSA issued an updated set of guidelines, in which prolonged antibiotics were explicitly rejected as a valid approach, the physicians allied with ILADS rightly worried that a part of their livelihoods faced an existential threat. To understand this, it’s important to realize that licensed physicians are given a pretty wide latitude in their clinical practice. It is extremely unusual for individual physicians to be subject to sanctions by fellow professionals for opting to treat their patients even in unconventional ways. As a rule, most doctors run afoul of the system by engaging in unprofessional conduct (such as sexual harassment, insurance fraud, or narcotics abuse) rather than for showing questionable medical judgment. However, if a state medical board could be persuaded that the alternative Lyme physicians repeatedly flouted accepted medical practice, mainstream physicians could conceivably use this strategy to eliminate the alternative approach. Indeed, a small number of chronic Lyme doctors had already been disciplined by these groups. The guidelines could accelerate the process, the reasoning went.

  For this fight, not only did the alternative camp have a reasonably sympathetic ear in the media, but it had enlisted one of the most powerful allies one could hope for in such a dispute: government itself, which came in the form of Richard Blumenthal, the attorney general of the state of Connecticut, who had long been allied with the advocates of chronic Lyme disease. The 2006 mainstream IDSA guidelines gave alternative groups like ILADS and their supporters, through the use of the power of Blumenthal’s office, reason to go on offense. The attorney general opened up an investigation of the IDSA within months of the publication of the guidelines on the theory that the IDSA violated antitrust law and that the guidelines were going to interfere with “legitimate diagnosis and treatment options for patients.” Blumenthal’s goal, it appeared, was to have IDSA reverse or negate its recommendations, thus giving the chronic Lyme approach, at least indirectly, the imprimatur of scientific respectability by stifling IDSA’s criticism. It would also make any state medical board think very carefully before undertaking any disciplinary action against a chronic Lyme physician, lest they find themselves in court as well.

  Blumenthal’s allegations required a clever, unconventional premise. The problem he had, in arguing that IDSA had set up the guidelines as part of a medical monopoly to squelch competition, was to identify the smoking financial gun in a scenario where doctors were very clearly advocating for less treatment. The common complaint of patient and consumer advocacy groups is that physicians have far too comfortable a relationship with the pharmaceutical industry, which results in an all-drugs-all-the-time approach to medicine. Based on this reasoning, it would appear that the IDSA’s stance of limiting antibiotics was laudable. Thus, in order to allege financial conflict of interest among the IDSA panel members, Blumenthal required a different group to play the role of villain.

  Ironically, that group would be one of the largest industries in Blumenthal’s home state of Connecticut: insurers. The logic was that IDSA had colluded with the insurance lobby to limit access to prolonged treatments. By denying antibiotics to chronically ill patients, the IDSA recommendations enabled insurance companies to line their pockets. The investigation, his office announced, was designed in part to discover whether or not there was a quid pro quo for the Lyme panel members.

  As with many assertions made by chronic Lyme advocates, the charges had a surface plausibility. Big medicine is big business, after all, and the idea that a panel of physicians might be biased based on lucrative arrangements with companies who have good reasons to influence the final recommendations makes a great deal of sense. But, as with other claims of the chronic Lyme lobby, of which Richard Blumenthal had now become much more than a mere figurehead, they make less sense on closer investigation.

  Why, for instance, would the mainstream IDSA suddenly opt to play footsie with the insurance industry by limiting the total amount of antibiotics given to their patients when so many other fields of medicine have benefited financially from a cozy relationship with Big Pharma? From a purely monetary standpoint, issuing such guidelines makes no sense. Drug companies have a well-deserved reputation for enticing physicians, through all manner of trinkets both trivial and luxurious, to prescribe expensive drugs even if they have little clinical benefit; the new recommendations would leave any company driven by profits with very little desire to try to persuade doctors to prescribe this or that for Lyme because the standard treatment advised by the IDSA for most cases of Lyme is ten to twenty-one days of doxycycline, a generic drug that usually costs a few bucks. Moreover, rigid adherence to the new guidelines would mean fewer office visits for generalists and infectious disease specialists alike, so ultimately following the new recommendations would produce less income for such doctors.

  Contrast this with the economic incentives of the physicians affiliated with ILADS. The medical management offered by these providers involves frequent office visits, sometimes for years on end. The more serious treatments, such as prolonged intravenous antibiotics, are major moneymakers for a practice, because they can be billed to the insurance companies under special procedure codes. The insertion of an IV line typically is a reimbursable expense paid to the physician’s office, and whole clinics are devoted to servicing scores of patients who come in several times a week for infusions. That’s an impressive number of office charges, especially when compared to the single visit that is typically required for managing an episode of Lyme disease in the mainstream medical world.

  Which of these two groups of providers has benefited more in financial terms from the IDSA guidelines—the one that ignored them, or the one that followed them?

  At any rate, if there were such seriously inappropriate quid pro quo arrangements between the IDSA and the insurance industry, they became of secondary importance, and by 2008 the IDSA and Blumenthal came to an agreement.* In exchange for ending the investigation, and the crippling legal expenses that had arisen from defending themselves against it, the IDSA agreed to have an independent panel review the guidelines. The idea was to convene a group of scientists affiliated with the finest medical and scientific institutions in the country, who had no ties to Lyme research or Lyme treatment or Lyme anything. Their expertise would come in their collective ability to judge the quality of evidence surrounding theories of chronic Lyme, comprising essentially a very specialized and disinterested set of fresh eyes on this contentious matter. The chronic Lyme advocates would be welcome to present their viewpoints side by side with the mainstream physicians, including some of the IDSA panel members. Both Blumenthal and the IDSA were gambling that a neutral group would side with them.

  None has ever been discovered.

  The panel would be overseen by an ombudsman that IDSA and Blumenthal’s office had mutually agreed upon: Dr. Howard Brody of the Institute for the Medical Humanities at the University of Texas Medical Branch in Galveston. The panel convened a one-day hearing in 2009, allowing two patients and more than a dozen researchers and clinicians to present evidence. Not long after, Blumenthal’s office claimed victory: “the investigation . . . uncovered serious flaws in the process for writing its 2006 Lyme disease guidelines,” a triumphant press release noted. “The [IDSA] guideline panel improperly ignored or minimized consideration of alternative medical opinion and evidence regarding chronic Lyme disease, potentially raising serious
questions about whether the recommendations reflected all relevant science.”

  That press release was issued long before the review panel had completed its work. That wouldn’t come until the middle of 2010, and its report could only be described as a stinging rebuke of the attorney general’s most cherished notions about chronic Lyme or the value of prolonged antibiotics.

  The panel was composed of eight members whose scientific integrity and objectivity was deemed unimpeachable by both parties. They reviewed every single recommendation from the 2006 Lyme guidelines from the mainstream IDSA and voted up or down as to whether they found each recommendation to be based on solid science and clinical reasoning. Think of it as something akin to a scientific Supreme Court assembled solely to adjudicate the question of Lyme diagnosis and treatment.

  In total, the panel reviewed forty-eight separate recommendations specifically devoted to Lyme in the 2006 guidelines (the remainder dealt with other tick-borne diseases). Of these, forty-seven of the recommendations were upheld in 8–0 votes. The forty-eighth recommendation was this: “to date, there is no convincing biologic evidence for the existence of symptomatic Borrelia burgdorferi infection among patients after receipt of recommended treatment regimens for Lyme disease.” Instead of the unanimous endorsement that all of the other recommendations received, this was upheld by a 7–1 vote. (That’s 383 votes supporting the IDSA to 1 against. Contrast this almost complete unanimity with the actually contentious JNC8 blood pressure guidelines, where about a quarter of experts, whose credentials nobody questioned, had split away from the majority.)

  The final section of the Lyme guideline review, though, made in the characteristically dry prose of a governmental report, contains an unmistakable message. By “unmistakable,” I don’t mean to imply that they used exceptionally lucid language, but rather that it was literally unmistakable: they changed the font to boldface, as I do here. They noted that the “trials for extended antibiotic treatment of Lyme disease have demonstrated considerable risk of harm, including potentially life-threatening adverse events . . . [but likewise] have demonstrated little benefit. . . . [T]he risk/benefit ratio from prolonged antibiotic therapy strongly discourages prolonged antibiotic courses for Lyme disease.” These sentences all but scream at the chronic Lyme advocates to cut it out.