The patient has been treated, but is she cured? The standard treatment may work, but just to a degree. Are the remaining symptoms -- in medical jargon, the sequelae-- part of the same illness, needing more of the same treatment? Or must these patients now soldier on, wounded and in pain, resigned that medicine has done all it can do?
Lyme disease is a fascinating example of the phenomenon, because studies have been used to discount these leftover symptoms, to say they cannot be considered part of the original, now "cured" disease --even while documenting those symptoms present in legion force.
The Lyme sequelae in question have been quantified in studies conducted by academic scientists of impeccable credentials and published in major peer-reviewed journals. Indeed, as the decade of the 1990s inched toward the millennium and beyond, academic scientists studied the outcome of treatments they dispensed in literally dozens of studies (many double-blinded and controlled) involving hundreds of patients. The studies are, by and large, consistent with each other. What's more, the raw data is solid, not a matter of dispute. There is so much data saying the same thing and contested by so few --yet the numbers have been analyzed in different ways by different experts. Some experts insist that studies show that the patients are somatisizing, imaginging the problems and making mountains out of molehills. Other experts say the studies show the patients are deeply, disturbingly ill.
To any layperson with horse sense, the dispute might seem nonsensical: Either one has gotten better, or one has not. After a course of standard treatment you are either well or you are still afflicted with symptoms caused by the disease.
Examine the studies themselves, however, and you'll see the slant of statistics support the various views. Two studies in particular stand out as representative of this group.
In the first study, a Tufts-Harvard team that included researchers Nancy Shadick, Eric Logigian, and Allen Steere, among others, contacted patients along Argylia Road, in Ipswitch, MA, where Lyme had been meticulously studied in the past. Of 38 patients diagnosed with and treated for Lyme disease on the street, 13 --or 34%-- sustained symptoms, including musculoskeletal, neurological, or neurocognitive impairment. Some 16% suffered coordination difficulties, 16% had trouble concentrating, 18% were emotionally irritable, 47% suffered sleep disorder, and 26% reported unusual fatigue.
As to memory scores on an assortment of tests, Lyme patients tested below controls across the board. A primary finding to come out of the Shadick study was a correlation between duration of disease and residual symptoms, including neurological impairment. Indeed, the 13 patients with permanent problems had gone undiagnosed and untreated an average of 35 months, while those reporting complete recovery were treated, on average, 2.7 months after the infection began.
Shadick's results were reinforced the the second study, when scientists at New York Medical College studied Lyme disease patients from Westchester County, NY. The scientists evaluated 215 extremely well-documented Lyme disease patients who had been treated at least a year before. The findings: "A history of relapse with major organ involvement had occurred in 28%. At follow-up, 38% of the patients were asymptomatic, while persistent symptoms involving the joints, the heart, or the nervous system were documented in 53%. About a third of the patients reported symptoms that included just joint pain (without swelling) or fatigue. Just like the Massachusetts patients, the New York patients were increasingly likely to suffer permanent impairment the longer treatment was delayed.
When I stuck to the peer-reviewed literature --to the medical journals-- I felt a sense of clarity on the issue of sequelae: They were more pronounced in those treated late, and they were certainly real. But going out in the field, speaking to experts, I couldn't help but get confused. Neurologist John Halperin of North Shore University Hospital in Manhasset, New York, for instance, said that most remaining symptoms --including those mentioned in the studies-- were "subjective," that is, while patients reported them the researchers could find no objective proof they were there. And it was true -the studies themselves had made this distinction. Treated Lyme patients reported great distress, but scientists conducting the studies hadn't been able to measure the symptoms on any objective test.
"A lot of people have the subjective perception that they're not doing as well as they would like to," Halperin told me. "But when we do formal neurocognitive testing we often find the problem is an inability to concentrate instead of an impairment in processing itself." As to the Lyme encephalopathy that chronic patients described as so disabling, Halperin said the label was a misnomer. "Those with true Lyme encephalopathy suffer infection and inflammation and respond to antibiotic therapy," he said. "Months after therapy, when the inflammation goes down, they are cured."
And what of those who continued to suffer? Whatever was bothering these patients, Halperin opined, it was probably "unrelated to active Lyme infection. As a consequence of all the popular notions about Lyme disease," he said, "once somebody has the label applied to them, they start to attribute normal daily symptoms to Lyme and become concerned about them. They become convinced they have a chronic disease. This then leads to a self-perpetuating complex of symptoms and distress leading to increased attention to symptoms and increased distress. When you look at outcome studies," Halperin concluded, "you find that treated Lyme patients have no statistically significant differences in objective measures of disease. From the point of view of the patients suffering, it's very real and interferes with their life to a major extent, but the mechanism is not remotely clear."
As strongly as Halperin insisted the outcome for patients was overwhelmingly positive, that is how vehemently other practitioners contended a significant minority remained distressingly ill.
"This is the old subjective/objective game," said Robert Bransfield, a psychiatrist from New Jersey. Bransfied said that mental status exams always factored both subjective and objective findings into the clinical formulation. "The practitioner's objective observations of the patient with so-called subjective symptoms constitutes objective evidence," Bransfield told me. "And many common and highly significant complaints and symptoms cannot be validated by objective findings due to the limitations of our current technical abilities. Ignoring subjective findings would be malpractice." What's more, Bransfield added, "many so-called objective findings are actually subjective. For example, the interpretation of the Western Blot is highly subjective. In summary, most often there is no clear demarcation between what is subjective and objective. All medical diagnoses are a combination of both. "
Harold Smith, a Pennsylvania physician treating Lyme patients, added that symptoms might be misconstrued as subjective or vague if the doctor isn't doing his job. "If a doctor asks the patient whether he's tired and the patient responds, simply, ‘yes,' without any detail, there is nothing objective to report," Smith says. "But the problem is the physician, not the patient. The doctor's question was vague. If the practitioner asks for objective information, he can elicit it: Does sleep restore you? Is your sleep associated with drenching night sweats that soak your hair and pajamas? Does it take days to recover from raking a 20 foot patch of your yard? There are corresponding physical exam findings to go with such answers, including loss of muscle bulk, lowered core temperatures; slow heart rates; and abnormal hypothalamic pituitary hormone levels, among many others. These impairments can be objectively measured and reversed with treatment." In other words, says Smith, if physicians discount fatigue as subjective it's because they aren't seeking objective data, as they should.
Likewise, he said, doctors "can elicit objective findings in every organ infected with Borreliosis- --from skin to bone and everything in between." These objective findings are described in the medical literature in great detail, but the physician won't document them if he doesn't ask the right questions or know where to look, if he's inexperienced or untrained. "Some physicians dismiss important symptoms as subjective, "added Smith, "because they have a bias against those symptoms as vague in the first place and have decided there will be no objective findings before the patient even walks in the room.."
Brian Fallon, a psychiatrist at Columbia University in New York City, felt strongly, too.
"One of the problems plaguing Lyme disease from early on was the attempt to codify what is and isn't objective," he said. Those first describing Lyme disease in the medical literature were trained in rheumatology and dermatology. The "objective signs" they recognized -frankly swollen joints, antibody production, and an erythema migrans rash-- derived from the specialty-specific training they had. Later, neurologists added their specialty-specific "signs" to the mix: cranial nerve palsy, gross meningitis with central nervous system antibody production, and measurably damaged nerves.
"By these standards, virtually 100 percent of those treated for Lyme disease no longer have objective signs of the illness, and so, in the eyes of certain medical specialties, are fine, but that ignores the fact that a huge number of patients still have symptoms of Lyme disease -cognitive problems, fatigue, joint pain, mood swings. Because those symptoms weren't objectified early in the history of the disease, by the specific specialties first involved, many doctors still think they don't count. As psychiatrists we are used to dealing with diseases that can't be objectified with the tools of rheumatology, even the tools of neurology, but they do count. If someone has schizophrenia, that counts. If someone has severe bipolar disorder, there's no blood test for that, but to psychiatrists, that counts. If someone has personality problems that get them fired from their job or destroy their marriage that counts. Because Lyme disease was originally researched by the rheumatologists and neurologists, there was a lack of appreciation for these other ways of defining illness and objectifying signs and symptoms of disease."
Halperin countered that "neurologists do not for a moment minimize the distress suffered by these patients, nor the disruption caused to their lives. Rather, they consider it inaccurate to label a patient's problem as ‘neurologic' if there is no evidence of damage to the nervous system, and inappropriate to label it a nervous system infection, when all usual measures of nervous system infection are normal."
It's easy to see why doctors, self-selected by patients detecting a "match," perceive the Lyme experience through a filtered lens. John Halperin understands the dilemma: Patients treated extensively with antibiotics sometimes come to him for a new perspective, he says, and "understand what I am going to tell them in advance." The patients, there in hopes of curtailing antibiotics, "feel much better once the antibiotics are stopped," Halperin reports.
Pediatrician Charles Ray Jones, currently under charges in Connecticut for treating Lyme far more aggressively than Halperin and like-minded colleagues ever would, understands the dilemma. I tell him John Halperin has estimated that just one in 1000 Lyme disease patients suffer gross encephalomyeltis --obvious inflammation of the brain-- and Jones tosses out a figure of his own: Such patients comprise easily 60 percent of his practice, he says.
Are Jones and Halperin at odds with each other?
"Not necessarily," Jones says. "I have a biased practice." And it's true --Jones is often a family's final stab at treatment for Lyme disease before moving on to another diagnosis, and children coming his way are generally especially sick. Notably, while Halperin says his patients feel much better off antibiotics, Jones reports his patients feel much better once appropriate antibiotic treatment targets the Lyme disease or other coinfections he has found they have.
To scientists and clinicians Lyme disease was laden with history, territoriality, philosophy, and training. On the other hand, new patients came to the scene fresh. Because patients stayed with doctors based on treatment outcome --and because outcome varied so widely depending upon who you talked to-- it was impossible to say that John Halperin and Charles Ray Jones were treating the same kind of patient. Even if the precipitating infections had once been identical, was it now the same disease?
Pamela Weintraub is the author of Cure Unknown: Inside the Lyme Epidemic and senior editor at Discover Magazine.