https://c.ymcdn.com/sites/www.improvediagnosis.org/resource/resmgr/files/ImproveDx_April2018finalX.pdf  By Susan Carr

Diagnosis at the Center of the Lyme Wars

Controversy erupted soon after Lyme disease was discovered more than 40 years ago. Debates focused on both diagnosis and treatment are often characterized by heated exchanges and accusations. The existence of conflicting sets of clinical guidelines1,2—with their own societies and communities of physicians—reflects the way Lyme disease has travelled on two separate tracks since the 1980s.

The disease was identified as a tick-borne illness by Alan Steere in 1975 and named for towns in Connecticut where it was studied by Steere and his col- leagues.3 In 1980, other researchers linked a specific bacteria (Borrelia burgdorferi) to a species of ticks (Ixodes scapularis), which informed the use of antibiotics to treat the disease.4

By 1990, Steere was hearing about patients suffering from long-term symptoms associated with Lyme. He questioned both the diagnosis of a chronic version of the disease and long-term antibiotics used by some physicians to treat it, triggering a strong response from physicians and patients. During testimony before a US Senate committee in 1993, Steere was challenged by a physician and a young Lyme patient in a wheelchair who quietly pleaded that Steere help find a treatment for his afflic- tion. People in the gallery shouted, “He’s wrong! He’s wrong!” as Steere spoke.5

The rancorous environment, often referred to as the “Lyme Wars,”6,7,8 continues, and patients seeking treatment for persistent symptoms must choose between sides engaged in an active battle. Most patients who are diagnosed and treated early respond well to antibiotic treatment. The controversy surrounds those who remain ill after treatment or those whose diagnosis is delayed, for whom treatment becomes more difficult.9

People who find they or their children have been bitten by a tiny tick and turn to the internet for advice will find alarming information about where an untreated infection may lead. If they dig deep enough, they will find ugly comments common on the internet but unusual in the medical community.

On a brighter note, some are attempting to work collaboratively on issues related to Lyme, in groups that represent a diversity of expertise and opinion. While this is a hopeful sign, the process of working together on issues related to research, diag- nosis, and treatment is slow, with results not expected for years.

Problems with Diagnosis

Diagnosis is central to the controversy. Lyme disease is diagnosed based on signs and symptoms that include a rash—sometimes but not always erythema migrans (EM)—and “flu-like” symptoms, including fever, chills, headache, fatigue, aches, and swollen lymph nodes, which occur within 30 days of infection.10,11,12 The patient’s history, including whether they have observed a tick bite or spent time outdoors in areas where Lyme is known to occur, may help the physician make a diagnosis. There is general acceptance that most cases of Lyme detected soon after infection are treated successfully with a 10-to-21-day course of oral antibiotics.13

Existing laboratory blood tests for Lyme disease are problematic especially in patients with acute Lyme.13 The lack of a dependable laboratory test and reliance on common signs and symp- toms often mean that the diagnosis is missed or delayed, which can lead to more serious ill- ness.14,15,16,17 In addition to the EM rash, which can emerge or recur long after infection, symp- toms of untreated Lyme disease include chronic pain, fatigue, neuro-cognitive and behavioral problems.11

Diagnosis at the Center of the Lyme Wars

The existence of other tickborne diseases that cause similar symptoms and can co-infect with Lyme further complicate diagnosis.18

Diagnosis of disease in patients with long-term symptoms is a central issue in the controversy. One side believes that Lyme disease is an acute infection and short-term treatment is curative. They conclude that on-going symptoms reflect “post-treatment Lyme disease” symptoms or syndrome (PTLDS).13,19,20 The other side believes that Lyme disease with persistent symp- toms—“chronic Lyme”—requires longer treat- ment durations or a combination of antibiotics to effect cure.

Those in the PTLDS camp say that most patients diagnosed with chronic Lyme either don’t have the disease—have something else—or have relapsed after initial treatment. The PTLDS camp says there is no evidence that the infection persists following treatment and recommend against long-term use of antibiotics.17 Some believe that individuals with chronic symptoms may have had an autoimmune response to the initial Lyme infection.

Patient Community Working on Research

Lyme is quite common—the CDC estimates that more than 300,000 people in the US are infected each year (see sidebar page 3)—but being common doesn’t mean the disease is well understood. Lack of definitive, large-scale clinical treatment trials leaves many questions unanswered.

Inspired by the experience of community and patient advocates who influenced developments in AIDS and cystic fibrosis, the Lyme patient community is working to accelerate progress in diagnosis and treatment

According to Lorraine Johnson, chief operating officer of LymeDisease.org and one of SIDM’s patient partners (see p5), the National Institutes of Health has funded only four studies of patients with persisting symptoms of Lyme disease, the largest of which had 129 enrollees. LymeDisease.org is conducting a research project called MyLymeData, which includes patient-reported health information for more than 10,000 Lyme patients (personal communication with Lorraine Johnson,March23,2018).

The large number of patients in MyLymeData will allow researchers to study biomarkers and treatment effects in subpopulations, potentially helping to understand why some patients respond well to initial treatment and others don’t. Patients involved in this research are long-term Lyme disease patients diagnosed by physicians. Johnson says that, in addition to conducting on-going observational data, MyLymeData will serve as a research platform to help conduct clinical trials—including trials that might lead to better diagnostic tools. The National Science Foundation has awarded an $800,000 3-year grant to a team of big-data researchers to explore predictive data analytics using the more than 2 million data points collected in the registry.23

Johnson takes heart from the experience of the cystic fibrosis (CF) community. During the 1960s and 1970s, without a definitive diagnostic test or initial agreement about optimal treatment regimens, physicians in a handful of hospitals were able to improve the quality of life and outcomes, including life expectancy, for cystic fibrosis patients. Working outside the box of traditional guidelines and in partnership with patients and families, physicians experimented with treatments, focused intently on patient response, and openly shared data about their results.24 Following those improvements and discovery of the gene that causes CF, stakeholders including patients and advocacy groups have continued to find synergies that promote research and learning beyond what would be possible acting alone.25

HHS Collaborative Working Group

The US Department of Health & Human Services’ Tick-Borne Disease Working Group currently represents the best hope of national collaboration for improvement in Lyme disease. Established in 2016 as part of the 21st Century Cures Act, members of the working group—13 members plus many more serving on subcommittees—represent a diversity of opinions and experience. The group is chartered to monitor and guide federal research and to provide expertise to research and prevention efforts. The group had its first meetings in December 2017 and February 2018 and is expected to issue its first report to Congress in December 2018. It will con- tinue to report every other year until its charter expires in 2022.26

No one expects quick solutions to the challenges posed by Lyme and other tick-borne diseases. In addition to working on better options for diagnosis and treatment, many groups, including federal and local agencies, advise preventing tick bites through the use of insect repellent, checking for ticks after being outside, and seeing a physician quickly if symptoms develop. Patients with chronic symptoms associated with Lyme, whether or not they have been treated previously, must choose among competing expert opinions. Some will feel they need to become experts themselves and perhaps work with one of the patient-led information and advocacy groups.

Lyme activists cite the AIDS movement as a model for patient expertise and activism that fought against the medical establishment and ultimately affected the science of diagnosis and treatment.27 AIDS has been called the first “large-scale conversion of disease ‘victims’ into activist-experts.”28(p8) Reviewing a 1996 book about power struggles that occurred during the early years of the AIDS epidemic, David Rochefort says:
Epstein shows that scientific findings are seldom ‘definitive’; rather, they are constructed as
such on the basis of complicated, sometimes contradictory evidence that is filtered through
a politics of knowledge in which a variety of persons, organizations, and institutions compete to control the outcome.29(p262)

It will not be clear for some time who will win the Lyme Wars. It seems certain, however, that patients and their organizations will have played an important, perhaps leading, role in the final outcome. And even if the traditional medical establishment turns out to be correct in its appraisal of long-term Lyme symptoms, the Lyme Wars may be seen as a challenging and pivotal episode in the development of patient expertise and power.

References
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