Fifteen years. That’s how long scientists have been trying to prove a negative: that “chronic Lyme disease” does not exist, and that long-term antibiotic usage does not help with symptoms that include joint pain and fatigue. This past week, a study in the New England Journal of Medicine showed that long-term antibiotic usage–the favorite treatment prescribed by doctors who call themselves “Lyme literate”–is a failure. Will it convince any of those doctors to change their practice? I doubt it.
Lyme disease is a serious illness, caused by bacteria that are transmitted through tick bites. Although the disease has been infecting humans for centuries, it got its name relatively recently, in 1975, when two Yale doctors, Stephen Malawista and Allen Steere, investigated a cluster of illnesses near the town of Lyme, Connecticut. The symptoms included joint pain that resembles arthritis, so much so that Malawista initially called it “Lyme arthritis.” A few years later, biologist Willy Burgdorfer discovered the true cause, and the bacterium Borrelia burgdorferi was named after him. As deer have spread through the suburbs of modern society, ticks traveling with them have spread Lyme disease far and wide; the NIH reported over 36,000 cases in the U.S. in 2013. (Note that the CDC estimates the true number of cases may be closer to 300,000, ten times the number actually reported to health authorities.) Lyme is also common in Europe.
Luckily for most of us, a brief course of antibiotics usually cures people completely of Lyme disease. For some people, though, symptoms including fatigue and joint pain can linger for up to six months. The cause of these longer-term symptoms remains a mystery, and is an active area of current research. One possible explanation from the CDC is that:
“the lingering symptoms are the result of residual damage to tissues and the immune system that occurred during the infection.”
Unfortunately, the lack of a scientific explanation has opened the door to wildly speculative treatments, based on little or no evidence, by doctors who think they know the answer. These doctors, some of whom have adopted the label “Lyme literate,” insist that their patients suffer from what they call Chronic Lyme Disease. Among other things, they’ve formed an association called ILADS that claims that:
“Most cases of chronic Lyme disease require an extended course of antibiotic therapy to achieve symptomatic relief” and “many patients with chronic Lyme disease require prolonged treatment until the patient is symptom-free.”
Not only do these treatments cost far more than the two-week course of treatment recommended by the Infectious Disease Society of America, but they also have the potential to cause harm: it’s just not good for you to be on antibiotics for months or years. Indeed, one of the first studies (in 2001, by Mark Klempner and colleagues) to look at the efficacy of long-term antibiotic use explained its motivation as follows:
“Case reports and uncontrolled trials describe success with prolonged antibiotic therapy, often with a recurrence of the symptoms after the discontinuation of therapy. In view of the substantial morbidity and even death associated with prolonged parenteral antibiotic treatment of Lyme disease, it is important to determine the efficacy of such therapy.”
“Substantial morbitity and even death”: Clearly, long-term antibiotic treatment is not something to be prescribed lightly. The 2001 study found no benefit from long-term versus short-term antibiotic usage for the treatment of Lyme disease.
Despite the science, some doctors persist in prescribing–against the advice of professional societies–long-term courses of antibiotics. Because the practice continues, a European group conducted a new study of long-term antibiotic use in patients who claim to have persistent symptoms from Lyme disease. Anneleen Berende and colleagues reported the results of this well-designed double-blind, placebo-controlled study in the New England Journal of Medicine just last week. Their findings matched those of the 2001 study: Long-term antibiotic use has no benefits for patients.
The study had three arms: a placebo group and two different treatment groups, who were given two different antibiotics. Everyone got a two-week treatment with real antibiotics, followed by 12 more weeks of either antibiotics or placebo. The pills were created just for this study to look identical, so that neither the doctors nor the patients knew who was getting the placebo.
In an editorial accompanying the article, my Hopkins colleagues Michael Melia and Paul Auwaerter explain that the take-home message is that:
“Patients with subjective, vexing symptoms attributed to Lyme disease should not anticipate that even longer courses of antibiotics will produce relief, a finding that is in concert with results from previous trials.”
I doubt that “Lyme literate” doctors will accept the latest results and stop prescribing long-term antibiotic use; their websites indicate that they already know that they are right. I hope, though, that patients will start to question doctors who put them on long-term, possibly harmful antibiotic regimens that don’t provide any benefit.