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When Lyme Lingers

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Looking back on how such a genetic variation might have evolved, Steere believes something happened in Europe that killed off people who didn’t have the mutated gene, which may have helped others survive the plague or another deadly contagion. But it’s a disadvantage with Borrelia burgdorferi because it leads to greater inflammation that may not be dampened even when antibiotics have killed off the spirochetes.

Intense inflammation in joints and the difficulty in controlling it set the scene for a third complication: the potential for an autoimmune reaction. In studies published in the journal Arthritis & Rheumatism in 2013 and 2014, MGH researchers reported the identification of the first autoantigen known to trigger autoimmune damage in some patients with antibiotic-refractory Lyme arthritis. An autoantigen is a human protein that comes under attack from a patient’s own immune system. That never happens under normal circumstances, but it may occur within an area of intense inflammation, and in Lyme arthritis, this immune attack can obliterate small blood vessels within the joint.

In another puzzling development, someone who has had Lyme disease will develop pain, neurocognitive symptoms or fatigue, a condition sometimes called post-Lyme disease syndrome. In some patients, symptoms of headache, joint pain and fatigue, which typically occur with early Lyme disease, may persist for weeks or months after standard antibiotic therapy and then go away. However, unlike patients with antibiotic-refractory Lyme arthritis, these patients don’t have swollen, inflamed joints.

In still another variation, a small percentage of patients, after feeling well for several months following treatment, will have diffuse pain, difficulty concentrating, or incapacitating fatigue that continues indefinitely. Here, too, standard tests don’t show inflammation, and anti-inflammatory therapies often don’t help much. Four double-blind, placebo-controlled trials involving such patients failed to show sustained benefits of additional antibiotic therapy. That leaves few options for effective treatment.

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1. “Lyme Disease,” by Eugene Shapiro, The New England Journal of Medicine, May 2014. This paper walks readers through the diagnostic and prescriptive steps Shapiro takes in caring for a pregnant 32-year-old woman with a skin rash who had been bitten by a tick.

2. “Lyme Disease,” by Allen C. Steere, The New England Journal of Medicine, July 2001. This seminal review cited many times in medical literature covers how the spirochete is transmitted and goes about its business, as well as the various physical manifestations of its presence in a human host.

3. “Lyme borreliosis,” by Allen C. Steere, Harrison’s Principles of Internal Medicine, 18th Edition, Chapter 173, pp. 1401–1406. Harrison’s Principles is the most widely read book of its kind. Steere’s contribution covers guidelines for diagnosis and treatment and other essential information.

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