Lyme disease: controversial issues

John J Halperin MD (Dr. Halperin of Overlook Medical Center and Sidney Kimmel Medical College of Thomas Jefferson University has stock ownership in Merck, Abbott, and Johnson & Johnson.)
Raymond P Roos MD, editor. (Dr. Roos of the University of Chicago owns stock in Amgen, Best Doctors, Express Scripts, Isis, and Merck.)
Originally released May 22, 2001; last updated April 28, 2016; expires April 28, 2019

Overview

Lyme disease continues to hold a unique position on the battlefront between evidence-based medicine and populist-supported, anecdote-derived care. Studies support the efficacy of standard courses of antimicrobial therapy in patients with active Lyme disease and demonstrate the lack of benefit of prolonged courses in patients with chronic, nonspecific symptoms. National organizations of infectious disease specialists and of neurologists have analyzed all available evidence and concluded current recommendations are appropriate. A counter culture has promulgated its own “evidence-based guidelines,” neither citing additional evidence nor incorporating current models of evidence assessment. Patients are caught in the middle. Against this backdrop, the author reviews the current understanding of this disease and its treatment, focusing on the key sources of controversy and highlighting studies further supporting the standard diagnostic and therapeutic approach.

Key points

 

Borrelia burgdorferi, the tick-borne spirochete that causes Lyme disease, can infect the central or peripheral nervous system in up to 10% to 15% of patients.

 

• Clinical phenomena associated with neuroborreliosis typically include cranial neuropathy (most often the facial nerve), radiculopathy, and lymphocytic meningitis.

 

• Serodiagnosis after the first month of infection, using 2-tiered testing, is highly accurate.

 

• Treatment with a 2- to 4-week course of oral doxycycline is curative in most patients. Parenteral treatment may be needed either if there is evidence of brain or spinal cord parenchymal involvement or if objectively demonstrable active disease persists after oral treatment.

Historical note and terminology

The term "Lyme disease" was first coined in the mid-1970s. Over the course of the ensuing 4 decades, a previously unrecognized pathogen has been well characterized, diagnostic tests for its presence have been developed, the clinical spectrum of disease has been described, and therapeutic regimens have been refined. At the same time, small areas of scientific uncertainty have been disproportionately emphasized to justify inappropriate diagnosis and ever more aggressive and biologically implausible treatment regimens.

Part of the controversy derives from the notion that this disease is entirely novel and had never been described before the 1970s. In fact, a closely related disorder was recognized in Europe a century ago. The typical expanding erythroderm (termed erythema migrans), and an acute meningoradiculitis syndrome with pain and weakness (that came to be known as Garin-Bujadoux-Bannwarth syndrome) were linked to bites by hard-shelled Ixodes ticks. Then, in the 1970s, several mothers in Old Lyme, Connecticut, recognized a surprisingly high incidence of what was diagnosed as juvenile rheumatoid arthritis among children in a small geographical region. Excellent epidemiological detective work led to the understanding that this was not juvenile rheumatoid arthritis, but a tick-borne infection. Within a few years the causative organism, Borrelia burgdorferi, was identified. At the same time, the strong similarities to the European syndrome of Garin-Bujadoux-Bannwarth were recognized, and parallel research in Scandinavia led to the identification of the closely related Borrelia species responsible for that syndrome.

With the characterization of the causative organisms, serologic tests were rapidly developed to identify individuals exposed to it. Unfortunately for the field, microbiological culture and other direct diagnostic testing (polymerase chain reaction, antigen detection) have been far more technically challenging than in most other bacterial infections. This coupled with the normal technical vagaries of serologic testing has led to an interesting pair of phenomena. Growing from the disease's populist roots, some physicians and patients have adopted an ever more expansive interpretation of the range of disorders thought to be linked to it, feeling that patients may have the diagnosis based purely on a clinical gestalt despite the complete absence of objectively verifiable evidence. Others contend that only phenomena linked to this disease by at least a century of medical tradition can legitimately be considered part of "Lyme borreliosis”. As always, the truth lies somewhere in between, but discovering where exactly that is remains the dilemma (Committee on Lyme Disease and Other Tick-Borne Diseases 2011).

The debate revolves around 3 areas that, although conceptually separate, form important and mutually reinforcing sources of confusion: (1) diagnostic testing, (2) clinical phenomenology, and (3) treatment response (Halperin et al 2013).

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