• Document: A Critical Appraisal of Chronic Lyme Disease
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The n e w e ng l a n d j o u r na l of m e dic i n e Review article Current Concepts A Critical Appraisal of “Chronic Lyme Disease” Henry M. Feder, Jr., M.D., Barbara J.B. Johnson, Ph.D., Susan O’Connell, M.D., Eugene D. Shapiro, M.D., Allen C. Steere, M.D., Gary P. Wormser, M.D., and the Ad Hoc International Lyme Disease Group* L  From the Departments of Family Medi- yme disease, the most common tick-borne infection in the north- cine and Pediatrics, Connecticut Chil- ern hemisphere, is a serious public health problem. In North America, it is dren’s Medical Center, Hartford, and University of Connecticut Health Center, caused exclusively by Borrelia burgdorferi sensu stricto (hereafter referred to as Farmington (H.M.F.); Microbiology Lab- B. burgdorferi), whereas in Europe it is cau sed by B. afzelii, B. garinii, B. burgdorferi, and oratory, Division of Vector-Borne Infec- occasionally by other species of borrelia.1 tious Diseases, Centers for Diseases Control and Prevention, Fort Collins, CO This complex infection has a number of objective manifestations, including a char- (B.J.B.J.); Lyme Borreliosis Unit, Health acteristic skin lesion called erythema migrans (the most common presentation of Protection Agency Microbiology Labora- early Lyme disease), certain neurologic and cardiac manifestations, and pauciarticu- tory, Southampton General Hospital, Southampton, United Kingdom (S.O.); lar arthritis (the most common presentation of late Lyme disease), all of which usu- Departments of Pediatrics and Epidemi- ally respond well to conventional antibiotic therapy.2 Despite resolution of the objec- ology and Public Health, Yale University tive manifestations of infection after antibiotic treatment, a minority of patients School of Medicine, New Haven, CT (E.D.S.); Division of Rheumatology, Al- have fatigue, musculoskeletal pain, difficulties with concentration or short-term lergy and Immunology, Massachusetts memory, or all of these symptoms. In this article, we refer to these usually mild and General Hospital, Harvard Medical self-limiting subjective symptoms as “post–Lyme disease symptoms,” and if they last School, Boston (A.C.S.); and the Division of Infectious Diseases, Department of longer than 6 months, we call them “post–Lyme disease syndrome.” Medicine, New York Medical College, The word “chronic” has been applied to Lyme disease in a wide variety of contexts Valhalla (G.P.W.) Address reprint re- and is sometimes used interchangeably with the preferred term “late Lyme disease.” quests to Dr. Feder at the Departments of Family Medicine and Pediatrics, Uni- For example, in Europe, certain late neurologic manifestations of previously untreated versity of Connecticut Health Center, or inadequately treated infection, such as borrelial encephalomyelitis or long-standing Farmington, CT 06030, or at hfeder@ meningitis, have been referred to as “chronic neuroborreliosis” (Table 1).1-3 In the nso2.uchc.edu. United States, reports have described untreated patients with recurrent or persistent *Other members of the Ad Hoc Interna- arthritis that lasts for up to several years, presumably because of active infection.4 tional Lyme Disease Group who were The focus of this review, however, is not the objective manifestations of late Lyme authors are listed in the Appendix. disease but rather the imprecisely defined condition referred to as “chronic Lyme N Engl J Med 2007;357:1422-30. disease.” This term is used by a small number of practitioners (often self-designated Copyright © 2007 Massachusetts Medical Society. as “Lyme-literate physicians”) to describe patients whom they believe have persistent B. burgdorferi infection, a condition they suggest requires long-term antibiotic treat- ment and may even be incurable.5 Although chronic Lyme disease clearly encom- passes post–Lyme disease syndrome, it

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