Epidemiology of Lyme Disease

and myalgia. Complications include shock, organ dysfunction, and death. Mortality is less than 1% with appropriate treatment. Doxycy-cline is first line treatment for all ages. Start it empirically if symptoms and risk factors suggest HGA. PCR is the confirmatory test of choice.


Franc Strle and Gary P. Wormser
Erythema migrans, an expanding erythematous skin lesion that develops days to weeks following an Ixodes species tick bite, is the most common clinical manifestation of Lyme disease. Presentations in the United States differ somewhat from that in Europe, presumably because of the different etiologic agents. Diagnosis is based on the appearance of the skin lesion, rather than on laboratory testing. After treatment with an appropriate oral antibiotic for 10 to 14 days, the prognosis is excellent. Two conditions that cause a similar skin lesion following a tick bite, but are of unknown cause, are Southern tick-associated rash illness in the United States and tickassociated rash illness in Japan.

Tyler Crissinger and Kelly Baldwin
Early disseminated Lyme disease can involve the peripheral or central nervous system, but with early diagnosis and treatment, prognosis for full recovery is excellent. The typical clinical presentations of neuroborreliosis are highlighted, and an approach to diagnosis and treatment is described.

Richard V. Shen and Carol A. McCarthy
Lyme carditis is an uncommon manifestation of Lyme disease. Most cases present with heart block of varying degrees, but the spectrum of disease includes other transient arrhythmias and structural manifestations, such as myopericarditis or cardiomyopathy. Antibiotics hasten the resolution of Lyme carditis, and cardiac pacing can be an adjunctive therapy. Outcomes are generally good, but there are rare fatalities associated with Lyme carditis. The latter underscores the continued need for improved modes of prevention of Lyme disease and the importance of its early recognition and treatment.

Lyme Arthritis 563
Sheila L. Arvikar and Allen C. Steere Arthritis is the most common late manifestation of Borrelia burgdorferi infection in the United States, usually beginning months after the tick bite. In most patients with Lyme arthritis (LA) today, arthritis is the presenting manifestation of the disease. Patients have swelling and pain in one or a few large joints, especially the knee. Serologic testing is the mainstay of diagnosis. Responses to antibiotic treatment are generally excellent, although a small percentage of patients have persistent, postinfectious synovitis after 2 to 3 months of oral and IV antibiotics, which respond to antiinflammatory therapies. Herein we review the clinical presentation, diagnosis, and management of LA.

Nervous System Lyme Disease-Facts and Fallacies 579
John J. Halperin The central or peripheral nervous systems may be involved in up to 15% of patients with untreated infection with B burgdorferi sensu lato, characteristic involvement including meningitis, cranial neuritis, and radiculoneuritis. Diagnosis, based on a logical combination of clinical context and antibody-based testing, is usually straightforward, as is treatment. Misconceptions about what does and does not constitute neurologic disease, and about laboratory testing in this infection, have resulted in widespread anxiety that a broad range of other disorders may be attributable to nervous system Lyme disease. This article will review the reasons for these misunderstandings and the arguments against them.

Lyme Disease in Children 593
Carol A. McCarthy, Jason A. Helis, and Brian E. Daikh Lyme disease is now the most frequently reported vector-borne disease in the United States. The highest incidence is in children aged 5 to 9 years with a male predominance. The most common manifestation, erythema migrans, is sometimes not recognized, leading to risk of complications. Testing for Lyme disease should only be done if there is a consistent clinical syndrome with exposure in a Lyme-endemic area. Most forms of Lyme disease are successfully treated with short courses of oral therapy. Prevention and management of tick bites is important.

Takaaki Kobayashi and Paul G. Auwaerter
Standard 2-tier testing (STTT), incorporating a screening enzyme immunoassay (EIA) or an immunofluorescence assay (IFA) that reflexes to IgM and IgG immunoblots, has been the primary diagnostic test for Lyme disease since 1995. In 2019, the Food and Drug Administration approved a modified 2-tier test strategy using 2 EIAs: offering a faster, less expensive, and more sensitive assay compared with STTT. New technologies examine early immune responses to Borrelia burgdorferi have the potential to diagnose Lyme disease in the first weeks of infection when existing serologic testing is not recommended due to low sensitivity.

Persistent Symptoms After Treatment of Lyme Disease 621
Adriana Marques Most patients with Lyme disease will fully recover with recommended antibiotic therapy. However, some patients report persisting nonspecific symptoms after treatment, referred to as posttreatment Lyme disease symptoms (PTLDs) or syndrome (PTLDS), depending on the degree to which the individual's symptoms impact their quality of life. PTLDs occur in a portion of patients diagnosed with chronic Lyme disease (CLD), a controversial term describing different patient populations, diagnosed based on unvalidated tests and criteria. Practitioners should review the evidence for the Lyme disease diagnosis and not overlook unrelated conditions. Current evidence shows that prolonged antibiotic therapy provides little benefit and carries significant risk. Further research to elucidate the mechanisms underlying persistent symptoms after Lyme disease and to understand CLD is needed.

Douglas MacQueen and Felipe Centellas
Human granulocytic anaplasmosis (HGA) is a bacterial infection caused by Anaplasma phagocytophilum and transmitted by the bite of the blacklegged (deer tick) in North America. Its incidence is increasing. HGA can be transmitted after 24 to 48 hours of tick attachment. The incubation period is 5 to 14 days after a tick bite. Symptoms include fever, chills, headache, and myalgia. Complications include shock, organ dysfunction, and death. Mortality is less than 1% with appropriate treatment. Doxycycline is first line treatment for all ages. Start it empirically if symptoms and risk factors suggest HGA. PCR is the confirmatory test of choice.

Human Babesiosis 655
Rami Waked and Peter J. Krause Babesiosis is caused by intraerythrocytic parasites that are transmitted primarily by ticks, infrequently through blood transfusion, and rarely through transplacental transmission or organ transplantation. Human babesiosis is found throughout the world, but the incidence is highest in the Northeast and upper Midwestern United States. Babesiosis has clinical features that resemble malaria and can be fatal in immunocompromised and older patients. Diagnosis is confirmed by identification of