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Image of tick in amber carrying spirochetes from Wikimedia Commons | George Poinar, Jr, courtesy of Oregon State University. [CC-BY-SA 2.0.]

Lyme Disease

Russell W Steele, MD | July 10, 2023 | Contributor Information

Lyme disease (Lyme borreliosis) remains the most common vector-borne infection in the Northern Hemisphere.[1-3] It is usually caused by the spirochetal organism Borrelia burgdorferi sensu lato, which is transmitted to humans and animals by Ixodes ticks. The nymphs of these vectors, being relatively hard and smaller than 2 mm, look like dirt or environmental particles and are difficult to see. Adults, being larger and even harder, are more easily visible and thus more likely to be identified and removed rapidly. Ticks must remain attached for 36-48 hours before they can transmit the bacterial pathogen; this is a very important factor for prevention.

Prevention relies on identification and avoidance of tick exposure and rapid removal upon identification. Disease is suspected after likely exposure and suggestive cutaneous, neurologic, or rheumatologic manifestations, along with functional changes such as fatigue or joint pain. Of these manifestations, the most diagnostic finding is the classic rash. Laboratory confirmation is best supported with a two-tier serologic test (eg, enzyme-linked immunosorbent assay [ELISA] followed by Western blot or immunoassay), but again, the most diagnostic step is documentation of the unique rash.

Top images from Centers for Disease Control and Prevention (CDC) | James Gathany. [Public domain.] Bottom left image from CDC. [Public domain.] Bottom right image from Wikimedia Commons | Lamiot. [CC by-SA 3.0.]

Lyme Disease

Russell W Steele, MD | July 10, 2023 | Contributor Information

Lyme disease is endemic in North America, Europe, and Asia. The distribution of the tick vectors accounts for its incidence. Ixodes scapularis (top left) is the principal vector in the Northeast and Central United States and Canada, whereas Ixodes pacificus (top right) is more common on the Pacific coast. Ixodes ricinus (bottom left) is the main vector in Europe (a male I ricinus tick attached to the ventral surface of a female is shown). The vector in Asia is the taiga tick, Ixodes persulcatus (bottom right).

In order of frequency in the United States per 100,000 population, the highest incidences of Lyme disease are in Maine, Vermont, Pennsylvania, Rhode Island, and Connecticut.[4]

Darkfield microscopy of Borrelia burgdorferi (400x magnification). Image from CDC. [Public domain.]

Lyme Disease

Russell W Steele, MD | July 10, 2023 | Contributor Information

Lyme disease is primarily caused by B burgdorferi sensu lato, which has the following three genospecies: B burgdorferi sensu stricto, B garinii, and B afzelii. In European patients with erythema migrans, B afzelii accounts for 80% of lesions and B garinii for 15%.[5]

As a consequence of genomic variation, these genospecies are associated with different clinical presentations. Infection with B burgdorferi sensu stricto has a particular predilection for joints. B afzelii most often infects the skin but may persist there and cause various cutaneous manifestations, including acrodermatitis chronica atrophicans. B garinii is neurotropic and accounts for most cases of lymphocytic meningoradiculitis (Bannwarth syndrome) and encephalitis.

Life cycle of deer tick. Image from Wikimedia Commons | Cfhand15. [CC BY-SA 4.0.]

Lyme Disease

Russell W Steele, MD | July 10, 2023 | Contributor Information

The infectious cycle of B burgdorferi and its tick vectors spans over 2 years, involving colonization of animals, infection of Ixodes ticks, and then transmission to a broad range of mammalian hosts, including humans.[6]

The larvae feed on a variety of small animals, primarily the white-footed mouse. The following spring, the larvae emerge as nymphs. The following fall, nymphs molt into adults and feed once on larger animals, with the white-tailed deer the preferred host. Ticks carry B burgdorferi organisms in their midgut, translocating them from the gut to the salivary glands and transmitting them to humans through bites.

Erythema migrans initial rash occurring 3-14 days after tick bite. Image courtesy of Russell Steele, MD.

Lyme Disease

Russell W Steele, MD | July 10, 2023 | Contributor Information

The clinical manifestations of Lyme disease generally follow three stages of progression: early localized, early disseminated, and chronic disseminated. Primary or early localized infection occurs within 30 days of the tick bite. Most patients present with a characteristic target-appearing rash (erythema migrans) at the site of the bite 3-14 days after the tick attaches and bites.[7]

Nonspecific flulike symptoms may include fatigue, myalgia, and fever. Treatment at the onset of the rash prevents progression of disease.

It should be emphasized that most tick bites produce a circular area of erythema at the site of the bite that fades 1-3 days after the bite; this is not erythema migrans.

Image from Aucott J, Morrison C, Munoz B, Rowe PC, Schwarzwalder A, West SK. BMC Infect Dis. 2009;9:79. [Open access.] PMID: 19486523; PMCID: PMC2698836. [CC by 2.0.]

Lyme Disease

Russell W Steele, MD | July 10, 2023 | Contributor Information

Stage 2 or early disseminated disease occurs weeks to months after the bite. Multiple 3- to 8-cm erythematous patches (shown) may be seen, though musculoskeletal and neurologic symptoms are more common.[8] The dermatologic inflammatory response to B burgdorferi likely explains the multiple lesions of erythema migrans, in that almost all patients with multiple lesions are seropositive, regardless of the duration of the disease.

Antibodies against this spirochetal organism cross-react with neural and connective tissues. This molecular mimicry likely generates an autoimmune inflammatory reaction, the probable pathophysiology underlying the late manifestations of disease.

Information from Association of Public Health Laboratories (APHL).

Lyme Disease

Russell W Steele, MD | July 10, 2023 | Contributor Information

The best diagnostic test for Lyme disease is documentation of an erythema migrans rash, particularly in endemic regions and instances of recent tick exposure. These patients require immediate antibiotics. When the diagnosis is unclear, serologic testing is recommended using either the concurrent or the sequential two-tier approach.[9,10]

In July 2019, the US Food and Drug Administration (FDA) approved the use of concurrent or sequential enzyme immunoassay (EIA) testing for diagnosis of Lyme disease, guided by data from clinical studies showing that this alternative approach (the modified two-tier test; shown) is as accurate as testing with EIA or immunofluorescence assay (IFA) plus Western blot.

  • EIA or IFA - Total Lyme titer or immunoglobulin G (IgG) and IgM titers
  • Western blot testing is rarely necessary but may be considered if EIA or IFA test results are positive or equivocal. If signs and symptoms have been present for no longer than 30 days, both IgM and IgG Western blot testing are performed; if signs and symptoms have been present for longer than 30 days, only IgG Western blot testing is necessary. Of note, serologic testing is difficult to interpret and has relatively low sensitivity and specificity.
Most clinicians consider oral doxycycline preferred treatment for early Lyme disease. Image from National Institute of Allergy and Infectious Diseases (NIAID) via Flickr. [CC by 2.0.]

Lyme Disease

Russell W Steele, MD | July 10, 2023 | Contributor Information

Recommended treatment of Lyme disease is as follows:

  • Adult patients with early localized or early disseminated Lyme disease associated with erythema migrans - Doxycycline, amoxicillin, or cefuroxime axetil
  • Children younger than 8 years and pregnant or nursing individuals with early localized or early disseminated Lyme disease - Amoxicillin or cefuroxime axetil
  • Neurologic Lyme disease - Intravenous (IV) penicillin, ceftriaxone, or cefotaxime; oral doxycycline, when not contraindicated, in patients with Lyme-associated meningitis, facial nerve palsy, or radiculitis

Adults and children with early Lyme disease should be treated for 10-14 days.[1-3,11] For adults with associated erythema migrans, a 10-day course of doxycycline and a 14-day course of amoxicillin or cefuroxime axetil appear to be equally effective, though there are more published data for doxycycline. Pregnant and nursing people should avoid doxycycline. Children younger than 8 years can receive doxycycline for up to 21 days without teeth staining[12]; amoxicillin or cefuroxime axetil also are recommended.[12]

For neurologic disease, including meningitis, facial nerve palsy, or radiculitis, IV therapy with penicillin, ceftriaxone, or cefotaxime is effective.

Infant with Lyme arthritis and erythema migrans rash near site of joint involvement. Image courtesy of Russell Steele, MD.

Lyme Disease

Russell W Steele, MD | July 10, 2023 | Contributor Information

Lyme Arthritis

In patients with late disease, the most common manifestation is arthritis, primarily involving large joints, especially the knee. Warmth, swelling from effusion, and limited range of motion help distinguish arthritis from simple arthralgia.

If treatment is delayed, patients are more likely to develop acute arthritis, chronic musculoskeletal symptoms, difficulties with memory and concentration, and chronic fatigue. These can be debilitating and difficult to manage. The pathogenic mechanism for chronic arthritis is thought to be immunologic rather than active infection. This condition is more prevalent among those with human leukocyte antigen (HLA)-DR2, HLA-DR3, or HLA-DR4 allotypes.

Lyme arthritis resists antibiotic treatment but typically responds to nonsteroidal anti-inflammatory drugs (NSAIDs) and local symptomatic treatment, usually with gradual but complete resolution.[13-16]

Recommended treatment of Lyme arthritis is as follows:

  • Oral antibiotics for 28 days
  • Retreatment with oral antibiotics for mild residual joint swelling
  • Retreatment with IV antibiotics for refractory cases
  • Oral antibiotics for another month in patients with positive polymerase chain reaction (PCR) assay of synovial fluid
  • NSAIDs in patients with negative PCR, supplemented (if necessary) with hydroxychloroquine
  • Consideration of arthroscopic synovectomy in patients unresponsive to symptomatic therapy
Image courtesy of Medscape.

Lyme Disease

Russell W Steele, MD | July 10, 2023 | Contributor Information

If Lyme disease is treated early, the prognosis is excellent. Mortality is very low, with most reported fatalities occurring in patients with one or more severe comorbidities. Cardiac involvement is rarely chronic, but patients with complete third-degree heart block (shown) often require insertion of a temporary pacemaker and, rarely, a permanent pacemaker.[5,6] In 10-20% of patients, symptoms may linger for more than 6 months.[6,15,16]

Posttreatment Lyme disease syndrome may occur and include neurologic changes such as cognitive disturbances, headaches, hearing loss, vertigo, mood disturbances, and paresthesia.[17] Other reported late changes are fatigue, joint or muscle pain, and difficulty in sleeping. No evidence suggests that prolonged antibiotic therapy is effective for this condition.[15,18]

Lyme carditis may be treated with either oral or parenteral antibiotic therapy for 14 days (range, 14-21 d). Hospitalization and continuous monitoring, with consideration of temporary pacing, are advisable for patients with any of the following:

  • Associated symptoms (eg, syncope, dyspnea, or chest pain)
  • Second-degree or third-degree atrioventricular block
  • First-degree heart block with prolongation of the PR interval to more than 300 ms (the degree of block may fluctuate and worsen very rapidly in such patients)
Tick removal using forceps as close to the skin as possible, employing slow, gentle traction. Image courtesy of Medscape.

Lyme Disease

Russell W Steele, MD | July 10, 2023 | Contributor Information

It is essential to provide education about Lyme disease to parents and children who live in areas where the disease is endemic. Anticipatory guidance should focus on preventive measures, such as the use of insect repellents (30% diethyltoluamide [DEET]), the wearing of long-sleeve shirts and long pants, and daily examination of children for the presence of ticks, keeping in mind that the nymphs are tiny (< 2 mm) and tend to be found on the child's head.

The preferred method for tick removal involves the use of fine-tipped forceps.[14] When removing a tick, wear gloves to avoid possible infection. Grasp the tick as close to the skin surface as possible, clamping on the mouth parts, and pull upward with steady, gentle traction. Do not twist or jerk the tick, because this may cause the mouth parts to break off and remain in the skin.

Vaccines

A vaccine was licensed and made available for ages 15-70 years in 1998, but it was discontinued by the manufacturer in 2002 because of poor sales secondary to safety concerns. At present, newer vaccines are under investigation that are immunogenic and without safety issues.[19]

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