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Lyme Borreliosis

Chapter 191 | Part 5: Infectious Diseases

KEY CLINICAL POINTS

  • Lyme borreliosis is caused by Borrelia burgdorferi sensu lato, transmitted via Ixodes ticks.
  • Clinical stages include localized (erythema migrans), disseminated (neurological, cardiac, arthritis), and persistent (chronic arthritis, neuroborreliosis).
  • Doxycycline is the preferred treatment for early-stage disease; ceftriaxone for severe neurologic involvement.
  • Posttreatment Lyme disease syndrome (PTLDS) may occur in 10–20% of patients despite adequate antibiotic therapy.
  • The Jarisch-Herxheimer reaction (JHR) is common during treatment, requiring close monitoring.

1. DEFINITION & OVERVIEW

Lyme borreliosis is a multisystem spirochetal infection caused by Borrelia burgdorferi sensu lato, transmitted via Ixodes ticks. It presents with a characteristic erythema migrans lesion (EM) in stage 1, followed by disseminated infection (stage 2) and persistent infection (stage 3).

Table 191-1 Algorithm for Testing for and Treating Lyme Disease

PRETEST PROBABILITY EXAMPLE RECOMMENDATION
High Patients with erythema migrans Empirical antibiotic treatment without serologic testing
Intermediate Patients with oligoarticular arthritis Serologic testing and antibiotic treatment if test results are positive
Low Patients with nonspecific symptoms (myalgias, arthralgias, fatigue) Neither serologic testing nor antibiotic treatment

1.1 Etiologic Agent

Borrelia burgdorferi sensu lato (B. burgdorferi, B. garinii, B. afzelii, B. bavariensis) are fastidious, microaerophilic spirochetes with a genome of ~1.5 Mb. They possess over 100 lipoproteins, many of which are immunogenic.

1.2 Transmission

Ixodes ticks (Ixodes scapularis in North America, I. ricinus in Europe) transmit the spirochete. Nymphal ticks are primarily responsible for human transmission, peaking in early summer.

2. EPIDEMIOLOGY

Lyme disease is the most common vector-borne infection in the U.S. and Europe. Incidence peaks in endemic regions (e.g., northeastern U.S., Europe). Risk factors include tick exposure, outdoor activities, and immunocompromised status. Annual cases in the U.S. exceed 476,000, with 30,000 reported annually.

2.1 Geographical Distribution

B. burgdorferi (U.S.), B. afzelii/B. garinii (Europe), and B. miyamotoi (Asia) are regional variants. Ixodes persulcatus vectors are found in eastern Russia, China, and Japan.

2.2 Risk Factors

Residing in wooded areas, tick bites, immunosuppression, and co-infections (e.g., anaplasmosis, babesiosis).

3. ETIOLOGY & PATHOPHYSIOLOGY

B. burgdorferi survives in ticks and mammals, adapting to different environments. It expresses outer-surface protein A (OspA) in ticks and OspC in mammals. Virulence factors include surface proteins that bind host tissues and evade immune responses.

3.1 Immune Evasion

Spirochetes downregulate OspC and upregulate VlsE for antigenic variation. Complement resistance via Factor H binding and surface proteins.

3.2 Pathogenesis

Dissemination via hematogenous spread leads to arthritis, neuroborreliosis, and carditis. Persistent infection may cause chronic symptoms due to immune dysregulation.

4. CLINICAL FEATURES

Early: EM (stage 1), disseminated infection (stage 2) with arthritis, neurologic symptoms, or carditis. Late: Persistent arthritis, chronic neurologic disease, or acrodermatitis chronica atrophicans.

4.1 Early Infection (Stage 1)

EM: expanding erythematous lesion with central clearing. Often asymptomatic, but may present with fatigue, headache, or mild fever.

4.2 Disseminated Infection (Stage 2)

Arthritis (oligoarticular), meningitis, cranial neuritis, carditis, and migratory musculoskeletal pain. JHR may occur.

4.3 Persistent Infection (Stage 3)

Chronic arthritis, encephalopathy, polyneuropathy, or acrodermatitis. PTLDS may develop with fatigue, cognitive dysfunction, or musculoskeletal pain.

5. DIFFERENTIAL DIAGNOSIS

Erythema multiforme, cellulitis, staphylococcal scalded skin syndrome, other tick-borne infections (e.g., anaplasmosis, babesiosis), and autoimmune disorders.

5.1 Mimicking Conditions

Bell’s palsy (facial palsy without EM), rheumatoid arthritis, systemic lupus erythematosus, and fibromyalgia.

5.2 Atypical Presentations

STARI (tick-associated rash illness) with EM-like rash but no B. burgdorferi DNA. Co-infections with Ehrlichia or Babesia may complicate diagnosis.

6. INVESTIGATIONS & DIAGNOSIS

Serologic testing (ELISA, Western blot) for IgM/IgG. PCR for B. burgdorferi DNA in joint fluid or CSF. Cultures in BSK medium are less practical.

Western Blot Bands for Lyme Disease

IgM Bands (kDa) IgG Bands (kDa)
23, 39, 41 18, 23, 28, 30, 39, 41, 45, 58, 66, 93

6.1 Serologic Testing

Two-step approach: ELISA followed by Western blot. IgM positive in early stages, IgG in later stages. False positives may occur with co-infections.

6.2 PCR and Imaging

PCR detects B. burgdorferi DNA in joint fluid or CSF. MRI may show meningeal or spinal cord inflammation in neuroborreliosis.

7. MANAGEMENT & TREATMENT

Antibiotic therapy is effective for early-stage disease. IV antibiotics for severe neurologic/cardiac involvement. PTLDS is managed with symptomatic treatment.

Treatment Algorithm for Lyme Disease Manifestations

Manifestation Recommended Therapy
Skin infection Oral doxycycline 100 mg bid x14–21 days
Arthritis Oral doxycycline 100 mg bid x28–30 days
Neuroborreliosis IV ceftriaxone 2 g qd x14–28 days
Carditis IV ceftriaxone 2 g qd x14–28 days

7.1 Early-Stage Treatment

Doxycycline (100 mg bid) for 14–21 days. Alternatives: amoxicillin (500 mg tid) or cefuroxime axetil (500 mg bid).

7.2 Neurologic/Cardiac Involvement

IV ceftriaxone (2 g qd) or penicillin G (5 million units q6h) for 14–28 days. Monitor for JHR and cardiac arrhythmias.

7.3 Chronic Symptoms (PTLDS)

No proven benefit from prolonged antibiotics. Symptomatic management with NSAIDs, physical therapy, or cognitive behavioral therapy.

8. PROGNOSIS & COMPLICATIONS

Mortality is <2% with treatment. Complications include arthritis, neuroborreliosis, carditis, and PTLDS. Untreated, mortality ranges from 10–70%.

8.1 Complications

Chronic arthritis, encephalopathy, polyneuropathy, acrodermatitis, and cardiac arrhythmias. Co-infections may worsen outcomes.

8.2 Pregnancy

Lyme disease may cause abortion or stillbirth. Avoid doxycycline; use amoxicillin or ceftriaxone.

9. SPECIAL CONSIDERATIONS

Avoid doxycycline in pregnancy. Use alternative antibiotics for renal impairment. Monitor for JHR and cardiac arrhythmias during treatment.

9.1 Pediatric Considerations

Amoxicillin is preferred in children. Avoid doxycycline in children <8 years old.

9.2 Co-Infections

Anaplasmosis, babesiosis, and ehrlichiosis may co-occur. PCR and blood smear testing are essential for diagnosis.

10. KEY POINTS & CLINICAL PEARLS

  1. Early EM is the hallmark of Lyme disease. 2. Doxycycline is first-line for early-stage infection. 3. JHR is common during treatment. 4. PTLDS is managed with symptomatic care. 5. Serologic testing has limited utility in early stages.