Lyme Borreliosis¶

Chapter 191 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial · Chapter 191

Key Clinical Points¶

Erythema migrans (EM) is the hallmark early sign; diagnosis is clinical without serology in early disease.
Two-step serologic testing (ELISA followed by Western Blot) is standard for late disease or equivocal early cases.
Doxycycline (100 mg BID) is first-line for early Lyme disease and co-infections (Anaplasmosis, Babesiosis).
Ceftriaxone (2 g IV daily) or Penicillin G is required for neurologic involvement or third-degree AV block.
Posttreatment Lyme Disease Syndrome (PTLDS) symptoms are not caused by active infection; repeated antibiotics are not recommended.
Borrelia burgdorferi sensu lato includes B. burgdorferi, B. garinii, B. afzelii, and B. bavariensis.
Co-infections (Babesia, Anaplasma) are common in the same tick vector and should be screened for.
Western Blot positivity requires specific band criteria: IgM (2 of 3 bands: 23, 39, 41 kDa), IgG (5 of 10 bands).
Mortality is low (2-5% for LBRF) with treatment; untreated mortality is 10-70%.
Pregnancy requires standard therapy; maternal-fetal transmission is rare.

1. DEFINITION & OVERVIEW¶

Lyme borreliosis is caused by Borrelia burgdorferi sensu lato (Borreliella spp.), transmitted by Ixodes ticks. The infection progresses through three stages:

• Stage 1 (Localized): Erythema migrans (EM) appears at the tick bite site, expanding to form an annular lesion with central clearing. • Stage 2 (Disseminated): Hematogenous spread may cause secondary skin lesions, meningitis, cranial neuritis, carditis, or musculoskeletal pain. • Stage 3 (Persistent): Months to years later, arthritis, encephalopathy, or polyneuropathy may develop.

Definition (Harrison's 22e): Lyme disease was recognized as a separate entity in 1976 because of a geographic cluster of children in Lyme, Connecticut, who were thought to have juvenile rheumatoid arthritis. It became apparent that Lyme disease was a multisystem illness that affected primarily the skin, nervous system, heart, and joints.

1.1 Etiologic Agent¶

• Pathogen: B. burgdorferi is a fastidious microaerophilic spirochete. ◦ Genome: ~1.5 Mb, contains linear chromosomes and plasmids. ◦ Plasmids: Encode over 100 lipoproteins (many immunogenic) critical for host interaction. ◦ Strains: Classified by typing schemes (e.g., OspC, RST, WGS); WGS type A strains are most virulent and associated with epidemic outbreaks.

1.2 Stages of Infection¶

• Stage 1: Incubation period 3–32 days; EM begins as a red macule/papule expanding to an annular lesion (often warm, not painful). ◦ Note: ~20% of patients lack EM. • Stage 2: Hematogenous spread occurs within weeks. Manifestations include: - Secondary skin lesions - Meningitis, cranial neuritis, radiculoneuritis, carditis, or migratory musculoskeletal pain • Stage 3: Months to years later, ~60% of untreated US patients develop arthritis (knees most common), chronic encephalopathy, or polyneuropathy. Acrodermatitis chronica atrophicans is associated with B. afzelii in Europe/Asia.

2. EPIDEMIOLOGY¶

Lyme disease is the most common vector-borne infection in the US and Europe.

• Vectors: Ixodes scapularis (NE US, Midwest), I. pacificus (West), I. ricinus (Europe), I. persulcatus (Eurasia). • Reservoirs: White-footed mice in the US; other rodents in Europe/Asia. • Transmission Cycle: Requires horizontal transmission between nymphs and mice, then larvae and mice. Nymphal ticks transmit to humans during early summer.

2.1 Prevention¶

Prevention focuses on reducing tick exposure and post-exposure prophylaxis:

• Personal Measures: Repellents (DEET, permethrin), clothing, tick checks. • Environmental Control: Reduce tick habitats, rodent-proof homes. • Post-exposure Prophylaxis: Doxycycline 100 mg BID for 4 days after tick bite in high-risk areas.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

B. burgdorferi survives in ticks and mammals by expressing different surface proteins:

• In ticks: OspA (midgut), OspC (salivary glands, binds Salp15 for mammalian infection). • In humans: VlsE lipoprotein undergoes antigenic variation to evade immune response.

Pathogenesis Mechanisms:

• Adherence: To host tissues via plasminogen binding, complement evasion (Factor H binding), and decorin-binding proteins. • Dissemination: Facilitated by platelet/fibrinogen receptor interactions. • Immune Response: Innate (complement, cytokines) and adaptive (antibodies, T cells).

3.1 Clinical Pathophysiology¶

• Neurologic (~15%): Meningitis, facial palsy, radiculoneuritis, or encephalopathy. • Cardiac (~8%): Atrioventricular block (Wenckebach, complete), myopericarditis, rare pancarditis. • Arthritis: ~60% of untreated US patients develop oligoarticular arthritis (knees most common); linked to IFN-γ dysregulation and autoantibodies against vascular/ECM antigens.

4. CLINICAL FEATURES¶

Clinical manifestations vary by stage:

• Early Stage (Stage 1): EM (90% of cases), often asymptomatic; ~20% lack skin lesions. • Early Stage (Stage 2): Systemic symptoms (fever, headache, fatigue, arthralgia); neurologic signs (meningitis, facial palsy, radiculoneuritis); cardiac (atrioventricular block). • Late Stage (Stage 3): Arthritis (intermittent oligoarticular, primarily knees), chronic encephalopathy, polyneuropathy, or acrodermatitis chronica atrophicans.

4.1 Posttreatment Lyme Disease Syndrome (PTLDS)¶

• Symptoms: Fatigue, headache, musculoskeletal pain, paresthesias, cognitive impairment. • Mechanism: No evidence of active infection; linked to immune dysregulation.

5. DIFFERENTIAL DIAGNOSIS¶

Key differentials:

• EM Mimics: Contact dermatitis, tinea corporis, insect bite reactions. • Facial Palsy Differential: Bell palsy (idiopathic), stroke, or Ramsay Hunt syndrome (herpes zoster).

6. INVESTIGATIONS & DIAGNOSIS¶

Diagnostic approach:

Clinical Diagnosis: • EM is diagnostic in early disease.

Serologic Testing: • Two-step algorithm: ELISA (IgM/IgG) followed by Western Blot. • Western Blot Criteria: - IgM: 2 of 3 bands (23, 39, 41 kDa) - IgG: 5 of 10 bands

PCR/CSF Analysis: • Useful in neurologic cases or when serology is equivocal.

Pretest Probability (Table 191-1): • High Probability: Patients with EM or oligoarticular arthritis → Empirical treatment without serologic testing. • Low Probability: Patients with nonspecific symptoms (myalgias, arthralgias, fatigue) → Neither serologic testing nor antibiotic treatment.

6.1 Diagnostic Criteria & Interpretation¶

Diagnosis based on clinical features and serology:

• Early disease: EM alone is sufficient. • Late disease: Serologic confirmation required (Western Blot criteria above). • Neurologic cases: CSF pleocytosis (~100 cells/μL) → elevated protein → normal glucose.

6.2 Testing Algorithm¶

Clinical suspicion (EM, symptoms) → ELISA screening → Confirmatory Western Blot (if ELISA positive or equivocal) → PCR/CSF analysis (for neurologic cases).

7. MANAGEMENT & TREATMENT¶

Treatment depends on disease stage and organ involvement:

Early Disease (Stage 1): • Doxycycline 100 mg BID for 20–30 days. • Alternatives: Amoxicillin 500 mg TID or Cefuroxime 500 mg BID.

Disseminated Disease (Stage 2): • Same as early disease if no neurologic/cardiac involvement.

Neurologic/Cardiac Involvement (Stage 3): • IV Ceftriaxone 2 g daily for 14–28 days or Penicillin G 18–24 million units/day.

Postinfectious Arthritis: • No evidence of active infection; avoid repeated antibiotics.

Co-infections: • Babesiosis: Atovaquone + Proguanil, or Clindamycin + Quinine. • Anaplasmosis: Doxycycline 100 mg BID.

7.1 Treatment Regimens (Duration)¶

• Early disease: 20–30 days oral therapy. • Neurologic/cardiac: 14–28 days IV therapy. • Postinfectious arthritis: No antibiotic recommended.

7.2 Treatment Algorithm (Figure 191-2)¶

Decision pathways based on clinical presentation:

• Path A (Skin Infection): Erythema migrans/Acrodermittis → Oral selection based on age/pregnancy → Duration: 14 days (localized), 30 days (acrodermittis), or 30 days (general). • Path B (Joint Arthritis): Joint Arthritis → Oral (Amoxicillin or Cefuroxime) for 28 days → If no response → Intravenous. • Path C (Heart Block): Heart AV block → Intravenous (Ceftriaxone, Cefotaxime, or Penicillin G) → 28 days (or until resolution of high-degree AV block). • Path D (Nervous System): Nervous system involvement (Facial palsy, Meningitis, Encephalopathy) → Intravenous (Ceftriaxone or Cefotaxime) → 28 days.

Dosage Summary: • Ceftriaxone: 2 g qd • Cefotaxime: 2 g every 8h • Penicillin G: 5 million U q6h (or 18–24 million units/day)

8. PROGNOSIS & COMPLICATIONS¶

Prognosis:

• With treatment: Mortality <5% (LBRF). • Without treatment: Mortality 10–70%.

Complications: • Chronic arthritis, neurologic sequelae, acrodermatitis chronica atrophicans.

8.1 Posttreatment Sequelae¶

PTLDS: Fatigue, headache, musculoskeletal pain, cognitive impairment. No evidence of active infection; repeated antibiotics are not recommended.

9. SPECIAL CONSIDERATIONS¶

• Pregnancy: - Avoid doxycycline in first trimester. - Use Amoxicillin or Cefuroxime. - Maternal-fetal transmission is rare.

• Pediatrics: - Doxycycline safe in children ≥ 8 years. - < 8 years: Amoxicillin (50 mg/kg/day TID) or Cefuroxime (15 mg/kg/day BID).

9.1 Pregnancy¶

No evidence of fetal harm with appropriate therapy (Amoxicillin/Cefuroxime).

9.2 Pediatric Considerations¶

Doxycycline safe in children ≥ 8 years; Amoxicillin or Cefuroxime for younger patients.

10. KEY PEARLS & CLINICAL TRAPS¶

• Diagnostic Clue: EM is diagnostic in early disease; serology not required. • Serology Requirement: Only needed for late disease or equivocal early cases. • Treatment Logic: Use IV Ceftriaxone (2 g daily) for heart block or CNS involvement. • PTLDS Trap: Symptoms are NOT caused by active infection; do not treat with repeated antibiotics.

10.1 Diagnostic Clues¶

EM is the hallmark sign. Serology only required for late disease or equivocal early cases.

10.2 Exclusion Criteria¶

PTLDS symptoms not caused by active infection; repeated antibiotics ineffective.

Reference Tables¶

TABLE 191-1 Algorithm for Testing for and Treating Lyme Disease¶

Harrison's 22e, p.1451

PRETEST PROBABILITY	EXAMPLE	RECOMMENDATION
High	Patients with erythema migrans	Empirical antibiotic treatment without serologic testing
	Patients with oligoarticular arthritis
Low	Patients with nonspecific symptoms (myalgias, arthralgias, fatigue)	Neither serologic testing nor antibiotic treatment