What is the best treatment approach for a 14-year-old male with severe Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) symptoms and a positive Borrelia burgdorferi titer?

Treatment Approach for a 14-Year-Old Male with PANS and Positive Borrelia burgdorferi Serology

This patient requires standard antibiotic treatment for Lyme disease with doxycycline 100 mg twice daily for 14 days, while simultaneously addressing the PANS symptoms through appropriate neuropsychiatric management, recognizing that the positive Lyme serology may be incidental rather than causative of the neuropsychiatric presentation. 1, 2

Critical Diagnostic Considerations

The most important clinical question is whether this patient has active Lyme neuroborreliosis causing or contributing to the PANS symptoms, or whether the positive serology represents past exposure unrelated to the current neuropsychiatric presentation.

Guideline-Based Approach to Neuropsychiatric Symptoms

• The 2021 IDSA/AAN/ACR guidelines explicitly recommend AGAINST routine testing for Lyme disease in children presenting with developmental, behavioral, or psychiatric disorders (weak recommendation, low-quality evidence). 1

• Similarly, in patients with psychiatric illness, guidelines strongly recommend against routine testing for Lyme disease (strong recommendation, low-quality evidence). 1

• The guidelines only recommend testing when patients present with specific acute neurologic syndromes: meningitis, painful radiculoneuritis, mononeuropathy multiplex, acute cranial neuropathies (particularly VII, VIII), or evidence of spinal cord/brain inflammation with epidemiologically plausible tick exposure. 1

Interpreting the Positive Serology

The positive Western blot bands (p58, p66, p83-93) indicate exposure to Borrelia burgdorferi, but this does not automatically mean active infection is causing the PANS symptoms. 1

• Serology may remain positive for months or years after successful treatment and cannot be used as a marker of active infection. 3

• The critical next step is determining if there are objective neurologic findings consistent with Lyme neuroborreliosis, not just psychiatric/behavioral symptoms. 1

Recommended Treatment Algorithm

Step 1: Assess for Active Lyme Neuroborreliosis

If the patient has objective CNS involvement (meningitis, encephalitis, myelitis with documented inflammation):

• Intravenous ceftriaxone 2g once daily for 14 days (range 10-28 days) is recommended for parenchymal brain or spinal cord involvement. 1
• Alternative: IV cefotaxime or penicillin G. 1

If the patient has only peripheral nervous system involvement (cranial neuropathy, radiculopathy) without CNS parenchymal disease:

• Oral doxycycline 100 mg twice daily for 14 days is appropriate and effective. 1, 2
• For a 14-year-old, doxycycline is preferred as first-line therapy (4 mg/kg/day in 2 divided doses, maximum 200 mg/day). 2

If there are NO objective neurologic findings and only psychiatric/behavioral symptoms:

• Standard oral antibiotic therapy for presumed early or disseminated Lyme disease: doxycycline 100 mg twice daily for 14 days. 2, 3
• This treats any potential active Lyme infection while avoiding the assumption that Lyme is causing the PANS. 1

Step 2: Address PANS Symptoms Appropriately

• PANS requires its own specific management including immunomodulatory therapy, psychiatric medications, and treatment of other potential triggers (streptococcal infection, other infections). 1

• The severe neuropsychiatric symptoms should be managed by specialists familiar with PANS, as these symptoms are unlikely to resolve with antibiotics alone if Lyme is not the primary driver. 1

Step 3: Avoid Common Pitfalls

Do NOT use prolonged or repeated courses of antibiotics beyond standard treatment durations:

• Multiple studies show no benefit to extended antibiotic therapy for persistent symptoms after standard treatment. 1
• The 2006 IDSA guidelines explicitly state that prolonged antibiotic therapy lacks supporting data and may cause harm. 1, 2

Do NOT use ineffective antibiotics:

• First-generation cephalosporins (cephalexin) are ineffective against B. burgdorferi. 2
• Fluoroquinolones, carbapenems, vancomycin, and other non-recommended antibiotics should not be used. 1, 2

Do NOT assume all persistent symptoms are due to active infection:

• After standard antibiotic treatment, persistent subjective symptoms without objective findings do not indicate ongoing infection. 1
• Some patients develop fibromyalgia or other post-infectious syndromes that are not antibiotic-responsive. 1

Specific Antibiotic Recommendations for This 14-Year-Old

First-line oral therapy (preferred for most scenarios):

• Doxycycline 100 mg (or 4 mg/kg/day) twice daily for 14 days 2, 3
• Doxycycline has the advantage of covering potential co-infection with human granulocytic anaplasmosis (HGA). 1, 2
• Should be taken with 8 ounces of fluid to reduce esophageal irritation and with food to reduce GI intolerance. 2
• Patient should avoid sun exposure due to photosensitivity risk. 2

Alternative oral options if doxycycline contraindicated:

• Amoxicillin 50 mg/kg/day in 3 divided doses for 14 days (though patient is >8 years old, so doxycycline preferred). 2
• Cefuroxime axetil 30 mg/kg/day in 2 divided doses for 14 days. 2

Parenteral therapy (only if objective CNS parenchymal involvement documented):

• Ceftriaxone 50-75 mg/kg/day (maximum 2g) once daily IV for 14 days. 2, 3

Monitoring and Follow-Up

• Most patients respond promptly to appropriate antibiotic therapy, but patients who are more systemically ill at diagnosis may take longer to respond. 2

• Close follow-up within 24-48 hours is essential to ensure improvement, as tick-borne diseases can rapidly progress. 1

• If substantial improvement is not observed within 24-48 hours, the patient should return for re-evaluation. 1

• Less than 10% of individuals do not respond to antibiotic therapy as evidenced by persistent objective clinical manifestations—this is distinct from persistent subjective symptoms. 2

Key Clinical Caveat

The most critical error would be attributing severe PANS symptoms entirely to Lyme disease and pursuing prolonged antibiotic therapy. The evidence strongly suggests that in the absence of objective neurologic findings consistent with active Lyme neuroborreliosis, the positive serology likely represents past exposure, and the PANS requires its own comprehensive management approach beyond standard Lyme treatment. 1