What laboratory tests are needed for the diagnosis of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal (PANDAS) infections?

Laboratory Tests for PANDAS Diagnosis

For the diagnosis of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal (PANDAS) infections, antistreptococcal antibody tests including antistreptolysin O (ASO) and antideoxyribonuclease B (anti-DNase B) titers are the primary laboratory tests needed to establish evidence of recent streptococcal infection.

Core Diagnostic Laboratory Tests

• Throat culture and/or rapid antigen detection test (RADT) for Group A Streptococcus (GAS) to identify active infection 1
• Antistreptolysin O (ASO) titer - typically obtained first to detect evidence of recent GAS infection 2
• Anti-deoxyribonuclease B (anti-DNase B) titer - particularly important if ASO is negative, as it may remain elevated longer than ASO 2

Timing Considerations for Antibody Tests

• ASO titers begin rising approximately 1 week after infection and peak 3-6 weeks later 2
• Anti-DNase B titers begin rising 1-2 weeks after infection and peak 6-8 weeks later 2
• Both antibodies may remain elevated for several months after uncomplicated GAS infections 2

Interpretation Challenges

• Normal levels of streptococcal antibodies are higher in school-age children than in adults, which can lead to misinterpretation 2
• Traditional neutralization assays for ASO and anti-DNase B are being replaced by newer latex agglutination or nephelometric assays, which may not be well standardized against traditional tests 2
• A positive result requires careful interpretation in the context of clinical symptoms, as these antibodies reflect past rather than present immunologic events 2

Additional Laboratory Tests to Consider

• Complete blood count (CBC) to evaluate for inflammatory markers 3
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as non-specific markers of inflammation 4
• Neopterin as another non-specific marker of immune response 4
• Testing for antineuronal antibodies and D8/17 B cell marker (though these lack specificity) 4

Clinical Context for Laboratory Testing

• Laboratory testing should be performed in the context of meeting clinical criteria for PANDAS, which include: 5
  • Sudden onset of obsessive-compulsive symptoms and/or tics
  • Prepubertal age of onset
  • Episodic course of symptom severity
  • Association with neurological abnormalities
  • Temporal relationship with GAS infection

Important Caveats

• The American Heart Association does not recommend routine laboratory testing for GAS to diagnose PANDAS, as it is considered an "yet-unproven hypothesis" 2
• No single test reliably identifies PANDAS; diagnosis remains primarily clinical 4
• Multiple positive test results increase the likelihood of PANDAS diagnosis 4
• False positives can occur in children who are GAS carriers experiencing neuropsychiatric symptoms from another cause 1
• Urinalysis and urine cultures may be needed to rule out urinary tract infection in patients presenting with urinary symptoms (which can be a common presentation in PANDAS) 1

Follow-up Testing

• Post-treatment throat cultures are indicated only for patients who remain symptomatic or experience symptom recurrence 5
• Repeat antibody testing may be useful to monitor response to treatment in established cases 3