What is the current approach to managing Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal (PANDAS) infections?

Current Research and Management of PANDAS Syndrome

Critical Context: PANDAS Remains an Unproven Hypothesis

The American Heart Association explicitly states that PANDAS "should be considered only as a yet-unproven hypothesis," and this fundamental uncertainty should guide all clinical decision-making. 1, 2, 3

Diagnostic Approach

Core Clinical Features to Assess

• Sudden-onset obsessive-compulsive symptoms and/or tics precipitated by streptococcal infection are the hallmark features 1
• New motor or vocal tics (including choreiform movements) that weren't present before are key distinguishing features 3
• Abrupt symptom onset distinguishes PANDAS from classic OCD, which has gradual onset 2

Laboratory Testing Strategy

• Obtain anti-streptolysin O (ASO) titer and anti-DNase B titer to document recent strep exposure, with ASO peaking 3-6 weeks after infection and anti-DNase B peaking 6-8 weeks post-infection 3
• Throat culture is indicated if throat symptoms are present 3
• The American Heart Association recommends against routine laboratory testing for GAS solely to diagnose PANDAS 2, 3
• In research cohorts, ASO and anti-DNase B antibodies were positive in all PANDAS subjects but negative in PANS cases 4

First-Line Treatment: Antibiotic Therapy

Acute Treatment for Active Streptococcal Infection

The initial treatment for PANDAS should be antibiotics to eradicate the streptococcal infection, specifically penicillin or amoxicillin for 10 days. 1

Preferred Antibiotic Options:

• Oral penicillin V 500 mg four times daily for 10 days (first-line) 1, 2
• Amoxicillin 500 mg three times daily for 10 days (equally effective alternative, often preferred in young children due to better taste acceptance) 1, 2
• For penicillin-allergic patients: Erythromycin 1, 2
• Clindamycin 300 mg four times daily for 10 days (especially for eradication failures) 1, 2
• Azithromycin (maximum 500 mg once daily for 3-5 days) for penicillin-allergic patients 1, 2
• Intramuscular benzathine penicillin G for patients unlikely to complete oral therapy 1

Treatment Failures

• For treatment failures, consider clindamycin, narrow-spectrum cephalosporins, or amoxicillin-clavulanic acid 1
• Consider combination therapy with penicillin plus rifampin for treatment failures 1

Post-Treatment Monitoring

• Post-treatment throat cultures are indicated only in patients who remain symptomatic, experience symptom recurrence, or have a history of rheumatic fever 1

Long-Term Antibiotic Prophylaxis: Controversial but Used in Practice

Evidence from Recent Research

• A 2019 Italian cohort study of 371 children (345 PANDAS, 26 PANS) used benzathine benzylpenicillin prophylaxis for at least 5 years to prevent subsequent streptococcal infections 4
• In this cohort, 75% of PANDAS patients showed improvement of neurologic symptoms within 3-5 months, and 88.4% of PANS patients improved after 6-12 months 4
• Infection-related relapses occurred in 45% of patients during long-term follow-up 4
• A 2021 Italian study confirmed that antibiotic prophylaxis was efficacious in managing acute neurological symptoms 5

Guideline Position on Prophylaxis

• The American Heart Association does not recommend long-term antistreptococcal prophylaxis to prevent PANDAS 1, 2
• This creates a significant gap between guideline recommendations and emerging clinical practice data 4, 5

Evidence Quality Assessment

• A 2018 systematic review found limited evidence for antibiotic efficacy, with no single study showing statistically significant results, though some evidence suggests benefit in reducing neuropsychiatric symptoms 6
• The review noted that use of eradicating antibiotic therapy during active infections is well established, but evidence for long-term prophylaxis remains insufficient 6

Psychiatric and Behavioral Interventions

Symptomatic Treatment Approach

• Psychiatric and behavioral symptoms need simultaneous treatment while addressing underlying infectious processes to decrease suffering and improve adherence 7
• Typical evidence-based interventions are appropriate for the varied symptoms of PANDAS and PANS 7

Psychotherapy

• Psychotherapy significantly resulted in the most efficacious relief of OCD in multivariate analysis (P = 0.042), reducing stress in patients and their parents 5
• Psychotherapy was administered in 53.2% of cases in a 2021 cohort study 5

Psychopharmacologic Considerations

• Individual differences in expected response to psychotropic medication may require marked reduction of initial treatment dose 7
• Antipsychotic treatments were used in 24.2% of cases in recent cohorts 5

Immunomodulatory Therapies: Not Recommended as First-Line

The American Heart Association does not recommend immunoregulatory therapy (e.g., IVIG, plasma exchange) as first-line treatment. 1, 2, 3

Current Evidence Status

• Plasma exchange has been proposed but lacks strong evidence 1
• A 2023 review noted that IVIG and immunomodulatory therapies are increasingly being used, particularly by allergist-immunologists, based on the autoimmune hypothesis involving molecular mimicry 8
• The evidence suggests a subgroup in the pediatric OCD population that is sensitive to immunomodulatory therapy, independent of ongoing infectious conditions 6

PANS vs. PANDAS: Clinical Distinctions

Differential Features

• PANS patients show significantly more irritability, aggressivity, and food restriction compared to PANDAS (P = 0.024 and P = 0.0023) 5
• Anti-Mycoplasma pneumoniae antibodies were positive in 42.3% and anti-EBV antibodies in 19.2% of PANS patients 4
• PANS patients improved after 6-12 months compared to 3-5 months for PANDAS 4

Differential Diagnosis

• Sydenham chorea is a major manifestation of rheumatic fever and shares a similar autoimmune mechanism with PANDAS 2

Common Pitfalls and Caveats

• Behavioral changes alone (screaming, crying, tantrums) are too nonspecific and could represent normal developmental variation 3
• The diagnosis requires sudden onset of symptoms, not gradual progression 2
• Infection-related relapses are common (45%) even with prophylaxis, requiring ongoing monitoring 4
• The field lacks high-quality randomized controlled trials comparing antibiotics with other therapies and assessing long-term safety 6