What is PANDA (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections)?

What is PANDAS?

PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) is a controversial clinical syndrome characterized by the sudden onset of obsessive-compulsive disorder (OCD) and/or tics following group A streptococcal infection, though the American Heart Association considers it "a yet-unproven hypothesis" that requires cautious interpretation. 1, 2, 3

Core Clinical Features

PANDAS presents with a distinctive constellation of symptoms that differentiate it from typical psychiatric conditions:

• Abrupt onset of obsessive-compulsive symptoms and/or motor/vocal tics that are temporally related to streptococcal infection 3, 4
• New choreiform movements (involuntary, irregular, dance-like movements) are key distinguishing features to assess 2
• The sudden onset pattern contrasts sharply with classic OCD, which typically has gradual onset 3
• Additional neuropsychiatric symptoms may include behavioral changes, anxiety, and emotional lability 4, 5

Proposed Pathophysiology

The underlying mechanism is thought to involve an aberrant autoimmune response:

• Following group A beta-hemolytic streptococcal infection, antibodies may cross-react with neuronal tissue in the basal ganglia 6, 7
• Neuropathological examination has shown CD4- and CD25-positive T cell infiltration in basal ganglia, suggesting neuroinflammation 7
• The autoimmune hypothesis remains unproven despite these findings 1, 3

Diagnostic Approach

The American Heart Association explicitly recommends against routine laboratory testing for group A streptococcus solely to diagnose PANDAS 2, 3, but when clinical suspicion is high:

• Obtain anti-streptolysin O (ASO) titer and anti-DNase B titer to document recent strep exposure, with ASO peaking 3-6 weeks post-infection and anti-DNase B peaking 6-8 weeks post-infection 2
• Throat culture is indicated only if throat symptoms are present 2
• Post-treatment throat cultures are indicated only in symptomatic patients, those with symptom recurrence, or those with rheumatic fever history 1

Important Diagnostic Caveats

• Behavioral changes like screaming, crying, and tantrums alone are too nonspecific and could represent normal developmental variation 2
• PANDAS should be distinguished from Sydenham chorea, which is a major manifestation of rheumatic fever and shares similar autoimmune mechanisms 3

Treatment Recommendations

First-Line Treatment: Antibiotics

When PANDAS is suspected with confirmed or likely streptococcal infection, the initial treatment is antibiotics to eradicate the infection 1, 3:

Preferred antibiotic regimens:

• Penicillin V: 500 mg four times daily for 10 days 1, 3
• Amoxicillin: 500 mg three times daily for 10 days (or 50 mg/kg once daily, maximum 1000 mg, for children) 1, 2, 3

For penicillin-allergic patients:

• Erythromycin 1, 3
• Azithromycin: maximum 500 mg once daily for 3-5 days 1, 3
• Clindamycin: 300 mg four times daily for 10 days, especially for eradication failures 1, 3

For treatment failures:

• Consider alternative antibiotics: clindamycin, narrow-spectrum cephalosporins, or amoxicillin-clavulanic acid 1
• Consider combination therapy with penicillin plus rifampin 1
• Intramuscular benzathine penicillin G for patients unlikely to complete oral therapy 1

What NOT to Do

The American Heart Association explicitly recommends against:

• Long-term antistreptococcal prophylaxis to prevent PANDAS 1, 2, 3
• Immunoregulatory therapy (intravenous immunoglobulin, plasma exchange) as first-line treatment 1, 2, 3
• Tonsillectomy or adenotonsillectomy does not improve neuropsychiatric course, antibody titers, or symptom severity 6

Evidence Quality and Controversy

A critical caveat: rigorously conducted research on PANDAS treatments is scarce, and published studies have high risk of bias 8. The systematic review evidence reveals:

• The evidence base for PANDAS treatment consists primarily of case reports and small studies with methodological limitations 8
• The American Heart Association's position that PANDAS remains "an unproven hypothesis" reflects the lack of definitive evidence for the autoimmune mechanism 1, 2, 3

Long-Term Considerations

Even after resolution of acute symptoms, patients may experience persistent difficulties:

• Relative impairments in executive functions (attentional regulation, inhibitory control, processing speed) 5
• Reduced graphomotor skills and academic fluency (reading and math) despite normal core academic abilities 5
• Ongoing anxiety, depression, inattention, and social skills difficulties requiring clinical intervention 5
• The majority of patients may require special education services or accommodations 5