What is the appropriate management for a patient with a history of strep (streptococcal) throat followed by the development of paranoid obsessive-compulsive disorder (OCD) symptoms suggestive of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS)?

USMLE Step 3 Clinical Vignette: PANDAS

Clinical Vignette

A 7-year-old boy is brought to the clinic by his parents for evaluation of sudden-onset behavioral changes that began 2 weeks ago. The parents report that 3 weeks prior, their son had a sore throat with mild fever that resolved after a few days without medical attention. Over the past 2 weeks, he has developed severe hand-washing rituals (washing hands 30-40 times daily until they bleed), extreme preoccupation with germs, and refusal to touch doorknobs. He also exhibits frequent daytime urinary urgency and frequency without dysuria, fever, or incontinence; these symptoms completely disappear at night. The parents note he has become increasingly irritable and has developed facial tics. His teacher reports he can no longer concentrate in class and repeatedly asks to use the bathroom. The child has no prior psychiatric history and was previously well-adjusted. Physical examination reveals mild pharyngeal erythema without exudate. Urinalysis is negative.

Question: What is the most appropriate next step in management?

A) Start sertraline and refer to psychiatry
B) Obtain throat culture and anti-streptolysin O (ASO) titer, start penicillin if positive
C) Start prophylactic penicillin and refer for plasma exchange
D) Reassure parents this is normal childhood behavior and observe
E) Order brain MRI and EEG

Correct Answer: B

Explanation and Management Approach

The most appropriate initial management is to obtain throat culture and streptococcal antibody titers (ASO and anti-DNase B), and if positive for recent streptococcal infection, initiate antibiotic therapy with penicillin or amoxicillin for 10 days. 1, 2

Diagnostic Recognition

• This presentation is highly suggestive of PANDAS based on the abrupt onset of severe OCD symptoms (hand-washing, germ preoccupation) and tics following a recent sore throat, along with the characteristic daytime urinary urgency/frequency that disappears at night 3

• The daytime urinary urgency and frequency without dysuria, fever, or incontinence with negative urinalysis is a notable and specific symptom seen in 58% of PANDAS cases 3

• The temporal relationship between streptococcal throat infection and neuropsychiatric symptoms is key: symptoms typically appear within weeks of the infection 3, 4

Initial Diagnostic Workup

• Obtain throat culture if the patient has any residual throat symptoms 5

• Obtain ASO titer and anti-DNase B titer to document recent streptococcal exposure, with ASO peaking 3-6 weeks after infection and anti-DNase B peaking 6-8 weeks post-infection 5

• In confirmed PANDAS cases, anti-streptolysin O and anti-DNase B titers are typically 10-fold higher than in other conditions 6

First-Line Treatment: Antibiotics

If streptococcal infection is confirmed, the first-line treatment is antibiotics to eradicate the infection: 1, 2

• Penicillin V 500 mg four times daily for 10 days (preferred option) 1, 2

• Amoxicillin 500 mg three times daily for 10 days (equally effective alternative, often preferred in children due to better taste acceptance) 1, 2

• For penicillin-allergic patients: erythromycin or azithromycin (maximum 500 mg once daily for 3-5 days) 1, 2

• For treatment failures: clindamycin 300 mg four times daily for 10 days 1, 2

• Prospective studies demonstrate that OCD symptoms promptly disappear in children treated with antibiotics effective in eradicating GABHS infection at the sentinel episode 3

Important Caveats and Pitfalls

The American Heart Association explicitly states that PANDAS "should be considered only as a yet-unproven hypothesis" and the evidence base remains controversial 7, 2, 5

Despite this caveat, the following are NOT recommended as first-line approaches: 7, 2, 5

• Do NOT initiate long-term antistreptococcal prophylaxis without evidence of recurrent infections 7, 2, 5

• Do NOT use immunoregulatory therapy (IVIG or plasma exchange) as first-line treatment 7, 2, 5

• Do NOT perform routine laboratory testing for GAS solely to diagnose PANDAS in the absence of clinical evidence of infection 7, 5

Psychiatric Management Considerations

• If OCD symptoms persist after antibiotic treatment, psychotherapy is the most efficacious intervention for relieving OCD symptoms and reducing stress in patients and parents 6

• Sertraline and other SSRIs are FDA-approved for OCD and can be considered if symptoms do not resolve with antibiotics alone, though they were less effective in the acute PANDAS setting in some case series 8, 9

• Antidopaminergic therapy has shown efficacy in case reports when serotonergic therapy fails, targeting altered central dopamine signaling 9

Follow-Up and Monitoring

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

• Monitor for recurrence of OCD symptoms, as each recurrence is typically associated with evidence of acute GABHS infection and responds to antibiotic therapy 3

• Distinguish from GABHS carriers: true PANDAS recurrences show negative follow-up throat cultures between episodes 3

Differential Diagnosis Considerations

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

• Classic OCD has a more gradual onset, differing from the abrupt onset characteristic of PANDAS 2

• PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) is a broader disorder with sudden-onset OCD symptoms that can occur in response to various infections and insults, not just streptococcal 7

• Irritability, aggressivity, and food restriction are more prevalent in PANS than PANDAS 6

Why Other Answer Choices Are Incorrect

Option A (Start sertraline and refer to psychiatry): While SSRIs are appropriate for OCD, this ignores the temporal relationship with streptococcal infection and misses the opportunity for targeted antibiotic treatment that has been shown to resolve symptoms promptly in PANDAS cases 3

Option C (Prophylactic penicillin and plasma exchange): The American Heart Association explicitly recommends against long-term prophylaxis and immunoregulatory therapy as first-line treatment 7, 2, 5

Option D (Reassure and observe): The severity and sudden onset of symptoms, along with functional impairment, warrant immediate evaluation and treatment 3

Option E (Brain MRI and EEG): These are not indicated in the initial workup of suspected PANDAS when the clinical presentation is classic 3