What is the best course of management for a 35-year-old female with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal (PANDAS) infections and autism spectrum disorder (Autism) presenting with unusual fatigue for two weeks?

Management of Unusual Fatigue in a 35-Year-Old Female with PANDAS and Autism

This patient requires a comprehensive medical workup to identify treatable causes of fatigue, as PANDAS in adults is an unproven hypothesis and fatigue is not a core feature of this condition. 1, 2

Initial Diagnostic Approach

The presenting complaint of unusual fatigue for two weeks warrants systematic evaluation for common medical causes rather than attribution to PANDAS, which remains controversial even in pediatric populations. 1, 3

Essential Laboratory Testing

• Complete blood count to evaluate for anemia, infection, or hematologic abnormalities 1
• Comprehensive metabolic panel including liver and renal function to assess for metabolic derangements 1
• Thyroid function tests (TSH, free T4) as thyroid disorders commonly cause fatigue
• Erythrocyte sedimentation rate (ESR) as an inexpensive measure of systemic inflammation 1
• Anti-streptolysin O (ASO) titer and anti-DNase B titer only if there is clinical suspicion of recent streptococcal infection 2, 4

Clinical History Priorities

Focus on identifying:

• Recent infectious symptoms, particularly pharyngitis or upper respiratory symptoms 1, 2
• Medication changes that could contribute to fatigue 1
• Sleep quality and duration, as sleep disturbances are common in autism and can cause significant fatigue 1
• Changes in obsessive-compulsive symptoms or tics that might suggest disease activity 1
• Functional decline in activities of daily living 1

PANDAS-Specific Considerations

Critical Limitations of PANDAS Diagnosis in Adults

The American Heart Association explicitly states that PANDAS "should be considered only as a yet-unproven hypothesis" and emphasizes this concept applies primarily to pediatric populations. 1, 2, 3 The evidence base is controversial and lacks rigorous research support. 5

If Streptococcal Infection is Documented

Only if there is laboratory evidence of recent streptococcal infection (elevated ASO or anti-DNase B titers) AND active pharyngeal symptoms should antibiotic therapy be initiated: 2, 4

• First-line: Penicillin V 500 mg four times daily for 10 days 2, 3
• Alternative: Amoxicillin 500 mg three times daily for 10 days 2, 3
• Penicillin allergy: Azithromycin (maximum 500 mg once daily for 3-5 days) or clindamycin 300 mg four times daily for 10 days 3

The American Heart Association recommends against: 1, 2, 3, 4

• Long-term antistreptococcal prophylaxis
• Immunoregulatory therapy (IVIG, plasma exchange) as routine treatment
• Routine laboratory testing for streptococcal infection without clinical indication

Management of Fatigue in Context of Autism

Addressing Deconditioning

Protracted fatigue can become a deconditioned state that persists after resolution of any acute process. 1

• Physical therapy referral for assessment and treatment of "generalized weakness" with structured reconditioning protocols 1
• Reconditioning programs should continue for several weeks to months depending on duration of deconditioning 1
• Medical release from work or obligations may be justified during acute fatigue 1

Sleep Optimization

Given the high prevalence of sleep disorders in autism, address sleep quality systematically: 1

• Sleep diary documenting bedtime, rise time, duration, and night wakings 1
• Melatonin therapy if sleep-onset delay or maintenance insomnia is present: 1-3 mg 30-60 minutes before bedtime, with dose escalation up to 6 mg if needed 1
• Sleep hygiene education and behavioral interventions 1

Psychiatric Symptom Management

If Psychiatric Symptoms Require Treatment

Only prescribe psychotropic medications after formal diagnosis of a DSM-5 psychiatric disorder as part of a comprehensive treatment plan. 2

• Atypical antipsychotics (such as aripiprazole) are preferred over first-generation antipsychotics in patients with developmental disabilities due to lower risk of extrapyramidal symptoms 2
• Psychotherapy has demonstrated efficacy for obsessive-compulsive symptoms in PANS/PANDAS populations and should be considered first-line for behavioral symptoms 6, 7
• Start psychotropic medications at markedly reduced initial doses in PANS/PANDAS patients due to individual differences in medication response 6

Common Pitfalls to Avoid

• Do not attribute all symptoms to PANDAS without excluding common medical causes of fatigue 1, 3
• Do not initiate immunomodulatory therapy (IVIG, plasma exchange) as these are not recommended by the American Heart Association 1, 2, 3
• Do not start long-term antibiotic prophylaxis as this lacks evidence support 1, 3
• Do not overlook sleep disorders, which are highly prevalent in autism and treatable 1
• Recognize that PANDAS research is predominantly pediatric and extrapolation to adults is not evidence-based 1

Monitoring and Follow-Up

If systemic inflammation is present (elevated ESR), repeat weekly to monitor improvement. 1 If streptococcal titers are elevated, repeat in 2-4 weeks to document resolution. 2 Functional assessment should focus on return to baseline activities and quality of life rather than laboratory values alone. 1