What is the appropriate evaluation and treatment for a school‑age male twin with autism spectrum disorder and attention‑deficit/hyperactivity disorder, on fluoxetine for >1 year and a single dose of risperidone causing marked sedation, who now presents after an upper‑respiratory infection with rapid regression of speech, social interaction, sensory tolerance, motor skills, new repetitive pacing, meltdowns, and food aversion—suspected PANS/PANDAS?

Urgent Evaluation and Treatment for Suspected PANS/PANDAS in a Child with ASD and ADHD

This child requires immediate comprehensive medical evaluation for PANS/PANDAS, with priority given to ruling out active infection, documenting neuropsychiatric regression, and initiating appropriate immunomodulatory therapy if diagnostic criteria are met. The dramatic 8-year regression following an upper respiratory infection, combined with new-onset sensory aversions, motor stereotypies, and food restriction, strongly suggests an autoimmune neuropsychiatric process rather than simple ASD progression. 1

Immediate Diagnostic Workup

Obtain the following laboratory studies urgently:

• Throat culture and rapid strep test to detect active Group A streptococcal infection, as PANDAS is specifically triggered by streptococcal exposure 1
• Anti-streptolysin O (ASO) and anti-DNase B titers to document recent streptococcal infection even if throat culture is negative 1
• Complete blood count with differential to assess for immune activation 1
• Comprehensive metabolic panel to rule out metabolic derangements that could mimic neuropsychiatric symptoms 2
• C-reactive protein and erythrocyte sedimentation rate as markers of systemic inflammation 1

Document the acute onset and temporal relationship between the febrile illness and neuropsychiatric deterioration, as the hallmark of PANS/PANDAS is dramatic symptom onset or exacerbation within 24-48 hours of infection 1

Primary Treatment Strategy

If Active Streptococcal Infection is Confirmed

Initiate antibiotic therapy immediately with either penicillin or azithromycin to eradicate the triggering infection, as this represents first-line treatment for PANDAS 1. The systematic review identified antibiotics as one of the few evidence-based interventions, though the overall quality of evidence remains limited 1.

For Severe, Acute Neuropsychiatric Symptoms

Consider immunomodulatory therapy if symptoms are severe and functionally debilitating:

• Intravenous immunoglobulin (IVIG) has been studied in PANDAS and may provide benefit for acute, severe presentations 1
• Plasma exchange represents a more aggressive option for refractory cases with profound functional impairment 1
• NSAIDs or corticosteroids may be considered for anti-inflammatory effects, though evidence is limited 1

Critical caveat: The evidence base for PANS/PANDAS treatments is characterized by high risk of bias and limited rigorously conducted research 1. Treatment decisions must weigh the severity of functional impairment against the risks of immunomodulatory interventions.

Management of Behavioral Symptoms During Acute Phase

Addressing the Risperidone Response

Do not continue risperidone given the "zombie-like" sedation after a single dose 3. Children with intellectual disability and ASD are more sensitive to antipsychotic side effects and require conservative dosing 3.

If severe irritability or aggression requires pharmacologic intervention:

• Start aripiprazole at 2 mg daily (not the standard 5 mg starting dose) and titrate slowly by 2 mg every 2 weeks, as it may cause less sedation than risperidone while maintaining efficacy for irritability 3
• Target dose range is 5-15 mg daily for irritability in ASD, but this child may require lower doses given his sensitivity 3
• Monitor closely for sedation, weight gain, and metabolic effects with baseline and 3-month metabolic screening 3

Continuing Fluoxetine

Maintain fluoxetine 8 mg daily as abrupt discontinuation could worsen anxiety and obsessive symptoms 3. SSRIs like fluoxetine may help with repetitive behaviors and anxiety in ASD 4.

Addressing ADHD Symptoms

Initiate or optimize stimulant therapy for the underlying ADHD, as untreated ADHD contributes to functional impairment:

• Start methylphenidate 2.5-5 mg twice daily and titrate by 2.5-5 mg weekly based on response 5
• Methylphenidate has 49% efficacy in children with ASD versus 15.5% on placebo, though effect sizes are smaller than in typical ADHD 3
• Monitor for increased irritability or anxiety as stimulants can occasionally worsen these symptoms in ASD 5

Alternative if stimulants are not tolerated:

• Atomoxetine starting at 0.5 mg/kg/day, titrating to 1.2 mg/kg/day over 2-4 weeks, may be better tolerated in children with ASD and anxiety 5

Behavioral and Environmental Interventions

Implement intensive behavioral support immediately:

• Applied Behavior Analysis (ABA) with differential reinforcement strategies should be intensified, as medication facilitates but does not replace behavioral intervention 3
• Parent training in behavioral management is moderately more efficacious when combined with medication than medication alone 3
• Occupational therapy should focus on sensory integration techniques to address the new tactile aversions and sensory sensitivities 3

Environmental modifications:

• Remove or gradually reintroduce decorations if they triggered the initial decompensation 2
• Maintain predictable routines to reduce anxiety and support re-engagement 2
• Use preferred foods and textures to prevent further nutritional decline while gradually expanding food repertoire 2

Monitoring and Follow-Up

Schedule weekly visits during the acute phase to assess:

• Neuropsychiatric symptom trajectory using standardized scales like the Aberrant Behavior Checklist 3
• Nutritional status and hydration given the severe food and fluid restriction 2
• Medication tolerability if psychotropics are initiated or adjusted 3
• Response to antibiotic or immunomodulatory therapy if PANDAS is confirmed 1

Refer to pediatric neurology or immunology if PANS/PANDAS is confirmed or if symptoms do not improve with initial interventions, as specialized expertise is needed for complex autoimmune neuropsychiatric disorders 1.

Critical Pitfalls to Avoid

• Do not attribute all regression to ASD progression when acute onset following infection suggests PANS/PANDAS 1
• Do not use standard antipsychotic dosing in children with ASD and intellectual disability who are more sensitive to side effects 3
• Do not delay antibiotic treatment if streptococcal infection is documented, as early treatment may prevent further neuropsychiatric deterioration 1
• Do not rely solely on medication without intensive behavioral intervention, as combined treatment is superior to medication alone 3
• Do not ignore nutritional decline as severe food restriction can cause medical complications requiring urgent intervention 2