Overview
Definition:
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a hypothesized condition characterized by a sudden, dramatic onset of obsessive-compulsive disorder (OCD) or tic disorders, often preceded by a streptococcal infection
The underlying mechanism is proposed to involve an autoimmune response where antibodies produced against streptococcal antigens cross-react with basal ganglia neurons, leading to neuropsychiatric symptoms.
Epidemiology:
The prevalence and incidence of PANDAS are subjects of ongoing debate and research, with estimates varying widely
Some studies suggest it may account for a significant proportion of childhood-onset OCD and tic disorders, while others posit a much lower prevalence
It is thought to affect children and adolescents, typically between the ages of 3 and 12 years, with a slight female predilection
The exact etiological role of Group A Streptococcus (GAS) and other potential triggers is still being investigated.
Clinical Significance:
Understanding the controversies surrounding PANDAS diagnosis is critical for pediatricians and residents preparing for DNB and NEET SS examinations
Misdiagnosis can lead to inappropriate treatments, including unnecessary antibiotic courses with associated risks of resistance and side effects
Conversely, timely and accurate identification, when applicable, can guide appropriate management and reduce patient and family distress
The concept of PANDAS highlights the complex interplay between infection, autoimmunity, and neuropsychiatric manifestations in children.
Diagnostic Controversies
Nosological Status:
The primary controversy lies in PANDAS's status as a distinct diagnostic entity
Unlike well-established autoimmune neurological disorders, robust, universally accepted biomarkers or diagnostic criteria are lacking
This makes it challenging to differentiate PANDAS from other pediatric neuropsychiatric disorders with similar presentations.
Causality Vs Correlation:
Establishing a definitive causal link between streptococcal infection and symptom onset is difficult
While temporal association is observed, it's unclear if the infection is a direct trigger, a co-factor, or merely coincidental
The concept of "pediatric acute-onset neuropsychiatric syndrome" (PANS) has emerged as a broader term, encompassing PANDAS but also other potential infectious or inflammatory triggers.
Diagnostic Criteria Evolution:
The original PANDAS criteria proposed by the NIMH required symptom onset between ages 4-18, presence of OCD/tic disorder, sudden symptom onset/exacerbations, association with GAS infection (e.g., positive throat culture, elevated ASO titer), and neurological abnormalities (e.g., hyperactivity, motor disincoordination)
However, these criteria have been revised and debated due to their sensitivity and specificity
Current thinking favors a more nuanced approach, considering a constellation of factors rather than strict adherence to rigid criteria.
Biomarker Research:
The lack of a specific diagnostic biomarker (e.g., a pathognomonic antibody or inflammatory marker) is a major hurdle
Research is ongoing to identify reliable immunological or neurological markers that can differentiate PANDAS from other conditions
Current serological tests (ASO, anti-DNase B) indicate past or current streptococcal infection but do not confirm an autoimmune process targeting the brain.
Clinical Presentation
Symptoms:
Sudden onset of obsessive-compulsive behaviors
Sudden onset or worsening of motor and/or vocal tics
Abrupt emotional lability, including irritability, aggression, or anxiety
Regression in developmental skills, such as handwriting or mathematical abilities
Behavioral changes including defiance, mood swings, and sleep disturbances
Sensory sensitivities and food aversion can also occur.
Signs:
Inability to elicit a history of preceding Group A Streptococcus infection is common
Presence of choreiform movements or dysgraphia
Impaired motor coordination
Increased aggression or emotional volatility
Anxiety and panic attacks
Significant distress related to obsessions or compulsions
May exhibit normal neurological examination otherwise, or subtle findings.
Diagnostic Criteria Guidelines:
The clinical diagnosis of PANDAS remains largely based on a pattern of symptoms and exclusion
The modified PANDAS/PANS criteria suggest consideration if a child presents with a sudden onset of neuropsychiatric symptoms (OCD, eating disorders, emotional dysregulation) and/or neurological abnormalities, particularly if there is a history of acute onset or dramatic exacerbation
While not a formal diagnostic criterion, a documented preceding GAS infection and evidence of autoimmune process are supportive
The PANS/PANS Working Group emphasizes ruling out other causes and observing a temporal relationship between trigger and symptom onset.
Diagnostic Approach
History Taking:
Detailed history of symptom onset and evolution is paramount
Specifically inquire about the timing of neuropsychiatric symptoms relative to documented or suspected infections, especially Group A Streptococcus
Ascertain previous episodes of pharyngitis, scarlet fever, or peritonsillar abscess
Document prior diagnoses of OCD, tic disorders, or other psychiatric conditions
Assess family history of autoimmune disorders, rheumatic fever, or neuropsychiatric conditions
Inquire about behavioral changes, developmental regressions, and sleep disturbances.
Physical Examination:
A thorough general and neurological examination is essential to rule out other conditions
Look for signs of current or recent streptococcal infection (e.g., pharyngeal erythema, exudates, rash of scarlet fever)
Assess for choreiform movements, tics, gait abnormalities, and dysgraphia
Evaluate for signs of other systemic autoimmune diseases
A complete psychiatric assessment should be performed by a qualified professional.
Investigations:
Throat swab for rapid antigen detection or culture to confirm GAS infection
Serological tests for streptococcal antibodies, including Anti-Streptolysin O (ASO) titer and Anti-DNase B titer, can indicate a recent or past infection, but elevated titers alone do not confirm PANDAS
Normal or low titers do not rule out PANS
Other autoimmune markers (e.g., ANA, ESR, CRP) may be helpful to assess for underlying autoimmune conditions
Neuroimaging (MRI brain) is generally not diagnostic for PANDAS but can rule out structural lesions
EEG may be considered if seizures are suspected.
Differential Diagnosis:
Tourette Syndrome, Obsessive-Compulsive Disorder (OCD) not associated with GAS, Sydenham's Chorea (rheumatic chorea), other PANS subtypes with different triggers, PANDAS mimicking conditions like Pervasive Developmental Disorder (PDD), Attention Deficit Hyperactivity Disorder (ADHD), Anxiety Disorders, Bipolar Disorder, Schizophrenia, and other autoimmune encephalopathies
It is crucial to differentiate from primary psychiatric disorders and other neurological conditions.
Management And Antibiotic Stewardship
Acute Infection Management:
If Group A Streptococcus infection is confirmed, prompt and appropriate antibiotic treatment is indicated to eradicate the infection and prevent complications like rheumatic fever
Penicillin V or amoxicillin are first-line treatments for pharyngitis
For penicillin-allergic patients, alternatives include cephalosporins, clindamycin, or azithromycin
Treatment duration typically follows standard guidelines for streptococcal pharyngitis.
Antibiotic Stewardship Principles:
The use of antibiotics specifically for PANDAS is controversial and not universally recommended
Long-term or prophylactic antibiotic therapy for presumed PANDAS is not supported by robust evidence and carries significant risks, including antibiotic resistance, Clostridioides difficile infection, and disruption of the gut microbiome
Antibiotic stewardship emphasizes judicious use of antibiotics only when clearly indicated for an active bacterial infection
Prophylactic use should be avoided unless there is a clear and compelling indication based on established guidelines (e.g., recurrent rheumatic fever prevention).
Immunomodulatory Therapies:
For patients with severe or refractory symptoms who meet PANDAS/PANS criteria and have evidence suggestive of an autoimmune component, immunomodulatory therapies may be considered
These can include intravenous immunoglobulin (IVIG) or plasmapheresis
These treatments are often reserved for severe cases and should be managed by specialists, with careful consideration of risks and benefits
Steroids are also sometimes used
Non-pharmacological therapies such as cognitive behavioral therapy (CBT) for OCD and tic management strategies are crucial adjuncts.
Supportive Care:
Psychosocial support for the child and family is vital
Education about the condition and management strategies can reduce anxiety
Behavioral interventions, psychotherapy, and school support are essential components of care
Regular follow-up with pediatricians, neurologists, and psychiatrists is recommended to monitor symptom progression and treatment response.
Prognosis
Factors Affecting Prognosis:
Prognosis is variable and depends on several factors, including the severity of initial symptoms, the timeliness and appropriateness of treatment (both for infection and neuropsychiatric symptoms), and the presence of any underlying autoimmune predisposition
Early intervention and comprehensive management, addressing both infectious and neuropsychiatric aspects, generally lead to better outcomes.
Outcomes:
Many children with PANDAS-like symptoms experience resolution or significant improvement with appropriate management
Some may have relapsing-remitting courses, with symptom exacerbations triggered by subsequent infections
A subset of individuals may continue to experience chronic OCD, tic disorders, or other neuropsychiatric sequelae, necessitating ongoing long-term management
The long-term impact on cognitive and emotional development is an area of ongoing research.
Follow Up:
Long-term follow-up is essential for children with suspected PANDAS
This includes monitoring for recurrent infections, continued assessment of neuropsychiatric symptoms, and ongoing management of any chronic conditions
Regular check-ups with primary care physicians, pediatric neurologists, and child psychiatrists are recommended
Emphasis should be placed on appropriate antibiotic prescribing practices to prevent the development of resistance.
Key Points
Exam Focus:
Understand the diagnostic controversies surrounding PANDAS, including the lack of definitive biomarkers and evolving diagnostic criteria
Differentiate PANDAS from PANS
Recognize the importance of antibiotic stewardship, avoiding prophylactic antibiotic use for PANDAS without clear evidence
Know the first-line antibiotics for GAS pharyngitis and indications for alternative agents.
Clinical Pearls:
Always obtain a detailed history of symptom onset relative to infections
Remember that elevated ASO/anti-DNase B titers indicate past GAS infection, not necessarily PANDAS
Consider PANS as a broader diagnostic umbrella
Prioritize evidence-based treatments and avoid unnecessary or prolonged antibiotic use
Collaborate with specialists (neurology, psychiatry) for comprehensive management.
Common Mistakes:
Diagnosing PANDAS solely based on elevated streptococcal antibody titers without considering the full clinical picture and other differential diagnoses
Prescribing long-term antibiotics for presumed PANDAS without a clear indication for active infection, thereby contributing to antibiotic resistance
Failing to consider alternative neuropsychiatric conditions that mimic PANDAS
Inadequate psychiatric or behavioral assessment and management.