BASICS
DESCRIPTION
- Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) most commonly presents as obsessive-compulsive disorder (OCD) and/or tic disorder developing abruptly or acutely worsening during or following a group A ²-hemolytic Streptococcus (GABHS) infection
- Proposed associations are GABHS pharyngitis or skin or soft tissue infection.
- Symptoms with abrupt onset (hours), peaking by 24 to 48 hours
- Symptoms include motor tics, vocal tics, obsessions and/or compulsions, anxiety attacks, separation anxiety, bed wetting, hyperactivity.
- It remains unclear if PANDAS represents a true entity distinct from similar disorders in children.
EPIDEMIOLOGY
Incidence
- Unknown, thought to be rare
- Considered a subset of pediatric acute-onset neuropsychiatric syndrome (PANS), abrupt onset of OCD, and associated symptoms not better explained by a known neuropsychiatric condition (1)[A]
- GABHS infection likely accounts for a small proportion of antecedents of exacerbations among patients meeting diagnostic criteria for PANS (1)[A].
ETIOLOGY AND PATHOPHYSIOLOGY
- Unknown, several hypotheses
- Proposed "pseudoautoimmunity. " GABHS antibodies target brain tissue (basal ganglia) possibly causing OCD, tics, and other neuropsychiatric symptoms (2)[C].
- Genetic factors (susceptible host) and environmental trigger (GABHS) (3)[B]
RISK FACTORS
- Streptococcal infection
- Tic disorder, Tourette syndrome, OCD
- More common in boys (3)[B]
- More common in children with family history of rheumatic fever (3)[B]
DIAGNOSIS
HISTORY
- PANDAS is a clinical diagnosis.
- Diagnostic criteria (2)[C],(3)[B]
- Presence of OCD or a tic disorder
- Onset between 3 years of age and the beginning of puberty
- Abrupt onset of symptoms or a course characterized by dramatic exacerbations of symptoms
- The onset or the exacerbations of symptoms is temporally related to infection with GABHS.
- Abnormal results of neurologic examination (hyperactivity, choreiform movements, and/or tics) during an exacerbation
- Diagnostic criteria are problematic (4)[A].
- PANDAS and diagnostic criteria of new-onset Tourette syndrome are similar.
- Age criteria do not fit with proposed pathophysiology (i.e., susceptible adults should bear similar risk for PANDAS with acute GABHS infection).
- Symptoms of Tourette syndrome and tic disorders characteristically wax and wane, similar to PANDAS.
- Difficult to differentiate recent acute GABHS infection and carrier state; high prevalence of both
- Abnormal neurologic findings could be explained by alternate diagnoses.
PHYSICAL EXAM
- Exam should rule out signs of acute rheumatic fever, Sydenham chorea.
- Exam may reveal signs of GABHS infection: erythematous oropharynx, tonsillar exudates, abdominal pain, perianal irritation.
- Neurologic abnormalities including motor tics, hyperactivity, chorea
DIFFERENTIAL DIAGNOSIS
- OCD
- Tourette syndrome
- Sydenham chorea
- Anxiety disorders
- Conversion disorder
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
Tests used to confirm an acute or recent diagnosis of GABHS infection:
- Rapid GABHS test
- Throat culture
- Antistreptococcal titers (antistreptolysin O, DNAse B): two separate blood tests separated by several weeks showing rising titer if symptoms have been present for over a week
Follow-Up Tests & Special Considerations
- In suspected cases without pharyngitis, consider occult GABHS infections: sinuses, anus, vagina, urethra (2)[C].
- Confirm immune dysfunction (ANA, ESR, CRP) before immunomodulatory therapy (IVIG or plasmapheresis) (2)[C].
- Refer to infectious disease or immunology specialist if immunomodulatory therapy is considered (4)[A].
TREATMENT
GENERAL MEASURES
- Antibiotics are indicated only for treatment of acute GABHS infections (2)[C],(4)[A].
- Symptomatic treatment of OCD/tics with cognitive behavioral therapy or selective serotonin reuptake inhibitors (4)[A]
- Sterilizing/replacing toothbrushes during antibiotic treatment may prevent recurrent GABHS infection (2)[C].
- Consider throat cultures on household contacts to detect GABHS carriers.
MEDICATION
First Line
- If identified, treat acute GABHS infection with penicillin (250 mg PO BID for children <27 kg or 500 mg PO BID for children and adults ≥27 kg) for 10 days or with an alternative antibiotic according to treatment guidelines (2)[C],(4)[A].
- Evidence-based medical therapy and/or psychotherapy to treat neuropsychiatric symptoms (4)[A]
Second Line
- Antibiotic prophylaxis against GABHS is not recommended (1,4)[A],(2)[C],(5)[B].
- Given the risks associated with immunomodulatory therapy (IVIG or plasmapheresis), these treatments are only appropriate in the research setting when symptoms are severe, are clearly related to an inflammatory response (elevated ESR, CRP, ANA), and meet PANDAS criteria (4)[A].
ISSUES FOR REFERRAL
- Child psychiatry for management of OCD, anxiety symptoms (4)[A]
- Child neurology for management of Sydenham chorea
- Clinical research trials for consideration of immunomodulatory therapy
- Diagnosis and treatment provided outside of academic and/or research settings is often not based on best clinical practice (1)[A].
ADDITIONAL THERAPIES
- No controlled clinical trials support the use of antibiotics without evidence of acute or recent GABHS infection (1,4)[A],(2)[C].
- Symptomatic improvement with short courses of corticosteroids may indicate a role for immunomodulatory therapy in patients with evidence of an active inflammatory response (elevated ESR, CRP, or ANA); controversial (2)[C]
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Criteria for admission are based on clinical severity.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Primary care or pediatric infectious disease for recurrent episodes of GABHS infection
- Pediatric psychiatry
- Pediatric neurology
- Children enrolled in clinical trials are followed based on established protocol.
PROGNOSIS
Unclear and likely influenced by type and severity of symptoms
REFERENCES
11 Shulman ST. Pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS): update. Curr Opin Pediatr. 2009;21(1):127 " 130.22 National Institute of Mental Health. Information about PANDAS. http://www.nimh.nih.gov/labs-at-nimh/research-areas/clinics-and-labs/pdnb/web.shtml. Accessed October 12, 2015.33 Swedo SE, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998;155(2):264 " 271.44 Kurlan R, Kaplan EL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: hypothesis or entity? Practical considerations for the clinician. Pediatrics. 2004;113(4):883 " 886.55 Kurlan R, Johnson D, Kaplan EL. Streptococcal infection and exacerbations of childhood tics and obsessive-compulsive symptoms: a prospective blinded cohort study. Pediatrics. 2008;121(6):1188 " 1197.
ADDITIONAL READING
- Red Book Online. Group A streptococcal infections. http://redbook.solutions.aap.org/chapter.aspx?sectionId=88187242&bookId=1484&resultClick=1#91040537. Accessed October 20, 2015.
- Swedo SE, Leonard HL, Rapoport JL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) subgroup: separating fact from fiction. Pediatrics. 2004;113(4):907 " 911.
CODES
ICD10
- B95.0 Streptococcus, group A, causing diseases classd elswhr
- D89.89 Other specified disorders involving the immune mechanism, not elsewhere classified
- F95.9 Tic disorder, unspecified
- F42 Obsessive-compulsive disorder
ICD9
- 041.02 Streptococcus infection in conditions classified elsewhere and of unspecified site, streptococcus, group B
- 279.49 Autoimmune disease, not elsewhere classified
- 307.20 Tic disorder, unspecified
- 300.3 Obsessive-compulsive disorders
SNOMED
Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (disorder)
CLINICAL PEARLS
- Consider testing for acute GABHS infection in children with abrupt onset of OCD symptoms or tics.
- Prophylactic antibiotics and/or immunomodulatory therapy to treat PANDAS is not recommended outside of the academic or research setting.