PANDAS stands for “Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus.” First identified in 1998, it is a type of autoimmune-mediated Obsessive-Compulsive Disorder and/or Tic Disorder that can occur in children (age 3 through puberty) following the body’s response to a Group A Beta-Hemolytic Streptococcus (GABHS) infection [12]. 

PANDAS is thought to be caused by the body’s immune reaction to streptococcus, not the bacteria itself. Dr. Susan Swedo of the National Institute of Mental Health (NIMH) set forth five diagnostic criteria that must be met for the diagnosis of PANDAS:

1. Meets diagnostic criteria for OCD and/or Tic Disorder
2. Onset occurs before puberty
3. Symptoms are episodic (relapsing-remitting)
4. There is a temporal association between GABHS infection and the acute development or significant worsening of symptoms
5. Association with other neurological abnormalities (motor hyperactivity, choreiform movements, behavioral changes, etc.)

[1, 12].

Of note, there is no complete consensus as to what constitutes “temporal association.” However, it is widely accepted that the syndrome must occur following or during a GABHS infection, yet the exact timing of symptom development following GABHS is somewhat up to judgment. 

The astute clinician should evaluate how closely the onset of symptoms follows the GABHS infection. It is also important to consider other risk factors or possible causes that may better explain the patient’s symptoms. If the symptoms appear long after the GABHS infection has resolved, there is a much greater chance that the symptoms are not actually due to PANDAS.

Following the introduction of the PANDAS diagnosis, researchers began to study the condition, observing many different neuropsychiatric phenomena affecting children following infections due to similar autoimmune responses to these infections. In 2012, researchers broadened the PANDAS diagnosis to PANS, which stands for “Pediatric Acute-Onset Neuropsychiatric Disorder,” for which PANDAS still remains a subtype of [2, 14]. According to the NIMH, to receive a diagnosis of PANS, one must meet several criteria:

1. Abrupt, dramatic onset of OCD and/or food restriction
2. Concurrent presence of additional neuropsychiatric symptoms, with similarly severe and acute onset from at least two of the following categories:
   1. Anxiety
   2. Emotional lability (extreme mood swings) and/or depression
   3. Irritability, aggression, and/or severely oppositional behaviors
   4. Behavioral regression (e.g., baby talk, temper tantrums, etc.)
   5. Deterioration in school performance
   6. Sensory or motor abnormalities (e.g., changes in handwriting)
   7. Somatic signs and symptoms, including sleep disturbances, bedwetting, or urinary frequency
   8. Symptoms are not better explained by a known neurologic or medical disorder, such as Sydenham chorea, systemic lupus erythematosus, Tourette disorder, or others
3. Symptoms are not better explained by a known neurologic or medical disorder, such as Sydenham chorea, systemic lupus erythematosus, Tourette disorder, or others

[1, 2, 14].

Like PANDAS, PANS is believed to be triggered by an autoimmune reaction following an infection. It has been seen following Epstein-Barr Virus, Mycoplasma pneumoniae, Borrelia burgdorferi, and influenza infections [2].  

If a prepubescent patient suddenly shows a dramatic change in behavior that is very different from their usual behavior, you should pay close attention. These changes might include things like increased anxiety, obsessive-compulsive behaviors, new motor symptoms (such as tics or changes in handwriting), acting younger than their age, doing worse in school, or losing control of their bladder during the day or night. If these symptoms can’t be better explained by another cause, or if earlier mild signs were missed and have now gotten worse, it is reasonable to consider PANS or PANDAS as a possible diagnosis. In that case, you should check if the patient meets the clinical criteria. 

Patients who meet clinical criteria for PANDAS/PANS and have current symptoms of streptococcal pharyngitis should be tested for Strep throat via rapid antigen test, nucleic acid amplification test, or throat culture. Streptococcal antibody testing is not recommended due to poor sensitivity and specificity for active infection. If there are active signs and symptoms of a streptococcal infection, one should treat the strep infection with antibiotics. Antibiotic management is only effective in the acute phase of PANS/PANDAS when youth meet criteria; there is no support for antibiotics for asymptomatic ASO titer elevation and no value in antibiotic management for patients with chronic symptoms of PANS/PANDAS [1].

The American Academy of Pediatrics recommends against work-up for other infectious causes of PANS, including but not limited to: Mycoplasma PCR, Antinuclear antibody test, Cunningham Panel, Lyme serologies, EBV antibodies, or other infectious agents [1].

The PANS/PANDAS Research Consortium categorizes the treatment of PANDAS/PANS into three buckets: antimicrobial, immunomodulatory, and psychotherapeutic.

There is no consensus amongst the scientific community as to whether antibiotic treatment, NSAIDs, corticosteroids, IVIG, plasmapheresis, tonsillectomy/adenoidectomy, SSRIs, or other psychotropic medications are helpful for PANDAS/PANS. The existing trials suffer from poor randomization, blinding, small sample sizes, heterogeneous dosing/timing strategies, and mixed results in efficacy, making it difficult to draw any conclusions [6, 11]. While a number of case reports exist suggesting improvements with these different treatments, the episodic nature of PANDAS/PANS makes it difficult to determine the duration of benefit. Our recommendations align with those set forth by the American Academy of Pediatrics:

First-line treatment for PANDAS/PANS-related OCD is the same as for typical OCD/anxiety: Cognitive-Behavioral Therapy (CBT; more specifically, the Exposure Response Prevention subcategory) and/or an SSRI (such as sertraline or fluoxetine) [12, 15]. PANDAS/PANS-related Tic disorders are treated with CBT (specifically the Comprehensive behavioral intervention for tics subcategory). Additionally, alpha-2 agonists (guanfacine or clonidine) and antipsychotics may also be helpful for tic disorders refractory [12].

Additionally, if your patient has clinical symptoms of a streptococcal infection and a subsequent positive culture/rapid antigen test/PCR [12], it is reasonable to treat with any one of the following options:

• Amoxicillin 50 mg/kg/day (not to exceed 1000 mg/day) divided into two doses daily for 10 days
• Cephalexin 20 mg/kg/day (not to exceed 500 mg/day) divided into two doses daily for 10 days
• Azithromycin 12 mg/kg/day (not to exceed 500 mg/day) once daily for 5 days, followed by 4 days of half the initial dose 

(3).

In select cases where there is a clear case of PANS/PANDAS that is refractory to CBT and SSRI use, the use of NSAIDs and steroids may be indicated, but should be considered in concert with an interprofessional specialist team that includes pediatric neurology, child psychiatry, and other pediatric subspecialists with experience in the care of autoimmune conditions. 

We recommend against more invasive treatments such as IVIG, plasmapheresis, and tonsillectomy/adenoidectomy until further evidence is available.

There is limited data on the prognosis of PANDAS. However, the evidence that does exist suggests that most patients improve significantly within months following the prompt initiation of treatment. Of note, many children will experience a relapsing and remitting course, often occurring around subsequent strep infections [7, 8]. Evidence is lacking to consider long-term antibiotic prophylaxis in these cases due to a lack of evidence and the potential risk to the patient  [5, 11]. Furthermore, some children will develop a more chronic form of the condition similar to non-immune mediated OCD/tic disorders, which should be managed using evidence-based, standard psychotherapeutic and psychotropic approaches for those conditions [7].