What are PANS and PANDAS? Origins, Clinical Diagnosis and Treatment

At Sky Psychiatry. we have heard frequent questions from clinicians, patients and parents about the role of infectious diseases in mental health symptoms. I aim to give you a better understanding of these disorders which you may have heard of as well.

In 1998, Dr. Susan Swedo and colleagues at the National Institute of Mental Health (NIMH) published the first historical description of the disorder called PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection).

This characterization arose from an initial broader series of clinical cases in which OCD symptoms were thought to be related to Sydenham’s Chorea with respect to etiologic/causative agents. These cases were preceded by a bacterial or viral infection (such as influenza, varicella and Group A streptococcal pharyngitis). This initial, broader series was described as "Pediatric Infection-Triggered Autoimmune Neuropsychiatric Disorder (PITAND).” The cases associated with the onset of OCD symptoms following Group A Streptococcal infection became the specific case-series for which the term PANDAS was identified.

The PANDAS diagnostic criteria include the presence of OCD or tic disorder, prepubertal onset of symptoms, acute symptom onset and episodic course of symptoms, temporal association between Group A streptococcal infection and symptom onset/exacerbations and association with neurological abnormalities such as motoric hyperactivity and choreiform movements.

One of the clinical challenges in connecting Group A streptococcal infection with the onset of PANDAS is that the initial streptococcal infection may have occurred months prior to the onset of symptoms in which case laboratory testing for active bacterial infection and antibody titers would not be as helpful. Since Group A streptococcal infections are quite a common finding among school-age children, the converse is also a clinical challenge when positive cultures and high antibody titers may be wholly unrelated to the symptoms of neuropsychiatric illness.

There has also been difficulty in making a distinction between the acute onset pattern of tics in the PANDAS subgroup versus the “non-PANDAS” subgroup of tic disorders.

Key patterns to consider include "acute and dramatic symptom onset."

PANDAS criteria modifications to exclude a requirement for specific etiologic factors and to clarify the initial clinical presentation, provide a basis for the diagnostic criteria of PANS.

Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is broader in its characterization than PANDAS such that it includes post-pubertal onset of symptoms and also includes disorders without an apparent environmental precipitant or without immune dysfunction.

PANS criteria include the "abrupt, dramatic onset of obsessive-compulsive disorder or severely restricted food intake." An additional criterion for patients is the "concurrent presence of at least two additional neuropsychiatric symptoms with similarly severe and acute onset."

These additional symptoms may include anxiety; emotional lability and depression; aggression, irritability and oppositional behaviours; behavioural (developmental) regression; sudden deterioration school performance or learning abilities; sensory and motor abnormalities; or somatic signs and symptoms.

The symptoms of PANS are not better explained by a known neurologic or medical disorder such as Sydenham’s Chorea, Systemic Lupus Erythematosus or Tourette’s Disorder.

Does the presence of OCD symptoms or tics with a history of prior Group A streptococcal infection mean that the diagnosis of PANDAS should be made?

Streptococcal infections are common among children of school-going age and may simply be coincidental to the subsequent occurrence of OCD symptoms or tics. Specific PANDAS criteria should be considered in the diagnosis of PANDAS.  

What are some relevant evaluations/laboratory investigations in PANS/PANDAS?

Testing for streptococcal infection with a rapid test and culture of a throat swab is recommended.

In addition, a rising titer of a specific form of antibody known as Anti-Streptolysin O (ASO) between the first 1-2 weeks post-infection and 4-8 weeks after infection indicates support for a streptococcal trigger for clinical symptoms. A single ASO tier is of limited benefit.

Other investigations may be clinically indicated for specific symptoms concerns and to rule out other possible immune-mediated illness such as Lyme disease, Systemic Lupus Erythematosus, Sydenham’s Chorea and Celiac Disease

Is there a role for Penicillin or other antibiotics in PANS/PANDAS treatment?

PANDAS is thought to be caused by an auto-immune response (development of autoantibodies in response to a streptococcal infection).

Penicillin treats active streptococcal infection but does not directly reduce the levels of the auto-immune response.

There is no clear evidence supporting the role of penicillin in the absence of active streptococcal infection.

What are PANS/PANDAS treatment modalities?

Mainstays of treatment include the use of symptom-specific medications and psychotherapies targeting OCD symptoms (SSRI-type of medications, CBT) and/or tics (Alpha-agonists, anti-dopaminergic medications, dopamine modulating agents, Habit Reversal Training).

In moderate/severe illness, there may be justification for a role of brief NSAID (non-steroidal anti-inflammatory drugs) and/or corticosteroid (to reduce the auto-immune response) treatment, the use of intravenous immunoglobulin (IVIG, by providing anti-idiotypic antibodies to absorb and reduce the auto-immune response) and/or plasmapheresis (to reduce the auto-immune response by eliminating the autoantibodies).

Although the treatment modalities mentioned above have been thought to have been associated with clinical benefit in PANS/PANDAS, a recent systematic review study examined the impact of anti-inflammatory, antibacterial and immunomodulatory treatment in children with PANS. The study outcomes indicated no clear evidence of benefit of these modalities.

What is the prognosis for PANS/PANDAS?

There have been limited longitudinal follow-up studies of these PANS/PANDAS patient cohorts, In one such study, a majority of patients who have achieved improvement of symptoms with treatment have had a relapsing pattern of symptom occurrence and full remission has been rare.

-       Dr. Waqar Waheed, Editor, The Sky Room blog