Author: Frances Copp / Editor: Liz Herrieven / Codes: SaC3, SLO5 / Published: 09/03/2021

With potential to wreak systemic havoc for years following initial infection, Group A beta-haemolytic Streptococcus pyogenes (or, far more conveniently, ‘GAS’) are organisms truly worthy of our inner nerd.

Neuropsychiatric sequelae of acute infections have only been identified within the last 20-30 years, yet these post-acute disorders are estimated to affect up to 1 in 200 children.

Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS) is a subgroup of Paediatric Acute onset Neuropsychiatric Syndrome (PANS).

Picture of blue ovals joined together on a red background - streptococcus.

It’s a bit of a mouthful, but PANS encompasses a spectrum of similar acute neuropsychiatric presentations with varying severity and impact, caused by an immune-mediated response to an infection (in the case of PANDAS, GAS infection specifically) or environmental trigger – in such instances the initial causative episode may not be obvious:

Resultant characteristics arise from autoimmune mimicry, similar to that implicated in post-GAS glomerulonephritis and rheumatic carditis, where cross reactive anti-neuronal antibodies affect the neurones of the basal ganglia to produce typical symptoms of acute behavioural disturbance: acute onset obsessive compulsive disorder (OCD), and/or chorea-like movements or tics (such as those found in Sydenham’s Chorea (SC)) are common:

Here we will focus on the identification and management of PANDAS from an Emergency Department (ED) perspective, but the overarching diagnosis of PANS may be considered if there any doubt over history of GAS infection, or failure to respond to first line therapies for PANDAS.

ED clinicians will be far more accustomed to acute infective presentations, yet a parent grappling with an unexplained and acute change in behaviour or mood in their child may present in desperation: awareness and suspicion are key to diagnosis and access to definitive management.

Recent history: when to suspect

PANDAS usually presents within 3-6 months of initial acute suppurative infection in children from 3 years of age until puberty, with a male predominance. It may relapse with further episodes of acute GAS infection, and symptoms may also vary or worsen with hormonal change.

Clinical features may be difficult to discern, ranging from a mild change in behaviour (‘they’re just not themselves’) or difficulties with tasks that before posed no problem (‘their concentration seems to have suddenly changed – school-work is suffering’), to an acute onset of more obvious behavioural, emotional or movement disruption.

Whilst rheumatic carditis may manifest with Sydenham’s chorea, PANDAS has been defined as a separate entity entirely; in very rare cases, rheumatic carditis or glomerulonephritis may present in tandem with PANDAS, however presence of mitral valve involvement may be used to exclude a diagnosis of PANDAS in cases of isolated movement disorder.

Other possible organic or psychosocial causes must be considered – see below for red flag symptoms suggesting a non PANDA diagnosis. Thorough review of mental state and social circumstances are necessary in addition to medical history, with a focus on autoimmune signs and symptoms, family history and history of infection.

Mental state examination will be dependent on the age of the child: in younger children, observation of behaviour and interaction with family members will give clues, in addition to the history as reported by parents/guardians.

Older children may have insight into an increase in anxiety, anger or emotional lability, and may be concerned by any new difficulties at school or with their peers. Of particular importance are focussed questions around mood, somatic symptoms (eating, drinking, sleeping, tics etc), and any identified triggers or coping strategies.

Social history is essential: any identified stresses, changes at home/school/relationships, how is the child coping at nursery/school/home? Observe the relationship and interaction between child and parent/guardian: any concerns? Any safeguarding triggers?

Whilst it may be appropriate to discuss the psychosocial elements in the presence of an accompanying parent/guardian, sensitivity and discretion is paramount: offering a private space to talk to both parent/guardian and the child may yield additional and crucial information.

In the past: playing infection detection

When no clinical documentation or microbiology reports are available to help identify a possible infectious trigger, look for the common causes in the history (see Figure 6), tracking back through at least the last 6 months.

Whilst almost certainly the most common source, not all patients will present with the typical history of tonsillitis or pharyngitis (with positive pharyngeal GAS swab in 20% of asymptomatic and 37% of sore-throat symptomatic school aged children). Additionally, many mild infections will resolve without ever coming under the clinical radar. Note in particular any history of

  •  symptoms of upper respiratory tract infection
  • URTI where tonsils have been implicated, especially with the Scarlet Fever trio of fever, sandpaper rash (‘scarlatina’ – 98% specific) and strawberry tongue – all courtesy of release of that pesky exotoxin.
  • any documentation or parental reports of palatial petechiae: this sign has a strong correlation with GAS infection and has been considered for addition to the scoring systems used for GAS infection identification, with 95% specificity.
  • skin infections
  • episodes of spontaneously resolving fever, not requiring clinician review
  • complaints of sore throat/poor appetite or refusal of foods (particularly in younger children, or those unable to communicate symptoms other than through behaviour)
  • infective contacts (travel, school, close contacts reporting symptoms)

Remember, possibility of later immune-mediated complication cannot be ruled out by lack of corresponding acute infective episode in the history alone: the patient/parents may be unable to remember a brief and/or minimally symptomatic episode. Not all patients will have come to medical attention or have been given antibiotics.

Physical examination: what to look for and what to rule out

A full and careful systemic review is necessary – with best cajoling skills for tonsils!

Particularly take note of:

  • any signs of recent infection – symptoms of PANDAS may reactivate or worsen with a further episode of acute GAS infection
  • any new cardiac murmur, hypertension, or evidence of fluid retention – which may suggest presence of other immune-mediated complications (glomerulonephritis, or rheumatic carditis as underlying cause of chorea-like movements)
  • signs consistent with other autoimmune disease
  • jaundice, Kayser-Fleischer rings – Wilsons’ Disease is another possible differential

Investigations: where to begin?

Diagnosis of PANS or PANDAS relies on excluding other causes of the presenting symptoms. Investigations in the emergency setting can be somewhat restricted by the time frame of consultation, and difficulty reviewing results – especially those that take a few days to return from the lab.

When prioritising exclusion of any condition requiring immediate management, initial tests could be limited to baseline bloods, vitamin D, thyroid function and ASOT (Anti-Streptolysin O Titre), with response to any red flag symptoms accordingly (for example, urgent neuro-imaging).

In order to prevent further trauma in terms of unnecessary repeated blood tests, early discussion with the Paediatric team prior to bloods may guide further initial investigation and facilitate appropriate follow-up, enabling a more comprehensive panel (see figure 6) to be taken.

Whilst evidence suggests that it is unusual for several systemic non-suppurative complications to present concurrently, investigation for rheumatic fever (with cardiac imaging) and glomerulonephritis (urine, serum renal function and renal ultrasound) should also be considered if the patient presents with any systemic symptoms, or should any suspicion arise on physical examination.


If strongly suspected, with no concerning red flag symptoms and no features suggestive of another possible diagnosis, a trial of treatment may be appropriate.

Current advice in primary care is to commence immediate treatment in cases where suspicion of PANDAS is high, without waiting for results of all investigations: a 14-day course of antibiotics according to local GAS infection guidelines (whichever antibiotics are recommended for acute streptococcal pharyngitis/tonsillitis). However, from an ED perspective, this would usually be suggested and commenced following discussion and review by the Paediatric team.

Paediatric team referral is essential for ongoing follow-up (usually outpatient is sufficient, unless any concerning features), with onward referral to a Paediatric Neurologist or Immunologist for consideration of immunomodulatory therapy if there has been no improvement with the initial course of antibiotic treatment. Whilst antibiotic therapy is the accepted standard first-line, efficacy across the full range of presenting symptoms is not fully known: studies suggest it has particular use in those presenting with symptoms of OCD. Cognitive behavioural therapy is also thought to be effective in antibiotic-resistant cases of OCD.

Considerations for future practice – and a note on prescription of antibiotics in acute sore throat…

PANDAS/PANS is perhaps not the most common of Paediatric presentations, but certainly worth considering for children presenting with acute changes in behaviour, mood or movement.

When faced with the far more familiar presentation of sore throat/tonsillitis, tools such as the FeverPain and Centor scoring systems aid identification of probable GAS infection, and so help identify cases that may benefit from antibiotics.

However, the risk of developing latter immune-mediated consequences remains low even without acute antibiotic coverage, and it remains unclear whether antibiotics specifically reduce prevalence of PANDAS further.

The current vogue is turning against routine antibiotic prescription for sore throats, even in uncomplicated cases of suspected GAS. With ever-increasing antibiotic resistance, symptom reduction by 6-12 hours only, and potentially only a small decrease in risk of future sequelae with prescription of antibiotics in uncomplicated primary infection, overall benefit is questionable, and may be insufficient to justify antibiotic coverage unless GAS infection has been proven via swab.

As a final note, it is worth remembering that diagnosis of PANDAS/PANS may not be a straightforward process for the child or their family, and the acute presentation of sometimes extremely bizarre symptoms in a previously normally developing child can be a source of great anxiety in itself. As ever in Paediatrics, a holistic view of the family unit is crucial in provision of adequate support and quality care.

Further Resources:

For both clinical and patient information, up to date information may be found on the UK PANS/PANDAS website.

  • PANDAS and PANS Treatment Guidelines V1.6, Developed by the UK PANDAS/PANS physicians network, edited by Dr Tim Ubhi, Consultant Paediatrician and Clinical Director of the Children’s ehospital, Nov 2018

For further reading see:


And for further discussion regarding antibiotics in sore throats:


(1) Group A Streptococci, image reproduced with permission from the Wellcome Collection Digital Image bank,, Credit: David Goulding, Wellcome Trust Sanger Institute CC BY-NC

(2) PANS Diagnostic Criteria, taken directly from UK PANS/PANDAS Guidelines (2018)

(3) PANS Diagnostic Criteria, taken directly from UK PANS/PANDAS Guidelines (2018)

(4) Red flag symptoms/signs suggestive of alternative diagnosis

(5) Differentials: taken from UK guidelines PANS/PANDAS. NOTE: ordered into groups of presentation to aid recall – note there may be significant overlap between conditions and their presentation, and also causation

(6) Pathogenesis of Streptococcus pyogenes infections. Adapted from Baron’s Medical Microbiology Chapter 13,’Streptococcus’, by Maria Jevitz Patterson

(7) Suggested investigations

[i] Elisabetta Burchi, Stefano Pallanti, ‘Antibiotics for PANDAS? Limited Evidence: Review and Putative Mechanisms of Action’, Prim Care Companion CMS Disord 2018: 20(3): 17r02232

[ii] Eric A Storch et al, ‘Cognitive-behavioural therapy for PANDAS-related obsessive compulsive disorder: findings from a preliminary waitlist controlled open trial’ J Am Acad Child Adolesc Psychiatry 2006 Oct; 45(10):1171-8; Joshua M. Nadeau et al

[iii] Denise Calaprice et al, ‘A Survey of Pediatric Acute-Onset Neuropsychiatric Syndrome Characteristics and Course’, J Child Adolesc Psychopharmacol. 2017 Sep;27(7): 607-618

[iv] Anand Swaminathan ‘Do Patients with Strep Throat Need to be Treated with Antibiotics?’ Rebel EM blog, 2015; Jan 5

[v] Daan Van Brusselen et al, ‘Streptococcal pharyngitis in children: to treat or not to treat?’ European Journal of Pediatrics 2014; 173: 1275-1283

[i] Shaikh, N., et al, ‘ Accuracy and precision of the signs and symptoms of streptococcal pharyngitis in children: A systemic review’, J Pediatrics 2012; 160: 487-493

[ii] Kumara V. Nibhanipudi, ‘A Study to Determine if Addition of Palatial Petechiae to Centor Criteria Adds More Significance to Clinical Diagnosis of Acute Strep Pharyngitis in Children’, Global Pediatric Health 2016; 3:1-4

[iii] Shaikh, N., et al, ‘ Accuracy and precision of the signs and symptoms of streptococcal pharyngitis in children: A systemic review’, J Pediatrics 2012; 160: 487-493