Tonsillitis? With you in a tic… Neuropsychiatric Sequelae of Group A Streptococcal Infection

Author: Frances Copp / Editor: Liz Herrieven / Reviewer: Katie Gaskell / Codes: / Published: 09/03/2021 / Reviewed: 28/04/2026

With potential to wreak systemic havoc for years following initial infection, Group A beta-haemolytic Streptococcus pyogenes (or, far more conveniently, GAS) is an organism 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 thought to be 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, thought to be 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:

It is thought that resultant characteristics are due to 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 Sydenhams 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 of acute neuropsychological issues may be difficult to discern, ranging from a mild change in behaviour (theyre 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.

Figure 4: Red Flag symptoms/signs suggestive of alternative diagnosis

Other possible organic or psychosocial causes must be considered see below for red flag symptoms suggesting a non-PANDAS 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.

Figure 5: Differentials taken from UK guidelines PANS/PANDAS. NOTE: ordered into groups of presentation to aid recall – there may be significant overlap as well as causation between conditions and their presentation.

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 or caregivers. Family may also have video clips, if asked, from before and after changes in behaviour which can be helpful.

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 or guardian, sensitivity and discretion is paramount. As much as possible, talking to both parents or guardian and child separately can give additional information.

In the past: playing infection detection

When no clinical documentation or microbiology reports are available to help identify a possible infectious trigger, ask about the common causes in the history (see Figure 6).This might be easier said than done, as the causative infection might be up to 6 months prior.

Figure 6: Pathogenesis of Streptococcus pyogenes infections

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. With younger children catching an average of 6 to 10 infections each year, there may also be several red herrings in your net!

Remember, also, the possibility of a later immune-mediated complication cannot be ruled out by lack of corresponding acute infective episode in the history alone.

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 and, even with the diagnostic criteria, specialist input will likely be needed to confirm the diagnosis. 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 come back.

In terms of exclusion of conditions requiring immediate management, inflammatory markers, U&Es and, if any red flag symptoms, urgent neuroimaging might be considered. Investigations for other differentials can probably be carried out a little later, although if taking blood in ED its worth liaising with the paediatric team to avoid the child having to be re-bled later possible investigations are listed in Figure 7.

Figure 7 – Suggested investigations

Although it is unusual for several systemic non-suppurative complications to present together, 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.

Treatment

Treatment in cases of PANS or PANDAS has two aspects to its approach. One is to target the most impairing neuropsychiatric symptoms and the other is to address the underlying infection.

Psychiatric interventions for obsessive-compulsive symptoms include CBT and educational and supportive therapies for symptoms which are causing mild impairment. For those which are moderate to severe, referral to a paediatric mental health team may be required and pharmacological treatment may be considered in addition to psychological therapies.

The decision to treat with i should be based on local GAS guidelines or, for an alternative identified or strongly suspected bacterial infective source, based on usual regional guidelines.

Paediatric team referral is essential for ongoing follow-up (usually outpatient is sufficient, unless there are any concerning features), and multidisciplinary management is likely to be needed with mental health input, and 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.

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

PANDAS and PANS are 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, 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 later immune-mediated consequences remains low even without acute antibiotic coverage, and it remains unclear whether antibiotics specifically reduce the 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

As a final note, it is worth remembering that diagnosis of PANDAS or PANS may not be a straightforward process. The acute presentation of sometimes extremely bizarre symptoms in a previously normally developing child can be a source of great anxiety and the disease course may follow a relapsing and remitting trajectory. 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 Childrens ehospital, Nov 2018

Further reading:

  1. Pfeiffer HCV, et al. Clinical guidance for diagnosis and management of suspected Pediatric Acute-onset Neuropsychiatric Syndrome in the Nordic countries. Acta Paediatr. 2021 Dec;110(12):3153-3160.
  2. Frankovich J, Xie Y. Paediatric acute-onset neuropsychiatric syndrome. BMJ Best Practice. 2023.
  3. Consensus statement on childhood neuropsychiatric presentations, with a focus on PANDAS/ PANS. British Paediatric Neurology Association. 2023
  4. Thienemann M, et al. Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part I-Psychiatric and Behavioral Interventions. J Child Adolesc Psychopharmacol. 2017 Sep;27(7):566-573.
  5. Frankovich J, et al. Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part II-Use of Immunomodulatory Therapies. J Child Adolesc Psychopharmacol. 2017 Sep;27(7):574-593.
  6. Cooperstock MS, Swedo SE, Pasternack MS, Murphy TK. Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part III-Treatment and Prevention of Infections. J Child Adolesc Psychopharmacol. 2017 Sep;27(7):594-606.

Further discussion regarding antibiotics in sore throats:

Figures

(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) & (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 Patterson MJ. Streptococcus. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 13.

(7) Suggested investigations:

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