PANS and PANDAS: Diagnosis and Treatment

Medscape

17-07-2025

While anxiety symptoms are common in prepubertal children, they occasionally present suddenly and with a high degree of severity. In these circumstances, parents may turn to you, the pediatrician, to address the possibility that these syndromes are autoimmune, under the diagnostic umbrellas of pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). While the clinical community continues to debate many aspects of these diagnoses, families may seek treatment based on their own online research. Your understanding of what is known about the prevalence and assessment of immune-related neuropsychiatric disorders will help you to provide these patients and their families with meaningful support and responsible guidance for the management of these syndromes.
Prevalence and Controversy
Susan D. Swick, MD
In 1989, researchers studying Sydenham chorea noted a high prevalence of obsessive thoughts and compulsive behaviors in children with rheumatic fever without chorea. Susan Swedo, MD, and colleagues at the National Institutes of Health eventually characterized this syndrome as PANDAS, occurring in 50 children who developed acute-onset obsessive compulsive disorder (OCD), anxiety, or tics with a preceding or concurrent group A streptococcal (GAS) infection.
In 2012, PANS or childhood acute-onset neuropsychiatric syndrome was proposed to broaden the criteria to include similar abrupt-onset psychiatric symptoms (OCD and restricted eating) with inciting events other than GAS infection, including mycoplasma, influenza, Lyme disease, or even psychosocial stressors.
Reliable prevalence estimates remain elusive, largely because of small numbers, diagnostic uncertainty, and lack of consensus criteria to be applied across studies. In the original studies, the mean age of onset was 6.3 years for tics and 7.4 years for OCD symptoms. The ratio of males to females was 4.7 to 1 under the age of 8 years. In one prospective study, only 10 cases were identified among 30,000 participants with throat cultures that were positive for GAS. The broader category of PANS has proven even more difficult to quantify, given its heterogeneous triggers. The high rate of GAS exposure and anxiety disorders in prepubertal children make the establishment of a causal link very difficult.
Michael S. Jellinek, MD
This has led to significant controversy over the diagnosis and treatment of PANDAS and PANS. While there is research interest in the role of the immune system in some psychiatric illnesses, neither diagnosis is listed in the DSM-V or the ICD-10. Nonetheless, there are parents who will come to you with questions about PANS and some small number of children each year who will develop it. Helpfully, the American Academy of Pediatrics (AAP) published a clinical report on PANS (encompassing PANDAS) in March 2025 to provide guidance. Our aim is to review the current guidance and help you use your best clinical judgment to treat all children thoughtfully and responsibly.
Clinical Presentation and Assessment
The hallmark symptom of PANDAS and PANS is the sudden, dramatic onset of symptoms of OCD, severely restricted food intake, or tic disorder, often appearing literally overnight in a prepubertal child. There are typically multiple severe symptoms starting abruptly together, like an 'explosion.' PANS diagnosis requires concurrent abrupt onset of additional severe neuropsychiatric symptoms in at least two of the following areas: anxiety, emotional lability or depression, irritability or aggression, developmental regression, deterioration in school performance, sensory or motor abnormalities, or somatic signs (sleep disturbances, enuresis, or urinary frequency). When any syndrome is sudden and severe, it is normal for parents to be very concerned and distressed. Express understanding and validation as you begin your assessment, which should include:
Clinical History: Timing of symptom onset (Was it abrupt and severe? Did it reach a crescendo in 24-48 hours?)
Assessment for signs of Sydenham chorea, Tourette, encephalitis, and anorexia nervosa
History of developmental or psychiatric disorders
Any recent illnesses, particularly GAS pharyngitis (documented via throat culture) Physical and Neurological Exam: To rule out signs of infection, systemic illness, or neurologic disease
Motor examination, with attention to choreiform movements Laboratory Workup: Throat culture or rapid strep with symptomatic pharyngitis (although a negative rapid test may be inaccurate)
Routine screening for GAS, antistreptolysin O, and anti-DNase B titers are not recommended by the AAP
When the neurological examination is suggestive, lumbar puncture or MRI may be warranted to assess CNS inflammation
If there is no evidence of GAS infection, PANDAS is unlikely. In general, the onset of OCD (and other anxiety disorders) is usually gradual and persistent, although children may internalize and hide symptoms until they no longer can. Tic disorders usually begin with isolated, intermittent motor or vocal tics, not an 'explosion.' The presence of cognitive decline, psychosis, catatonia, new seizures, or movement disorders other than tics should lead to an expanded and thorough neurological workup, including for autoimmune encephalitis. The AAP specifies that further laboratory testing and imaging have no evidence to support their use in the workup for PANS.
Management Strategies
If your assessment suggests PANS, how do you begin treatment? Explain to the family that treatment will address any confirmed infection, psychiatric symptoms, and inflammation. While some children may improve with antibiotics alone (symptoms may resolve fully within several weeks), most children will require treatment of persistent psychiatric symptoms even when all signs of GAS infection have resolved. Treatment typically involves three concurrent pathways:
1. Medical Management of Infection and Inflammation: Start with treatment of the GAS infection, if there is one.
Antibiotics: The AAP recommends a standard (10-day) course with appropriate antibiotics for a positive culture in a symptomatic child. The AAP does not recommend prophylactic or long-term use of antibiotics, or treatment of asymptomatic positive culture (colonization). Some children's neuropsychiatric symptoms respond to antibiotics; others do not.
The AAP recommends a standard (10-day) course with appropriate antibiotics for a positive culture in a symptomatic child. The AAP does not recommend prophylactic or long-term use of antibiotics, or treatment of asymptomatic positive culture (colonization). Some children's neuropsychiatric symptoms respond to antibiotics; others do not. Anti-inflammatory Treatment: The AAP does not recommend NSAIDS or more aggressive anti-inflammatories, given the absence of evidence and considerable side effects.
The AAP does not recommend NSAIDS or more aggressive anti-inflammatories, given the absence of evidence and considerable side effects. Immune Modulation: Invasive therapies like intravenous immunoglobulin or plasmapheresis have no evidence to support their use in PANS. Patients with severe, persistent neuropsychiatric symptoms should have an expanded neurological and rheumatologic assessment before any consideration of these treatments.
2. Psychiatric Symptom Management: An infection may have caused the psychiatric symptoms or simply exacerbated or unmasked an underlying illness that will require independent treatment.
OCD: Cognitive behavioral therapy (CBT) — specifically, exposure and response prevention (ERP) — is the gold standard for managing OCD symptoms, regardless of etiology. Selective serotonin reuptake inhibitors (SSRIs) are similarly effective and the combination of the two has demonstrated superior efficacy to either treatment alone. Each treatment may take 12 weeks or more to be effective. ERP may be difficult to access. SSRIs should be started at low doses and titrated gradually as they may cause temporary activation if started at too high a dose. They are not contraindicated in OCD, anxiety disorders, or PANS, and parents should be offered education to prevent any concern about these effective treatments.
Cognitive behavioral therapy (CBT) — specifically, exposure and response prevention (ERP) — is the gold standard for managing OCD symptoms, regardless of etiology. Selective serotonin reuptake inhibitors (SSRIs) are similarly effective and the combination of the two has demonstrated superior efficacy to either treatment alone. Each treatment may take 12 weeks or more to be effective. ERP may be difficult to access. SSRIs should be started at low doses and titrated gradually as they may cause temporary activation if started at too high a dose. They are not contraindicated in OCD, anxiety disorders, or PANS, and parents should be offered education to prevent any concern about these effective treatments. Tics: Tics are only treated when they interfere with a child's function or lead to significant embarrassment or bullying. A behavioral psychotherapy (comprehensive behavioral intervention for tics, CBIT) has demonstrated efficacy. Medications (alpha-2 agonists) have modest efficacy and can be used in more severe cases.
Tics are only treated when they interfere with a child's function or lead to significant embarrassment or bullying. A behavioral psychotherapy (comprehensive behavioral intervention for tics, CBIT) has demonstrated efficacy. Medications (alpha-2 agonists) have modest efficacy and can be used in more severe cases. Food Restriction ( Avoidant/Restrictive Food Intake Disorder, ARFID): Almost all children with ARFID and PANS also have underlying OCD. Treatment starts with a medical assessment of nutritional and hydration status and weight restoration and correction of electrolyte abnormalities, if needed. Then CBT (ERP again) is the effective treatment for the avoidant behaviors around food. This is a specialized treatment that requires a clinician who has training in CBT and experience working with ARFID specifically.
Avoidant/Restrictive Food Intake Disorder, Almost all children with ARFID and PANS also have underlying OCD. Treatment starts with a medical assessment of nutritional and hydration status and weight restoration and correction of electrolyte abnormalities, if needed. Then CBT (ERP again) is the effective treatment for the avoidant behaviors around food. This is a specialized treatment that requires a clinician who has training in CBT and experience working with ARFID specifically. Additional Symptoms: Sleep disturbances and separation anxiety both can be addressed with CBT, with an additional component of parental skill building to complement and support the child's work.
3. Family Support: The sudden, severe onset of disruptive behavioral symptoms is bound to be very distressing for your patient and particularly for their parents, whatever the cause.
Families of children with severe, sudden psychiatric symptoms experience significant stress and distress. If they suspect it might be caused by a current or recent infection, it is important that their pediatrician is genuinely curious about their observations and concerns. Some families may think they have been treated dismissively when they are told that there is 'no evidence' to support their observations. Remember, they are the experts on their children. When they have experienced your genuine curiosity and respect, it will be easier for them to trust your judgment should you conclude that their child may need treatment beyond antibiotics. Support, reassurance, and education are vital. Build a team with a psychiatrist and psychotherapist and engage the school to provide accommodations during treatment (eg, reduced workload and support for attention deficits or anxiety).
The Pediatrician is Critical
Pediatricians are the first point of contact when children present with symptoms that suggest PANS. Your responsiveness, targeted workup, and collaborative management are critical. Your ability to provide the family with meaningful support will create a strong foundation of trust that will improve the course of their child's care. Given the complex and uncertain nature of these diagnoses, your partnership with the parents is the critical first step. Acknowledge that inflammation is emerging as an important factor in many medical and psychiatric conditions, but that it may not always guide treatment. It should not be a matter of medical illness or psychiatric illness. Help families to understand that even if a strep infection triggered the psychiatric symptoms, they will both need treatment. Treatment may be slow, but with your guidance and partnership the child will recover. A parent's trust in you is the essential foundation for this process.
Conclusion
PANS and PANDAS are emerging clinical entities residing at the intersection of psychiatry, pediatrics, and immunology. While more research is needed to understand their pathophysiology and optimal treatment strategies, the reality is that affected children may be presenting to your offices today — suffering and in need of thoughtful, coordinated care. Maintain a curious, compassionate posture, acknowledge uncertainty where it exists, and provide clarity about our ability to offer reasonable and effective treatments guided by evidence and good judgment even when there is uncertainty.