Urgent Rebuttal and Request for Retraction of AAP’s March 2025 Clinical Report on PANS until a Revision is Possible
DATE: July 31, 2025
RE: Urgent Rebuttal and Request for Retraction of AAP’s March 2025 Clinical Report on PANS until a Revision is Possible
TO:
Dr. Susan J. Kressly, M.D., FAAP President, Board of Directors American Academy of Pediatrics 345 Park Boulevard Itasca, IL 60143
Dr. Pamela K. Shaw, M.D., FAAP President-Elect, Board of Directors American Academy of Pediatrics 345 Park Boulevard Itasca, IL 60143
Dr. Moira A. Szilagyi, M.D., Ph.D., Past President-Elect, Board of Directors American Academy of Pediatrics 345 Park Boulevard Itasca, IL 60143
Dr. Brian P. Sanders, M.D., FAAP Secretary/Treas., Board of Directors American Academy of Pediatrics 345 Park Boulevard Itasca, IL 60143
Mark D. Del Monte, J.D. CEO/Executive Vice-President, Board of Directors American Academy of Pediatrics 345 Park Boulevard Itasca, IL 60143
Robert F. Kennedy Jr HHS Secretary Health & Human Services Hubert H. Humphrey Building 200 Independence Avenue, S.W. Washington, D.C. 20201
Dear American Academy of Pediatrics Leadership,
The Alex Manfull Fund, together with the undersigned PANS/PANDAS organizations, expresses grave concerns about the American Academy of Pediatrics’ (AAP) March 2025 Clinical Report on Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS, hereinafter referred to as “The Report” (Board of Directors, 2025). These concerns are urgent and scientifically founded: without retraction, The Report threatens to block access to essential care, risking irreversible neuropsychiatric damage, lifelong disability, and even death.
We Urge the AAP to:
Although The Report acknowledges PANS as “likely a valid diagnosis,” it simultaneously casts doubt on its legitimacy—undermining decades of research and clinical experience. The Report fails to incorporate key scientific literature, omits critical studies and expert input, disregards established clinical guidelines, and lacks transparency regarding authorship and conflicts of interest. It also misrepresents diagnostic standards by denying essential medical rule-outs and dismissing well-supported diagnostic tests and treatments. Alarmingly, insurers are already citing this flawed report to deny necessary care, putting vulnerable children and young adults at serious risk. By condoning its misuse as a clinical guideline, The Report becomes not only outdated and misleading—but actively dangerous.
Retract the current report until a revised version can be developed that addresses the aforementioned failures and incorporates the full body of peer-reviewed evidence. This retraction should be clearly communicated as not stemming from any question of diagnostic validity, but rather as a necessary step to incorporate all relevant research.
Ensure transparent and inclusive development of the future report Future versions of The Report must adhere to rigorous standards of transparency and inclusivity by:
Aligning all diagnostic testing, evaluation, and treatment recommendations with established PANS/PANDAS clinical guidelines (Chang et al., 2015; Thienemann et al., 2017; Frankovich et al., 2017; Cooperstock et al., 2017; and PANDAS Physicians Network, n.d.) and established infectious disease protocols as outlined by Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 9th Edition (Cherry et al., 2024).
Including multidisciplinary contributors with direct expertise in PANS/PANDAS, including pediatric neurologists, infectious disease specialists, rheumatologists, immunologists, psychiatrists, psychologists and researchers.
Reinforcing the DSM-5-TR requirement for thorough medical evaluations to rule out underlying medical causes before assigning psychiatric diagnoses (American Psychiatric Association, 2022).
Disclosing authorship and conflicts of interest in full compliance with International Committee of Medical Journal Editors (ICMJE, 2025) guidelines.
Until such a revision is produced, the current report poses a risk of being misused to justify clinical inaction, treatment denials, and/or mischaracterization of a medically complex condition affecting thousands of young people and their families.
Below, we detail critical areas where the AAP’s March 2025 Clinical Report on PANS fails to meet the standards of scientific accuracy, clinical relevance, and ethical responsibility. These failures include the omission of key research, lack of expert consultation, misrepresentation and disregard of current treatment practices, and guidance that directly contradicts established diagnostic protocols. Left uncorrected, these shortcomings risk reinforcing systemic barriers to care, worsening health outcomes (potentially even leading to death), and further delaying urgently needed treatment for affected children and young adults.
1. Lack of Transparency and Conflict of Interest Disclosures
The Report does not disclose the names or credentials of its authors, nor does it identify the specialists who were consulted during its development. There is no indication that pediatric immunologists, infectious disease experts, neuroimmunologists, psychiatrists, rheumatologists or physician scientists from the PANS/PANDAS Research Consortium, PANDAS Physicians Network, major PANS/PANDAS research centers, or multidisciplinary clinics contributed to The Report.
Additionally, the absence of conflict-of-interest disclosures undermines transparency and credibility. According to ICMJE guidelines, all potential conflicts—even those that may merely appear to influence content—must be disclosed. This omission raises serious concerns about the neutrality, validity, and reliability of The Report.
2. Disregard for Established Clinical Guidelines and Key Research
Leading academic and medical institutions—including Stanford, Georgetown, Dartmouth, Columbia, University of Arizona, Virginia Commonwealth University, Massachusetts General Hospital, and Harvard Medical School—use protocols developed by the PANS/PANDAS Research Consortium (Chang et al., 2015; Thienemann et al., 2017; Frankovich et al., 2017; and Cooperstock et al., 2017), the PANDAS Physicians Network (PANDAS Physicians Network, n.d.), and Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 9th Edition (Cherry, et al., 2024).
These guidelines reflect decades of research and clinical experience and are continuously updated (see Bibliography in Addendum 1). The AAP failed to reference or incorporate these established standards when completing the 2025 Clinical Report on PANS.
Additionally, the AAP’s review omitted relevant peer-reviewed publications published between 2018 and 2025 and failed to include foundational studies from earlier periods (PANDAS Physicians Network, 2025). The literature expanded and advanced substantially during this time period, especially regarding the effectiveness of treatments like antimicrobial therapy, NSAIDs, steroids, IVIG, and plasmapheresis (see Bibliography in Addendum 1). Specifically, The Report’s initial literature search was conducted in April 2020, supplemented by a secondary search in June 2023. However, only 5 of 47 references are from after the first search. By not considering the complete and evolving body of research, The Report draws conclusions that do not reflect current scientific understanding or clinical practice.
The AAP’s report further fails to acknowledge recent evidence proving the clinical value of immunoglobulin therapy (IVIG) in treating PANS (see Addendum 1 & Addendum 2). A 2025 Phase III trial (NCT04508530) of PANZYGA® in PANS patients showed a 31.1% symptom reduction vs. 12.1% with placebo. While the primary outcome narrowly missed statistical significance (p = 0.072), the secondary measure did reach it (p = 0.017), confirming clinical relevance (Octapharma USA, 2025). Meanwhile, the Centers for Medicare & Medicaid Services (CMS) recognize the medical necessity of IVIG for diagnostic codes commonly used in PANS/PANDAS cases (D89.89, G04.81) (Centers for Medicare & Medicaid Services, 2019).
3. Failure to Comply with the Imperative of Medical Rule-Out in Psychiatric Diagnoses
According to DSM-5-TR guidelines, mental health professionals must rule out other medical conditions before assigning psychiatric diagnoses (American Psychiatric Association, 2022). The Report largely overlooks this essential step, favoring psychiatric treatments over thorough investigation of potential infectious, immune, or inflammatory causes. This not only risks medical negligence but may result in denial of care that could otherwise restore health and save lives. Without enforcing this basic clinical safeguard, The Report contradicts psychiatric diagnostic standards and perpetuates misdiagnosis and inappropriate treatment.
Regarding obsessions and compulsions, the cardinal symptoms of PANDAS and PANS, it should be noted that the DSM-5-TR recognizes the importance of a medical condition rule-out by including a diagnostic category called “Obsessive-Compulsive and Related Disorder Due to Another Medical Condition” (American Psychiatric Association, 2022). Both Sydenham’s chorea and PANDAS and PANS are mentioned.
An abundance of recent findings underscore a growing trend toward investigating the immune system’s role in psychiatric conditions. Consider the article entitled “Immunological causes of obsessive-compulsive disorder: is it time for the concept of an ‘autoimmune OCD’ subtype?” (Endres et al., 2022). Although traditionally viewed through a purely neuropsychiatric lens, Endres et al. argue that disorders like OCD should be reconsidered in light of evidence suggesting an organic cause such as immune dysregulation. It is imperative that such research advances be recognized and incorporated, in order to adequately diagnose and treat those individuals presenting with neuropsychiatric symptoms.
4. Restriction of Access and Failure to Weigh Risks Appropriately
The Report imposes a narrowly defined diagnostic framework for PANS that significantly restricts access to essential evaluation and treatment. By focusing almost exclusively on group A Streptococcus (GAS) and discouraging broader infectious workups—including for Mycoplasma pneumoniae, SARS- CoV-2, influenza, sinusitis, Lyme disease and other vector-borne infections—this report overlooks well-established infectious contributors to neuropsychiatric symptoms. This restrictive stance delays accurate diagnoses and timely interventions for young people whose symptoms are triggered or exacerbated by non-GAS infections and have asymptomatic GAS. These diagnostic limitations directly contradict the AAP’s own Red Book (AAP, 2024), which recognizes the potential severity of asymptomatic GAS infections.
In addition, discouraging brain imaging if indicated in the setting of abrupt onset neuropsychiatric symptoms risks missing critical findings in patients presenting with acute-onset neuropsychiatric changes.
Equally concerning, The Report minimizes or dismisses treatment strategies that are well-supported by clinical experience, peer-reviewed research, and guidelines from leading medical institutions (Chang et al., 2015; Thienemann et al., 2017; Frankovich et al., 2017; Cooperstock et al., 2017; PANDAS Physicians Network, n.d.). Interventions such as extended antibiotic courses (>10 days), short-term corticosteroids, and immunomodulatory NSAIDs are excluded or downplayed, despite their demonstrated benefits in managing acute flares. These treatments have a relatively low risk profile but substantial demonstrated benefit, especially in mild to moderate cases. It should be noted that psychiatric labels and SSRIs are not without their own risks and harms and while they are the mainstay of treatment for patients with PANS/PANDAS, the use of psychopharmacologic interventions requires modification in the setting of these conditions (Thienemann et al., 2017).
Although The Report concedes that IVIG, other immunotherapies, and plasmapheresis are options that “may be considered,” it paradoxically labels them “not recommended,” dismissing clinical and peer reviewed research, clinical guidelines, and Centers for Medicare & Medicaid Services (CMS) guidance for medical necessity use of IVIG for several relevant diagnoses (Centers for Medicare & Medicaid Services, 2019).
Rather than supporting flexible, severity-based care, The Report promotes rigid, uniform treatment recommendations that disregard the highly variable and episodic nature of PANS/PANDAS. It fails to differentiate between mild, moderate, and severe presentations, thereby undermining the creation of individualized treatment plans that appropriately balance the risks of intervention with the severity of the patient’s illness.
Ultimately, by minimizing the risks of inaction while overstating the risks of intervention, The Report undermines clinical decision-making and contributes to widespread care denials. Its restrictive diagnostic stance, incomplete risk assessment, and inflexible treatment guidance pose a serious threat to vulnerable children and young adults. A multifaceted, tiered, patient-centered, and evidence-based framework is essential to ensure access to timely, individualized, and effective care that aligns with the real-world complexities of this condition.
5. Condonement of Misuse as a Clinical Guideline
Despite disclaiming clinical guideline status, The Report actively involves itself in state-level policy debates over access to care. It specifically references the growing advocacy for IVIG treatment and notes that several states—including Arkansas, Delaware, Illinois, Indiana, Maryland, Minnesota, and New Hampshire—have enacted legislation mandating insurance coverage for IVIG in PANS/PANDAS. By commenting on these developments and encouraging pediatricians to engage with local chapters, The Report takes a position on the broader landscape of access, implicitly influencing both policy and insurer behavior.
Dr. Warris Bokhari (personal communication, July 16, 2025), co-founder of Claimable, reported a concerning trend: of nearly 100 PANS/PANDAS insurance appeals submitted since November 2024, the success rate for reversals has dropped significantly—from approximately 80% to just 60%. Notably, insurers are increasingly citing the American Academy of Pediatrics Clinical Report as justification for denying coverage of IVIG and other interventions, often without clinical justification or consultation with relevant medical specialists (see Addendum 2).
The Report is already contributing to insurance denials, delays in care prescribed by multidisciplinary teams at preeminent academic centers and widening disparities in care. Without a retraction of The Report and the subsequent issuance of a comprehensive, evidence-based update, the AAP’s silence is being interpreted as tacit endorsement of these denials.
A Tragic Case and the Indefensible Cost of Delay: Alex Manfull’s Story
Alex Manfull died at age 26 from complications of untreated PANDAS following years of misdiagnosis and denial of care. In her memory, The Alex Manfull Fund established the POND Brain Bank at Georgetown University—the world’s first and only brain bank dedicated to “PANDAS/PANS and Other Neuroimmune Disorders.” In less than three years, and without any active promotion, the POND Brain Bank has received the brains or brain tissue from eight additional young people who died from complications of PANDAS/PANS (Harris, B.T., personal communication, May 14, 2025)
Preliminary findings, such as those published in Development Neuroscience (Kulumani Mahadevan et al., 2023), confirm neuroinflammatory pathology consistent with clinical PANDAS diagnosis. Specifically, the neuropathology team found mild gliosis and Alzheimer type II astrocytes/metabolic glia in the hippocampus and basal ganglia. Based on immunostaining, there was noted parenchymal/perivascular astrogliosis and increased numbers of CD3, CD4, and CD25 positive lymphocytes.
These losses of life are a haunting testament to the consequences of delay and denial. PANDAS was first described over two decades ago. For years, the AAP denied its validity with devastating consequences—and The Report continues that trend. We cannot wait even another day to recognize existing diagnostics and treatments. No more lives of young people should be lost.
A Call for Scientific Collaboration
Leading clinicians and researchers welcome the opportunity to share comprehensive literature reviews, vast clinical experience, treatment guidelines, and access to multidisciplinary experts. We urge the AAP to collaborate now in the interest of providing pediatricians and other medical professionals with trusted, evidence-based care pathways.
Working collaboratively with leading researchers and clinicians in the field is essential to developing guidance that truly reflects best practices in the diagnosis and care of young people suffering from PANS. The time for inaction has passed; no more young lives should be lost due to misrepresentation, denial, or delay. We remain ready to work collaboratively to protect children and young adults and to ensure that families and pediatricians and others have access to the most accurate, timely, and scientifically grounded resources.
The AAP plays a critical leadership role with a unique capability to build consensus through dialogue that informs, unites and drives progress in the battle against this devastating disease. We implore the AAP to reconsider its position, retract its recent clinical report, and work collaboratively to move the medical community forward.
We are confident the AAP will do the right thing. Pediatricians, patients and families are counting on you.
Sincerely,
Susan Manfull, PhD. Executive Director The Alex Manfull Fund
Asociación Pans Pandas Perú
Rocío Del Pilar Saavedra Ambrosio, President
ASPIRE – Alliance to Solve PANS & Immune-Related Encephalopathies
Gabriella True, President
Associazione Genitori PANS PANDAS BGE OdV
Fabridi Lalli, Executive Director
Bamboo Ranch
Christine Case, President,
Brain Inflammation Collaborative
Christy Jagdfeld, CPA, CEO
California Coalition for PANS/PANDAS Advocacy
April Ronay, Founding Member
Shari Strulson, Founding Member
EXPAND, The European Immuno-Neuropsychiatric Association
René C. Blanchard Akre, Chairman of the Board of Directors
Representing:
Associazione Genitori Pans Pandas Bge (Italy) Autism Support Famagusta (Cyprus) Expand (Europe) Fundacja dzieciom z zespołem PANS i Pandas oraz ich rodzinom (Poland) nAUkaTIZAM – Association for Science and Autism (the Balkan region) PANDAS PANS Srbija (Serbia) PANDAS/PANS Deutschland (Germany) PANS Pandas Italia APS (Italy) PANS/PANDAS Belgique (Belgium) PANS/PANDAS Croatia (Croatia) PANS/PANDAS Espana (Spain) Pans/Pandas Foreningen (Denmark) PANS/PANDAS Foundation Ireland (Ireland) PANS/PANDAS France (France) PANS/PANDAS Nederland Patiëntenvereniging (Netherlands) Pans/Pandas Suomessa (Finland) PANS/PANDAS Switzerland (Switzerland) PANS/PANDAS UK (United Kingdom) SANE Norge (Norway) SANE Sweden (Sweden)
Inflamed Brain Alliance
Marnie Deschenes, BMus, RMT, Co-Founder
Look. Foundation
Jennifer M. Vitelli, MBA, Executive Director
Massachusetts Coalition for PANDAS/PANS Legislation
Sheilah M. Gauch, LICSW, M.Ed, Co-Leader
Northwest PANDAS/PANS Network
Sarah Lemley, MPA; HA, Executive Director
PANDAS Network
Diana Pohlman, Executive Director
Southeastern PANS/PANDAS Association (SEPPA)
Heather Ward, President
Virginia Alliance for PANS/PANDAS Action
Krissie Nunnally, Co-Founder
References
American Psychiatric Association. (2022). Diagnostic and statistical manual of mental disorders (5th ed., text rev.; DSM-5-TR). American Psychiatric Publishing. https://doi.org/10.1176/appi.books.9780890425787
Chang, K., Frankovich, J., Cooperstock, M., et al. (2015). Clinical evaluation of youth with PANS: Recommendations from the 2013 Consensus Conference. Journal of Child and Adolescent Psychopharmacology, 25(1), 3–13. https://pubmed.ncbi.nlm.nih.gov/25325534/
Cherry, J. D., Kaplan, S. L., Demmler‑Harrison, G. J., Steinbach, W. J., Hotez, P. J., & Williams, J. V. (Eds.). (2024). Feigin and Cherry’s textbook of pediatric infectious diseases (9th ed., 2 vols.). Elsevier.
Cooperstock, M. S., Swedo, S. E., Pasternack, M. S., Murphy, T. K., & PANS/PANDAS Consortium. (2017). Clinical management of PANS: Part III—Treatment and prevention of infections. Journal of Child and Adolescent Psychopharmacology, 27, 594–606. https://doi.org/10.1089/cap.2016.0151
Endres, D., Pollak, T. A., Bechter, K., Denzel, D., Pitsch, K., Nickel, K., Runge, K., Pankratz, B., Klatzmann, D., Tamouza, R., Mallet, L., Leboyer, M., Prüss, H., Voderholzer, U., Cunningham, J. L., ECNP Network Immuno-NeuroPsychiatry, Domschke, K., van Elst, L. T., & Schiele, M. A. (2022). Immunological causes of obsessive-compulsive disorder: Is it time for the concept of an “autoimmune OCD”? Translational Psychiatry, 12(1), 5. https://doi.org/10.1038/s41398-021-01700-4
Frankovich, J., Swedo, S., Murphy, T., et al. (2017). Clinical management of PANS: Part II—Use of immunomodulatory therapies. Journal of Child and Adolescent Psychopharmacology, 27(7), 574–593. https://pubmed.ncbi.nlm.nih.gov/36358107/
International Committee of Medical Journal Editors. (2025, April). Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals. https://www.icmje.org/
Kulumani Mahadevan L.S., Murphy M., Selenica M., Latimer E., & Harris B.T. Clinicopathologic characteristics of PANDAS in a young adult: A case report. Dev Neurosci. 2023;45(6):335-341. https://pubmed.ncbi.nlm.nih.gov/37699369/ . Epub 2023 Sep 12. PMID: 37699369; PMCID: PMC10753865.
PANDAS Physicians Network. (2025a, March). PANS/PANDAS Research and Resources: A compilation of studies and articles (2018–2025). Retrieved June 24, 2025, fromhttps://www.pandasppn.org/research‑updates/
Thienemann, M., Murphy, T., Leckman, J., et al. (2017). Clinical management of PANS: Part I—Psychiatric and behavioral interventions. Journal of Child and Adolescent Psychopharmacology, 27(7), 566–573. https://pubmed.ncbi.nlm.nih.gov/28722481/
Addendum 2 Comparison of AAP Report Claims vs Literature Evidence
AAP REPORT CLAIM
EVIDENCE-BASED RESPONSE
IVIG lacks a robust evidence base for efficacy in treating PANS
Two randomized, placebo-controlled trials show significant improvements with IVIG. At least seven additional studies demonstrate benefits in neuropsychiatric outcomes and immune markers. Animal models also show abnormal behavior reversed after IVIG, supporting its mechanism of action.
IVIG carries significant risks
In every trial to date, IVIG was well tolerated in PANS. The most common adverse events are headache, nausea, and vomiting, which are typically mild or moderate and self-limiting (e.g. Melamed 2021).
The pathophysiology of PANS is unclear
PANS is an immune-mediated neuroinflammatory disorder as is evidenced by a) animal model demonstrating Th17-mediated blood brain barrier breakdown, b) elevations in inflammatory monocytes and immune activation markers during flares, c) abnormal cytokine levels in patients, d) extremely high rate of family history of autoimmunity and known association with genetic variants affecting immune system, e) microbiome alterations in patients, f) association with immunoglobulin deficiencies, g) elevated markers of neuronal damage, h) autopsy data, i) polysomnography abnormalities similar to other basal ganglia disorders, j) neuroimaging studies showing basal ganglia edema during flares, k) elevated anti dopamine receptor antibodies, l) clinical similarities including treatment response to Sydenham Chorea, a well-recognized post-infectious neuroimmune disorder.
RCT and Systematic Reviews Are Inconclusive
Two randomized controlled trials (Perlmutter 1998 and Daines 2025—publication pending, data available online) have demonstrated the benefit of IVIG. The most authoritative review (Frankovich 2017) reflects consensus from experts in psychiatry, pediatrics, infectious disease, neurology, immunology, and related fields across NIH, major academic centers, and large practices. These RCTs and expert guidelines support IVIG for severe or refractory PANS and PANDAS. The PANDAS Physicians Network, an international consortium of researchers and clinicians, maintains updated treatment guidelines that continue to recommend IVIG as safe and effective in such cases.
Should Not Be Used Outside Clinical Trials or Specialty Centers
Currently, there is no clinical trial of IVIG in PANS in progress. Specialty centers lack capacity to manage the volume of cases in the community. Stanford’s Immune Behavioral Health Clinic, for instance, can accept only 10% of referrals. Waiting lists for all PANS specialty centers are months to years. For this reason, PPN provides guidelines for community physicians such as “Seeing Your First Child with PANDAS/PANS,” since delaying care to wait for a trial or tertiary appointment is associated with worse neurological outcomes and more persistent disease.
Note: This table was adapted from Bokhari, W. (2025). Unpublished work for Claimable.
Urgent Rebuttal and Request for Retraction of AAP’s March 2025 Clinical Report on PANS until a Revision is Possible
DATE: July 31, 2025
RE: Urgent Rebuttal and Request for Retraction of AAP’s March 2025 Clinical Report on PANS until a Revision is Possible
American Academy of Pediatrics
345 Park Boulevard Itasca, IL 60143
American Academy of Pediatrics
345 Park Boulevard Itasca, IL 60143
M.D., Ph.D., Past President-Elect, Board
of Directors
American Academy of
Pediatrics
345 Park Boulevard Itasca, IL 60143
American Academy of Pediatrics
345 Park Boulevard Itasca, IL 60143
American Academy of Pediatrics
345 Park Boulevard Itasca, IL 60143
Health & Human Services
Hubert H. Humphrey Building 200 Independence Avenue,
S.W. Washington, D.C. 20201
Dear American Academy of Pediatrics Leadership,
The Alex Manfull Fund, together with the undersigned PANS/PANDAS organizations, expresses grave concerns about the American Academy of Pediatrics’ (AAP) March 2025 Clinical Report on Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS, hereinafter referred to as “The Report” (Board of Directors, 2025). These concerns are urgent and scientifically founded: without retraction, The Report threatens to block access to essential care, risking irreversible neuropsychiatric damage, lifelong disability, and even death.
We Urge the AAP to:
Although The Report acknowledges PANS as “likely a valid diagnosis,” it simultaneously casts doubt on its legitimacy—undermining decades of research and clinical experience. The Report fails to incorporate key scientific literature, omits critical studies and expert input, disregards established clinical guidelines, and lacks transparency regarding authorship and conflicts of interest. It also misrepresents diagnostic standards by denying essential medical rule-outs and dismissing well-supported diagnostic tests and treatments. Alarmingly, insurers are already citing this flawed report to deny necessary care, putting vulnerable children and young adults at serious risk. By condoning its misuse as a clinical guideline, The Report becomes not only outdated and misleading—but actively dangerous.
Future versions of The Report must adhere to rigorous standards of transparency and inclusivity by:
Disclosing authorship and conflicts of interest in full compliance with International Committee of Medical Journal Editors (ICMJE, 2025) guidelines.
Until such a revision is produced, the current report poses a risk of being misused to justify clinical inaction, treatment denials, and/or mischaracterization of a medically complex condition affecting thousands of young people and their families.
Below, we detail critical areas where the AAP’s March 2025 Clinical Report on PANS fails to meet the standards of scientific accuracy, clinical relevance, and ethical responsibility. These failures include the omission of key research, lack of expert consultation, misrepresentation and disregard of current treatment practices, and guidance that directly contradicts established diagnostic protocols. Left uncorrected, these shortcomings risk reinforcing systemic barriers to care, worsening health outcomes (potentially even leading to death), and further delaying urgently needed treatment for affected children and young adults.
1. Lack of Transparency and Conflict of Interest Disclosures
The Report does not disclose the names or credentials of its authors, nor does it identify the specialists who were consulted during its development. There is no indication that pediatric immunologists, infectious disease experts, neuroimmunologists, psychiatrists, rheumatologists or physician scientists from the PANS/PANDAS Research Consortium, PANDAS Physicians Network, major PANS/PANDAS research centers, or multidisciplinary clinics contributed to The Report.
Additionally, the absence of conflict-of-interest disclosures undermines transparency and credibility. According to ICMJE guidelines, all potential conflicts—even those that may merely appear to influence content—must be disclosed. This omission raises serious concerns about the neutrality, validity, and reliability of The Report.
2. Disregard for Established Clinical Guidelines and Key Research
Leading academic and medical institutions—including Stanford, Georgetown, Dartmouth, Columbia, University of Arizona, Virginia Commonwealth University, Massachusetts General Hospital, and Harvard Medical School—use protocols developed by the PANS/PANDAS Research Consortium (Chang et al., 2015; Thienemann et al., 2017; Frankovich et al., 2017; and Cooperstock et al., 2017), the PANDAS Physicians Network (PANDAS Physicians Network, n.d.), and Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 9th Edition (Cherry, et al., 2024).
These guidelines reflect decades of research and clinical experience and are continuously updated (see Bibliography in Addendum 1). The AAP failed to reference or incorporate these established standards when completing the 2025 Clinical Report on PANS.
Additionally, the AAP’s review omitted relevant peer-reviewed publications published between 2018 and 2025 and failed to include foundational studies from earlier periods (PANDAS Physicians Network, 2025). The literature expanded and advanced substantially during this time period, especially regarding the effectiveness of treatments like antimicrobial therapy, NSAIDs, steroids, IVIG, and plasmapheresis (see Bibliography in Addendum 1). Specifically, The Report’s initial literature search was conducted in April 2020, supplemented by a secondary search in June 2023. However, only 5 of 47 references are from after the first search. By not considering the complete and evolving body of research, The Report draws conclusions that do not reflect current scientific understanding or clinical practice.
The AAP’s report further fails to acknowledge recent evidence proving the clinical value of immunoglobulin therapy (IVIG) in treating PANS (see Addendum 1 & Addendum 2). A 2025 Phase III trial (NCT04508530) of PANZYGA® in PANS patients showed a 31.1% symptom reduction vs. 12.1% with placebo. While the primary outcome narrowly missed statistical significance (p = 0.072), the secondary measure did reach it (p = 0.017), confirming clinical relevance (Octapharma USA, 2025). Meanwhile, the Centers for Medicare & Medicaid Services (CMS) recognize the medical necessity of IVIG for diagnostic codes commonly used in PANS/PANDAS cases (D89.89, G04.81) (Centers for Medicare & Medicaid Services, 2019).
3. Failure to Comply with the Imperative of Medical Rule-Out in Psychiatric Diagnoses
According to DSM-5-TR guidelines, mental health professionals must rule out other medical conditions before assigning psychiatric diagnoses (American Psychiatric Association, 2022). The Report largely overlooks this essential step, favoring psychiatric treatments over thorough investigation of potential infectious, immune, or inflammatory causes. This not only risks medical negligence but may result in denial of care that could otherwise restore health and save lives. Without enforcing this basic clinical safeguard, The Report contradicts psychiatric diagnostic standards and perpetuates misdiagnosis and inappropriate treatment.
Regarding obsessions and compulsions, the cardinal symptoms of PANDAS and PANS, it should be noted that the DSM-5-TR recognizes the importance of a medical condition rule-out by including a diagnostic category called “Obsessive-Compulsive and Related Disorder Due to Another Medical Condition” (American Psychiatric Association, 2022). Both Sydenham’s chorea and PANDAS and PANS are mentioned.
An abundance of recent findings underscore a growing trend toward investigating the immune system’s role in psychiatric conditions. Consider the article entitled “Immunological causes of obsessive-compulsive disorder: is it time for the concept of an ‘autoimmune OCD’ subtype?” (Endres et al., 2022). Although traditionally viewed through a purely neuropsychiatric lens, Endres et al. argue that disorders like OCD should be reconsidered in light of evidence suggesting an organic cause such as immune dysregulation. It is imperative that such research advances be recognized and incorporated, in order to adequately diagnose and treat those individuals presenting with neuropsychiatric symptoms.
4. Restriction of Access and Failure to Weigh Risks Appropriately
The Report imposes a narrowly defined diagnostic framework for PANS that significantly restricts access to essential evaluation and treatment. By focusing almost exclusively on group A Streptococcus (GAS) and discouraging broader infectious workups—including for Mycoplasma pneumoniae, SARS- CoV-2, influenza, sinusitis, Lyme disease and other vector-borne infections—this report overlooks well-established infectious contributors to neuropsychiatric symptoms. This restrictive stance delays accurate diagnoses and timely interventions for young people whose symptoms are triggered or exacerbated by non-GAS infections and have asymptomatic GAS. These diagnostic limitations directly contradict the AAP’s own Red Book (AAP, 2024), which recognizes the potential severity of asymptomatic GAS infections.
In addition, discouraging brain imaging if indicated in the setting of abrupt onset neuropsychiatric symptoms risks missing critical findings in patients presenting with acute-onset neuropsychiatric changes.
Equally concerning, The Report minimizes or dismisses treatment strategies that are well-supported by clinical experience, peer-reviewed research, and guidelines from leading medical institutions (Chang et al., 2015; Thienemann et al., 2017; Frankovich et al., 2017; Cooperstock et al., 2017; PANDAS Physicians Network, n.d.). Interventions such as extended antibiotic courses (>10 days), short-term corticosteroids, and immunomodulatory NSAIDs are excluded or downplayed, despite their demonstrated benefits in managing acute flares. These treatments have a relatively low risk profile but substantial demonstrated benefit, especially in mild to moderate cases. It should be noted that psychiatric labels and SSRIs are not without their own risks and harms and while they are the mainstay of treatment for patients with PANS/PANDAS, the use of psychopharmacologic interventions requires modification in the setting of these conditions (Thienemann et al., 2017).
Although The Report concedes that IVIG, other immunotherapies, and plasmapheresis are options that “may be considered,” it paradoxically labels them “not recommended,” dismissing clinical and peer reviewed research, clinical guidelines, and Centers for Medicare & Medicaid Services (CMS) guidance for medical necessity use of IVIG for several relevant diagnoses (Centers for Medicare & Medicaid Services, 2019).
Rather than supporting flexible, severity-based care, The Report promotes rigid, uniform treatment recommendations that disregard the highly variable and episodic nature of PANS/PANDAS. It fails to differentiate between mild, moderate, and severe presentations, thereby undermining the creation of individualized treatment plans that appropriately balance the risks of intervention with the severity of the patient’s illness.
Ultimately, by minimizing the risks of inaction while overstating the risks of intervention, The Report undermines clinical decision-making and contributes to widespread care denials. Its restrictive diagnostic stance, incomplete risk assessment, and inflexible treatment guidance pose a serious threat to vulnerable children and young adults. A multifaceted, tiered, patient-centered, and evidence-based framework is essential to ensure access to timely, individualized, and effective care that aligns with the real-world complexities of this condition.
5. Condonement of Misuse as a Clinical Guideline
Despite disclaiming clinical guideline status, The Report actively involves itself in state-level policy debates over access to care. It specifically references the growing advocacy for IVIG treatment and notes that several states—including Arkansas, Delaware, Illinois, Indiana, Maryland, Minnesota, and New Hampshire—have enacted legislation mandating insurance coverage for IVIG in PANS/PANDAS. By commenting on these developments and encouraging pediatricians to engage with local chapters, The Report takes a position on the broader landscape of access, implicitly influencing both policy and insurer behavior.
Dr. Warris Bokhari (personal communication, July 16, 2025), co-founder of Claimable, reported a concerning trend: of nearly 100 PANS/PANDAS insurance appeals submitted since November 2024, the success rate for reversals has dropped significantly—from approximately 80% to just 60%. Notably, insurers are increasingly citing the American Academy of Pediatrics Clinical Report as justification for denying coverage of IVIG and other interventions, often without clinical justification or consultation with relevant medical specialists (see Addendum 2).
The Report is already contributing to insurance denials, delays in care prescribed by multidisciplinary teams at preeminent academic centers and widening disparities in care. Without a retraction of The Report and the subsequent issuance of a comprehensive, evidence-based update, the AAP’s silence is being interpreted as tacit endorsement of these denials.
A Tragic Case and the Indefensible Cost of Delay: Alex Manfull’s Story
Alex Manfull died at age 26 from complications of untreated PANDAS following years of misdiagnosis and denial of care. In her memory, The Alex Manfull Fund established the POND Brain Bank at Georgetown University—the world’s first and only brain bank dedicated to “PANDAS/PANS and Other Neuroimmune Disorders.” In less than three years, and without any active promotion, the POND Brain Bank has received the brains or brain tissue from eight additional young people who died from complications of PANDAS/PANS (Harris, B.T., personal communication, May 14, 2025)
Preliminary findings, such as those published in Development Neuroscience (Kulumani Mahadevan et al., 2023), confirm neuroinflammatory pathology consistent with clinical PANDAS diagnosis. Specifically, the neuropathology team found mild gliosis and Alzheimer type II astrocytes/metabolic glia in the hippocampus and basal ganglia. Based on immunostaining, there was noted parenchymal/perivascular astrogliosis and increased numbers of CD3, CD4, and CD25 positive lymphocytes.
These losses of life are a haunting testament to the consequences of delay and denial. PANDAS was first described over two decades ago. For years, the AAP denied its validity with devastating consequences—and The Report continues that trend. We cannot wait even another day to recognize existing diagnostics and treatments. No more lives of young people should be lost.
A Call for Scientific Collaboration
Leading clinicians and researchers welcome the opportunity to share comprehensive literature reviews, vast clinical experience, treatment guidelines, and access to multidisciplinary experts. We urge the AAP to collaborate now in the interest of providing pediatricians and other medical professionals with trusted, evidence-based care pathways.
Working collaboratively with leading researchers and clinicians in the field is essential to developing guidance that truly reflects best practices in the diagnosis and care of young people suffering from PANS. The time for inaction has passed; no more young lives should be lost due to misrepresentation, denial, or delay. We remain ready to work collaboratively to protect children and young adults and to ensure that families and pediatricians and others have access to the most accurate, timely, and scientifically grounded resources.
The AAP plays a critical leadership role with a unique capability to build consensus through dialogue that informs, unites and drives progress in the battle against this devastating disease. We implore the AAP to reconsider its position, retract its recent clinical report, and work collaboratively to move the medical community forward.
We are confident the AAP will do the right thing. Pediatricians, patients and families are counting on you.
Sincerely,
Susan Manfull, PhD.
Executive Director
The Alex Manfull Fund
Asociación Pans Pandas Perú
Rocío Del Pilar Saavedra Ambrosio, President
ASPIRE – Alliance to Solve PANS & Immune-Related Encephalopathies
Gabriella True, President
Associazione Genitori PANS PANDAS BGE OdV
Fabridi Lalli, Executive Director
Bamboo Ranch
Christine Case, President,
Brain Inflammation Collaborative
Christy Jagdfeld, CPA, CEO
California Coalition for PANS/PANDAS Advocacy
April Ronay, Founding Member
Shari Strulson, Founding Member
EXPAND, The European Immuno-Neuropsychiatric Association
René C. Blanchard Akre, Chairman of the Board of Directors
Representing:
Associazione Genitori Pans Pandas Bge (Italy)
Autism Support Famagusta (Cyprus)
Expand (Europe)
Fundacja dzieciom z zespołem PANS i Pandas oraz ich rodzinom (Poland)
nAUkaTIZAM – Association for Science and Autism (the Balkan region)
PANDAS PANS Srbija (Serbia)
PANDAS/PANS Deutschland (Germany)
PANS Pandas Italia APS (Italy)
PANS/PANDAS Belgique (Belgium)
PANS/PANDAS Croatia (Croatia)
PANS/PANDAS Espana (Spain)
Pans/Pandas Foreningen (Denmark)
PANS/PANDAS Foundation Ireland (Ireland)
PANS/PANDAS France (France)
PANS/PANDAS Nederland Patiëntenvereniging (Netherlands)
Pans/Pandas Suomessa (Finland)
PANS/PANDAS Switzerland (Switzerland)
PANS/PANDAS UK (United Kingdom)
SANE Norge (Norway)
SANE Sweden (Sweden)
Inflamed Brain Alliance
Marnie Deschenes, BMus, RMT, Co-Founder
Look. Foundation
Jennifer M. Vitelli, MBA, Executive Director
Massachusetts Coalition for PANDAS/PANS Legislation
Sheilah M. Gauch, LICSW, M.Ed, Co-Leader
Northwest PANDAS/PANS Network
Sarah Lemley, MPA; HA, Executive Director
PANDAS Network
Diana Pohlman, Executive Director
Southeastern PANS/PANDAS Association (SEPPA)
Heather Ward, President
Virginia Alliance for PANS/PANDAS Action
Krissie Nunnally, Co-Founder
References
American Psychiatric Association. (2022). Diagnostic and statistical manual of mental disorders (5th ed., text rev.; DSM-5-TR). American Psychiatric Publishing. https://doi.org/10.1176/appi.books.9780890425787
Board of Directors. Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): Clinical Report. Pediatrics. 2025 Mar 1;155(3):e2024070334. https://publications.aap.org/pediatrics/article/155/3/e2024070334/200384/Pediatric-Acute-Onset-Neuropsychiatric-Syndrome?autologincheck=redirected . PMID: 39676248.
Bokhari, W. (2025). Comparison of AAP Report Claims vs Literature Evidence [Unpublished table] https://www.getclaimable.com/
Centers for Medicare & Medicaid Services. (2019, July 25). Billing and coding: Intravenous immunoglobulin (IVIG) (Article A56718). Medicare Coverage Database. https://www.cms.gov/medicare-coverage-database/view/article.aspx?articleId=56718
Chang, K., Frankovich, J., Cooperstock, M., et al. (2015). Clinical evaluation of youth with PANS: Recommendations from the 2013 Consensus Conference. Journal of Child and Adolescent Psychopharmacology, 25(1), 3–13. https://pubmed.ncbi.nlm.nih.gov/25325534/
Cherry, J. D., Kaplan, S. L., Demmler‑Harrison, G. J., Steinbach, W. J., Hotez, P. J., & Williams, J. V. (Eds.). (2024). Feigin and Cherry’s textbook of pediatric infectious diseases (9th ed., 2 vols.). Elsevier.
Cooperstock, M. S., Swedo, S. E., Pasternack, M. S., Murphy, T. K., & PANS/PANDAS Consortium. (2017). Clinical management of PANS: Part III—Treatment and prevention of infections. Journal of Child and Adolescent Psychopharmacology, 27, 594–606. https://doi.org/10.1089/cap.2016.0151
Endres, D., Pollak, T. A., Bechter, K., Denzel, D., Pitsch, K., Nickel, K., Runge, K., Pankratz, B., Klatzmann, D., Tamouza, R., Mallet, L., Leboyer, M., Prüss, H., Voderholzer, U., Cunningham, J. L., ECNP Network Immuno-NeuroPsychiatry, Domschke, K., van Elst, L. T., & Schiele, M. A. (2022). Immunological causes of obsessive-compulsive disorder: Is it time for the concept of an “autoimmune OCD”? Translational Psychiatry, 12(1), 5. https://doi.org/10.1038/s41398-021-01700-4
Frankovich, J., Swedo, S., Murphy, T., et al. (2017). Clinical management of PANS: Part II—Use of immunomodulatory therapies. Journal of Child and Adolescent Psychopharmacology, 27(7), 574–593. https://pubmed.ncbi.nlm.nih.gov/36358107/
International Committee of Medical Journal Editors. (2025, April). Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals. https://www.icmje.org/
Kulumani Mahadevan L.S., Murphy M., Selenica M., Latimer E., & Harris B.T. Clinicopathologic characteristics of PANDAS in a young adult: A case report. Dev Neurosci. 2023;45(6):335-341. https://pubmed.ncbi.nlm.nih.gov/37699369/ . Epub 2023 Sep 12. PMID: 37699369; PMCID: PMC10753865.
Octapharma. (2025, June 10). Octapharma releases results for phase 3 superiority study of pediatric acute‑onset neuropsychiatric syndrome [Press release]. Octapharma. https://www.octapharmausa.com/news/press‑release/2025/octapharma‑releases‑results‑phase3‑superiority‑study‑pediatric‑acuteonset‑neuropsychiatric‑syndrome
PANDAS Physicians Network. (n.d.). How to diagnose PANS & PANDAS. Retrieved June 24, 2025, from https://www.pandasppn.org/diagnose/
PANDAS Physicians Network. (n.d.). Flowchart: Diagnosing PANS & PANDAS. Retrieved June 24, 2025, from https://www.pandasppn.org/diagnose/
PANDAS Physicians Network. (2025a, March). PANS/PANDAS Research and Resources: A compilation of studies and articles (2018–2025). Retrieved June 24, 2025, from https://www.pandasppn.org/research‑updates/
PANDAS Physicians Network. (2025b, March 26). Urgent appeal to the AAP regarding its PANS clinical report. https://www.pandasppn.org/urgent-appeal-to-the-aap/
Thienemann, M., Murphy, T., Leckman, J., et al. (2017). Clinical management of PANS: Part I—Psychiatric and behavioral interventions. Journal of Child and Adolescent Psychopharmacology, 27(7), 566–573. https://pubmed.ncbi.nlm.nih.gov/28722481/
Addendum 2
Comparison of AAP Report Claims vs Literature Evidence
Note: This table was adapted from Bokhari, W. (2025). Unpublished work for Claimable.