Joint Rebutttal Statement to the AAP

JOINT STATEMENT FROM FOUR NATIONAL PANS/PANDAS NON-PROFITS AND CLAIMABLE, A COMPANY SUPPORTING AFFECTED FAMILIES

 

Read: Full Joint Letter to AAP and below.

 Four leading PANS/PANDAS organizations, ASPIRE, NWPPN, PANDAS Network and the Look. Foundation, together with Claimable, a company providing advocacy and support for families navigating PANS/PANDAS, are raising serious concerns about the American Academy of Pediatrics’ (AAP) 2024 Clinical Report on PANS/PANDAS.

The AAP Report is not a clinical guideline—yet some pediatricians are citing it to block diagnosis and treatment, and by insurers to justify denials of critical therapies, including IVIG.

This misuse is deeply concerning and has real-world consequences.

The report:

• Omits key studies supporting the use of IVIG and steroids
• Conflicts with peer-reviewed clinical guidelines from institutions like Stanford, Columbia, and the NIMH
• Lacks transparency regarding authorship and expert input
• Advises against important diagnostic tools like strep testing

As a result, children are being misdiagnosed, undertreated, or denied care altogether—leading to psychiatric crises, medical complications, and devastating impacts on families.

We respectfully urge the following actions:

• The AAP should retract and revise the report to address its omissions and clarify its intended use
• Pediatricians should rely on the established, peer-reviewed clinical guidelines (JCAP) for diagnosing and treating PANS/PANDAS
• Insurers should stop using the report to deny care and revisit all IVIG denials based on it

This is about more than policy—it’s about protecting children from preventable suffering. We stand united in calling for an evidence-based, compassionate, and transparent approach to care.

#PANS #PANDAS #AAPReport #AccessToCare #ChildHealth #EvidenceBasedCare #SupportFamilies

 

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DATE: July 25, 2025
RE: Rebuttal to the American Academy of Pediatrics Clinical Report on PANS (12/16/24)

Dear Drs. Kressly, Shaw, Szilagyi, and Sanders, Mr. Del Monte, and Secretary Kennedy:

We are compelled to respond to the American Academy of Pediatrics (“AAP”) Pediatric
Acute-Onset Neuropsychiatric Syndrome (PANS): Clinical Report (“Report”) published on December 16, 2024, which is now being misused by pediatric providers to diagnose and treat
PANDAS/PANS, as well as by insurers to justify the denial of IVIG coverage.The AAP itself explicitly states that this document is not a clinical guideline and should not be used to dictate treatment decisions:

“Because they are limited by the present level of evidence on the topic, the findings are
presented as a report rather than a clinical practice guideline.”

Despite this disclaimer, pediatric providers are misapplying the report by disregarding
established clinical guidelines, leading to failures in properly diagnosing and treating
PANDAS/PANS. At the same time, insurers are misusing the report as definitive evidence against
IVIG, ignoring its limitations, lack of transparency, and omitted research. This misrepresentation
threatens access to critical treatment and delays necessary medical care.

OUR IMMEDIATE REQUEST

Given the serious flaws in the AAP Report and the inappropriate ways in which it is being
used,we call for the following immediate actions.:

• The AAP must retract this report until its flaws are corrected and its intended use is
  clarified. Its lack of transparency, omitted research, and misrepresentation of IVIG
  make it unreliable and misleading.
• The imperative of medical rule-out in psychiatric diagnoses: Under the DSM-5
  guidelines, mental health practitioners and physicians must rule out any underlying
  medical cause before assigning a psychiatric diagnosis. However, much of this report
  relies heavily on psychiatric labeling. Failing to perform an “etiological medical
  rule-out” not only risks medical negligence but can also deny patients access to
  accurate, potentially life-saving diagnoses and treatments.
• Insurers must stop using this report to deny care. It is not a clinical guideline, and
  its misuse harms families and obstructs physician-led treatment.
• All IVIG denials based on this report must be reconsidered immediately in light of
  strong medical evidence supporting its use for moderate-severe PANS/PANDAS

CONSEQUENCES OF A FAILURE TO ACT

The failure to act allows pediatricians and insurers to continue leveraging an incomplete
document at the expense of patient care, forcing children into needless suffering and
irreversible harm. Without treatment, these children may experience a panoply of consequences,
including:

• Severe neuropsychiatric decline, leaving them unable to speak, eat, or attend school
• Malnutrition and medical starvation, requiring hospitalization and feeding tubes
• Increase in autoimmune biomarkers demonstrated in 54.2% of children in a 2024 cohort
  study by Ma et al
• Psychiatric crises, leading to emergency interventions and long-term disability
• Permanent cognitive and developmental regression, forcing families into financial
  hardship
• Fatalities – The POND brainbank was established in 2022 with the goal of understanding the pathogenesis and mechanisms associated with PANS/PANDAS. The 11 specimens within the brain bank were donated by the families of their deceased children.

When pediatric providers rely on a non-guideline document to guide diagnosis and treatment, it
undermines evidence-based care and delays appropriate interventions, worsening outcomes and
increasing long-term costs. Likewise, denying IVIG does not reduce costs—it escalates them,
shifting the burden to emergency hospitalizations, feeding interventions, and more expensive
treatments like plasmapheresis. Both examples fail to recognize established diagnostic and
treatment guidelines published by subject experts having worked in the field of PANDAS/PANS for 30 years.

Why the AAP Report Fails as Pediatric Clinical Guidance and Justification for IVIG Denial

1 It Is Not a Clinical Guideline

The AAP explicitly states that this report does not provide oicial treatment recommendations. It lacks consensus-based standards and does not establish clear directives for insurers to follow. This may represent misuse of clinical reports in medical practice.

2 Impedes Access to Testing and Diagnosis

The 2024 AAP Report on PANS/PANDAS restricts key diagnostic tools, advising against routine streptococcus testing (e.g., throat cultures, rapid antigen tests) unless classic symptoms like
pharyngitis are present, and discouraging brain imaging (e.g., MRI) unless focal neurological signs
suggest alternative diagnoses such as autoimmune encephalitis. The imposed limitations risk
delaying or preventing accurate diagnosis, making it harder for families to access appropriate
testing, specialist care, and insurance coverage—ultimately obstructing timely intervention for
children with acute-onset neuropsychiatric symptoms while driving up longer term direct and
indirect costs to families, employers and insurers.

3. Lack of Transparency and Expert Input

The AAP report does not disclose its authors or the specialists consulted, raising serious
credibility concerns. There is no indication that experts in pediatric neuroimmunology, infectious
disease, or immunology—fields essential to understanding PANS/PANDAS as well as IVIG’s
role—were involved.

The AAP did not consult any of the major multidisciplinary university clinics that research and
treat PANS/PANDAS. These institutions represent thousands of cases of collective experience,
yet their input was neither sought nor included.

By failing to adequately disclose potential conflicts of interest, the AAP violated transparency
standards, calling the report’s validity into question. According to International Committee of
Medical Journal Editors (ICMJE) standards: “Authors should disclose relationships and activities that readers could perceive to have influenced, or that give the appearance of potentially influencing, their work. This includes, but is not limited to, relationships with for-profit and not-for-profit third parties whose interests may be affected by the content of the manuscript.”

4. Omits Key Studies and Is Already Outdated

The review period for the AAP report ended in 2023, meaning it fails to incorporate newer
research—including Melamed et al. (2024)— which demonstrated statistically significant
improvements in OCD-related symptoms following IVIG treatment. Additionally, the omission of
studies on the use of steroids to shorten the duration of flares.

Even within its stated review period, the report omitted clinical guidelines and studies that
support the use of steroids and IVIG, including:

• Swedo, Cooperstock, Frankovich, Thienemann et al. (2017): Consensus Guidelines
  explicitly include IVIG as a recommended treatment for severe cases. These expert-driven
  guidelines remain a valid and authoritative clinical framework.
• Pavone (2020), Hajjari (2022), and Eremija (2023): All demonstrated IVIG’s eectiveness
  for severe or persistent cases.
• Melamed et al. (2021): A multi-site, open-label study of 21 patients over six months
  showed measurable improvements in psychological function with IVIG. Results were
  statistically significant.
• Brown K, Farmer C, Farhadian B, Hernandez J, Thienemann M, Frankovich J. (2017) Corticosteroids may be a helpful treatment intervention in patients with new-onset and relapsing/remitting PANS and PANDAS, hastening symptom improvement or resolution. When corticosteroids are given earlier in a disease flare, symptoms improve more quickly and patients achieve clinical remission sooner. Additionally, the AAP report selectively dismisses positive IVIG studies due to small sample sizes while accepting weak or inconclusive evidence against IVIG without applying the same scrutiny, introducing bias into its conclusions.

Further, standard prescribing and coverage policies routinely approve off-label pediatric
treatments (Carmack et al., 2020; Allen et al., 2018; Shah et al., 2007) and therapies for small
patient populations using similar evidence standards. PANS/PANDAS is widely accepted to be a
rare disease, and thus large multi-arm randomized and double-blinded studies are
methodologically impractical.

A 2025 randomized, placebo-controlled Phase III study (NCT04508530) of PANZYGA® in PANS
patients demonstrated a clinically meaningful reduction in CY-BOCS scores (31.1% improvement
vs. 12.1% in placebo), though the p-value narrowly missed statistical significance (p = 0.072).
However, the secondary endpoint—the Clinical Global Impression scale (CGI-I)—achieved
statistical significance (p = 0.017), validating PANZYGA®’s real-world clinical benefit across
multiple domains of functioning. These findings directly contradict the AAP Report’s implication
that evidence for IVIG is weak or unreliable.

5. Denials Based on This Report Contradicts Cost-Saving Measures

Blocking access to IVIG is not only harmful—it is financially irresponsible. Calaprice et al. (2023)
found that unrestricted access to care for PANS results in more symptom-free days, significantly
reducing the need for costly hospitalizations, psychiatric admissions, emergency
interventions, and lost wages for caregiving parents.

When IVIG is denied, families face greater financial and medical burdens, including:

• Severe psychiatric hospitalizations
• Feeding tube interventions due to OCD-driven food refusal
• Plasmapheresis, a far more expensive treatment that could have been avoided with
  IVIG

Families who are denied access based on the AAP Report have been forced to pay out of pocket,
which serves to further widen the disparities associated outcomes along socioeconomic lines.
Access problems caused by sequential denials may only be ameliorated with access to legal
counsel, which again is generally not widely available to many families.

PEDIATRIC PROVIDERS ARE FAILING TO PROPERLY DIAGNOSE AND TREAT PANDAS/PANS — AND INSURERS ARE MISUSING THE AAP REPORT TO JUSTIFY DENIALS

Many pediatric providers are citing the AAP Report to justify treating PANS/PANDAS solely as a
psychiatric condition—directly contradicting peer-reviewed, evidence-based guidelines
developed by the PANS Research Consortium. These guidelines were published in
JCAP in 2017 and 2019, authored by leading experts from institutions including Stanford, Columbia, and the NIMH. Yet due to the AAP’s institutional weight, its flawed report is often prioritized over these more specialized clinical standards.

This widespread clinical misapplication is not occurring in isolation—insurers are seizing on it to
justify treatment denials and further restrict access to care.

A review of over 100 denied PANS/PANDAS-related cases shows an accelerating pattern since
early 2025: insurers are increasingly invoking the 2024 AAP Report in ways that distort its intent.
Although the report explicitly states it is not a clinical guideline, it is being treated as one—used to
justify denials and restrict access to care, often without appropriate clinical justification or
specialty input.

For example, Wellmark justified a denial by stating:

“A recent AAP review article-position published recently indicates essentially nothing has
changed regarding the utilization of IVIG in the treatment of presumed PANS-PANDAS.”

Here, Wellmark conflates the AAP Report and the outdated AAP Red Book, using both to assert a lack of evidence while disregarding more current, supportive data.

Premera Blue Cross similarly cited the AAP to dismiss IVIG, asserting:

“ In 2024, the American Academy of Pediatrics (AAP) published a clinical report in which
their expert panel concluded… there are no well-designed trials that provide
evidence-based guidance on treatment for PANS’ symptoms…”

Premera’s framing misrepresents the evidence base, and the denial falsely implies that psychiatric
and antibiotic care alone is sufficient—despite acknowledging that PANS is likely a valid diagnosis.

These examples demonstrate a dangerous pattern: insurers are using a non-guideline report to
undermine medical judgment, deny treatment access, and sidestep robust clinical evidence.

CONCLUSION

The AAP report is not a clinical guideline and should not be used to dismiss diagnosis or treatment
of PANS/PANDAS by pediatric providers, nor to justify IVIG denials. Coverage decisions must be
based on clinical needs and strong medical evidence supporting IVIG for PANS/PANDAS.
We urge the following immediate actions:

• Pediatricians must stop using the flawed AAP report in place of well-established,
  evidence-based clinical guidelines that are essential for the proper diagnosis and
  treatment of PANS/PANDAS.
• The AAP should retract the report until its flaws are addressed and its intended use
  clarified.
• Insurers must stop using the report for utilization management to deny care.
• Insurers must reconsider all IVIG denials based on this report.
• Employer fiduciaries of self-funded plans must ensure the AAP report is not used to
  restrict care.
• State Departments of Insurance should sanction insurers for misusing unsound evidence in unsound coverage determinations.

The continued misuse of this non-guideline report to dismiss diagnosis and deny treatment is an
unacceptable violation of the principles of non-maleficence (do no harm) and beneficence (act in
the patient’s best interest). Denying IVIG based on this flawed report is medically unsound,
financially reckless, and ethically indefensible—contradicting clinical guidelines, increasing
long-term costs, and undermining clinician authority.

 

Sincerely,

Gabriella True, President – ASPIRE

Warris Bokhari, MD, CEO & Co-Founder – Claimable

Jennifer M. Vitelli, MBA, Executive Director – Look. Foundation

Sarah Lemley MPA; HA, Executive Director – Northwest PANDAS/PANS Network

Diana Pohlman, Executive Director – PANDAS Network

COMPARISON OF AAP REPORT CLAIM VS. LITERATURE EVIDENCE

AAP REPORT vs 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, h) polysomnography abnormalities similar to other basal ganglia disorders, i) neuroimaging studies showing basal ganglia edema during flares, j) elevated anti dopamine receptor antibodies, k) 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.

 

REFERENCES

CLINICAL RESEARCH STUDIES

Calaprice-Whitty D, Tang A, Tona J. Factors associated with symptom persistence in PANS: Part I-Access to care. J Child Adolesc Psychopharmacol. 2023;33(9):356-364. doi:10.1089/cap.2023.0022. Epub 2023 Oct 30. PMID: 37902790.

Kulumani Mahadevan LS, Murphy M, Selenica M, Latimer E, Harris BT. Clinicopathologic characteristics of PANDAS in a young adult: a case report. Dev Neurosci. 2023;45(6):335-341. doi:10.1159/000534061. Epub 2023 Sep 12. PMID: 37699369; PMCID: PMC10753865.

Pavone P, Falsaperla R, Cacciaguerra G, et al. PANS/PANDAS: clinical experience in IVIG treatment and state of the art in rehabilitation approaches. NeuroSci. 2020;1:75–84. doi:10.3390/neurosci1020007.

Melamed I, Kobayashi RH, O’Connor M, et al. Evaluation of intravenous immunoglobulin in pediatric acute-onset neuropsychiatric syndrome. J Child Adolesc Psychopharmacol. 2021;31(2):118-128. doi:10.1089/cap.2020.0100.

Hajjari P, Oldmark MH, Fernell E, et al. Pediatric acute-onset neuropsychiatric syndrome (PANS) and intravenous immunoglobulin (IVIG): comprehensive open-label trial in ten children. BMC Psychiatry. 2022;22(1):535. doi:10.1186/s12888-022-04181-x. PMID: 35933358; PMCID: PMC9357317.

Eremija J, Patel S, Rice S, Daines M. Intravenous immunoglobulin treatment improves multiple neuropsychiatric outcomes in patients with pediatric acute-onset neuropsychiatric syndrome. Front Pediatr. 2023;11:1229150. doi:10.3389/fped.2023.1229150. PMID: 37908968; PMCID: PMC10613689.

Melamed I, Rahman S, Pein H, et al. IVIG response in pediatric acute-onset neuropsychiatric syndrome correlates with reduction in pro-inflammatory monocytes and neuropsychiatric measures. Front Immunol. 2024;15:1383973. doi:10.3389/fimmu.2024.1383973.

Vreeland A, et al. Postinfectious inflammation, autoimmunity, and obsessive-compulsive disorder: Sydenham chorea, pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection, and pediatric acute-onset neuropsychiatric disorder. Dev Neurosci. 2023;45(6):361-374. doi:10.1159/000534261.

Carmack M, Hwang T, Bourgeois FT. Pediatric Drug Policies Supporting Safe And Effective Use Of Therapeutics In Children: A Systematic Analysis. Health Aff (Millwood). 2020 Oct;39(10):1799-1805. doi:10.1377/hlthaff.2020.00198. PMID: 33017255.

Allen HC, Garbe MC, Lees J, Aziz N, Chaaban H, Miller JL, Johnson P, DeLeon S. Off-Label Medication use in Children, More Common than We Think: A Systematic Review of the Literature. J Okla State Med Assoc. 2018 Oct;111(8):776-783. PMID: 31379392; PMCID: PMC6677268.

Zheng J, Frankovich J, McKenna ES, et al. Association of Pediatric Acute-Onset Neuropsychiatric Syndrome With Microstructural Differences in Brain Regions Detected via Diffusion-Weighted Magnetic Resonance Imaging. JAMA Network Open. 2020;3(5):e204063. doi:10.1001/jamanetworkopen.2020.4063.

Johnson M, Ehlers S, Fernell E, et al. Anti-Inflammatory, Antibacterial and Immunomodulatory Treatment in Children With Symptoms Corresponding to the Research Condition PANS (Pediatric Acute-Onset Neuropsychiatric Syndrome): A Systematic Review. PloS One. 2021;16(7):e0253844.

Trifiletti R, Lachman HM, Manusama O, et al. Identification of Ultra-Rare Genetic Variants in Pediatric Acute Onset Neuropsychiatric Syndrome (PANS) by Exome and Whole Genome Sequencing. Scientific Reports. 2022;12(1):11106.

Xu J, Frankovich J, Liu RJ, et al. Elevated Antibody Binding to Striatal Cholinergic Interneurons in Patients With Pediatric Acute-Onset Neuropsychiatric Syndrome. Brain, Behavior, and Immunity.

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Michael Daines, MD (PI). A Superiority Phase 3 Study to Compare the Effect of Panzyga Versus Placebo in Patients with Paediatric Acute-Onset Neuropsychiatric Syndrome, protocol NGAM-13.

Perlmutter SJ, Leitman SF, Garvey MA, Hamburger S, Feldman E, Leonard HL, et al. Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet. 1999;354(9185):1153–8. https://doi.org/10.1016/S0140-6736(98)12297-3