Clinical management of pediatric acute-onset neuropsychiatric syndrome: Part II-Use of Immunomodulatory Therapies
Open accessAbstract
Introduction: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a clinically heterogeneous disorder with a number of different etiologies and disease mechanisms. Inflammatory and postinfectious autoimmune presentations of PANS occur frequently, with some clinical series documenting immune abnormalities in 75%–80% of patients. Thus, comprehensive treatment protocols must include immunological interventions, but their use should be reserved only for PANS cases in which the symptoms represent underlying neuroinflammation or postinfectious autoimmunity, as seen in the PANDAS subgroup (Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infections). Methods: The PANS Research Consortium (PRC) immunomodulatory task force is comprised of immunologists, rheumatologists, neurologists, infectious disease experts, general pediatricians, psychiatrists, nurse practitioners, and basic scientists with expertise in neuroimmunology and PANS-related animal models. Preliminary treatment guidelines were created in the Spring of 2014 at the National Institute of Health and refined over the ensuing 2 years over conference calls and a shared web-based document. Seven pediatric mental health practitioners, with expertise in diagnosing and monitoring patients with PANS, were consulted to create categories in disease severity and critically review final recommendations. All authors played a role in creating these guidelines. The views of all authors were incorporated and all authors gave final approval of these guidelines. Results: Separate guidelines were created for the use of immunomodulatory therapies in PANS patients with (1) mild, (2) moderate-to-severe, and (3) extreme/life-threatening severity. For mildly impairing PANS, the most appropriate therapy may be “tincture of time” combined with cognitive behavioral therapy and other supportive therapies. If symptoms persist, nonsteroidal anti-inflammatory drugs and/or short oral corticosteroid bursts are recommended. For moderate-to-severe PANS, oral or intravenous corticosteroids may be sufficient. However, intravenous immunoglobulin (IVIG) is often the preferred treatment for these patients by most PRC members. For more severe or chronic presentations, prolonged corticosteroid courses (with taper) or repeated high-dose corticosteroids may be indicated. For PANS with extreme and life-threatening impairment, therapeutic plasma exchange is the first-line therapy given either alone or in combination with IVIG, high-dose intravenous corticosteroids, and/or rituximab. Conclusions: These recommendations will help guide the use of anti-inflammatory and immunomodulatory therapy in the treatment of PANS.
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A Comprehensive Review of Tic Disorders in Children
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Current Research Updates on PANDAS and PANS
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Tourette Syndrome and Tic Disorders
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Self-citationSymptom flares after COVID-19 infection versus vaccination among youth with PANS/PANDAS
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Pediatric Postviral Autoimmune Disorders of the CNS
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McMillan, D. J., Ketheesan, S., Rafeek, R. A. M., Thapa, R., Munif, M. R., Hamlin, A. S., Tully, P. J., Norton, R. E., White, A. A., & Ketheesan, N. (2024) · Heart and Mind · doi:10.4103/hm.hm-d-23-00069 · Cited by 4 · see citing works
Wald, E. R. (2019) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0000000000002295 · Cited by 4 · see citing works
Occupational performance patterns in children with paediatric acute‐onset neuropsychiatric syndrome
Newby, M. J., Lane, S. J., Haracz, K., Tona, J., Palazzi, K. L., & Lambkin, D. (2024) · Australian Occupational Therapy Journal · doi:10.1111/1440-1630.12995 · Cited by 4 · see citing works
Dore, S., Satta, D., Zinellu, A., Boscia, G., Carta, A., Fruschelli, M., Serra, R., & Pinna, A. (2024) · Diseases · doi:10.3390/diseases12050083 · Cited by 3 · see citing works
Role of tonsillectomy and adenoidectomy in parental satisfaction of treatments for PANDAS
Prasad, N. R., Johng, S. Y., Powell, D. S., Williams, M., Latimer, E., & Harley, E. H. (2021) · American Journal of Otolaryngology · doi:10.1016/j.amjoto.2021.102963 · Cited by 3 · see citing works
Self-citationSensory processing in children with Paediatric Acute‐onset Neuropsychiatric Syndrome
Newby, M. J., Lane, S. J., Haracz, K., Tona, J., Palazzi, K. L., & Lambkin, D. (2024) · Australian Occupational Therapy Journal · doi:10.1111/1440-1630.12935 · Cited by 3 · see citing works
Newby, M. J., Lane, S. J., Haracz, K., Tona, J., Palazzi, K. L., & Lambkin, D. (2024) · Australian Occupational Therapy Journal · doi:10.1111/1440-1630.12999 · Cited by 3 · see citing works
Neuropsychiatric symptoms following sore throat in a young boy
Jadah, R. H. S., & Mujeeb, A. A. (2019) · BMJ Case Reports · doi:10.1136/bcr-2018-227540 · Cited by 3 · see citing works
Current Approaches to PANS/PANDAS Diagnostics and Management
Kostik, I. A., & Kostik, M. M. (2020) · Вопросы современной педиатрии · doi:10.15690/vsp.v18i5.2055 · Cited by 3 · see citing works
New Research in Obsessive-Compulsive Disorder and Major Depression
Aouizerate, B., & Haffen, É. (2019) · Brain Sciences · doi:10.3390/brainsci9060140 · Cited by 3 · see citing works
Parent perceptions of various treatment approaches for PANS and PANDAS
Dailey, M. M., Colombo, G. M., Pinciotti, C. M., Sadek, S. J., Muscal, E., Saxena, K., Goodman, W. K., & Storch, E. A. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.10.100 · Cited by 2 · see citing works
Self-citationBiological Mechanisms and Treatment of Obsessive–Compulsive Disorder
Pittenger, C. (2026) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-081423-020516 · Cited by 2 · see citing works
Brown, C. E., & Hawley, K. M. (2021) · Evidence-Based Practice in Child and Adolescent Mental Health · doi:10.1080/23794925.2020.1855611 · Cited by 2 · see citing works
Ringer, N., Benjaminson, C., & Bejnö, H. (2023) · Cogent Psychology · doi:10.1080/23311908.2023.2259745 · Cited by 2 · see citing works
Developmental Impacts of PANS/PANDAS and Inadequate Support for Children and Families
LaRusso, M. D., & Abadía‐Barrero, C. E. (2024) · Child Psychiatry & Human Development · doi:10.1007/s10578-024-01723-0 · Cited by 2 · see citing works
Strydom, J. P., Brand, L., Viljoen, F. P., & Wolmarans, D. W. (2024) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-024-00778-y · Cited by 2 · see citing works
European advocacy organizations respond to PANS/PANDAS article
Gerland, G., Mogyorosi-Post, A., Cafferky, K., Galardini, G., Granli, K., & Tuckey, G. (2018) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2018.09.056 · Cited by 2 · see citing works
Tang, A. W., Jimenez, P. M. P., Miller, I. K. T., Madan, J. C., Nguyen, J. B., Ma, M., Silverman, M. A., Farhadian, B., Wilson, J. L., Goyal, A., et al. (2025) · Developmental Neuroscience · doi:10.1159/000543969 · Cited by 1 · see citing works
Self-citationJasser, M. T., Ferland, T., Bocian, T., Goff, M., Gauch, A., Heinz, M. V., Joffrey, E., Morse, R. P., Albert, D., Frankovich, J., et al. (2025) · Developmental Neuroscience · doi:10.1159/000545349 · Cited by 1 · see citing works
Self-citationDale, R. C., & Patel, S. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-10944-7.00140-2 · Cited by 1 · see citing works
Self-citationNeuroimmunology of tics and Gilles de la Tourette Syndrome
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Șchiopu, C. G., Dobre, C. E., Alexinschi, O., Oprea, D. C., Boloș, A., Nogueira, G., Lupușoru, C. G., Gurbet, A., Găină, M.-A., & Ștefănescu, C. (2026) · Psychiatry International · doi:10.3390/psychiatryint7040155 · Cited by 1 · see citing works
How Parents of Students with PANDAS or PANS Perceive the Educational Process
Doran, P. R., & O'Hanlon, E. (2019) · Journal of the American Academy of Special Education Professionals · doi:10.64546/jaasep.405 · Cited by 1 · see citing works
Brown, L. W. (2018) · Elsevier eBooks · doi:10.1016/b978-0-323-51147-6.00004-1 · Cited by 1 · see citing works
Neuropsychiatric Symptoms and Tick-Borne Diseases
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The Immune-Brain Interface: Exploring PANS and PANDAS in Pediatric Neuropsychiatry
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PANDAS and PANS: An Inflammatory Hypothesis for a Childhood Neuropsychiatric Disorder
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Self-citationTherapeutic Apheresis in Neurology
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(2019) · Psychiatry and Clinical Psychopharmacology · doi:10.1080/24750573.2019.1606883 · Cited by 1 · see citing works
Pediatric Inflammatory Brain Disease
Tran, P., Frankovich, J., Mater, H. V., Dale, R. C., Or‐Geva, N., McHugh, A., & Thienemann, M. (2018) · Elsevier eBooks · doi:10.1016/b978-0-323-51147-6.00014-4
Self-citationAction in the face of uncertainty?
Thienemann, M., & Frankovich, J. (2018) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2018.08.014
Self-citationTreating pediatric acute-onset neuropsychiatric syndrome
Heavey, E. J., & Peterson, K. (2019) · The Nurse Practitioner · doi:10.1097/01.npr.0000553400.88847.5d
PANDAS: behov for nasjonale retningslinjer
Berger, M. F., Aarli, Å., & Griffiths, S. T. (2021) · Tidsskrift for Norsk psykologforening · doi:10.52734/5tfiz496
- Authors
- Frankovich, J., Swedo, S., Murphy, T., Dale, R. C., Agalliu, D., Williams, K., Daines, M., Hornig, M., Chugani, H., Sanger, T., Muscal, E., Pasternack, M., Cooperstock, M., Gans, H., Zhang, Y., Cunningham, M., Bernstein, G., Bromberg, R., Willett, T., Brown, K., Farhadian, B., Chang, K., Geller, D., Hernandez, J., Sherr, J., Shaw, R., Latimer, E., Leckman, J., Thienemann, M., & PANS/PANDAS Consortium
- Affiliations
- Lucile Packard Children's Hospital (US)
- National Institutes of Health (US)
- University of South Florida (US)
- The University of Sydney (AU)
- Columbia University (US)
- Harvard University (US)
- University of Arizona (US)
- Columbia University Irving Medical Center (US)
- Alfred I. duPont Hospital for Children (US)
- University of Southern California (US)
- Baylor College of Medicine (US)
- University of Missouri (US)
- Stanford Medicine (US)
- Tufts University (US)
- University of Oklahoma Health Sciences Center (US)
- University of Minnesota (US)
- Pediatric Rheumatology, Miami Rheumatology, LLC, Miami, Florida.
- Georgetown University Medical Center (US)
- Yale University (US)
- Corresponding author
- Frankovich, Jennifer
- ORCID
- Frankovich, Jennifer
- Swedo, Susan
- Murphy, Tanya
- Dale, Russell C.
- Agalliu, Dritan
- Daines, Michael
- Hornig, Mady
- Chugani, Harry
- Sanger, Terence
- Muscal, Eyal
- Gans, Hayley
- Zhang, Yujuan
- Cunningham, Madeleine
- Bernstein, Gail
- Brown, Kayla
- Chang, Kiki
- Geller, Daniel
- Hernandez, Joseph
- Shaw, Richard
- Leckman, James
- Thienemann, Margo
- Venue
- Journal of Child and Adolescent Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2017-09-01
- Volume
- 27
- Issue
- 7
- Pages
- 574-593
- ISSN
- 1044-5463 (ISSN-L)
- 1557-8992
- PMC
- PMC9836706
- OpenAlex
- W2739465988
- Cited by
- 139
- References
- 118
- Citations by year
- 2026: 20 · 2025: 10 · 2024: 25 · 2023: 18 · 2022: 9 · 2021: 13 · 2020: 10 · 2019: 15 · 2018: 14 · 2017: 5
- FWCI
- 8.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Child and Adolescent Psychopharmacology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Brain and Behavior Research Foundation
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Massachusetts General Hospital
- American Academy of Child and Adolescent Psychiatry
- Biogen
- Teva Pharmaceutical Industries
- International OCD Foundation
- F. Hoffmann-La Roche
- Sunovion
- Psyadon Pharmaceuticals
- Neurocrine Biosciences
- Forest Research Institute
- University of Oxford
- Multiple Sclerosis Australia
- Karolinska Institutet
- Shire
- UBS Optimus Foundation
- Medac
- National Institutes of Health
- Centers for Disease Control and Prevention
- National Health and Medical Research Council
- National Institute of Mental Health (R21MH087849)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD080096)
- Topics
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- pediatric acute-onset neuropsychiatric syndrome, PANS, PANDAS, immunomodulatory therapy, corticosteroids, intravenous immunoglobulin, plasma exchange, rituximab, neuroinflammation, treatment guidelines, disease severity classification, cognitive behavioral therapy, nonsteroidal anti-inflammatory drugs
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