Clinical management of pediatric acute-onset neuropsychiatric syndrome: Part II—use of immunomodulatory therapies

Jennifer Frankovich, Susan Swedo, Tanya Murphy, Russell C. Dale, Dritan Agalliu, Kyle Williams, Michael O Daines, Mady Hornig, Harry Chugani, Terence Sanger, Eyal Muscal, Mark Pasternack, Michael Cooperstock, Hayley Gans, Yujuan Zhang, Madeleine Cunningham, Gail Bernstein, Reuven Bromberg, Theresa Willett, Kayla BrownBahare Farhadian, Kiki Chang, Daniel Geller, Joseph Hernandez, Janell Sherr, Richard Shaw, Elizabeth Latimer, James Leckman, Margo Thienemann

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)574-593
Number of pages20
JournalJournal of Child and Adolescent Psychopharmacology
Volume27
Issue number7
DOIs
StatePublished - Sep 1 2017

Fingerprint

Immunomodulation
Pediatrics
Adrenal Cortex Hormones
Guidelines
Intravenous Immunoglobulins
Therapeutics
Plasma Exchange
Nurse Practitioners
National Institutes of Health (U.S.)
Physiologic Monitoring
Cognitive Therapy
Advisory Committees
Clinical Protocols
Autoimmunity
Research
Communicable Diseases
Psychiatry
Mental Health
Anti-Inflammatory Agents
Animal Models

Keywords

  • Corticosteroids
  • IVIG
  • NSAIDs
  • PANDAS
  • PANS
  • Plasmapheresis

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Clinical management of pediatric acute-onset neuropsychiatric syndrome : Part II—use of immunomodulatory therapies. / Frankovich, Jennifer; Swedo, Susan; Murphy, Tanya; Dale, Russell C.; Agalliu, Dritan; Williams, Kyle; Daines, Michael O; Hornig, Mady; Chugani, Harry; Sanger, Terence; Muscal, Eyal; Pasternack, Mark; Cooperstock, Michael; Gans, Hayley; Zhang, Yujuan; Cunningham, Madeleine; Bernstein, Gail; Bromberg, Reuven; Willett, Theresa; Brown, Kayla; Farhadian, Bahare; Chang, Kiki; Geller, Daniel; Hernandez, Joseph; Sherr, Janell; Shaw, Richard; Latimer, Elizabeth; Leckman, James; Thienemann, Margo.

In: Journal of Child and Adolescent Psychopharmacology, Vol. 27, No. 7, 01.09.2017, p. 574-593.

Research output: Contribution to journalArticle

Frankovich, J, Swedo, S, Murphy, T, Dale, RC, Agalliu, D, Williams, K, Daines, MO, 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 2017, 'Clinical management of pediatric acute-onset neuropsychiatric syndrome: Part II—use of immunomodulatory therapies', Journal of Child and Adolescent Psychopharmacology, vol. 27, no. 7, pp. 574-593. https://doi.org/10.1089/cap.2016.0148
Frankovich, Jennifer ; Swedo, Susan ; Murphy, Tanya ; Dale, Russell C. ; Agalliu, Dritan ; Williams, Kyle ; Daines, Michael O ; Hornig, Mady ; Chugani, Harry ; Sanger, Terence ; Muscal, Eyal ; Pasternack, Mark ; Cooperstock, Michael ; Gans, Hayley ; Zhang, Yujuan ; Cunningham, Madeleine ; Bernstein, Gail ; Bromberg, Reuven ; Willett, Theresa ; Brown, Kayla ; Farhadian, Bahare ; Chang, Kiki ; Geller, Daniel ; Hernandez, Joseph ; Sherr, Janell ; Shaw, Richard ; Latimer, Elizabeth ; Leckman, James ; Thienemann, Margo. / Clinical management of pediatric acute-onset neuropsychiatric syndrome : Part II—use of immunomodulatory therapies. In: Journal of Child and Adolescent Psychopharmacology. 2017 ; Vol. 27, No. 7. pp. 574-593.
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T1 - Clinical management of pediatric acute-onset neuropsychiatric syndrome

T2 - Part II—use of immunomodulatory therapies

AU - Frankovich, Jennifer

AU - Swedo, Susan

AU - Murphy, Tanya

AU - Dale, Russell C.

AU - Agalliu, Dritan

AU - Williams, Kyle

AU - Daines, Michael O

AU - Hornig, Mady

AU - Chugani, Harry

AU - Sanger, Terence

AU - Muscal, Eyal

AU - Pasternack, Mark

AU - Cooperstock, Michael

AU - Gans, Hayley

AU - Zhang, Yujuan

AU - Cunningham, Madeleine

AU - Bernstein, Gail

AU - Bromberg, Reuven

AU - Willett, Theresa

AU - Brown, Kayla

AU - Farhadian, Bahare

AU - Chang, Kiki

AU - Geller, Daniel

AU - Hernandez, Joseph

AU - Sherr, Janell

AU - Shaw, Richard

AU - Latimer, Elizabeth

AU - Leckman, James

AU - Thienemann, Margo

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

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KW - Corticosteroids

KW - IVIG

KW - NSAIDs

KW - PANDAS

KW - PANS

KW - Plasmapheresis

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