Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part II—Use of Immunomodulatory Therapies

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 webbased document. Seven pediatric mental health practitioners, with expertise in diagnosing and monitoring patients with Stanford PANS Clinic and Research Program at Lucile Packard Children’s Hospital, Stanford University School of Medicine, Palo Alto, California. Pediatric Allergy, Immunology, and Rheumatology, Stanford University School of Medicine, Palo Alto, California. Pediatrics and Developmental Neuroscience Branch, National Institute of Mental Health, Bethesda, Maryland. Rothman Center for Pediatric Neuropsychiatry, Pediatrics and Psychiatry, University of South Florida Morsani College of Medicine, Tampa, Florida. Paediatrics and Child Health, Institute for Neuroscience and Muscle Research, the Children’s Hospital at Westmead, University of Sydney, Sydney, Australia. Pathology and Cell Biology (in Neurology and Pharmacology), Columbia University, New York, New York. Pediatric Neuropsychiatry and Immunology Program in the OCD and Related Disorders Program, Harvard Medical School, Boston, Massachusetts. Allergy, Immunology, and Rheumatology, The University of Arizona College of Medicine Tuscon, Tuscon, Arizona. Epidemiology, Center for Infection and Immunity, Columbia University Medical Center, New York, New York. Pediatric Neurology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware. Neurology, University of Southern California Pediatric Movement Disorders Center, Children’s Hospital of Los Angeles, Los Angeles, California. Pediatric Rheumatology, Baylor College of Medicine, Houston, Texas. Pediatric Infectious Disease, Harvard Medical School, Boston, Massachusetts. Pediatric Infectious Diseases, University of Missouri School of Medicine, Columbia, Missouri. Pediatric Infectious Diseases, Stanford University School of Medicine, Stanford, California. Pediatric Rheumatology, Tufts University School of Medicine, Boston, Massachusetts. Microbiology and Immunology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Child and Adolescent Psychiatry, University of Minnesota Medical School, Minneapolis, Minnesota. Pediatric Rheumatology, Miami Rheumatology, LLC, Miami, Florida. Psychiatry and Behavioral Sciences, Child and Adolescent Psychiatry, Stanford University School of Medicine, Palo Alto, California. Pediatric OCD and Tic Disorder Program, Harvard Medical School, Boston, Massachusetts. Pediatric Neurology, Georgetown University Hospital, Washington, District of Columbia. Child Psychiatry, Psychiatry, Psychology and Pediatrics, Yale Child Study Center, Yale School of Medicine, New Haven, Connecticut. a Jennifer Frankovich et al. 2017; Published by Mary Ann Liebert, Inc. This article is available under the Creative Commons License CC-BY-NC (http://creativecommons.org/licenses/by-nc/4.0). This license permits non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. Permission only needs to be obtained for commercial use and can be done via RightsLink. JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume 27, Number 7, 2017 Mary Ann Liebert, Inc. Pp. 1–16 DOI: 10.1089/cap.2016.0148 1 D ow nl oa de d by U ni ve rs ity O f A ri zo na f ro m o nl in e. lie be rt pu b. co m a t 0 8/ 30 /1 7. F or p er so na l u se o nl y. 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 lifethreatening 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.