Therapeutic Plasma Apheresis as a Treatment for 35 Severely Ill Children and Adolescents with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections
Publication: Journal of Child and Adolescent Psychopharmacology
Volume 25, Issue Number 1
Abstract
Background: Because of its reported similarities to Sydenham chorea, therapeutic plasma apheresis (TPA) has been proposed as a potential treatment of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). To date, support for the use of TPA has been limited to a few anecdotal reports and a small placebo-controlled trial demonstrating dramatic symptom improvements at 1 month and 1 year follow-up. To evaluate the safety and efficacy of TPA further, we undertook a retrospective review of all PANDAS patients treated with TPA at Georgetown University Hospital between August 2009 and October 2013.
Methods: Forty patients were identified, and sufficient information was available from medical records and telephone interview for 35 cases (88%). All 35 (23 boys; 12 girls) met diagnostic criteria for PANDAS (Swedo et al. 1998) and had severe symptoms. The TPA procedures were performed at Georgetown University Hospital using a protocol that processes a total of 4.5 blood volumes over 3–5 days (three treatments of 1.5 volumes each). Overall symptom improvements at 6 months post-TPA and long-term follow-up were estimated by parents, who also rated changes in individual symptoms to provide information about patterns of improvement.
Results: All patients were reported to have received at least some benefit from TPA, with average improvement of 65% at 6 months post-TPA and 78% at longer-term follow-up. A decrease in the number of reported symptoms also occurred, with particular improvements in obsessive-compulsive disorder (OCD), anxiety, tics, and somatic symptoms, including dysgraphia, sleep difficulties, and urinary urgency or frequency. Contrary to expectations, preceding duration of illness was not correlated with degree of improvement following TPA, suggesting that acuity of illness is not a factor affecting response. Only two adverse events were reported: both involved reopening of the site where the central line had been placed and resolved immediately following application of pressure and re-dressing of the puncture site.
Conclusions: Therapeutic plasma apheresis is an invasive medical intervention that should be reserved for treatment of children and adolescents who are severely affected by PANDAS. In such patients, it appears to be a safe, well-tolerated, and beneficial treatment option.
Get full access to this article
View all available purchase options and get full access to this article.
References
Brimberg L, Benhar I, Mascaro-Blanco A, Alvarez K, Lotan D, Winter C, Klein J, Moses AE, Somnier FE, Leckman JF, Swedo SE, Cunningham MW, Joel D: Behavioral, pharmacological, and immunological abnormalities after streptoccal exposure: A novel rat model of Sydenham chorea and related neuropsychiatric disorders. Neuropsychopharmacology 37:2076–87, 2012.
Cortese I, Chaudhry V, So YT, Cantor F, Cornblath DR, Rae-Grant A: Evidence-based guideline update: Plasmapheresis in neurologic disorders: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 76:294–300, 2011.
Dale RC: Post-streptococcal autoimmune disorders of the central nervous system. Dev Med Child Neurol 47:785–91, 2005.
Elia J, Dell ML, Friedman DF, Zimmerman RA, Balamuth N, Ahmed AA, Pati S: PANDAS with catatonia: A case report. Therapeutic response to lorazepam and plasmapheresis. J Am Acad Child Adolesc Psychiatry 44:1145–1150, 2005.
Garvey MA, Giedd J, Swedo SE: PANDAS: The search for environmental triggers of pediatric neuropsychiatric disorders. Lessons from rheumatic fever. J Child Neurol 13:413–423, 1998.
Garvey MA, Perlmutter SJ, Allen AJ, Hamburger S, Lougee L, Leonard HL, Witowski ME, Dubbert B, Swedo SE: A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections. Biol Psychiatry 45:1465–1571, 1999.
Garvey MA, Snider LA, Leitman SF, Werden R, Swedo SE: Treatment of Sydenham's chorea with intravenous immunoglobulin, plasma exchange, or prednisone. J Child Neurol 5:424–429, 2005.
Kirvan CA, Swedo SE, Kurahara D, Cunningham MW: Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of Sydenham chorea Autoimmunity 39:21–29, 2006a.
Kirvan CA, Swedo SE, Snider LA, Cunningham MW: Antibody-mediated neuronal cell signaling in behavior and movement disorders. J Neuroimmunol 179:173–179, 2006b.
Murphy ML, Pichichero ME: Prospective identification and treatment of children with pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS). Arch Pediatr Adolesc Med 156:356–361, 2002.
Murphy TK, Parker-Athill EC, Lewin AB, Storch EA, Mutch PJ: Cefdinir for recent onset pediatric neuropsychiatric disorders: A pilot randomized trial. J Child Adolesc Psychopharmacol 2014 Oct 9 [Epub ahead of print].
Nicolson R, Swedo SE, Lenane M, Bedwell J, Wudarsky M, Gochman P, Hamburger SD, Rapoport JL: An open trial of plasma exchange in childhood-onset obsessive-compulsive disorder without poststreptococcal exacerbations. J Am Acad Child Adolesc Psychiatry 39:1313–1315, 2000.
Perlmutter SJ, Leitman SF, Garvey MA, Hamburger S, Feldman E, Leonard HL, Swedo SE: Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet 354:1153–1158, 1999.
Snider LA, Lougee L, Slattery M, Grant P, Swedo SE: Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders. Biol Psychiatry 57:788–792, 2005.
Swedo SE: Sydenham's chorea. A model for childhood autoimmune neuropsychiatric disorders. JAMA 272:1788–1791, 1994.
Swedo SE, Leckman JF, Rose NR: From research subgroup to clinical syndrome: Modifying the PANDAS criteria to describe PANS (pediatric Acute-onset neuropsychiatric syndrome. Pediatr Therapeut 2:113, 2012. https://doi.org/10.4172/2161-0665.1000113.
Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S, Lougee L, Dow S, Zamkoff J, Dubbert BK: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: Clinical description of the first 50 cases. Am J Psychiatry 155:264–271, 1998. Erratum in Am J Psychiatry 155:578, 1998.
Swedo SE, Leonard HL, Rapoport JL: The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: Separating fact from fiction. Pediatrics 113:907–911, 2004.
Swedo SE, Seidlitz J, Kovacevic M, Latimer ME, Hommer R, Lougee L, Grant P.: Clinical presentation of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) in research and community settings. J Child Adolesc Psychopharmacol 25:xxx—xxx, 2015.
Szczepiorkowski ZM, Bandarenko N, Kim HC, Linenberger ML, Marques MB, Sarode R, Schwartz J, Weinstein R, Shaz BH, Apheresis Applications Committee of theAmerican Society for Apheresis: Guidelines on the use of therapeutic apheresis in clinical practice: evidence-based approach from the Apheresis Applications Committee of the American Society for Apheresis. J Clin Apher 22:106–175, 2007a.
Szczepiorkowski ZM, Shaz BH, Bandarenko N, Winters JL: The new approach to assignment of AFA categories – introduction to the fourth special issue: Clinical applications of therapeutic apheresis. J Clin Apher 22:96–105, 2007b.
Tucker DM, Leckman JF, Scahill L, Wilf GE, LaCamera R, Cardona L, Cohen P, Heidmann S, Goldstein J, Judge J, Snyder E, Bult A, Peterson BS, King R, Lombroso P: A putative poststreptococcal case of OCD with chronic tic disorder, not otherwise specified. J Am Acad Child Adolesc Psychiatry 35:1684–1691, 1996.
Weinstein R: Therapeutic apheresis in neurological disorders: A survey of the evidence in support of current category I and II indications for therapeutic plasma exchange. J Clin Apher 23:196–201, 2008.
Information & Authors
Information
Published In

Journal of Child and Adolescent Psychopharmacology
Volume 25 • Issue Number 1 • February 2015
Pages: 70 - 75
PubMed: 25658452
Copyright
Copyright 2015, Mary Ann Liebert, Inc.
History
Published online: 19 February 2015
Published ahead of print: 6 February 2015
Published in print: February 2015
Topics
Authors
Disclosures
No competing financial interests exist.
Metrics & Citations
Metrics
Citations
Export Citation
Export citation
Select the format you want to export the citations of this publication.
View Options
Access content
To read the fulltext, please use one of the options below to sign in or purchase access.⚠ Society Access
If you are a member of a society that has access to this content please log in via your society website and then return to this publication.