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Challenging the Etiologic Constructs of Disordered Eating 6 140 Pediatrics 2017 ROUGH GALLEY PROOF 2

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Challenging the Etiologic Constructs of Disordered Eating 6 140 Pediatrics 2017 ROUGH GALLEY PROOF 2 Anorexia and Autoimmunity: ChallengingRebecca E. Hommer, MD, Susan E. Swedo, the MD Etiologic Constructs of Disordered Eating 6 Eating disorders, particularly anorexia disorders among adolescent boys.‍ A and bulimia nervosa, have traditionally family history of autoimmune and/or been viewed as arising from a autoinflammatory disorders in a first- conglomeration of psychological, 1 degree relative also increased the risk6 biological, and sociocultural factors.‍ of eating disorders among the youth.‍ 6 Family and individual psychotherapy The Zerwas et al study is the first NIH are mainstays of treatment, but not all to demonstrate a bidirectional and youth respond to these interventions, multigenerational association between Section on Behavioral Pediatrics, National Institute of leaving patients at increased risk eating disorders and diseases of Mental Health, Bethesda, Maryland of death from suicide or medical both innate and humoral immunity Opinions expressed in these commentaries are consequences1, 2 of their disordered in a large, population-based cohort those of the authors and not necessarily those eating.‍ The need for new and more of children and adolescents.‍ These of the American Academy of Pediatrics or its Committees. effective treatments has prompted results provide important context for investigations into the role of immune the small number of reports that have DOI: https:// doi. org/ 10. 1542/ peds. 2017- 3060 function in anorexia and bulimia.‍ linked disordered eating and pediatric Accepted for publication Sep 12, 2017 Similar lines of research have proven autoimmune and/or autoinflammatory Address correspondence to Rebecca E. Hommer, fruitful for a variety of mood, psychotic, diseases.‍ The first such cases were MD, NIH/NIMH/SBP, 10 Center Dr, MSC 1255, and neurodevelopmental disorders, reported nearly a century ago by Bethesda, MD 20892-1255. E-mail: rebecca. 7 [email protected] which have been linked to immune Hammes and described a cohort of dysfunction via epidemiologic,3 genetic, children with Sydenham chorea, the PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). and immunologic studies.‍ neurologic manifestation of acute rheumatic fever.‍ Food refusal was Copyright © 2017 by the American Academy of A few studies in adult populations “ Pediatrics common, and several children required have found that eating disorders and ” “ ” tube feedings because of psychotic FINANCIAL DISCLOSURE: The authors have autoimmune disease each confer an indicated they have no financial relationships worries that their food was doped, increased risk for the other disorder, 7 relevant to this article to disclose. poisoned, or otherwise contaminated.‍ but the role that immune disturbances FUNDING: Supported in part by the Intramural might play in the onset of eating Seven decades later, investigators “ Research Program of the National Institute of at the National Institute of Mental Mental Health (ZIAMH002666). Funded by the disorders among4, 5 youth remains largely unexplored.‍ In Eating Disorders, Health described restricted food intake National Institutes of Health (NIH). ” in a number of their patients with POTENTIAL CONFLICT OF INTEREST: The authors Autoimmune, and Autoinflammatory6 Disease, Zerwas et al address these Sydenham chorea, including 2 boys have indicated they have no potential conflicts of interest to disclose. gaps in the literature by documenting who developed distorted body image8 bidirectional associations between and engaged in excessive exercise.‍ COMPANION PAPER: A companion to this article 9 can be found online at www.pediatrics. or g/cgi/ doi/ autoimmune and/or autoinflammatory In 2000, Sokol described the clinical 10. 1542/ peds. 2016- 2089. diseases and eating disorders in a course of 4 children admitted ∼ large, population-based cohort study to an inpatient eating disorders To cite: Hommer RE and Swedo SE. Anorexia of 1 million Danish children and treatment facility who had a history of and Autoimmunity: Challenging the Etiologic adolescents.‍ These associations are streptococcal infection preceding the Constructs of Disordered Eating. Pediatrics. 2017; present in both sexes but appear to be onset of anorexia; all 4 experienced 140(6):e20173060 stronger for boys than girls, perhaps significant improvement in symptoms reflecting the relative rarity of eating after antibiotics were added to the Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 140, number 6, December 2017:e20173060 COMMENTARY Hommer and Swedo https://doi.‍org/10.‍1542/peds.‍2017-3060 December 2017 Anorexia and Autoimmunity: Challenging the Etiologic Constructs of Disordered Eating 6 140 Pediatrics 2017 ROUGH GALLEY PROOF 2. Arcelus J, Mitchell AJ, Wales J, Nielsen S. Mortality rates in patients typical regimen of care.‍ These in keeping with the stronger with anorexia nervosa and other children were given the diagnosis relationship between immune eating disorders. A meta-analysis ’ of 36 studies. Arch Gen Psychiatry. of acute-onset anorexia in the dysfunction and eating disorders in6 setting of pediatric autoimmune the boys observed in Zerwas et al s 2011;68(7):724–731 neuropsychiatric disorders Diagnosticstudy), and and the Statisticalsimilarities Manual between 3. Coutinho E, Vincent A. Autoimmunity in associated with streptococcal ofPANS Mental symptoms Disorders, and Fifth those Edition of the neuropsychiatric disorders. Handb Clin infection (PANDAS).‍ PANDAS, which Neurol. 2016;133:269–282 is typically characterized by the 4. Raevuori A, Haukka J, Vaarala O, et al. sudden onset of severe obsessive- diagnosis of avoidant/restrictive food The increased risk for autoimmune compulsive symptoms after a intake disorder.‍ diseases in patients with eating Group A streptococcal infection, 6 disorders. PLoS One. 2014;9(8):e104845 is thought to be a postinfectious In summary, Zerwas, et al make a neuroinflammatory disorder significant contribution to the growing 5. Mårild K, Størdal K, Bulik CM, et al. Celiac disease and anorexia nervosa: with similar pathophysiology to body of literature supporting an association between immune system a nationwide study. Pediatrics. Sydenham chorea.‍ Symptoms are 2017;139(5):e20164367 thought to reflect a misdirected dysfunction and eating disorders.‍ immune response in a genetically Further research is needed to 6. Zerwas S, Thornton L, Koch S, et al. vulnerable child in which the delineate the nature of this shared Eating disorders, autoimmune, and immune system directs its response pathophysiology and the extent to autoinflammatory disease. Pediatrics. which immune-mediated interventions 2017;140(6):e20162089 against host proteins as well as 10 Group A streptococcal epitopes.‍ may play a role in treatment.‍ Clinicians 7. Hammes EM. Psychoses associated – A follow-up study of 20 children are encouraged to consider the with Sydenham’s chorea. JAMA. – with PANDAS anorexia nervosa type possibility that patients with eating 1922;79(10):804–807 disorders may have underlying suggested that D8/17 positive B 8. Swedo SE, Leonard HL, Schapiro MB, autoimmune or autoinflammatory lymphocytes may be a marker for the et al. Sydenham’s chorea: physical and disorder, supporting the notion that conditions.‍ This is particularly psychological symptoms of St Vitus important for young boys who present the sudden onset of anorexia may, for dance. Pediatrics. 1993;91(4):706–713 with the abrupt onset of food or fluid some children, represent11 an immune- 9. Sokol MS. Infection-triggered mediated process.‍ intake restrictions and accompanying cognitive, emotional, behavioral, or anorexia nervosa in children: clinical description of four cases. somatic symptoms.‍ Conversely, we Meanwhile, interest in identifying J Child Adolesc Psychopharmacol. must also remain vigilant about the other environmental triggers for 2000;10(2):133–145 childhood neuropsychiatric disorders development of eating disorders 10. Williams KA, Swedo SE. Post-infectious has continued to grow.‍ Diagnostic among patients with autoimmune or autoinflammatory disorders.‍ autoimmune disorders: Sydenham’s criteria limit the cohort to those chorea, PANDAS and beyond. Brain Res. with the abrupt, dramatic onset of ABBREVIATIONS 2015;1617:144–154 obsessive compulsive disorder or 11. Sokol MS, Ward PE, Tamiya H, Kondo severely restricted food intake in DG, Houston D, Zabriskie JB. D8/17 conjunction with a constellation PANDAS: Pediatric Autoimmune expression on B lymphocytes in of other mood, behavioral,12 and Neuropsychiatric anorexia nervosa. Am J Psychiatry. sensorimotor symptoms.‍ These Disorders Associated 2002;159(8):1430–1432 patients are grouped together under with Streptococcal the umbrella of Pediatric Acute- 12. Swedo SE, Leckman JF, Rose NR. Infections From research subgroup to clinical onset Neuropsychiatric Syndrome PANS: Pediatric Acute-onset syndrome: modifying the PANDAS (PANS), which posits a number of Neuropsychiatric criteria to describe PANS (Pediatric potential etiologies, including a direct Syndrome Acute-onset Neuropsychiatric causal relationship between immune12 Syndrome). Pediatr Therapeut. dysfunction and disordered eating.‍ REFERENCES 2012;2(2):113 In a recent case review, Toufexis, 13 13. Toufexis MD, Hommer R, Gerardi et al describe this phenomenon in 1. Dulcan MK. Eating and Feeding Disorders. In: Dulcan MK, ed. Dulcan’s DM, et al. Disordered eating and 29 children with PANS, noting their – Textbook of Child and Adolescent food restrictions in children with young age (mean 9 years;
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