Newly Acquired Streptococcal Infections Obsessive-Compulsive Disorder: Relationship of Symptom Exacerbations to Prospective Longitudinal Study of Children With Tic Disorders

Background. It has been proposed that infection by group A -hemolytic streptococci (GABHS) can trigger acute symptom exacerbations among patients with Tourette’s syndrome (TS) or obsessive-compulsive disorder (OCD), via autoimmune mechanisms. Objective. To examine the temporal relationship between newly acquired GABHS infections (and other immunologic indices) and acute exacerbations of tics and obsessive-compulsive symptoms. Methods. Pediatric patients (7–17 years of age) with TS and/or OCD (N 47) and healthy control subjects (N 19) were prospectively monitored for newly acquired GABHS infections, nonspecific markers of acute inflammatory responses, and D8/17-reactive cells (a marker of rheumatic fever). Objective monthly ratings of tic and obsessive-compulsive symptom severity were used to determine the timing of symptom exacerbations. Results. The overall rate of acute exacerbations of neuropsychiatric symptoms was 0.56 exacerbations per patient per year. The average rate of new GABHS infections, using a stringent definition, was 0.42 infections per subject per year among patients, compared with 0.28 infections per subject per year for control subjects. The association between symptom exacerbations and new GABHS infections among patients was no greater than that expected on the basis of chance. At baseline, patients demonstrated significantly higher levels of D8/17-reactive cells and neopterin, compared with control subjects, but there was no consistent pattern of change when exacerbation time points were compared with baseline or follow-up time points. Conclusions. The results suggest no clear relationship between new GABHS infections and symptom exacerbations in an unselected group of patients with TS and/or OCD. Pediatrics 2004;113:e578–e585. URL: http://www. pediatrics.org/cgi/content/full/113/6/e578; Tourette’s syndrome, obsessive-compulsive disorder, PANDAS, group A -hemolytic streptococci, D8/17, neopterin, C-reactive protein. ABBREVIATIONS. ADHD, attention-deficit/hyperactivity disorder; ASO, anti-streptolysin O; BRR, B repeat region; CRP, C-reactive protein; CRR, C repeat region; Y-BOCS, Yale-Brown Obsessive-Compulsive Scale; GABHS, group A -hemolytic streptococci; OCD, obsessive-compulsive disorder; OC, obsessive compulsive; PANDAS, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections; RF, rheumatic fever; TS, Tourette’s syndrome; YGTSS, Yale Global Tic Severity Scale; IgG, immunoglobulin G. Tic disorders, obsessive-compulsive disorder (OCD), and related conditions affect as many as 3% of children and adolescents.1–6 The factors that contribute to the pathogenesis of these disorders are poorly defined. The hypothesis that infections can modulate the clinical appearance of tic disorders dates from the 1800s.7 The past decade has seen the reemergence of the hypothesis that postinfectious immune mechanisms account for at least some cases of Tourette’s syndrome (TS) and OCD. It is well known that group A -hemolytic streptococci (GABHS) can trigger immune-mediated diseases.8–10 Rheumatic fever (RF), one of the most wellrecognized examples of a delayed nonsuppurative complication of GABHS infection, usually occurs a few weeks to several months after streptococcal infection among susceptible persons. RF typically involves the heart, joints, and central nervous system. The central nervous system manifestations usually take the form of chorea (Sydenham’s chorea). However, some patients with RF also display motor or phonic tics, obsessive-compulsive (OC) symptoms, or features suggesting attention-deficit/hyperactivity disorder (ADHD).11–13 On the basis of these associations, Swedo et al14 proposed that pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) represents a distinct clinical entity that includes cases of TS and OCD. In this prospective longitudinal study, the temporal relationship between periods of neuropsychiatric symptom exacerbation and newly acquired GABHS infections was examined. On the basis of previous studies of RF, TS, and OCD patients,15–22 we also measured the levels of peripheral blood B lymphocytes expressing the D8/17 surface antigen at baseline, at exacerbation, and 2 months after neuropsychiatric symptom exacerbation. Nonspecific markers of acute inflammation, ie, neopterin and C-reactive protein (CRP), were also measured at those 3 time points. From the *Department of Ecology and Evolutionary Biology, ‡Child Study Center, §Department of Pediatrics, and Department of Psychiatry, Yale University, New Haven, Connecticut; and ¶Department of Microbiology and Immunology, New York Medical College, Valhalla, New York Received for publication Oct 20, 2003; accepted Dec 22, 2003. Reprint requests to (D.E.B.) Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595. PEDIATRICS (ISSN 0031 4005). Copyright © 2004 by the American Academy of Pediatrics. e578 PEDIATRICS Vol. 113 No. 6 June 2004 http://www.pediatrics.org/cgi/content/full/113/6/e578 at Pennsylvania State Univ on February 21, 2013 pediatrics.aappublications.org Downloaded from