PANDAS and Streptococcal Infections
PANDAS and Streptococcal Infections
Abstract & Commentary
By Hal B. Jenson, MD, FAAP, Chair, Department of Pediatrics and Director, Center for Pediatric Research, Eastern Virginia Medical School and Children’s Hospital of the King’s Daughters, Norfolk, VA, is Associate Editor for Infectious Disease Alert
Dr. Jenson is on the speaker’s bureau of Merck.
Synopsis: A case-controlled study provides epidemiologic evidence that obsessive-compulsive disorder, Tourette’s syndrome, and tic disorder in children are associated with preceding group A streptococcus infection. This provides further evidence of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) as a postinfectious, perhaps autoimmune phenomenon induced by childhood streptococcal infection.
Source: Mell LK, et al. Association Between Streptococcal Infection and Obsessive-Compulsive Disorder, Tourette’s Syndrome, and Tic Disorder. Pediatrics. 2005;116:56-60.
A population-based, case-control study was performed on children 4-13 years of age with an initial diagnosis of obsessive-compulsive disorder (OCD), Tourette syndrome (TS), or tic disorder during 1992-1999. All children received continuous healthcare in a large health maintenance organization in King County, Washington, from 4 years of age, and for a minimum of 2 years prior to diagnosis. Cases were matched to 1-5 controls each by birth date (+6 months), gender, primary physician, and healthcare-seeking behavior (difference in total number of outpatient visits < 10 in the 2 years prior to diagnosis). Children treated with a medication for attention-deficit/hyperactivity disorder (ADHD) were excluded to minimize potential confounding by drug-associated tic exacerbations.
Review of diagnostic codes identified 318 potential cases of OCD, TS, or tic disorder, with 202 cases accepted for analysis. Most cases were excluded because no specific diagnosis was established. Of the 202 accepted cases, 21 cases were excluded because of insufficient observation period (2 years) and 37 cases were unable to be matched with controls, leaving 144 cases. Of these, 106 were matched to 5 controls, and the remainder matched to 1-4 controls each. Streptococcal infection was identified by review of automated laboratory databases for positive streptococcal throat culture for group A or group B streptococcus during the 2 year observation period.
Most of the cases were male (71%), consistent with the known male predominance of TS and OCD. Using 4 categories of 0-3 years, 4-6 years, 7-9 years, and 10-13 years, symptom onset was highest among children 4-6 years of age (42%), with the age of diagnosis highest among children 7-9 years of age (42%).
Children with OCD, TS, or tic disorder were more than twice as likely than controls to have at least 1 episode of group A streptococcal infection in the 3 months preceding diagnosis (OR 2.50; 95%; CI, 1.09, 5.70) and almost twice as likely to have at least 1 episode in the 12 months preceding diagnosis (OR 1.81; 95%; CI, 1.17, 3.43). The overall risk was increased with > 2 group A streptococcal infections within the preceding 12 months (OR 3.46; 95%; CI, 1.75, 11.1) and was highest for TS (OR 13.6; 95%; CI, 1.93, 51.0). Cases with OCD and tic disorder were also more likely to have > 2 group A streptococcal infections in the 12 months preceding diagnosis, but these associations were not statistically significant.
Too few cases had > 1 streptococcal infection in the 3 months preceding diagnosis to permit this analysis. It was not possible to better define the temporal association between streptococcal infection and onset of neurologic symptoms. A subanalysis with < 5 outpatient visits in the 2 years before diagnosis did not change the results.
Commentary
A growing series of case reports and a case series of 50 patients reported in 1998 suggested the association of group A streptococcal infection to trigger or exacerbate OCD, TS, and tic disorder in prepubertal children. There have not been well-designed epidemiologic studies to substantiate this putative association. In this study, the risk of OCD, TS, or tic disorder was doubled in the 3 months after streptococcal infection, and tripled with multiple streptococcal infections within 12 months’ time.
In addition to age and gender, this study controlled for 2 additional important factors in this type of study—the primary care physician to control for the diagnostic behavior of individual physicians and healthcare-seeking behavior by matching for the number of outpatient visits before the diagnosis to control for the families’ response to symptoms in their children. A major limitation of the study is the lack of standardized examinations by pediatric neurologists for diagnosis.
It is biologically plausible that the incidence of PANDAS may be influenced by postinfectious autoimmune phenomenon from childhood group A streptococcal infection. Nonsuppurative postinfectious sequelae of streptococcal infection are well accepted and include rheumatic fever and poststreptococcal glomerulonephritis. An interesting feature of rheumatic fever is Sydenham chorea, which may present 1-6 months following streptococcal infection, and may be the sole diagnostic criterion that is present. Previous studies have shown that patients with TS or tic disorder have increased antistreptococcal antibodies, compared with controls, and patients with TS have increased antibodies titers against streptococcal M proteins.
Where does PANDAS fit with rheumatic fever? It is unlikely that PANDAS are part of the spectrum of rheumatic fever, although Sydenham chorea may represent part of the spectrum of neuropsychiatric or behavioral disorders such as OCD and TS. This study provides epidemiologic evidence that the incidence of PANDAS, specifically OCD, TS, and tic disorder-is influenced by streptococcal infection.
A population-based, case-control study was performed on children 4-13 years of age with an initial diagnosis of obsessive-compulsive disorder (OCD), Tourette syndrome (TS), or tic disorder during 1992-1999.Subscribe Now for Access
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