Published online October 31, 2008
PEDIATRICS Vol. 122 No. 5 November 2008, pp. 1157 (doi:10.1542/peds.2008-2118)
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LETTER TO THE EDITOR

The Role of Group A β-Hemolytic Streptococcal Infection in Neuropsychiatric Disorders

Pedro Gomes de Alvarenga, MD
Ana G. Hounie, MD, PhD
Eurípedes C. Miguel, MD, PhD
Department and Institute of Psychiatry,
University of Sao Paulo Medical School,
05403-010, Sao Paulo, Brazil

To the Editor.—

Kurlan et al1 have brought us reliable information based on an elegant prospective, blinded, case-control study of children who met diagnostic criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS),2 a controversial model of autoimmune neuropsychiatric disorders.3 Their striking finding is that the large majority of psychiatric exacerbations in this subgroup of patients could not be related to the acute group A β-hemolytic streptococcal (GABHS) infections, contradicting the hallmark of the PANDAS hypothesis.1 Their findings suggest that obsessive-compulsive disorder (OCD) and Tourette syndrome are complex and heterogeneous conditions that may include subgroups prone to be triggered by a possible array of precipitants, including GABHS infections.

Recent studies performed by our group revealed higher frequencies of obsessive-compulsive symptoms4,5 and OCD6 in patients with present or past rheumatic fever (RF) with or without Sydenham chorea. The presence of psychiatric disorders in patients with previous history of RF (not active) suggests that GABHS may trigger OCD and related disorders that may persist throughout life regardless of GABHS reinfections.

Recent family studies have reported that obsessive-compulsive–related disorders aggregate more frequently in first-degree relative RF probands when compared with controls.7 Moreover, 2 polymorphisms of the promoter region of the tumor necrosis factor {alpha} (TNF-{alpha}) gene have been associated with both OCD and RF, which is an interesting finding because TNF-{alpha} is a proinflammatory cytokine involved in RF and several other autoimmune diseases.8 Therefore, it is possible that both obsessive-compulsive–related disorders and RF share a common genetic vulnerability. Consistent with this hypothesis, there was a higher family history of RF in the GABHS group reported by Kurlan et al.

In conclusion, GABHS may still have a major role in PANDAS. PANDAS could precipitate an abnormal developmental process that moderates or mediates the expression of the Tourette syndrome/OCD phenotype. This phenotype would be more susceptible to exacerbations by GABHS or other unspecific factors. This moderating or mediating effect of GABHS infections could depend on specific genetic predisposition. Therefore, research into the interface between OCD and RF may also help to clarify this interesting debate on the validity of the PANDAS concept.

REFERENCES

  1. Kurlan R, Johnson D, Kaplan EL; Tourette Syndrome Study Group. Streptococcal infection and exacerbations of childhood tics and obsessive-compulsive symptoms: a prospective blinded cohort study. Pediatrics. 2008;121 (6):1188 –1197[Abstract/Free Full Text]
  2. Swedo SE, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases [published correction appears in Am J Psychiatry. 1998;155(4):578]. Am J Psychiatry. 1998;155 (2):264 –271[Abstract/Free Full Text]
  3. Singer HS. PANDAS-pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection: is it a specific clinical disorder [in Portuguese]? Rev Bras Psiquiatr. 2004;26 (4):220 –221[Medline]
  4. Alvarenga PG, Hounie AG, Mercadante MT, et al. Obsessive-compulsive symptoms in heart disease patients with and without history of rheumatic fever. J Neuropsychiatry Clin Neurosci. 2006;18 (3):405 –408[Abstract/Free Full Text]
  5. Hounie AG, Pauls DL, Mercadante MT, et al. Obsessive-compulsive spectrum disorders in rheumatic fever with and without Sydenham's chorea. J Clin Psychiatry. 2004;65 (7):994 –999[Web of Science][Medline]
  6. Mercadante MT, Filho GB, Lombroso PJ, et al. Rheumatic fever and co-morbid psychiatric disorders. Am J Psychiatry. 2000;157 (12):2036 –2038[Abstract/Free Full Text]
  7. Hounie AG, Pauls DL, do Rosario-Campos MC, et al. Obsessive-compulsive spectrum disorders and rheumatic fever: a family study. Biol Psychiatry. 2007;61 (3):266 –272[CrossRef][Web of Science][Medline]
  8. Hounie AG, Cappi C, Cordeiro Q, et al. TNF-alpha polymorphisms are associated with obsessive-compulsive disorder. Neurosci Lett. 2008;442 (2):86 –90[CrossRef][Web of Science][Medline]
PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics

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This Article
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Right arrow Articles by de Alvarenga, P. G.
Right arrow Articles by Miguel, E. C.
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Right arrow Infectious Disease & Immunity
Right arrowRelated AAP Red Book topics:
Non-Group A or B Streptococcal and...
Group A Streptococcal Infections
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