PEDIATRICS Vol. 123 No. 1 January 2009, pp. e171-e173 (doi:10.1542/peds.2008-3123)
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LETTER TO THE EDITOR |
Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcus: In Reply
Vilma Gabbay, MDBarbara J. Coffey, MD, MS
Leah Elizabeth Guttman, BA
NYU Child Study Center
New York University School of Medicine
New York, New York
We appreciate Dr Scolnick's comments regarding our study1 and welcome the opportunity to clarify some of the questions she raised.
As noted, the therapeutic efficacy of antibiotic treatment for obsessive-compulsive disorder (OCD) and tics was proposed on the basis of the observation that in a putative subgroup of children with OCD and/or a chronic tic disorder (referred to as pediatric autoimmune neuropsychiatric disorders associated with streptococcus [PANDAS]), symptoms emerged and/or were exacerbated in association with streptococcal infection. It remains unclear, however, whether PANDAS is a unique clinical entity.2,3 To date, treatment studies with antibiotics have yielded mixed results, insufficient to recommend antibiotic prophylactic treatment for PANDAS.4,5 Current practice guidelines advise that patients with PANDAS receive combined psychotherapy (eg, habit-reversal, cognitive-behavioral) and psychotropic medications, and that "[t]reatment with antibiotics should not be initiated without clinical evidence of infection and a positive throat culture. Experimental treatments based on the autoimmune theory, such as plasma exchange, immunoglobulin therapy, or prophylactic antibiotic treatment, should not be undertaken outside of formal clinical trials [Tourette Syndrome Association Medical Advisory Board: Practice Committee 2006]."6
Our clinical experience raised a question as to whether a PANDAS diagnosis was made without the application of the diagnostic criteria of Swedo et al7 and, subsequently, whether unwarranted antibiotics were prescribed to treat tics and OCD symptoms. These hypotheses were supported by our study; we found that many patients were treated with antibiotics for extended periods (some up to 4 years) and that patients who received false-positive PANDAS diagnoses in the community were less likely to receive evidence-based and appropriate conventional treatment.
Dr Scolnick argues for the utility of treating a variety of psychiatric symptoms, which she refers to as "psychiatric dysfunction," with antibiotics. She grounds these recommendations in her clinical observation that antibiotics are "helpful to a certain subset of patients," and that, "just possibly, the observations of parents and ‘community’ physicians have merit." Although we agree that anecdotal observations have merit, these observations should be followed with clinical trials to determine if a specific treatment is efficacious, particularly in the treatment of psychiatric disorders, which are known to have high placebo-response rates. Were such clinical trial data available, clinical management should be performed accordingly, as is the case in the treatment of children with OCD, tics, or PANDAS.6
Dr Scolnick further supports her argument by pointing to the possible effects of antibiotics (eg, minocycline) on cytokines, which may occur through changes in gut flora, and subsequently brain function. Indeed, converging lines of evidence have supported the role of cytokines in neuropsychiatric disorders, with most studies conducted in major depression8 and some in OCD and Tourette disorder.9 In addition, the therapeutic effects of antidepressants have been attributed partly to their effect on the cytokine network.10–12 However, we argue that current evidence linking antibiotics to cytokines is insufficient to conclude that antibiotics should be prescribed when treating psychiatric disorders. Does Dr Scolnick recommend antibiotic treatment for children with major depression rather than a combination of antidepressants and psychotherapy, both of which are evidence-based treatments?13 In specific response to Dr Scolnick's example, minocycline has been linked to autoimmune illnesses in children, and changes in gut flora subsequent to antibiotic treatment may be associated with pseudomembranous colitis.
Above all, Dr Scolnick fails to address the heightened medical risks associated with unwarranted antibiotic treatment, including diarrhea, pseudomembranous colitis, yeast infections, and, most importantly, increased rates of antibiotic resistance, a major public health concern. To this effect, the intent of our study was not to criticize community physicians but, rather, to emphasize the need for strict adherence to diagnostic criteria and appropriate management of treatment (eg, evidence based if available), abiding to "primum non nocere" (first do no harm), particularly when treating patients such complex conditions.
FOOTNOTES
Financial Disclosure: Dr Coffey reports research support from Boehringer Ingelheim, Bristol Myers Squibb, and Eli Lilly; she also serves on the advisory board for Jazz Pharmaceuticals, Eli Lilly, and Novartis. Dr Gabbay and Ms Guttman have indicated they have no financial relationships relevant to this article to disclose.
REFERENCES
1. Gabbay V, Coffey BJ, Babb JS, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcus: comparison of diagnosis and treatment in the community and at a specialty clinic.
Pediatrics. 2008;122
(2):273
–278
2. 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
3. Wolf DS, Singer HS. Pediatric movement disorders: an update. Curr Opin Neurol. 2008;21 (4):491 –496[Web of Science][Medline]
4. Kurlan R, Kaplan EL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: hypothesis or entity? Practical considerations for the clinician.
Pediatrics. 2004;113
(4):883
–886
5. Swedo SE, Leonard HL, Rapoport JL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: separating fact from fiction.
Pediatrics. 2004;113
(4):907
–911
6. Scahill L, Erenberg G, Berlin CM Jr, et al. Contemporary assessment and pharmacotherapy of Tourette syndrome. NeuroRx. 2006;3 (2):192 –206[CrossRef][Medline]
7. 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
8. Gabbay V, Klein RG, Alonso CM, et al. Immune system dysregulation in adolescent major depressive disorder. J Affect Disord. 2008; In press
9. Leckman JF, Katsovich L, Kawikova I, et al. Increased serum levels of interleukin-12 and tumor necrosis factor-alpha in Tourette's syndrome. Biol Psychiatry. 2005;57 (6):667 –673[CrossRef][Web of Science][Medline]
10. Kubera M, Kenis G, Bosmans E, et al. Stimulatory effect of antidepressants on the production of IL-6. Int Immunopharmacol. 2004;4 (2):185 –192[CrossRef][Web of Science][Medline]
11. Kubera M, Lin AH, Kenis G, Bosmans E, van Bockstaele D, Maes M. Anti-inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio. J Clin Psychopharmacol. 2001;21 (2):199 –206[CrossRef][Web of Science][Medline]
12. Maes M, Song C, Lin AH, et al. Negative immunoregulatory effects of antidepressants: inhibition of interferon-gamma and stimulation of interleukin-10 secretion. Neuropsychopharmacology. 1999;20 (4):370 –379[CrossRef][Web of Science][Medline]
13. March JS, Silva S, Petrycki S, et al. The Treatment for Adolescents With Depression Study (TADS): long-term effectiveness and safety outcomes [published correction appears in Arch Gen Psychiatry. 2008;65(1):101].
Arch Gen Psychiatry. 2007;64
(10):1132
–1143
PEDIATRICS (ISSN 1098-4275). ©2009 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
