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. 2021 Jul 1;16(7):e0253844.
doi: 10.1371/journal.pone.0253844. eCollection 2021.

Anti-inflammatory, antibacterial and immunomodulatory treatment in children with symptoms corresponding to the research condition PANS (Pediatric Acute-onset Neuropsychiatric Syndrome): A systematic review

Mats Johnson  1   2 , Stephan Ehlers  3 , Elisabeth Fernell  1   2 , Parisa Hajjari  4 , Constanze Wartenberg  5 , Susanna M Wallerstedt  5   6
Affiliations

Anti-inflammatory, antibacterial and immunomodulatory treatment in children with symptoms corresponding to the research condition PANS (Pediatric Acute-onset Neuropsychiatric Syndrome): A systematic review

Mats Johnson et al. PLoS One. .

Abstract

Objective: To assess effects of treatment against a hypothesized neuroinflammation in children with symptoms corresponding to the research condition Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) which is not included in current diagnostic systems.

Methods: Systematic literature searches were performed (1998 to June 2020) in PubMed, Embase, the Cochrane Library, CINAHL, PsycInfo, and HTA databases. Inclusion criteria: patients (P) were children (<18 years) with PANS; intervention (I)/comparison (C) was use of, versus no use of, anti-inflammatory, antibacterial or immunomodulating treatments; outcomes (O) were health-related quality of life (HRQL), level of functioning, symptom change, and complications.

Results: Four randomised controlled trials (RCTs) and three non-RCTs, including 23 to 98 patients, fulfilled the PICO. HRQL was not investigated in any study. Regarding level of functioning, two RCTs investigated antibiotics (penicillin V, azithromycin) and one RCT investigated immunomodulating treatments (intravenous immunoglobulins (IVIG), plasma exchange). Regarding symptoms, two non-RCTs investigated anti-inflammatory treatment (cyclooxygenase (COX) inhibitors, corticosteroids), two RCTs and one non-RCT investigated antibiotics (penicillin V, azithromycin), and two RCTs investigated immunomodulating treatments (IVIG, plasma exchange). Complications, reported in five studies, were consistent with those listed in the summary of products characteristics (SPC). All studies were assessed to have some or major problems regarding directness, the absence of an established diagnosis contributing to clinical diversity in the studied populations. All studies were assessed to have major risk of bias, including selection and detection biases. Due to clinical and methodological diversity, meta-analyses were not performed.

Conclusion: This systematic review reveals very low certainty of evidence of beneficial effects, and moderate certainty of evidence of adverse effects, of anti-inflammatory, antibacterial or immunomodulating treatments in patients with symptoms corresponding to the research condition PANS. Available evidence neither supports nor excludes potential beneficial effects, but supports that such treatment can result in adverse effects.

Registration: PROSPERO (CRD42020155714).

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Conflict of interest statement

M.J. and E.F. work at the Child Neuropsychiatry Centre and the Gillberg Neuropsychiatry Centre, to which referrals of patients occur, for assessments and treatment, when the research condition PANS/PANDAS is suspected. M. J. has received research grants from Shire and has been engaged as a speaker or consultant by Eli Lilly, Shire, Ginsana, PCM Scientific, Evolan, and New Nordic, all unrelated to the present work. S.E., P.H., C.W., and S.M.W. declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Flowchart of studies included in this systematic review.
Fig 2
Fig 2
Forest plots for the outcomes level of functioning according to CGAS for the comparison antibiotic versus no antibiotic (A), and symptoms according to CY-BOCS for the comparisons IVIG versus no IVIG (B). Due to clinical and methodological diversity, in the absence of an established diagnosis and with major risk of bias in all studies (e.g. selection and detection bias), we refrained from pooling the results.
See this image and copyright information in PMC

References

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