Elsevier

Journal of Endodontics

Volume 39, Issue 10, October 2013, Pages 1205-1217
Journal of Endodontics

Review Article
Can Apical Periodontitis Modify Systemic Levels of Inflammatory Markers? A Systematic Review and Meta-analysis

https://doi.org/10.1016/j.joen.2013.06.014Get rights and content

Abstract

Introduction

This systematic review and meta-analysis investigated evidence to support whether apical periodontitis (AP) can modify the systemic levels of inflammatory markers (IM) in humans.

Methods

The MEDLINE, Embase, Cochrane, and PubMed databases were searched between 1948 and 2012, with no language restriction. Additionally, the bibliography of all relevant articles and textbooks were manually searched. Based on inclusion and exclusion criteria, 2 reviewers independently rated the quality of each study based on the Newcastle-Ottawa Scale. The primary outcome variable for meta-analysis was determined by the serum levels of IMs in AP subjects versus healthy controls or in AP subjects before versus after treatment intervention.

Results

Among the 531 initially identified articles, 20 comprised the final analysis. Thirty-one different IMs were analyzed, with immunoglobulin (Ig) A, IgM, IgG, and C-reactive protein (CRP) being the most commonly investigated. CRP, interleukin (IL)-1, IL-2, IL-6, asymmetrical dimethylarginine, IgA, IgG, and IgM were shown to be increased in patients with AP compared with controls in most studies. Meta-analyses showed that serum levels of IgA (P = .001), IgG (P = .04), and IgM (P < .00001) were increased in humans with AP compared with healthy controls and serum levels of CRP, IgA, IgE, IgG, and IgM were not significantly different between patients with AP before and after treatment (P > .05).

Conclusions

Available evidence is limited but consistent, suggesting that AP is associated with increased levels of CRP, IL-1, IL-2, IL-6, asymmetrical dimethylarginine, IgA, IgG, and IgM in humans. These findings suggest that AP may contribute to a systemic immune response not confined to the localized lesion, potentially leading to increased systemic inflammation.

Section snippets

Literature Search Strategy

A search was undertaken to identify all the studies that reported on the relationship between AP and circulating or systemic levels of IMs. The MEDLINE (Ovid), Embase, PubMed, and Cochrane Library databases were searched for human studies published between 1948 and 2012 (last accessed September 13th, 2012) using the following key words: ("periapical diseases"/exp OR "lesions of endodontic origin" OR "periapical tissue"/exp OR "periapical lesions" OR "apical lesions" OR "periradicular lesions")

Results

Results from the electronic search yielded a total of 531 hits. After duplicate references were discarded, a subsequent search at the title and abstract level revealed 30 articles for full-text reading, 9 of which were identified through a hand search 62, 63, 64, 65, 66, 67, 68, 69, 70, 71. At this level, 10 studies were excluded, and reasons for exclusions are listed in Table 1.

Discussion

Systemic inflammation appears to play an important role in the development of many debilitating diseases including cardiovascular disease among others 2, 3. To our knowledge, the present study is novel in summarizing the available evidence to respond whether patients with AP present modifications in serum levels of IMs. Although the limitations related to available studies, findings from this systematic review reveal a generalized increase in systemic IMs in humans with AP compared with

Implications for Further Research

Available evidence is limited but consistent, suggesting that AP is associated with increased levels of systemic inflammation in humans. Thus, AP may add to the systemic inflammatory burden of affected individuals, and it seems reasonable to consider that untreated AP may have a proatherogenic effect with a potential role in patient's global vascular risk. Future large-scale prospective controlled studies designed to directly test this hypothesis are fundamental.

Conclusions

Available evidence suggest that AP is associated with increased levels of systemic inflammation in humans. Meta-analysis results suggest that serum levels of IgA, IgG, and IgM are increased in humans with apical periodontitis compared with healthy controls and serum levels of CRP, IgA, IgE, IgG, and IgM were not significantly different between patients with AP before and after the treatment intervention. There is a clear need for large-scale prospective controlled studies designed to directly

Acknowledgments

The authors thank Ms Mary Ann Williams, the librarian from the Health Sciences and Human Services Library, University of Maryland, for her valuable contribution during the literature search.

The authors deny any conflicts of interest related to this study.

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    Supported in part by the CAPES Foundation, Ministry of Education of Brazil (doctorate scholarship number 1433/11-3) and in part by the Military Police, State Government of Rio Grande do Sul, Brazil.

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