PONE-D-20-09664

Risk of metabolic syndrome in patients with lichen planus : A Systematic Review and Meta-analysis

PLOS ONE

Dear Dr. Xiang,

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Academic Editor

PLOS ONE

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Additional Editor Comments (if provided):

Please, carefully address the reviewers' comments. Also, please explain the protocol used for this review if any.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Major comments:

Why did the authors did not differ between the various clinical forms of LP?

What is new about the findings compared to previously published data since link between LP and MS hat been previously reported?

Reviewer #2: Overall meta-analysis is interesting and well prepared according to PRISMA. Selection of articles and applied methods are performed correctly. The results are important and may have practical application on lichen planus patients management.

I have some comments and suggestions:

1. The sentence in the Introduction: “MS is a complex group of metabolic disorders, which include central obesity, dyslipidemia, hypertension, and hyperglycemia. MS is implicated as an important risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) and has therefore attracted increasing attention in recent years.” is repeted in the Disscussion: “MS comprises a combination of metabolic disorders including central obesity, dyslipidemia, hypertension, and hyperglycemia that predispose individuals to T2DM and CVD.”

2. In the first sentence in Introduction it is better use the word “flat” instead of “plan”. The sentence: “Studies have indicated that insulin resistance[4], 3 oxidative stress injury[5] and chronic inflammatory[6] play important roles in the pathogenesis of MS” need to be corrected. Others grammar mistakes should be also corrected.

“…a similar chronic inflammatory dermatological condition with an autoimmune etiology, such as psoriasis[7] alopecia areata[8], hidradenitis suppurativa[9] and vitiligo[10]….”

3. The sentence: “T cell activation in LP triggers the release of pro-inflammatory cytokines such as IL-2, IL-4, IL-6, IL10, interferon-gamma, and TNF-α, which promote the release of more cytokines that attack keratinocytes resulting in dyslipidemia[29]” is unclear and should be rewrite.

4. “To our knowledge, this is the first systematic review and meta-analysis of studies that investigated the prevalence of MS in both patients with LP and the general population.” – what was the aim of the study, why authors have stated that it is the first study investigated the prevalence of MS in the general population?

5. In the Discussion the sentence: “Lipid abnormalities are significant contributors to the onset and aggravation of CVD. 11 The accumulation of cholesterol in cells and formation of lipid-laden foam cells produces fatty streaks in arterial walls, which predispose an individual to atherosclerotic plaques and consequent CVD[29]”

- the information is obvious and well known to readers of the journal and should be removed.

Reviewer #3: This article gives an interesting perspective on a little studied topic. It is a meta-analysis to analyze the association between metabolic syndrome and lichen planus and shows that compared with the general population, patients with lichen planus are more likely to develop metabolic syndrome. The work is a valuable contribution to the Plos One readers. However, it needs corrections, as suggested to the authors.

Materials and methods

Page 4

Data sources and searches

As the terms syndrome x, insulin resistance syndrome and Reaven syndrome were used for the search, specify these synonyms in the introduction.

Inclusion criteria

Outcome measures: "MS was diagnosed using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), the International Diabetes Federation (IDF) and other diagnostic criteria."

Cite the references for the criteria or define what they are.

Exclusion criteria

....(2) For all participants: a known diagnosis of oral lichenoid reactions (a drug-induced LP-like reaction), hypertension, diabetes, dyslipidemia, chronic liver disease, chronic kidney disease, human immunodeficiency virus infection, and hereditary diseases.

Why were participants with hypertension, diabetes and dyslipidemia excluded if these characteristics are criteria for the diagnosis of metabolic syndrome?

Page 6.

Literature search

"After a further reading, 11 studies with 1300 participants fulfilled the eligibility criteria".

Specify how many patients were in the lichen planus group and how many were controls.

Study characteristics

"The population for the controls without LP were apparently healthy individuals or outpatients with or without skin diseases other than LP".

There are diseases that are associated with metabolic syndrome. Were patients with these diseases excluded?

Results

Table 2, figures 2 and 3

In included studies complete with "et al." after the first author in studies that have more than one author.

Discussion

Page 10

First paragraph: "To our knowledge, this is the first systematic review and meta-analysis of studies that investigated the prevalence of MS in both patients with LP and the general population".

Change to: "To our knowledge, this is the first systematic review and meta-analysis of studies that investigated the prevalence of MS in patients with LP compared to the general population".

The authors should also include bibliographic references that mention the frequency of metabolic syndrome in the general population at the end of the paragraph.

Second paragraph: "...T cell activation in LP triggers the release of pro-inflammatory cytokines such as IL-2, IL-4, IL-6, IL- 10, interferon-gamma, and TNF-α, which promote the release of more cytokines that attack keratinocytes resulting in dyslipidemia".

It is not the attack on keratinocytes that results in dyslipidemia.

It would be more accurate to say: "These cytokines also play an important role in the development of dyslipidemia".

References

The references are not within the journal's formatting standards

The manuscript needs editing for language quality.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Risk of metabolic syndrome in patients with lichen planus : A Systematic Review and Meta-analysis

PONE-D-20-09664R1

Dear Dr. Xiang,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Beatrice Nardone

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The results presented in the manuscript are interesting and may have some significant influence on the management of lichen planus patients in clinical practice. The manuscript has been corrected and improved. The article may be published in this form.

Reviewer #3: The authors have adequately addressed my comments raised in a previous round of review and I feel that this manuscript is now acceptable for publication.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: Yes: Marilda Aparecida Milanez Morgado de Abreu