Dear Mr Xia,

Thank you very much for submitting your manuscript "Cutaneous disseminated sporotrichosis associated with diabetes: A case report and literature review" for consideration at PLOS Neglected Tropical Diseases. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the review recommendations.

Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to all review comments, and a description of the changes you have made in the manuscript.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Thank you again for your submission to our journal. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Joshua Nosanchuk, MD

Section Editor

PLOS Neglected Tropical Diseases

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Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #1: The structure and methodology of the case is adequate

Reviewer #2: Actually, the article format of this MS is case report instead of research article, so I suggest that this submission is more suited as case report format.

Besides, could the author offer the figure of direct microscopy, because it was stated that direct microscopy displayed slender hyphae. Moreover, it was stated that the patient healed after two months' therapy, but there are not any figures after healed.

Reviewer #3: The draft manuscript “Disseminated cutaneous sporotrichosis (CDS) refers to the case of a woman with diabetes mellitus associated with CDS”. Based on the laboratory findings, there was an increase in blood glucose and a decrease in the leukocyte count, standard for mycological diagnosis and confirmed by DNA sequencing. The study adequately described antifungal therapy. The paper can be accepted, but be interesting to adapt it to the suggestions below.

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Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1: The results of the case are adequate

Reviewer #2: The MS reviewed the literatures of CDS, but only cited the table in the results of male predominance. The table could review the data of underling disease and the duration of treatment.

Besides, the MS stated that the risk factor for CDS is diabetes but did not show the results of high-throughput genome sequencing or test for HIV.

Reviewer #3: The authors reported the results of the leukogram as its monitoring during the treatment, thus verifying the importance of the procedure but not the information on the red blood cells. In these patients, anemia and hypoalbuminemia may occur in parallel. Add the information, if possible, and insert the reference below.

Lao et al. (2020) found that invasive fungal disease in patients with type 2 diabetes mellitus does not have a good prognosis, with complications potentially fatal, as prolonged hyperglycemia results in unfavorable outcomes. In these patients, anemia and hypoalbuminemia occur in association, and their correction helps to improve the prognosis.

Lao et al. (2020) mention the relationship between diabetes and leukopenia, even if they do not observe its significance. The fact that the clinical improvement of the reported patient is favorable with the improvement of his leukogram suggests future investigations.

The authors mention that the patient had uncontrolled diabetes. It is relevant to report whether it is type 1 or type 2 diabetes and whether the treatment is adequate for your underlying disease.

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Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #1: The conclusions reached are correct.

Reviewer #2: The MS stated that the risk factor for CDS is diabetes but did not show the results of high-throughput genome sequencing or test for HIV.

Reviewer #3: The study would be more impactful if the authors added other studies of diabetes and fungal infections to transpose this information into sporotrichosis since is still obscure.

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Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #1: No

Reviewer #2: (No Response)

Reviewer #3: The study would be more impactful if the authors added other studies of diabetes and fungal infections to transpose this information into sporotrichosis since is still obscure.

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Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #1: It is an interesting case that emphasizes how cases of sporotrichosis can spread through the skin.

The only thing that I suggest to the authors that they add in the discussion is that these cases usually present little yeast presence, are similar to lymphangitic cases and that they behave differently when there is immunosuppression because the number of yeasts is greater

Reviewer #2: (No Response)

Reviewer #3: Suggestion of reference

Lao M, Li C, Li J, Chen D, Ding M, Gong Y. Opportunistic invasive fungal disease in patients with type 2 diabetes mellitus from Southern China: Clinical features and associated factors. J Diabetes Investig. 2020 May;11(3):731-744. doi: 10.1111/jdi.13183. Epub 2019 Dec 20. PMID: 31758642; PMCID: PMC7232281.

Format the references according to the journal's rules.

Reference 42 is incorrect.

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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.

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Reviewer #1: Yes: Alexandro Bonifaz

Reviewer #2: No

Reviewer #3: Yes: Roseli Freitas-Xavier

Figure Files:

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org.

Data Requirements:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

References

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article's retracted status in the References list and also include a citation and full reference for the retraction notice.

Dear Mr Xia,

Thank you very much for your thoughtful revision of your manuscript "Cutaneous disseminated sporotrichosis associated with diabetes: A case report and literature review" for consideration at PLOS Neglected Tropical Diseases. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the review recommendations.

Reviewer comments:

-Thank you for the revision.

-It is hard to find the slender hyphae in Figure 2A. And as slender hyphae are not commonly seen in direct smear, the author should discuss this finding.

-It is not clear if all lesions were culture positive. Please address this point.

Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to all review comments, and a description of the changes you have made in the manuscript.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Thank you again for your submission to our journal. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Joshua Nosanchuk, MD

Section Editor

PLOS Neglected Tropical Diseases

***********************

Figure Files:

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org.

Data Requirements:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

References

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article's retracted status in the References list and also include a citation and full reference for the retraction notice.

Dear Mr Xia,

Thank you for your thoughtful revisions! We are pleased to inform you that your manuscript 'Cutaneous disseminated sporotrichosis associated with diabetes: A case report and literature review' has been provisionally accepted for publication in PLOS Neglected Tropical Diseases.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Joshua Nosanchuk, MD

Section Editor

PLOS Neglected Tropical Diseases

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