Case Report: A Presentation of Early-Onset Immune-Mediated Bullous Pemphigoid in a Patient with Urothelial Cancer

Round 1

Reviewer 1 Report

 

General comment

The manuscript entitled “Case report: a presentation of early-onset immune mediated bullous pemphigoid in a patient with urothelial cancer” report the case of an early presentation of bullous pemphigoid onset in a patient undergoing a first cycle of atezolizumab after tree day from the drug administration. The severity of the condition, associated with the drug used could shine a light on potential, and not well-known, side effects related to immunotherapy in urothelial cancer.

As reported previously, the case is, to the authors' and my knowledge, the first of this type, characterized by a very early and severe onset of symptoms, justifying the potential publishing of the case.

A few corrections are however suggested:

INTRODUCTION

27: briefly report the main side and adverse effects of immunotherapy with ICIs. Furthermore, about the role of ICIs in urothelial cancer also see DOI: 10.3390/ijms23031133, DOI: 10.1007/s40487-022-00218-z and DOI: 10.3390/cancers13010131

29: as before, specify.

35: add references.

39: It would be better to provide, in order, the description of atezolizumab and then its use in urothelial cancer.

CASE PRESENTATION

49: briefly report the stages and the timings that delivered to diagnosis and treatment (symptoms > imaging > TURBT > cystectomy).

65: was the patient assuming other drugs? And had he other comorbidities?

90: specify the reason for treatment discontinuation and other, if done, treatments.

DISCUSSION

137-146: recall the main reasons for the exceptionality of this case. Additionally, add the limitations of your case, if present.

minor typos

Author Response

Dear Reviewer,

I wanted to provide an update on the revisions we've made to our manuscript in accordance with the journal editor's criteria, as well as to address the valuable suggestions you provided. We deeply appreciate your time and expertise in reviewing our work.

Firstly, we have successfully expanded the article to meet the required length of 2500 words. We have also meticulously incorporated the suggestions you shared, ensuring that the manuscript is enhanced both in content and structure.

In the introduction section, we have taken your suggestion to heart and expanded on the main side effects and adverse reactions associated with immunotherapy, particularly focusing on immune checkpoint inhibitors (ICIs).  We have referenced the specifics you mentioned, providing a solid foundation for our discussion.

Additionally, we have dedicated a substantial portion of the article to discussing atezolizumab and its specific application in urothelial cancer. We have carefully included the references you provided, ensuring that the information presented is accurate and well-supported.

In the case presentation, we have detailed the stages and the timings that led to the diagnosis and subsequent treatment. It's noteworthy to mention that the patient under study did not take any other drugs, but had a history of hypertension, obesity, and diabetes. We've incorporated literature that explains how these risk factors may contribute to the early onset of blood pressure issues, emphasizing the exceptional nature of this case. This highlights the necessity of considering other predisposing factors associated with toxicity that are not typically studied or well-known.

In the discussion section, we have thoroughly recalled the main reasons for the exceptionality of this case.

We genuinely appreciate your insightful feedback, which has significantly improved the quality and relevance of our work. If you have any further suggestions or specific areas you would like us to focus on, please do not hesitate to let us know. 

Thank you once again for your dedication to the peer review process.

Reviewer 2 Report

The MS depicts an atypical case of early onset of immune-mediated BP in the patient with a locally advanced bladder cancer. Within a few weeks, the cutaneous lesions were completely in remission due to the described treatment of BP.

My comments and suggestions.

1. The abstract (lines 10-11) states that "Cutaneous immune-related adverse events (cirAEs) are the most common side-effects of immune-checkpoints inhibitors (ICI) therapy (>50% for all grades)," while the “introduction” section (lines 31-32) states that "The most frequent irAEs are dermatotoxicities and they can occur up to 30-50% of patients receiving ICIs." The discrepancy should be removed.

2. In the abstract, the sentence "The onset generally occurs within the first few months of the treatment" (lines 15-16) essentially repeats the preceding sentence. This sentence can be removed from the text.

3. In the “results” subsection, it would be of interest to present data on the course of tumor disease in a patient after BP treatment.

4. The "discussion" subsection only presents literature data and does not discuss the presented case. Here it would be appropriate to indicate possible (presumed) reasons for the early development of immune-mediated BP in the described patient.

5. The precision of decoding abbreviations and their correct usage in the text should be verified by the authors.

Author Response

Dear Reviewer,

 I wanted to provide you with an update on the revisions we've made to our manuscript based on the valuable feedback received, both from you and from the other reviewers, and in alignment with the journal editor's criteria.

Firstly, we have successfully expanded the article to meet the required length of 2500 words. We have diligently incorporated the suggestions you provided, ensuring that the manuscript is enriched in both content and clarity.

One area we focused on was addressing the discrepancies in the text. We carefully reviewed the entire manuscript and made necessary corrections to ensure a consistent and coherent narrative. Additionally, we paid special attention to the precision of decoding abbreviations, ensuring that the readers can easily understand and follow the technical terminology.

We have also incorporated data on the course of the tumor disease in the case presentation. This addition provides a more comprehensive understanding of the patient's condition and the context in which immune-mediated BP developed. Furthermore, we have included a section that highlights possible (presumed) reasons for the early development of immune-mediated BP in the described patient. This insight adds depth to our discussion and encourages further exploration of the underlying mechanisms.

We truly appreciate your insightful feedback, which has significantly improved the overall quality and relevance of our work. If you have any additional suggestions, specific points you would like us to emphasize, or areas that require further attention, please do not hesitate to let us know.

Thank you once again for your dedication to the peer review process.

Round 2

Reviewer 1 Report

The authors improve the manuscript accordingly. I however suggest to add in your paper, and specifically in the introduction, the previously suggested papers: DOI: 10.3390/ijms23031133, DOI: 10.1007/s40487-022-00218-z and DOI: 10.3390/cancers13010131

none

Author Response

Dear Reviewer,

I am pleased to inform you that I have thoroughly revised the manuscript in accordance with the suggestions you provided. Your comments were invaluable in refining the content and structure of the paper. I have made the necessary changes to address the specific concerns you raised and have also taken the opportunity to further improve the overall coherence of the manuscript.

Additionally, I have incorporated a new paragraph into the introduction section of the manuscript. This paragraph succinctly summarizes the crucial information from the references you kindly provided. 

I have attached the revised manuscript to this email for your convenience. I kindly request you to review it at your earliest convenience and provide any further feedback you may have.

Thank you for your ongoing support and guidance.

Best regards

Author Response File: Author Response.docx

Reviewer 2 Report

I have no more comments.

Author Response

Dear Reviewer,

I am pleased to inform you that I have diligently addressed the minor suggestions that another reviewer provide.

The revised manuscript is attached to this email for your convenience. I kindly request your assistance in reviewing it once more and letting me know if any further refinements are necessary. 

Thank you once again for your dedication to reviewing my work and for providing valuable guidance.

Best regards.

Author Response File: Author Response.docx

Round 3

Reviewer 1 Report

No further corrections