Reviewer’s report
Title: 
Food elimination diet is a viable alternative therapy for eosinophilic
esophagitis responsive to proton pump inhibitors
Version: 
0 
Date: 
11 Jan 2023
Reviewer's report:
In this study, the authors retrospectively investigated whether patients with EoE
that responded histologically to PPIs could be maintained in histologic remission
with a food elimination diet. The topic is of interest, as only other small studies
have investigated maintenance of remission with a therapy different from the
therapy used for the induction of remission. However, I do have some major
concerns regarding the methodology of this study and a few other minor issues
to raise. 
MAJOR
Methods
1. The authors define histologic remission as <10 eos/HPF. However, the
established threshold for disease remission in EoE is <15 eos/HPF. Although
several clinical trials on novel drugs are assessing the threshold of <6 eos/HPF,
the threshold of <15 eos/HPF still remains the one that should be used in clinical
practice. To be useful in clinical practice, I believe the analysis should be done
considering remission as <15 eos/HPF.
2. It is unclear how the food elimination diet protocol was performed. Some
patients underwent 2-FED, other 4-FED and so on. However, it is unclear if non-
responders to for eg. A 2-FED underwent all the FEDs up to a 6-FED. 
3. It is unclear why the authors offered to FED responders the possibility to
undergo maintenance with FED+PPI on an as needed basis. What was the reason
for this? 
4. It is unclear if patients were histologically active before FED. If patients were
already in remission, how long after PPI discontinuation did patients undergo
FED monotherapy?
MINOR
1. Despite the affiliation of the authors is from the US, the use of English is often
awkward in the manuscript. I strongly suggest to carefully revise the language. 
2. In the methods section the authors state that they included patients that had
undergone a minimum of 8 weeks of PPI and subsequently FED 
before
histology evaluation. In the following paragraph, they state that a minimum of 6
weeks of treatment was performed. Please clarify. 
3. The questions of the surveys should be reported in a supplementary table 
4. The used episodes of food impaction or urgent visits as a surrogate of
healthcare resources utilization by patients under treatment. Can the authors
exclude that some patients might have be seen in a different centre? How? If not,
this should be mentioned in the limitations
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
No conflicts of interest
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Web of Science Reviewer Recognition
. Springer Nature can send verification
of this review directly to a Web of Science researcher profile (a subsidiary of
Clarivate Analytics). If you would like to take advantage of this service, please
click on the “Yes” option below. Your name, email address, title of the reviewed
manuscript, name of the journal, and date of your review submission (the
“Review Data”) will then be transmitted to Web of Science after the final
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Web of Science for a 
Web of Science researcher profile (this service was
previously known as “Publons”), they will notify you of the receipt of this
review and update your profile as per your settings and their policy. If you are
not registered with Web of Science, you will receive an email from them asking
you to register in order for them to be able to recognize your review on your new
profile page. Web of Science may use the Review Data to generate derivative
metadata for the benefit of Web of Science and you as a reviewer, carefully
considering the sensitivity of such information. For example, Web of Science
may verify your record as a reviewer by updating your profile published on its
webservice if you have registered for such service or help editors to identify
candidate reviewers. Please find the details of processing in Web of Science’s
privacy policy 
https://clarivate.com/privacy-center/notices-policies/privacy-
policy/
No
Reviewer’s report
Title: 
Food elimination diet is a viable alternative therapy for eosinophilic
esophagitis responsive to proton pump inhibitors
Version: 
0 
Date: 
11 Jan 2023
Reviewer's report:
In this study, the authors retrospectively investigated whether patients with EoE
that responded histologically to PPIs could be maintained in histologic remission
with a food elimination diet. The topic is of interest, as only other small studies
have investigated maintenance of remission with a therapy different from the
therapy used for the induction of remission. However, I do have some major
concerns regarding the methodology of this study and a few other minor issues
to raise. 
MAJOR
Methods
1. The authors define histologic remission as <10 eos/HPF. However, the
established threshold for disease remission in EoE is <15 eos/HPF. Although
several clinical trials on novel drugs are assessing the threshold of <6 eos/HPF,
the threshold of <15 eos/HPF still remains the one that should be used in clinical
practice. To be useful in clinical practice, I believe the analysis should be done
considering remission as <15 eos/HPF.
2. It is unclear how the food elimination diet protocol was performed. Some
patients underwent 2-FED, other 4-FED and so on. However, it is unclear if non-
responders to for eg. A 2-FED underwent all the FEDs up to a 6-FED. 
3. It is unclear why the authors offered to FED responders the possibility to
undergo maintenance with FED+PPI on an as needed basis. What was the reason
for this? 
4. It is unclear if patients were histologically active before FED. If patients were
already in remission, how long after PPI discontinuation did patients undergo
FED monotherapy?
MINOR
1. Despite the affiliation of the authors is from the US, the use of English is often
awkward in the manuscript. I strongly suggest to carefully revise the language. 
2. In the methods section the authors state that they included patients that had
undergone a minimum of 8 weeks of PPI and subsequently FED 
before
histology evaluation. In the following paragraph, they state that a minimum of 6
weeks of treatment was performed. Please clarify. 
3. The questions of the surveys should be reported in a supplementary table 
4. The used episodes of food impaction or urgent visits as a surrogate of
healthcare resources utilization by patients under treatment. Can the authors
exclude that some patients might have be seen in a different centre? How? If not,
this should be mentioned in the limitations
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
No conflicts of interest
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Web of Science Reviewer Recognition
. Springer Nature can send verification
of this review directly to a Web of Science researcher profile (a subsidiary of
Clarivate Analytics). If you would like to take advantage of this service, please
click on the “Yes” option below. Your name, email address, title of the reviewed
manuscript, name of the journal, and date of your review submission (the
“Review Data”) will then be transmitted to Web of Science after the final
decision on the manuscript has been made. If you have already registered with
Web of Science for a 
Web of Science researcher profile (this service was
previously known as “Publons”), they will notify you of the receipt of this
review and update your profile as per your settings and their policy. If you are
not registered with Web of Science, you will receive an email from them asking
you to register in order for them to be able to recognize your review on your new
profile page. Web of Science may use the Review Data to generate derivative
metadata for the benefit of Web of Science and you as a reviewer, carefully
considering the sensitivity of such information. For example, Web of Science
may verify your record as a reviewer by updating your profile published on its
webservice if you have registered for such service or help editors to identify
candidate reviewers. Please find the details of processing in Web of Science’s
privacy policy 
https://clarivate.com/privacy-center/notices-policies/privacy-
policy/
No
Please review this paper.
user
Reviewer’s report
Title: 
Food elimination diet is a viable alternative therapy for eosinophilic
esophagitis responsive to proton pump inhibitors
Version: 
0 
Date: 
11 Jan 2023
Reviewer's report:
In this study, the authors retrospectively investigated whether patients with EoE
that responded histologically to PPIs could be maintained in histologic remission
with a food elimination diet. The topic is of interest, as only other small studies
have investigated maintenance of remission with a therapy different from the
therapy used for the induction of remission. However, I do have some major
concerns regarding the methodology of this study and a few other minor issues
to raise. 
MAJOR
Methods
1. The authors define histologic remission as <10 eos/HPF. However, the
established threshold for disease remission in EoE is <15 eos/HPF. Although
several clinical trials on novel drugs are assessing the threshold of <6 eos/HPF,
the threshold of <15 eos/HPF still remains the one that should be used in clinical
practice. To be useful in clinical practice, I believe the analysis should be done
considering remission as <15 eos/HPF.
2. It is unclear how the food elimination diet protocol was performed. Some
patients underwent 2-FED, other 4-FED and so on. However, it is unclear if non-
responders to for eg. A 2-FED underwent all the FEDs up to a 6-FED. 
3. It is unclear why the authors offered to FED responders the possibility to
undergo maintenance with FED+PPI on an as needed basis. What was the reason
for this? 
4. It is unclear if patients were histologically active before FED. If patients were
already in remission, how long after PPI discontinuation did patients undergo
FED monotherapy?
MINOR
1. Despite the affiliation of the authors is from the US, the use of English is often
awkward in the manuscript. I strongly suggest to carefully revise the language. 
2. In the methods section the authors state that they included patients that had
undergone a minimum of 8 weeks of PPI and subsequently FED 
before
histology evaluation. In the following paragraph, they state that a minimum of 6
weeks of treatment was performed. Please clarify. 
3. The questions of the surveys should be reported in a supplementary table 
4. The used episodes of food impaction or urgent visits as a surrogate of
healthcare resources utilization by patients under treatment. Can the authors
exclude that some patients might have be seen in a different centre? How? If not,
this should be mentioned in the limitations
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
No conflicts of interest
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Web of Science Reviewer Recognition
. Springer Nature can send verification
of this review directly to a Web of Science researcher profile (a subsidiary of
Clarivate Analytics). If you would like to take advantage of this service, please
click on the “Yes” option below. Your name, email address, title of the reviewed
manuscript, name of the journal, and date of your review submission (the
“Review Data”) will then be transmitted to Web of Science after the final
decision on the manuscript has been made. If you have already registered with
Web of Science for a 
Web of Science researcher profile (this service was
previously known as “Publons”), they will notify you of the receipt of this
review and update your profile as per your settings and their policy. If you are
not registered with Web of Science, you will receive an email from them asking
you to register in order for them to be able to recognize your review on your new
profile page. Web of Science may use the Review Data to generate derivative
metadata for the benefit of Web of Science and you as a reviewer, carefully
considering the sensitivity of such information. For example, Web of Science
may verify your record as a reviewer by updating your profile published on its
webservice if you have registered for such service or help editors to identify
candidate reviewers. Please find the details of processing in Web of Science’s
privacy policy 
https://clarivate.com/privacy-center/notices-policies/privacy-
policy/
No
assistant