Reviewer’s report
Title: 
Whipple's Disease: the great masquerader. A high level of suspicion is the
key to diagnosis
Version: 
0 
Date: 
10 Nov 2020
Reviewer: 
Ian Beales
Reviewer's report:
The authors present three cases with relatively classic presentations in the
modern world of preceeding non-specific or rheumatolocgical feaures, failure to
repond to potent anti-inflammatory medicaton and eventual diagnosis of
Whipples's disease. There is nothing really new here. Although the authors
points about needing to consider what is always a rare diseease with protean
manifestation are important. Whipple's diease presenting as a treatment resistant
arthropathy is well documented and several studies have already highlighted that
many patients have been treated with anti-TNF or other biologics before a
diagnosis of Whipple's disease is made. Hence, although these cases are
generally well characterised, they are in no way unique. That does not mean that
publication to emphasize these issues with delayted diagnosis would not be
unreasonable.
Major points:
1. The paper is really too long for what amounts to 3 not unique case reports. In
their efforts to be inclusive of as much information as possible, the authors have
probably dilauted out their own message. Much of the detail of the exact details
within each patients timeline can be omitted without loss of clarity over the
overall points. For instance the details of which service the patient was admitted
under at any particualr time is really unnecessary. The cases have beed described
almost as they would be for a Grand Round presentaion but for the purposes of
publication a lot of extraneous information can be stripped out. For example, pn
page 11, any discussions about whether/how to perform a lymph node biopsy are
irrevelent. It is suffice to say that lymph nocde biopsy was performed.
2. The description of both cases 1 and 2 can be easily trimmed by at least 30 %.
3. 
Page 6 Line 14..he was in bad condition....is very poor English. It would be
suffice to say "his condition deteriorated"
4. Page 6, line 46. I do not understand what is meant by "fibres" in the
duodenum. The associated figure does ot clarify either, is this fibrin?
5. Was there any follow up on pateint 1?
6. What PCR assay was used for the diagnosis. Commercial or in house? Which
primers?
7. Page 10, line 54, TTE is used as an abbreviation without prior explanation?
8. It is interesting that the authors cite treatment recommendations from 2004
and have used treatments no longer recommended in more modern Europea
guidelines, with apparent good success, although we must accept that the
evidence base for such guidelines is poor. I agree with the authors statment about
the utility of early in therapy duodenal biopsy
8. It is not explicity stated but the assumption is that none of the patients had any
neurological or dermatological signs?
9. The figure legends need more detail. What is the magnification of the
histology pictures?
10. Table 1 is unnecessary, the point has already be sufficiently made that the
patient did not respond to potent immune modulators. Suggest this is removed.
11.Table 2 merely seems to have been lifted from another review paper. It is
irrelvent in this manuscript, suggst this is removed.
12. Figures 6 & are unnecessary and can be removed
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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.
I declare that I have no competing interests
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 publish my name with my
report.
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?
Yes
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Whipple's Disease: the great masquerader. A high level of suspicion is the
key to diagnosis
Version: 
0 
Date: 
10 Nov 2020
Reviewer: 
Ian Beales
Reviewer's report:
The authors present three cases with relatively classic presentations in the
modern world of preceeding non-specific or rheumatolocgical feaures, failure to
repond to potent anti-inflammatory medicaton and eventual diagnosis of
Whipples's disease. There is nothing really new here. Although the authors
points about needing to consider what is always a rare diseease with protean
manifestation are important. Whipple's diease presenting as a treatment resistant
arthropathy is well documented and several studies have already highlighted that
many patients have been treated with anti-TNF or other biologics before a
diagnosis of Whipple's disease is made. Hence, although these cases are
generally well characterised, they are in no way unique. That does not mean that
publication to emphasize these issues with delayted diagnosis would not be
unreasonable.
Major points:
1. The paper is really too long for what amounts to 3 not unique case reports. In
their efforts to be inclusive of as much information as possible, the authors have
probably dilauted out their own message. Much of the detail of the exact details
within each patients timeline can be omitted without loss of clarity over the
overall points. For instance the details of which service the patient was admitted
under at any particualr time is really unnecessary. The cases have beed described
almost as they would be for a Grand Round presentaion but for the purposes of
publication a lot of extraneous information can be stripped out. For example, pn
page 11, any discussions about whether/how to perform a lymph node biopsy are
irrevelent. It is suffice to say that lymph nocde biopsy was performed.
2. The description of both cases 1 and 2 can be easily trimmed by at least 30 %.
3. 
Page 6 Line 14..he was in bad condition....is very poor English. It would be
suffice to say "his condition deteriorated"
4. Page 6, line 46. I do not understand what is meant by "fibres" in the
duodenum. The associated figure does ot clarify either, is this fibrin?
5. Was there any follow up on pateint 1?
6. What PCR assay was used for the diagnosis. Commercial or in house? Which
primers?
7. Page 10, line 54, TTE is used as an abbreviation without prior explanation?
8. It is interesting that the authors cite treatment recommendations from 2004
and have used treatments no longer recommended in more modern Europea
guidelines, with apparent good success, although we must accept that the
evidence base for such guidelines is poor. I agree with the authors statment about
the utility of early in therapy duodenal biopsy
8. It is not explicity stated but the assumption is that none of the patients had any
neurological or dermatological signs?
9. The figure legends need more detail. What is the magnification of the
histology pictures?
10. Table 1 is unnecessary, the point has already be sufficiently made that the
patient did not respond to potent immune modulators. Suggest this is removed.
11.Table 2 merely seems to have been lifted from another review paper. It is
irrelvent in this manuscript, suggst this is removed.
12. Figures 6 & are unnecessary and can be removed
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (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 Publons upon publication of the manuscript. If you have already registered at
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 Publons, 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. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons 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
Publons’ privacy policy 
https://publons.com/about/terms
Yes
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.
I declare that I have no competing interests
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 publish my name with my
report.
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?
Yes
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Whipple's Disease: the great masquerader. A high level of suspicion is the
key to diagnosis
Version: 
0 
Date: 
10 Nov 2020
Reviewer: 
Ian Beales
Reviewer's report:
The authors present three cases with relatively classic presentations in the
modern world of preceeding non-specific or rheumatolocgical feaures, failure to
repond to potent anti-inflammatory medicaton and eventual diagnosis of
Whipples's disease. There is nothing really new here. Although the authors
points about needing to consider what is always a rare diseease with protean
manifestation are important. Whipple's diease presenting as a treatment resistant
arthropathy is well documented and several studies have already highlighted that
many patients have been treated with anti-TNF or other biologics before a
diagnosis of Whipple's disease is made. Hence, although these cases are
generally well characterised, they are in no way unique. That does not mean that
publication to emphasize these issues with delayted diagnosis would not be
unreasonable.
Major points:
1. The paper is really too long for what amounts to 3 not unique case reports. In
their efforts to be inclusive of as much information as possible, the authors have
probably dilauted out their own message. Much of the detail of the exact details
within each patients timeline can be omitted without loss of clarity over the
overall points. For instance the details of which service the patient was admitted
under at any particualr time is really unnecessary. The cases have beed described
almost as they would be for a Grand Round presentaion but for the purposes of
publication a lot of extraneous information can be stripped out. For example, pn
page 11, any discussions about whether/how to perform a lymph node biopsy are
irrevelent. It is suffice to say that lymph nocde biopsy was performed.
2. The description of both cases 1 and 2 can be easily trimmed by at least 30 %.
3. 
Page 6 Line 14..he was in bad condition....is very poor English. It would be
suffice to say "his condition deteriorated"
4. Page 6, line 46. I do not understand what is meant by "fibres" in the
duodenum. The associated figure does ot clarify either, is this fibrin?
5. Was there any follow up on pateint 1?
6. What PCR assay was used for the diagnosis. Commercial or in house? Which
primers?
7. Page 10, line 54, TTE is used as an abbreviation without prior explanation?
8. It is interesting that the authors cite treatment recommendations from 2004
and have used treatments no longer recommended in more modern Europea
guidelines, with apparent good success, although we must accept that the
evidence base for such guidelines is poor. I agree with the authors statment about
the utility of early in therapy duodenal biopsy
8. It is not explicity stated but the assumption is that none of the patients had any
neurological or dermatological signs?
9. The figure legends need more detail. What is the magnification of the
histology pictures?
10. Table 1 is unnecessary, the point has already be sufficiently made that the
patient did not respond to potent immune modulators. Suggest this is removed.
11.Table 2 merely seems to have been lifted from another review paper. It is
irrelvent in this manuscript, suggst this is removed.
12. Figures 6 & are unnecessary and can be removed
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (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 Publons upon publication of the manuscript. If you have already registered at
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 Publons, 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. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons 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
Publons’ privacy policy 
https://publons.com/about/terms
Yes
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.
I declare that I have no competing interests
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 publish my name with my
report.
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?
Yes
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant