Reviewer’s report
Title: 
Gastrointestinal symptoms as first remarkable signs of ANCA-associated
granulomatosis with polyangiitis: case report and review
Version: 
0 
Date: 
15 Aug 2020
Reviewer's report:
GENERAL COMMENTS
Reporting a case of GI involvement of AAV is very valuable, because it is very
rare in AAV, particularly, in GPA patients. 
MAJOR COMMENTS
BACKGROUND
1) Page 3, Line 45-48
The first paragraph does not seem closely related to the topic of this article, and
thus, it may be deleted.
2) page 3, Line 52
On the basis of 2012 revised International Chapel Hill Consensus Conference
Nomenclature of Vasculitides, "pauci-immune small vessel vasculitis" may be
changed to "ANCA-associated vasculitis" in the whole manuscript. 
3) Page 3, Line 57 and 58
Correction: (GPA, Wegener's granulomatosis) (EGPA, Churg-Strauss syndrome)
4) The authors should clarify why they selected this topic and describe the
limitations of previous reports in the background section. 
CASE PRESENTATION
5) It is better to clarify whether the first haematuria met the definition of "renal
vasculitis" on the basis of the classification of the ANCA-associated vasculitides
and polyarteritis nodosa for epidemiological studies (Ann Rheum Dis. 2007
Feb;66(2):222-7). Thus, the authors should provide more information on the
haematuria despite the normal kidney function, because renal involvement might
have preceded GI involvement of GPA.
6) were antibiotics administered to the patients prior to the initiation of
immunosuppressive drugs? Did not the authors doubt the GI infection? The
initial level of CRP (137 mg/L) was very high, which might clinically indicate
infection rather than renal limited AAV with GI symptoms.
7) Page5, Line 103-111
PR3-ANCA positivity cannot directly indicate the preference of diagnosis of
GPA rather than MPA. furthermore, the sentences should be shortened because
they seem redundant. Therefore, it may be better for the authors to briefly clarify
the clues of GPA according to the classification of the ANCA-associated
vasculitides and polyarteritis nodosa for epidemiological studies (Ann Rheum
Dis. 2007 Feb;66(2):222-7).
8) Page 5
On chest imaging tests, there were two types of lung lesions, small nodule and
GGO. In general, fixed nodules and cavitations are consider as surrogate markers
for Wegener's granulomatosis. However, GGO pattern is not one of surrogate
markers for WG. Was there any possibility of pneumonia or Tbc etc? 
9) This reviewer still does not consider a GI symptom to be the first clinical
symptom of GPA in this case, because renal manifestation seemed to precede GI
bleeding and perforation. At the first admission, there was no definite evidence
of GI involvement of GPA despite non-specific GI symptoms. 
10) Therefore, the authors should provide the histologic findings (pictures) of
resected bowel that support their argument that the bleeding and perforation of
the duodenum were owing to GI involvement of GPA. This reviewer believes
that histologic evidence is the most important and critical point of this review.
DISCUSSION and CONCLUSIONS
11) Page 6, Line 137-142
the first paragraph seems redundant and thus, it may be deleted. 
12) In addition, the description of previous reports is too vast and redundant that
it should be reduced.
13) Birmingham vasculitis activity score (BVAS) version 3 describes three cases
of abdominal manifestation of AAV, including peritonitis, bloody diarrhoea and
ischaemic abdominal pain (Ann Rheum Dis. 2009 Dec;68(12):1827-32.).
Meanwhile, BVAS for Wegener's granulomatosis describes only one case of
mesenteric ischaemia (Arthritis Rheum. 2001 Apr;44(4):912-20.). Therefore, this
reviewer asks the authors to provide evidence of bowel ischaemia with
histological findings. 
Publons Reviewer Recognition
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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 
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?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Gastrointestinal symptoms as first remarkable signs of ANCA-associated
granulomatosis with polyangiitis: case report and review
Version: 
0 
Date: 
15 Aug 2020
Reviewer's report:
GENERAL COMMENTS
Reporting a case of GI involvement of AAV is very valuable, because it is very
rare in AAV, particularly, in GPA patients. 
MAJOR COMMENTS
BACKGROUND
1) Page 3, Line 45-48
The first paragraph does not seem closely related to the topic of this article, and
thus, it may be deleted.
2) page 3, Line 52
On the basis of 2012 revised International Chapel Hill Consensus Conference
Nomenclature of Vasculitides, "pauci-immune small vessel vasculitis" may be
changed to "ANCA-associated vasculitis" in the whole manuscript. 
3) Page 3, Line 57 and 58
Correction: (GPA, Wegener's granulomatosis) (EGPA, Churg-Strauss syndrome)
4) The authors should clarify why they selected this topic and describe the
limitations of previous reports in the background section. 
CASE PRESENTATION
5) It is better to clarify whether the first haematuria met the definition of "renal
vasculitis" on the basis of the classification of the ANCA-associated vasculitides
and polyarteritis nodosa for epidemiological studies (Ann Rheum Dis. 2007
Feb;66(2):222-7). Thus, the authors should provide more information on the
haematuria despite the normal kidney function, because renal involvement might
have preceded GI involvement of GPA.
6) were antibiotics administered to the patients prior to the initiation of
immunosuppressive drugs? Did not the authors doubt the GI infection? The
initial level of CRP (137 mg/L) was very high, which might clinically indicate
infection rather than renal limited AAV with GI symptoms.
7) Page5, Line 103-111
PR3-ANCA positivity cannot directly indicate the preference of diagnosis of
GPA rather than MPA. furthermore, the sentences should be shortened because
they seem redundant. Therefore, it may be better for the authors to briefly clarify
the clues of GPA according to the classification of the ANCA-associated
vasculitides and polyarteritis nodosa for epidemiological studies (Ann Rheum
Dis. 2007 Feb;66(2):222-7).
8) Page 5
On chest imaging tests, there were two types of lung lesions, small nodule and
GGO. In general, fixed nodules and cavitations are consider as surrogate markers
for Wegener's granulomatosis. However, GGO pattern is not one of surrogate
markers for WG. Was there any possibility of pneumonia or Tbc etc? 
9) This reviewer still does not consider a GI symptom to be the first clinical
symptom of GPA in this case, because renal manifestation seemed to precede GI
bleeding and perforation. At the first admission, there was no definite evidence
of GI involvement of GPA despite non-specific GI symptoms. 
10) Therefore, the authors should provide the histologic findings (pictures) of
resected bowel that support their argument that the bleeding and perforation of
the duodenum were owing to GI involvement of GPA. This reviewer believes
that histologic evidence is the most important and critical point of this review.
DISCUSSION and CONCLUSIONS
11) Page 6, Line 137-142
the first paragraph seems redundant and thus, it may be deleted. 
12) In addition, the description of previous reports is too vast and redundant that
it should be reduced.
13) Birmingham vasculitis activity score (BVAS) version 3 describes three cases
of abdominal manifestation of AAV, including peritonitis, bloody diarrhoea and
ischaemic abdominal pain (Ann Rheum Dis. 2009 Dec;68(12):1827-32.).
Meanwhile, BVAS for Wegener's granulomatosis describes only one case of
mesenteric ischaemia (Arthritis Rheum. 2001 Apr;44(4):912-20.). Therefore, this
reviewer asks the authors to provide evidence of bowel ischaemia with
histological findings. 
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 after the final decision on the manuscript has been made. 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 
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?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
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: 
Gastrointestinal symptoms as first remarkable signs of ANCA-associated
granulomatosis with polyangiitis: case report and review
Version: 
0 
Date: 
15 Aug 2020
Reviewer's report:
GENERAL COMMENTS
Reporting a case of GI involvement of AAV is very valuable, because it is very
rare in AAV, particularly, in GPA patients. 
MAJOR COMMENTS
BACKGROUND
1) Page 3, Line 45-48
The first paragraph does not seem closely related to the topic of this article, and
thus, it may be deleted.
2) page 3, Line 52
On the basis of 2012 revised International Chapel Hill Consensus Conference
Nomenclature of Vasculitides, "pauci-immune small vessel vasculitis" may be
changed to "ANCA-associated vasculitis" in the whole manuscript. 
3) Page 3, Line 57 and 58
Correction: (GPA, Wegener's granulomatosis) (EGPA, Churg-Strauss syndrome)
4) The authors should clarify why they selected this topic and describe the
limitations of previous reports in the background section. 
CASE PRESENTATION
5) It is better to clarify whether the first haematuria met the definition of "renal
vasculitis" on the basis of the classification of the ANCA-associated vasculitides
and polyarteritis nodosa for epidemiological studies (Ann Rheum Dis. 2007
Feb;66(2):222-7). Thus, the authors should provide more information on the
haematuria despite the normal kidney function, because renal involvement might
have preceded GI involvement of GPA.
6) were antibiotics administered to the patients prior to the initiation of
immunosuppressive drugs? Did not the authors doubt the GI infection? The
initial level of CRP (137 mg/L) was very high, which might clinically indicate
infection rather than renal limited AAV with GI symptoms.
7) Page5, Line 103-111
PR3-ANCA positivity cannot directly indicate the preference of diagnosis of
GPA rather than MPA. furthermore, the sentences should be shortened because
they seem redundant. Therefore, it may be better for the authors to briefly clarify
the clues of GPA according to the classification of the ANCA-associated
vasculitides and polyarteritis nodosa for epidemiological studies (Ann Rheum
Dis. 2007 Feb;66(2):222-7).
8) Page 5
On chest imaging tests, there were two types of lung lesions, small nodule and
GGO. In general, fixed nodules and cavitations are consider as surrogate markers
for Wegener's granulomatosis. However, GGO pattern is not one of surrogate
markers for WG. Was there any possibility of pneumonia or Tbc etc? 
9) This reviewer still does not consider a GI symptom to be the first clinical
symptom of GPA in this case, because renal manifestation seemed to precede GI
bleeding and perforation. At the first admission, there was no definite evidence
of GI involvement of GPA despite non-specific GI symptoms. 
10) Therefore, the authors should provide the histologic findings (pictures) of
resected bowel that support their argument that the bleeding and perforation of
the duodenum were owing to GI involvement of GPA. This reviewer believes
that histologic evidence is the most important and critical point of this review.
DISCUSSION and CONCLUSIONS
11) Page 6, Line 137-142
the first paragraph seems redundant and thus, it may be deleted. 
12) In addition, the description of previous reports is too vast and redundant that
it should be reduced.
13) Birmingham vasculitis activity score (BVAS) version 3 describes three cases
of abdominal manifestation of AAV, including peritonitis, bloody diarrhoea and
ischaemic abdominal pain (Ann Rheum Dis. 2009 Dec;68(12):1827-32.).
Meanwhile, BVAS for Wegener's granulomatosis describes only one case of
mesenteric ischaemia (Arthritis Rheum. 2001 Apr;44(4):912-20.). Therefore, this
reviewer asks the authors to provide evidence of bowel ischaemia with
histological findings. 
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 after the final decision on the manuscript has been made. 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 
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?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant