Reviewer’s report
Title: 
Delayed hypersensitivity reaction to orodispersible budesonide in a case
with eosinophilic esophagitis
Version: 
0 
Date: 
03 Jun 2020
Reviewer's report:
Dear Authors,
I have read with true interest your manuscript 
"Delayed hypersensitivity reaction
to orodispersible budesonide (Jorveza®) in a case with eosinophilic esophagitis".
Please find here my comments:
1. Although authors clearly affirm that " how sensitization to budesonide
occurred remains open", they also affirm that Swallowed Topical Corticosteroids
(STCs) " can cause allergy that may hamper an optimal therapeutic course".
[abstract line 22 and page 5 line 47-48]. 
This is confusing because the terminology "can cause allergy" makes think that
Jorveza has caused a de novo allergy ( sensitization + allergic reaction) and this
is not obvious because:
i) 
the patient had already used inhaled budesonide years before and 
ii) the interval between the first intake of Jorveza and the onset of oral symptoms
was very short 
[page 4 - line 18 
"some hours after the intake of the first" dose of
Jorveza], which is not typical of a de 
novo delayed hypersensitivity drug reaction.
Authors should consider adopting a different terminology. Instead of " STCs can
cause allergy that may hamper an optimal therapeutic course", I would suggest "
allergic reactions to STCs may hamper an optimal therapeutic course".
2. In the abstract it should not be affirmed that " Three days after the first intake,
she developed oral mucosal symptoms" because symptoms occurred upon the
very first intake as reported at page 4 - line 18.
3. Was the patient symptoms free between day 1 and day 4? Or did she have
persisting oral symptoms? Authors should consider openly describing this, for
the sake of an accurate description of the temporal evolution of symptoms.
4. Authors report that the patient was prescribed inhaled budesonide for asthma
in 2003. 
Did the patient experience any symptoms during that 6 months period? 
Authors could consider reporting in the text whether the patient has been asked
this specific question or not ( and, in case, the answer should be reported).
Specific investigation about reactions to budesonide, although hampered by
possible recall biases, could give a speculative - albeit limited - clue for the
presence or absence of prior sensitization to budesonide. 
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
Not relevant to this manuscript
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
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)
Reviewer’s report
Title: 
Delayed hypersensitivity reaction to orodispersible budesonide in a case
with eosinophilic esophagitis
Version: 
0 
Date: 
03 Jun 2020
Reviewer's report:
Dear Authors,
I have read with true interest your manuscript 
"Delayed hypersensitivity reaction
to orodispersible budesonide (Jorveza®) in a case with eosinophilic esophagitis".
Please find here my comments:
1. Although authors clearly affirm that " how sensitization to budesonide
occurred remains open", they also affirm that Swallowed Topical Corticosteroids
(STCs) " can cause allergy that may hamper an optimal therapeutic course".
[abstract line 22 and page 5 line 47-48]. 
This is confusing because the terminology "can cause allergy" makes think that
Jorveza has caused a de novo allergy ( sensitization + allergic reaction) and this
is not obvious because:
i) 
the patient had already used inhaled budesonide years before and 
ii) the interval between the first intake of Jorveza and the onset of oral symptoms
was very short 
[page 4 - line 18 
"some hours after the intake of the first" dose of
Jorveza], which is not typical of a de 
novo delayed hypersensitivity drug reaction.
Authors should consider adopting a different terminology. Instead of " STCs can
cause allergy that may hamper an optimal therapeutic course", I would suggest "
allergic reactions to STCs may hamper an optimal therapeutic course".
2. In the abstract it should not be affirmed that " Three days after the first intake,
she developed oral mucosal symptoms" because symptoms occurred upon the
very first intake as reported at page 4 - line 18.
3. Was the patient symptoms free between day 1 and day 4? Or did she have
persisting oral symptoms? Authors should consider openly describing this, for
the sake of an accurate description of the temporal evolution of symptoms.
4. Authors report that the patient was prescribed inhaled budesonide for asthma
in 2003. 
Did the patient experience any symptoms during that 6 months period? 
Authors could consider reporting in the text whether the patient has been asked
this specific question or not ( and, in case, the answer should be reported).
Specific investigation about reactions to budesonide, although hampered by
possible recall biases, could give a speculative - albeit limited - clue for the
presence or absence of prior sensitization to budesonide. 
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
Not relevant to this manuscript
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
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)
Please review this paper.
user
Reviewer’s report
Title: 
Delayed hypersensitivity reaction to orodispersible budesonide in a case
with eosinophilic esophagitis
Version: 
0 
Date: 
03 Jun 2020
Reviewer's report:
Dear Authors,
I have read with true interest your manuscript 
"Delayed hypersensitivity reaction
to orodispersible budesonide (Jorveza®) in a case with eosinophilic esophagitis".
Please find here my comments:
1. Although authors clearly affirm that " how sensitization to budesonide
occurred remains open", they also affirm that Swallowed Topical Corticosteroids
(STCs) " can cause allergy that may hamper an optimal therapeutic course".
[abstract line 22 and page 5 line 47-48]. 
This is confusing because the terminology "can cause allergy" makes think that
Jorveza has caused a de novo allergy ( sensitization + allergic reaction) and this
is not obvious because:
i) 
the patient had already used inhaled budesonide years before and 
ii) the interval between the first intake of Jorveza and the onset of oral symptoms
was very short 
[page 4 - line 18 
"some hours after the intake of the first" dose of
Jorveza], which is not typical of a de 
novo delayed hypersensitivity drug reaction.
Authors should consider adopting a different terminology. Instead of " STCs can
cause allergy that may hamper an optimal therapeutic course", I would suggest "
allergic reactions to STCs may hamper an optimal therapeutic course".
2. In the abstract it should not be affirmed that " Three days after the first intake,
she developed oral mucosal symptoms" because symptoms occurred upon the
very first intake as reported at page 4 - line 18.
3. Was the patient symptoms free between day 1 and day 4? Or did she have
persisting oral symptoms? Authors should consider openly describing this, for
the sake of an accurate description of the temporal evolution of symptoms.
4. Authors report that the patient was prescribed inhaled budesonide for asthma
in 2003. 
Did the patient experience any symptoms during that 6 months period? 
Authors could consider reporting in the text whether the patient has been asked
this specific question or not ( and, in case, the answer should be reported).
Specific investigation about reactions to budesonide, although hampered by
possible recall biases, could give a speculative - albeit limited - clue for the
presence or absence of prior sensitization to budesonide. 
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
Not relevant to this manuscript
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
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)
assistant