Reviewer ’s report  
 
Title: The impact of diagnosis on health -related quality of life in people with coeliac disease: a 
UK popu lation -based longitudinal perspective  
 
Version: 0 Date: 17 Sep 2018  
 
Reviewer: Annalisa Schiepatti  
 
Reviewer's report:  
 
In this paper the Authors aim to assess changes over time in the prevalence of CD symptoms, 
time to diagnosis, quality of life before and after diagnosis of CD in the UK by using a postal 
questionnaire. The Authors conc lude that undiagnosed CD is associated with substantial 
decrement of the quality of life, which then returns to a normal level after a gluten -free diet has 
been started. Interestingly, time to diagnose CD has not changed significantly in the last decade 
in the UK. Although the topic is of great interest given the burden of CD on healthcare system, 
the general impression is that this paper rather little flies in the field of medicine. So, regrettably, 
I have the following major concerns:  
- The study populati on surveyed is represented by members of the society Coeliac UK and 
patients have been enrolled on the basis of a self -reported diagnosis of CD. The Authors do 
not provide any information about the criteria for diagnosis of CD in these patients 
(EMA/TTG po sitive? Villous atrophy on small -bowel biopsy?). In addiction we do not have 
information on the type of coeliac disease (potential, refractory…). Theoretically, without 
any confirmation about the serological and histological diagnosis of CD, the group surv eyed 
may include also a substantial part of non -coeliac patients, such as those affected by non -
coeliac gluten sensitivity or food allergies or some lifestylers, who perhaps self -reported 
some benefits after starting on a GFD. This would represent a huge s election bias with an 
enormous impact on the final results.  
 
- When assessing symptoms what do the Authors mean with "skin rash"? Whereas dermatitis 
herpetiformis is well -known to be within the extra -intestinal manifestations of CD, any other 
unspecified s kin rash may be the expression of a wide range of disorders that are different 
from CD, such as IgE -mediated food allergies or non -coeliac gluten sensitivity and that, 
however, may find a GFD beneficial.  
 
- The Authors consider among symptoms osteoporosis (that actually is a well -defined medical 
disorder, not its clinical manifestation), while do not take into account any other disorders 
that are known to be associated with CD and may have a relevant impact on quality of life 
(autoimmune thyroiditis, type I  diabetes etc..).    
 
I also have some minor concerns:  
- Background section, page 4: The sentence "Diagnosis is usually prompted by a range of 
intestinal and other symptoms" should be rephrased. Please consider the more specific term 
"extraintestinal sympt oms" instead of "other symptoms". Secondly, please, take into 
consideration also the possibility of high -risk groups, such as type 1 diabetes, first degree 
relatives of CD etc., that should be tested for CD.  
 
- Results section, page 7. The Authors state tha t "the majority of respondents (75%) resided in 
England". This statement is not completely clear to me. Does it mean that these people 
surveyed were British diagnosed in the UK who then moved abroad? Or were they non -
British people diagnosed in another Cou ntry who subsequently joined Coeliac UK? Please 
specify this point, considered that the study is a UK population -based  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are yo u 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.  
 
I am able  to assess the statistics  
 
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 o f 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 i nterests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. 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/ ). I understand that any comments  
which I do not wish to be included i n my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: The impact of diagnosis on health -related quality of life in people with coeliac disease: a 
UK popu lation -based longitudinal perspective  
 
Version: 0 Date: 17 Sep 2018  
 
Reviewer: Annalisa Schiepatti  
 
Reviewer's report:  
 
In this paper the Authors aim to assess changes over time in the prevalence of CD symptoms, 
time to diagnosis, quality of life before and after diagnosis of CD in the UK by using a postal 
questionnaire. The Authors conc lude that undiagnosed CD is associated with substantial 
decrement of the quality of life, which then returns to a normal level after a gluten -free diet has 
been started. Interestingly, time to diagnose CD has not changed significantly in the last decade 
in the UK. Although the topic is of great interest given the burden of CD on healthcare system, 
the general impression is that this paper rather little flies in the field of medicine. So, regrettably, 
I have the following major concerns:  
- The study populati on surveyed is represented by members of the society Coeliac UK and 
patients have been enrolled on the basis of a self -reported diagnosis of CD. The Authors do 
not provide any information about the criteria for diagnosis of CD in these patients 
(EMA/TTG po sitive? Villous atrophy on small -bowel biopsy?). In addiction we do not have 
information on the type of coeliac disease (potential, refractory…). Theoretically, without 
any confirmation about the serological and histological diagnosis of CD, the group surv eyed 
may include also a substantial part of non -coeliac patients, such as those affected by non -
coeliac gluten sensitivity or food allergies or some lifestylers, who perhaps self -reported 
some benefits after starting on a GFD. This would represent a huge s election bias with an 
enormous impact on the final results.  
 
- When assessing symptoms what do the Authors mean with "skin rash"? Whereas dermatitis 
herpetiformis is well -known to be within the extra -intestinal manifestations of CD, any other 
unspecified s kin rash may be the expression of a wide range of disorders that are different 
from CD, such as IgE -mediated food allergies or non -coeliac gluten sensitivity and that, 
however, may find a GFD beneficial.  
 
- The Authors consider among symptoms osteoporosis (that actually is a well -defined medical 
disorder, not its clinical manifestation), while do not take into account any other disorders 
that are known to be associated with CD and may have a relevant impact on quality of life 
(autoimmune thyroiditis, type I  diabetes etc..).    
 
I also have some minor concerns:  
- Background section, page 4: The sentence "Diagnosis is usually prompted by a range of 
intestinal and other symptoms" should be rephrased. Please consider the more specific term 
"extraintestinal sympt oms" instead of "other symptoms". Secondly, please, take into 
consideration also the possibility of high -risk groups, such as type 1 diabetes, first degree 
relatives of CD etc., that should be tested for CD.  
 
- Results section, page 7. The Authors state tha t "the majority of respondents (75%) resided in 
England". This statement is not completely clear to me. Does it mean that these people 
surveyed were British diagnosed in the UK who then moved abroad? Or were they non -
British people diagnosed in another Cou ntry who subsequently joined Coeliac UK? Please 
specify this point, considered that the study is a UK population -based  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are yo u 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.  
 
I am able  to assess the statistics  
 
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 o f 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 i nterests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. 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/ ). I understand that any comments  
which I do not wish to be included i n my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: The impact of diagnosis on health -related quality of life in people with coeliac disease: a 
UK popu lation -based longitudinal perspective  
 
Version: 0 Date: 17 Sep 2018  
 
Reviewer: Annalisa Schiepatti  
 
Reviewer's report:  
 
In this paper the Authors aim to assess changes over time in the prevalence of CD symptoms, 
time to diagnosis, quality of life before and after diagnosis of CD in the UK by using a postal 
questionnaire. The Authors conc lude that undiagnosed CD is associated with substantial 
decrement of the quality of life, which then returns to a normal level after a gluten -free diet has 
been started. Interestingly, time to diagnose CD has not changed significantly in the last decade 
in the UK. Although the topic is of great interest given the burden of CD on healthcare system, 
the general impression is that this paper rather little flies in the field of medicine. So, regrettably, 
I have the following major concerns:  
- The study populati on surveyed is represented by members of the society Coeliac UK and 
patients have been enrolled on the basis of a self -reported diagnosis of CD. The Authors do 
not provide any information about the criteria for diagnosis of CD in these patients 
(EMA/TTG po sitive? Villous atrophy on small -bowel biopsy?). In addiction we do not have 
information on the type of coeliac disease (potential, refractory…). Theoretically, without 
any confirmation about the serological and histological diagnosis of CD, the group surv eyed 
may include also a substantial part of non -coeliac patients, such as those affected by non -
coeliac gluten sensitivity or food allergies or some lifestylers, who perhaps self -reported 
some benefits after starting on a GFD. This would represent a huge s election bias with an 
enormous impact on the final results.  
 
- When assessing symptoms what do the Authors mean with "skin rash"? Whereas dermatitis 
herpetiformis is well -known to be within the extra -intestinal manifestations of CD, any other 
unspecified s kin rash may be the expression of a wide range of disorders that are different 
from CD, such as IgE -mediated food allergies or non -coeliac gluten sensitivity and that, 
however, may find a GFD beneficial.  
 
- The Authors consider among symptoms osteoporosis (that actually is a well -defined medical 
disorder, not its clinical manifestation), while do not take into account any other disorders 
that are known to be associated with CD and may have a relevant impact on quality of life 
(autoimmune thyroiditis, type I  diabetes etc..).    
 
I also have some minor concerns:  
- Background section, page 4: The sentence "Diagnosis is usually prompted by a range of 
intestinal and other symptoms" should be rephrased. Please consider the more specific term 
"extraintestinal sympt oms" instead of "other symptoms". Secondly, please, take into 
consideration also the possibility of high -risk groups, such as type 1 diabetes, first degree 
relatives of CD etc., that should be tested for CD.  
 
- Results section, page 7. The Authors state tha t "the majority of respondents (75%) resided in 
England". This statement is not completely clear to me. Does it mean that these people 
surveyed were British diagnosed in the UK who then moved abroad? Or were they non -
British people diagnosed in another Cou ntry who subsequently joined Coeliac UK? Please 
specify this point, considered that the study is a UK population -based  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are yo u 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.  
 
I am able  to assess the statistics  
 
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 o f 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 i nterests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. 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/ ). I understand that any comments  
which I do not wish to be included i n my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant