Reviewer's report
Title:Symptoms and signs in latent celiac disease - a validation study
Version: 1Date:5 May 2009
Reviewer: Kamran Rostami
Reviewer's report:
In this study Ludvigsson and his co-worker have identified 3,736 individuals with
positive serology and normal biopsy (Marsh 0). From this group they randomly
have selected 120 cases for this study and 112 fulfilled the criteria. They suggest
using a link between biopsy and serology is an effective model for identifying
latent coeliac disease (CD).
This study seems to me very interesting as the atypical presentation in CD (like
Microscopic enteritis) is predominant and the attention should be given to the
symptomatic patients with atypical serology and histology. I would be supporting
them if they would be willing to adjust their manuscript!
Let start with the fact that this study is difficult to read and there are some
confusions on the definition of some terminology like latent CD. The treatment
approach toward this subgroup of patient is different in this study compared to
what was recommended in previous guidelines. The authors do not explain why
they use this strategy. I don’t understand; based on what 13% (8-21%) of
patients with normal histology have been treated with GFD?
The authors identified 3,736 symptomatic individuals with positive serology and
normal biopsy and they consider them as having latent CD. They have selected
120 individuals with 40 +ve for tTGA, 40 +ve for EMA and 40 +ve for AGA for
manual reviews of biopsy reports and patients charts review.
As mentioned in discussion, AGA is far less sensitive and specific for CD. Latent
CD and the way is described in this study is confusing the clinician. Latent refers
specifically to patients who have abnormal antibody blood tests for celiac disease
and normal small intestines but no signs or symptoms of celiac disease. Latent
CD are not usually the best candidates for Gluten Free Diet for above reason.
Therefore I think the title is not representing the findings of this study and should
be changed.
Positive serology may occur in other condition too. How the authors are confident
that the antibodies are not due to other co-morbidities especially those with
positive AGA. The best would be to use the AGA positive group as AGA positive
not latent CD! And compare the clinical presentation with tTG and EMA positive
group!
Result
This statement is just inappropriate; We identified 3,736 individuals with latent
CD!
As mentioned above not every patient with positive serology means latent celiac
disease! Please revise; you may say that you identified 3.736 individuals with
positive serology and normal biopsy instead!
This is very confusing; In 90% (95% CI=83-95%; 103/114) of individuals
undergoing validation, latent CD could be confirmed through patient charts.
Or 46% (36-55%) had diarrhea, while 26% (18-35%) had anemia 90%, 46% and
26% of whom? You perhaps are talking about 114 selected cases. Please clarify
for the readers!
Histology
With all respect for the work of Swedish pathologists, Im not conformable with the
Swedish house criteria for diagnosing CD. It might be appropriate for internal
publication and use but as BMC Gastroenterology has a wider range of readers I
would suggest using the classical criteria Rostami et al, Sensitivity of
Antiendomysium and Antigliadin antibodies in untreated Celiac Disease:
disappointing in clinical practice. Am J Gastroenterol. 1999; 94:888-94 as used in
American;
Rostom A, Murray JA, Kagnoff MF.American Gastroenterological Association
(AGA) Institute technical review on the diagnosis and management of celiac
disease. Gastroenterology. 2006;131:1981-2002 and
European guidelines;
When is a coeliac a coeliac? Report of a working group of the United European
Gastroenterology Week in Amsterdam, 2001 Eur J Gastroenterol Hepatol.
2001;13:1123-8
This would give a more familiar histological picture to the readers!
-There are some confusing numbers used; in abstract 120 latent CD in results
114 in discussion 112 and in table/flowchart 118!!! Please unify!
What does all these % 46% (36-55%), 26% (18-35%) ,,, means
Discussion
Discussion is not focussed and the message is unclear and doesn’t appear to
come cross the way as it should!
In discussion the authors need to justify why this strategy is effective? why
should we look for latent CD?
In contrast to the authors finding Latent CD have no symptoms. However, the
reason for biopsy and serology in this study group was based mainly on their
symptoms. How do the authors explain this? The authors could bring more life in
their discussion by discussing the possibility of microenteropathy and
microscopic enteritis as a sole explanation for this fashion of presentation. We
know that relying on villous atrophy would result in missing a significant number
of cases. We also know that inflammatory anaemia and inflammatory
malabsorption would happen within normal looking mucosa.
Conclusion is not conclusion at all! It is a repeating version of results. Please
delete or change!
The authors may emphasise in conclusion that CD may present in a great deal
with microscopic enteritis and symptomatic seropositive cases might benefit from
a gluten free diet as absence of villous atrophy is not evidence of absence of CD.
Level of interest: An article of importance in its field
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
'I declare that I have no competing interests'
Reviewer's report
Title:Symptoms and signs in latent celiac disease - a validation study
Version: 1Date:5 May 2009
Reviewer: Kamran Rostami
Reviewer's report:
In this study Ludvigsson and his co-worker have identified 3,736 individuals with
positive serology and normal biopsy (Marsh 0). From this group they randomly
have selected 120 cases for this study and 112 fulfilled the criteria. They suggest
using a link between biopsy and serology is an effective model for identifying
latent coeliac disease (CD).
This study seems to me very interesting as the atypical presentation in CD (like
Microscopic enteritis) is predominant and the attention should be given to the
symptomatic patients with atypical serology and histology. I would be supporting
them if they would be willing to adjust their manuscript!
Let start with the fact that this study is difficult to read and there are some
confusions on the definition of some terminology like latent CD. The treatment
approach toward this subgroup of patient is different in this study compared to
what was recommended in previous guidelines. The authors do not explain why
they use this strategy. I don’t understand; based on what 13% (8-21%) of
patients with normal histology have been treated with GFD?
The authors identified 3,736 symptomatic individuals with positive serology and
normal biopsy and they consider them as having latent CD. They have selected
120 individuals with 40 +ve for tTGA, 40 +ve for EMA and 40 +ve for AGA for
manual reviews of biopsy reports and patients charts review.
As mentioned in discussion, AGA is far less sensitive and specific for CD. Latent
CD and the way is described in this study is confusing the clinician. Latent refers
specifically to patients who have abnormal antibody blood tests for celiac disease
and normal small intestines but no signs or symptoms of celiac disease. Latent
CD are not usually the best candidates for Gluten Free Diet for above reason.
Therefore I think the title is not representing the findings of this study and should
be changed.
Positive serology may occur in other condition too. How the authors are confident
that the antibodies are not due to other co-morbidities especially those with
positive AGA. The best would be to use the AGA positive group as AGA positive
not latent CD! And compare the clinical presentation with tTG and EMA positive
group!
Result
This statement is just inappropriate; We identified 3,736 individuals with latent
CD!
As mentioned above not every patient with positive serology means latent celiac
disease! Please revise; you may say that you identified 3.736 individuals with
positive serology and normal biopsy instead!
This is very confusing; In 90% (95% CI=83-95%; 103/114) of individuals
undergoing validation, latent CD could be confirmed through patient charts.
Or 46% (36-55%) had diarrhea, while 26% (18-35%) had anemia 90%, 46% and
26% of whom? You perhaps are talking about 114 selected cases. Please clarify
for the readers!
Histology
With all respect for the work of Swedish pathologists, Im not conformable with the
Swedish house criteria for diagnosing CD. It might be appropriate for internal
publication and use but as BMC Gastroenterology has a wider range of readers I
would suggest using the classical criteria Rostami et al, Sensitivity of
Antiendomysium and Antigliadin antibodies in untreated Celiac Disease:
disappointing in clinical practice. Am J Gastroenterol. 1999; 94:888-94 as used in
American;
Rostom A, Murray JA, Kagnoff MF.American Gastroenterological Association
(AGA) Institute technical review on the diagnosis and management of celiac
disease. Gastroenterology. 2006;131:1981-2002 and
European guidelines;
When is a coeliac a coeliac? Report of a working group of the United European
Gastroenterology Week in Amsterdam, 2001 Eur J Gastroenterol Hepatol.
2001;13:1123-8
This would give a more familiar histological picture to the readers!
-There are some confusing numbers used; in abstract 120 latent CD in results
114 in discussion 112 and in table/flowchart 118!!! Please unify!
What does all these % 46% (36-55%), 26% (18-35%) ,,, means
Discussion
Discussion is not focussed and the message is unclear and doesn’t appear to
come cross the way as it should!
In discussion the authors need to justify why this strategy is effective? why
should we look for latent CD?
In contrast to the authors finding Latent CD have no symptoms. However, the
reason for biopsy and serology in this study group was based mainly on their
symptoms. How do the authors explain this? The authors could bring more life in
their discussion by discussing the possibility of microenteropathy and
microscopic enteritis as a sole explanation for this fashion of presentation. We
know that relying on villous atrophy would result in missing a significant number
of cases. We also know that inflammatory anaemia and inflammatory
malabsorption would happen within normal looking mucosa.
Conclusion is not conclusion at all! It is a repeating version of results. Please
delete or change!
The authors may emphasise in conclusion that CD may present in a great deal
with microscopic enteritis and symptomatic seropositive cases might benefit from
a gluten free diet as absence of villous atrophy is not evidence of absence of CD.
Level of interest: An article of importance in its field
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
'I declare that I have no competing interests'
Please review this paper.
user
Reviewer's report
Title:Symptoms and signs in latent celiac disease - a validation study
Version: 1Date:5 May 2009
Reviewer: Kamran Rostami
Reviewer's report:
In this study Ludvigsson and his co-worker have identified 3,736 individuals with
positive serology and normal biopsy (Marsh 0). From this group they randomly
have selected 120 cases for this study and 112 fulfilled the criteria. They suggest
using a link between biopsy and serology is an effective model for identifying
latent coeliac disease (CD).
This study seems to me very interesting as the atypical presentation in CD (like
Microscopic enteritis) is predominant and the attention should be given to the
symptomatic patients with atypical serology and histology. I would be supporting
them if they would be willing to adjust their manuscript!
Let start with the fact that this study is difficult to read and there are some
confusions on the definition of some terminology like latent CD. The treatment
approach toward this subgroup of patient is different in this study compared to
what was recommended in previous guidelines. The authors do not explain why
they use this strategy. I don’t understand; based on what 13% (8-21%) of
patients with normal histology have been treated with GFD?
The authors identified 3,736 symptomatic individuals with positive serology and
normal biopsy and they consider them as having latent CD. They have selected
120 individuals with 40 +ve for tTGA, 40 +ve for EMA and 40 +ve for AGA for
manual reviews of biopsy reports and patients charts review.
As mentioned in discussion, AGA is far less sensitive and specific for CD. Latent
CD and the way is described in this study is confusing the clinician. Latent refers
specifically to patients who have abnormal antibody blood tests for celiac disease
and normal small intestines but no signs or symptoms of celiac disease. Latent
CD are not usually the best candidates for Gluten Free Diet for above reason.
Therefore I think the title is not representing the findings of this study and should
be changed.
Positive serology may occur in other condition too. How the authors are confident
that the antibodies are not due to other co-morbidities especially those with
positive AGA. The best would be to use the AGA positive group as AGA positive
not latent CD! And compare the clinical presentation with tTG and EMA positive
group!
Result
This statement is just inappropriate; We identified 3,736 individuals with latent
CD!
As mentioned above not every patient with positive serology means latent celiac
disease! Please revise; you may say that you identified 3.736 individuals with
positive serology and normal biopsy instead!
This is very confusing; In 90% (95% CI=83-95%; 103/114) of individuals
undergoing validation, latent CD could be confirmed through patient charts.
Or 46% (36-55%) had diarrhea, while 26% (18-35%) had anemia 90%, 46% and
26% of whom? You perhaps are talking about 114 selected cases. Please clarify
for the readers!
Histology
With all respect for the work of Swedish pathologists, Im not conformable with the
Swedish house criteria for diagnosing CD. It might be appropriate for internal
publication and use but as BMC Gastroenterology has a wider range of readers I
would suggest using the classical criteria Rostami et al, Sensitivity of
Antiendomysium and Antigliadin antibodies in untreated Celiac Disease:
disappointing in clinical practice. Am J Gastroenterol. 1999; 94:888-94 as used in
American;
Rostom A, Murray JA, Kagnoff MF.American Gastroenterological Association
(AGA) Institute technical review on the diagnosis and management of celiac
disease. Gastroenterology. 2006;131:1981-2002 and
European guidelines;
When is a coeliac a coeliac? Report of a working group of the United European
Gastroenterology Week in Amsterdam, 2001 Eur J Gastroenterol Hepatol.
2001;13:1123-8
This would give a more familiar histological picture to the readers!
-There are some confusing numbers used; in abstract 120 latent CD in results
114 in discussion 112 and in table/flowchart 118!!! Please unify!
What does all these % 46% (36-55%), 26% (18-35%) ,,, means
Discussion
Discussion is not focussed and the message is unclear and doesn’t appear to
come cross the way as it should!
In discussion the authors need to justify why this strategy is effective? why
should we look for latent CD?
In contrast to the authors finding Latent CD have no symptoms. However, the
reason for biopsy and serology in this study group was based mainly on their
symptoms. How do the authors explain this? The authors could bring more life in
their discussion by discussing the possibility of microenteropathy and
microscopic enteritis as a sole explanation for this fashion of presentation. We
know that relying on villous atrophy would result in missing a significant number
of cases. We also know that inflammatory anaemia and inflammatory
malabsorption would happen within normal looking mucosa.
Conclusion is not conclusion at all! It is a repeating version of results. Please
delete or change!
The authors may emphasise in conclusion that CD may present in a great deal
with microscopic enteritis and symptomatic seropositive cases might benefit from
a gluten free diet as absence of villous atrophy is not evidence of absence of CD.
Level of interest: An article of importance in its field
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
'I declare that I have no competing interests'
assistant