Title: Prevalence of oral manifestations in coeliac disease and associated factors
Version: 0 Date: 15 Oct 2024
Reviewer's report:
The aim of this study was to investigate different oral manifestations in 873 adult celiac
disease (CD). compared to 563 non CD controls, and  individual factors predisposing to these
manifestations . Enrolled patients and controls were interviewed and structured questionnaires
were used to assess the severity of gastrointestinal symptoms and quality of life. Oral
manifestations included dental enamel defects, recurrent aphthous ulceration and glossodynia.
Potential individual factors associated with oral manifestations were investigated using logistic
regression analysis. After data analysis, they found that: dental enamel defects were significantly
more common in CD patients than in non-CD controls (27% vs. 4%, p<0.001). Prior to the
CD diagnosis, 56% of the patients had experienced aphthous stomatitis (RAS)  and GFD
brought relief to 69% of them. While on GFD, CD patients had higher prevalence of RAS than
controls (17% vs. 13%, p=0.040), but this significance disappeared after adjusting for gender.
Glossodynia on GFD was more prevalent in the CD cohort than in the controls (14% vs 6%,
p <0.001). Oral manifestations at diagnosis and on GFD were associated with the presence of
abdominal symptoms at the time of CD diagnosis, long diagnostic delay and female gender. At
the time of the study, patients with oral symptoms had more severe gastrointestinal symptoms
and poorer quality of life than those without these symptoms. The authors concluded that oral
manifestations were more prevalent, at diagnosis and on GFD, in patients with CD than in the
controls, and they were associated with long diagnostic delay, abdominal symptoms, female
gender and impaired quality of life. GFD is beneficial in relieving recurrent aphthous ulcerations.
The study is of interest, however some issues should be addressed.
-overall,  56% of the CD patients reported having had RAS prior to the CD diagnosis, vs no
controls having RAS. How the authors could explain that in the comparison under GFD, CD
patients had higher prevalence (17%) of RAS than controls (13% vs no patients at the time of
enrollment). could this difference in the prevalente of RAS in controls due to interviewed and
structured questionnaires limits?
-previous studies on digestive mucosal damages in CD patients suggested a link between
clinical manifestations/symtoms and severity of duodenal mucosal severity degree. In this
regard, a pathogenetic hypothesis explaining RAS occurrence in CD patients might be linked to
immune.medianted mucosal damage since it has been previously demonstrated that a significant
rate of CD patients with severe mucosal damage (villous atrophy) develop serum anti-actin IgA
antibodies, as previously demonstrated (Clin Exp Immunol. 2004;137(2):386-92. doi: 10.1111/
j.1365-2249.2004.02541.x.). Could the Authors describe whether CD patients with RAS had a
more severe intestinal mucosal damage? If confirmed this association, it would be of interest
to investigate whether CD patients with anti-actin antibodies have a higher prevalence of RAS
and other oral manifestations.
-Glossodynia: the authors found that psychiatric disorders were more prevalent among patients
with glossodynia. Could the authors describe any mucosal/local inflammatory change observed
(if any)?
-patients with persistent RAS under GFD: it could be a clue for a suboptimal GFD compliance?
Have this CD patients group other CD-related symptoms?
-As reported in table 2, taking into account factors associated with dental enamel defects
and RAS at diagnosis in CD patients, there were 43 asymptomatic patients. How they
were diagnosed? previous report describe in CD "apparently" asymtpoamtic patients othe
digestive CD-related manifestations, in particular hypertransaminasemia of unknown origin
that may characterize CD patients who do not complain any gastrointestinal symptom and
resolve after GFD as previously described (Dig Liver Dis. 2001;33(5):420-5. doi: 10.1016/
s1590-8658(01)80014-1. ).
Title: Prevalence of oral manifestations in coeliac disease and associated factors
Version: 0 Date: 15 Oct 2024
Reviewer's report:
The aim of this study was to investigate different oral manifestations in 873 adult celiac
disease (CD). compared to 563 non CD controls, and  individual factors predisposing to these
manifestations . Enrolled patients and controls were interviewed and structured questionnaires
were used to assess the severity of gastrointestinal symptoms and quality of life. Oral
manifestations included dental enamel defects, recurrent aphthous ulceration and glossodynia.
Potential individual factors associated with oral manifestations were investigated using logistic
regression analysis. After data analysis, they found that: dental enamel defects were significantly
more common in CD patients than in non-CD controls (27% vs. 4%, p<0.001). Prior to the
CD diagnosis, 56% of the patients had experienced aphthous stomatitis (RAS)  and GFD
brought relief to 69% of them. While on GFD, CD patients had higher prevalence of RAS than
controls (17% vs. 13%, p=0.040), but this significance disappeared after adjusting for gender.
Glossodynia on GFD was more prevalent in the CD cohort than in the controls (14% vs 6%,
p <0.001). Oral manifestations at diagnosis and on GFD were associated with the presence of
abdominal symptoms at the time of CD diagnosis, long diagnostic delay and female gender. At
the time of the study, patients with oral symptoms had more severe gastrointestinal symptoms
and poorer quality of life than those without these symptoms. The authors concluded that oral
manifestations were more prevalent, at diagnosis and on GFD, in patients with CD than in the
controls, and they were associated with long diagnostic delay, abdominal symptoms, female
gender and impaired quality of life. GFD is beneficial in relieving recurrent aphthous ulcerations.
The study is of interest, however some issues should be addressed.
-overall,  56% of the CD patients reported having had RAS prior to the CD diagnosis, vs no
controls having RAS. How the authors could explain that in the comparison under GFD, CD
patients had higher prevalence (17%) of RAS than controls (13% vs no patients at the time of
enrollment). could this difference in the prevalente of RAS in controls due to interviewed and
structured questionnaires limits?
-previous studies on digestive mucosal damages in CD patients suggested a link between
clinical manifestations/symtoms and severity of duodenal mucosal severity degree. In this
regard, a pathogenetic hypothesis explaining RAS occurrence in CD patients might be linked to
immune.medianted mucosal damage since it has been previously demonstrated that a significant
rate of CD patients with severe mucosal damage (villous atrophy) develop serum anti-actin IgA
antibodies, as previously demonstrated (Clin Exp Immunol. 2004;137(2):386-92. doi: 10.1111/
j.1365-2249.2004.02541.x.). Could the Authors describe whether CD patients with RAS had a
more severe intestinal mucosal damage? If confirmed this association, it would be of interest
to investigate whether CD patients with anti-actin antibodies have a higher prevalence of RAS
and other oral manifestations.
-Glossodynia: the authors found that psychiatric disorders were more prevalent among patients
with glossodynia. Could the authors describe any mucosal/local inflammatory change observed
(if any)?
-patients with persistent RAS under GFD: it could be a clue for a suboptimal GFD compliance?
Have this CD patients group other CD-related symptoms?
-As reported in table 2, taking into account factors associated with dental enamel defects
and RAS at diagnosis in CD patients, there were 43 asymptomatic patients. How they
were diagnosed? previous report describe in CD "apparently" asymtpoamtic patients othe
digestive CD-related manifestations, in particular hypertransaminasemia of unknown origin
that may characterize CD patients who do not complain any gastrointestinal symptom and
resolve after GFD as previously described (Dig Liver Dis. 2001;33(5):420-5. doi: 10.1016/
s1590-8658(01)80014-1. ).
Please review this paper.
user
Title: Prevalence of oral manifestations in coeliac disease and associated factors
Version: 0 Date: 15 Oct 2024
Reviewer's report:
The aim of this study was to investigate different oral manifestations in 873 adult celiac
disease (CD). compared to 563 non CD controls, and  individual factors predisposing to these
manifestations . Enrolled patients and controls were interviewed and structured questionnaires
were used to assess the severity of gastrointestinal symptoms and quality of life. Oral
manifestations included dental enamel defects, recurrent aphthous ulceration and glossodynia.
Potential individual factors associated with oral manifestations were investigated using logistic
regression analysis. After data analysis, they found that: dental enamel defects were significantly
more common in CD patients than in non-CD controls (27% vs. 4%, p<0.001). Prior to the
CD diagnosis, 56% of the patients had experienced aphthous stomatitis (RAS)  and GFD
brought relief to 69% of them. While on GFD, CD patients had higher prevalence of RAS than
controls (17% vs. 13%, p=0.040), but this significance disappeared after adjusting for gender.
Glossodynia on GFD was more prevalent in the CD cohort than in the controls (14% vs 6%,
p <0.001). Oral manifestations at diagnosis and on GFD were associated with the presence of
abdominal symptoms at the time of CD diagnosis, long diagnostic delay and female gender. At
the time of the study, patients with oral symptoms had more severe gastrointestinal symptoms
and poorer quality of life than those without these symptoms. The authors concluded that oral
manifestations were more prevalent, at diagnosis and on GFD, in patients with CD than in the
controls, and they were associated with long diagnostic delay, abdominal symptoms, female
gender and impaired quality of life. GFD is beneficial in relieving recurrent aphthous ulcerations.
The study is of interest, however some issues should be addressed.
-overall,  56% of the CD patients reported having had RAS prior to the CD diagnosis, vs no
controls having RAS. How the authors could explain that in the comparison under GFD, CD
patients had higher prevalence (17%) of RAS than controls (13% vs no patients at the time of
enrollment). could this difference in the prevalente of RAS in controls due to interviewed and
structured questionnaires limits?
-previous studies on digestive mucosal damages in CD patients suggested a link between
clinical manifestations/symtoms and severity of duodenal mucosal severity degree. In this
regard, a pathogenetic hypothesis explaining RAS occurrence in CD patients might be linked to
immune.medianted mucosal damage since it has been previously demonstrated that a significant
rate of CD patients with severe mucosal damage (villous atrophy) develop serum anti-actin IgA
antibodies, as previously demonstrated (Clin Exp Immunol. 2004;137(2):386-92. doi: 10.1111/
j.1365-2249.2004.02541.x.). Could the Authors describe whether CD patients with RAS had a
more severe intestinal mucosal damage? If confirmed this association, it would be of interest
to investigate whether CD patients with anti-actin antibodies have a higher prevalence of RAS
and other oral manifestations.
-Glossodynia: the authors found that psychiatric disorders were more prevalent among patients
with glossodynia. Could the authors describe any mucosal/local inflammatory change observed
(if any)?
-patients with persistent RAS under GFD: it could be a clue for a suboptimal GFD compliance?
Have this CD patients group other CD-related symptoms?
-As reported in table 2, taking into account factors associated with dental enamel defects
and RAS at diagnosis in CD patients, there were 43 asymptomatic patients. How they
were diagnosed? previous report describe in CD "apparently" asymtpoamtic patients othe
digestive CD-related manifestations, in particular hypertransaminasemia of unknown origin
that may characterize CD patients who do not complain any gastrointestinal symptom and
resolve after GFD as previously described (Dig Liver Dis. 2001;33(5):420-5. doi: 10.1016/
s1590-8658(01)80014-1. ).
assistant