I read with extreme interest the recent pros and cons about the screening
of Coeliac Disease (CD) (1,2).
I share Fasano’s idea about a large screening of CD in clinical
practice. Since CD is one of the most common lifelong disorders, affecting
0.5-1% of the population (3), and based on our group experience,
several points are in favour of this approach:
1. Although CD was initially described as a paediatric gastrointestinal
condition, we currently know that it can affect people at any age and it
can manifest in a wide range of symptoms potentially affecting any organ
or body system (3,4). Many undiagnosed patients accept a state of chronic,
vague, ill health as normal. In our experience, most of patients are now
suffering from extra-intestinal diseases (for example, autoimmune
diseases) or are olygo-symptomatic (for example, iron-deficiency anaemia)
(5). Early detection based on clinical suspicion is therefore difficult,
and many patients remain undiagnosed for many years and exposed to the
risk of long term complications (6).
2. Most of patients are now affected by “silent” disease, that is the CD
with complete absence of any symptom. In our experience, these patients
represent about 20% of CD patients (5), and this is particularly true for
relatives. In fact we now know that the prevalence of CD in first-degree
relatives is now increasing, and the prevalence ranges from 11% to 17% (7-
10). Our recent experience confirms this increasing trend. In fact we
found a CD prevalence of 20% in CD relatives, and about 30% of them were
affected by “silent” disease (data submitted).
3. Histological recovery is slower than previously thought. We found that
older patients showed incomplete endoscopic and histological recovery even
24 months after starting a GFD (11). This is a key point in the follow-up
of patients with celiac disease: the persistence of histological lesions
beyond 24 months after starting and strictly adhering to a gluten-free
diet (GFD) may mean that patients with celiac disease remain at high risk
for celiac disease related complications for longer than previously
thought.
3. But also patients under GFD may be at risk of developing complications.
We recently found that about 4% of CD patients may develop complications
under GFD. Complications seem to affect more classical CD than subclinical
CD, and seem to be irrespective of optimal GFD adherence (12) (p= n.s.).
All the previous point are in favour of a screening mass program.
Although the prevalence of the antibodies currently used in CD practice
seems to be related to the degree of the histological damage (13-15),
serology remains the best method to perform an adequate screening. In
particular, it should be improved in family members of CD patients. Chang
and Green (16) performed recently a robust cost analysis on 3 different
follow-up strategies based on anti-tTG antibodies and HLA typing. They
showed that a strategy based on testing anti-tTG antibodies in 2 different
moments (‘‘tTG at t0 and t1’’) without HLA testing may offer the best
ratio between false-negative FMs and costs. This may be a very reasonable
strategy and the best timing for the second serologic test could be after
4 or 5 years, since the majority of first-degree relatives who
subsequently developed CD described in the literature developed CD less
than 4 years after the first testing (17-19).
But I think that the real problem to organize a screening program is that
gluten sensitivity (GS) may cause a lot of gastrointestinal symptoms,
including functional bowel disorder-like symptoms. It has been recently
hypothesized that, even in the absence of fully developed CD, gluten can
induce symptoms similar to functional bowel disorders. GS and post-
infectious irritable bowel syndrome (IBS) provide two triggers that can
therefore explain at least part of the spectrum that constitutes IBS (20).
In this way, we should understand whether these patients run the risk to
develop complication similar to that of patients with symptomatic or olygo
-symptomatic CD patients, and therefore whether these patients may obtain
the same beneficial from a gluten-free diet. This new interesting
hypothesis should be correctly kept in mind in the future screening
programs, taking a look also at new categories of patients with GS but
without a certain CD.
REFERENCES
1) Fasano A. Should we screen for celiac disease? Yes. BMJ 2009;339:b3592
2) Evans KE, McAllister R, Sanders DS. Should we screen for celiac
disease? No. BMJ 2009;339:b3674
3) Fasano A, Catassi C. Current approaches to diagnosis and treatment of
celiac disease: an evolving spectrum. Gastroenterology 2001;120:636-51
5) Tursi A, Giorgetti G, Brandimarte G, Rubino E, Lombardi D, Gasbarrini
G. Prevalence and clinical presentation of subclinical/silent celiac
disease in adults: an analysis on a 12-year observation.
Hepatogastroenterology 2001;48:462-4
6) Gasbarrini G, Malandrino N, Giorgio V, Fundarò C, Cammarota G, Merra G,
et al. Celiac disease: what’s new about it? Dig Dis 2008;26:121-7
7) Fasano A, Berti I, Gerarduzzi T, et al. Prevalence of celiac disease in
at-risk and not-at-risk groups in the United States: a large multicenter
study. Arch Intern Med 2003;163:286–292.
8) Almeida PL, Gandolfi L, Modelli IC, Martins Rde C, Almeida RC, Pratesi
R. Prevalence of celiac disease among first degree relatives of Brazilian
celiac patients. Arq Gastroenterol 2008;45:69-72
9) Rubio-Tapia A, Van Dyke CT, Lahr BD, Zinsmeister AR, El-Youssef M,
Moore SB et al. Predictors of family risk for celiac disease: a population
-based study. Clin Gastroenterol Hepatol 2008;6:983-7
10) Dube´ C, Rostom A, Sy R, Cranney A, Saloojee N, Garritty C, et al. The
prevalence of celiac disease in average-risk and at-risk Western European
Population: a systematic review. Gastroenterology 2005;128:S57–S6
11) Tursi A, Brandimarte G, Giorgetti GM, Elisei W, Inchingolo CD, Monardo
E et al. Endoscopic and histological findings in the duodenum of adults
with celiac disease before and after changing to a gluten-free diet: a 2-
year prospective study. Endoscopy 2006;38:702-7
12) Tursi A, Elisei W, Giorgetti GM, Brandimarte G, Aiello F.
Complications in celiac disease under gluten-free diet. Dig Dis Sci
2009;54:2175-82
13) Rostami K, Kerckhaert J, Tiemessen R, von Blomberg BM, Meijer JW,
Mulder CJ. Sensitivity of antiendomysium and antigliadin antibodies in
untreated celiac disease: disappointing in clinical practice. Am J
Gastroenterol 1999;94:888-94
14) Tursi A, Brandimarte G, Giorgetti G, Gigliobianco A, Lombardi D,
Gasbarrini G. Low prevalence of antigliadin and anti-endomysium antibodies
in subclinical/silent celiac disease. Am J Gastroenterol 2001;96:1507-10
15) Tursi A, Brandimarte G, Giorgetti GM. Prevalence of antitissue
transglutaminase antibodies in different degrees of intestinal damage in
celiac disease. J Clin Gastroenterol 2003;36:219-21
16) Chang M, Green PRH. Genetic Testing Before Serologic Screening in
Relatives of Patients With Celiac Disease as a Cost Containment Method. J
Clin Gastroenterol 2009;43:43–50
17) Niveloni S, Pedreira S, Sugai E, Vazquez H, Smecuol E, Fiorini A et
al. The natural history of gluten sensitivity: report of two new celiac
disease patients resulting from a long-term follow-up of nonatrophic,
first-degree relatives. Am J Gastroenterol 2000;95:463–8
18) Högberg L, Fälth-Magnusson K, Grodzinsky E, Stenhammar L. Familial
prevalence of coeliac disease: a twenty-year follow-up study. Scand J
Gastroenterol 2003;38:61–5
19) Pittschieler K, Gentili L, Niederhofer H. Onset of coeliac disease: a
prospective longitudinal study. Acta Paediatr 2003;92:1149–52
20) Verdu EF, Armstrong D, Murray JA. Between celiac disease and irritable
bowel syndrome: the "no man's land" of gluten sensitivity. Am J
Gastroenterol 2009;104:1587-94
Competing interests:
None declared
Competing interests:
No competing interests
24 September 2009
Antonio Tursi
Consultant Gastroenterologist
Service of Gastroenterology, ASL BAT, 70031 Andria (Italy)
Rapid Response:
Screening for coeliac disease should be done
Sir,
I read with extreme interest the recent pros and cons about the screening
of Coeliac Disease (CD) (1,2).
I share Fasano’s idea about a large screening of CD in clinical
practice. Since CD is one of the most common lifelong disorders, affecting
0.5-1% of the population (3), and based on our group experience,
several points are in favour of this approach:
1. Although CD was initially described as a paediatric gastrointestinal
condition, we currently know that it can affect people at any age and it
can manifest in a wide range of symptoms potentially affecting any organ
or body system (3,4). Many undiagnosed patients accept a state of chronic,
vague, ill health as normal. In our experience, most of patients are now
suffering from extra-intestinal diseases (for example, autoimmune
diseases) or are olygo-symptomatic (for example, iron-deficiency anaemia)
(5). Early detection based on clinical suspicion is therefore difficult,
and many patients remain undiagnosed for many years and exposed to the
risk of long term complications (6).
2. Most of patients are now affected by “silent” disease, that is the CD
with complete absence of any symptom. In our experience, these patients
represent about 20% of CD patients (5), and this is particularly true for
relatives. In fact we now know that the prevalence of CD in first-degree
relatives is now increasing, and the prevalence ranges from 11% to 17% (7-
10). Our recent experience confirms this increasing trend. In fact we
found a CD prevalence of 20% in CD relatives, and about 30% of them were
affected by “silent” disease (data submitted).
3. Histological recovery is slower than previously thought. We found that
older patients showed incomplete endoscopic and histological recovery even
24 months after starting a GFD (11). This is a key point in the follow-up
of patients with celiac disease: the persistence of histological lesions
beyond 24 months after starting and strictly adhering to a gluten-free
diet (GFD) may mean that patients with celiac disease remain at high risk
for celiac disease related complications for longer than previously
thought.
3. But also patients under GFD may be at risk of developing complications.
We recently found that about 4% of CD patients may develop complications
under GFD. Complications seem to affect more classical CD than subclinical
CD, and seem to be irrespective of optimal GFD adherence (12) (p= n.s.).
All the previous point are in favour of a screening mass program.
Although the prevalence of the antibodies currently used in CD practice
seems to be related to the degree of the histological damage (13-15),
serology remains the best method to perform an adequate screening. In
particular, it should be improved in family members of CD patients. Chang
and Green (16) performed recently a robust cost analysis on 3 different
follow-up strategies based on anti-tTG antibodies and HLA typing. They
showed that a strategy based on testing anti-tTG antibodies in 2 different
moments (‘‘tTG at t0 and t1’’) without HLA testing may offer the best
ratio between false-negative FMs and costs. This may be a very reasonable
strategy and the best timing for the second serologic test could be after
4 or 5 years, since the majority of first-degree relatives who
subsequently developed CD described in the literature developed CD less
than 4 years after the first testing (17-19).
But I think that the real problem to organize a screening program is that
gluten sensitivity (GS) may cause a lot of gastrointestinal symptoms,
including functional bowel disorder-like symptoms. It has been recently
hypothesized that, even in the absence of fully developed CD, gluten can
induce symptoms similar to functional bowel disorders. GS and post-
infectious irritable bowel syndrome (IBS) provide two triggers that can
therefore explain at least part of the spectrum that constitutes IBS (20).
In this way, we should understand whether these patients run the risk to
develop complication similar to that of patients with symptomatic or olygo
-symptomatic CD patients, and therefore whether these patients may obtain
the same beneficial from a gluten-free diet. This new interesting
hypothesis should be correctly kept in mind in the future screening
programs, taking a look also at new categories of patients with GS but
without a certain CD.
REFERENCES
1) Fasano A. Should we screen for celiac disease? Yes. BMJ 2009;339:b3592
2) Evans KE, McAllister R, Sanders DS. Should we screen for celiac
disease? No. BMJ 2009;339:b3674
3) Fasano A, Catassi C. Current approaches to diagnosis and treatment of
celiac disease: an evolving spectrum. Gastroenterology 2001;120:636-51
4) Guandalini S, Setty M. Celiac disease. Curr Opin Gastroenterol
2008;24:707-12
5) Tursi A, Giorgetti G, Brandimarte G, Rubino E, Lombardi D, Gasbarrini
G. Prevalence and clinical presentation of subclinical/silent celiac
disease in adults: an analysis on a 12-year observation.
Hepatogastroenterology 2001;48:462-4
6) Gasbarrini G, Malandrino N, Giorgio V, Fundarò C, Cammarota G, Merra G,
et al. Celiac disease: what’s new about it? Dig Dis 2008;26:121-7
7) Fasano A, Berti I, Gerarduzzi T, et al. Prevalence of celiac disease in
at-risk and not-at-risk groups in the United States: a large multicenter
study. Arch Intern Med 2003;163:286–292.
8) Almeida PL, Gandolfi L, Modelli IC, Martins Rde C, Almeida RC, Pratesi
R. Prevalence of celiac disease among first degree relatives of Brazilian
celiac patients. Arq Gastroenterol 2008;45:69-72
9) Rubio-Tapia A, Van Dyke CT, Lahr BD, Zinsmeister AR, El-Youssef M,
Moore SB et al. Predictors of family risk for celiac disease: a population
-based study. Clin Gastroenterol Hepatol 2008;6:983-7
10) Dube´ C, Rostom A, Sy R, Cranney A, Saloojee N, Garritty C, et al. The
prevalence of celiac disease in average-risk and at-risk Western European
Population: a systematic review. Gastroenterology 2005;128:S57–S6
11) Tursi A, Brandimarte G, Giorgetti GM, Elisei W, Inchingolo CD, Monardo
E et al. Endoscopic and histological findings in the duodenum of adults
with celiac disease before and after changing to a gluten-free diet: a 2-
year prospective study. Endoscopy 2006;38:702-7
12) Tursi A, Elisei W, Giorgetti GM, Brandimarte G, Aiello F.
Complications in celiac disease under gluten-free diet. Dig Dis Sci
2009;54:2175-82
13) Rostami K, Kerckhaert J, Tiemessen R, von Blomberg BM, Meijer JW,
Mulder CJ. Sensitivity of antiendomysium and antigliadin antibodies in
untreated celiac disease: disappointing in clinical practice. Am J
Gastroenterol 1999;94:888-94
14) Tursi A, Brandimarte G, Giorgetti G, Gigliobianco A, Lombardi D,
Gasbarrini G. Low prevalence of antigliadin and anti-endomysium antibodies
in subclinical/silent celiac disease. Am J Gastroenterol 2001;96:1507-10
15) Tursi A, Brandimarte G, Giorgetti GM. Prevalence of antitissue
transglutaminase antibodies in different degrees of intestinal damage in
celiac disease. J Clin Gastroenterol 2003;36:219-21
16) Chang M, Green PRH. Genetic Testing Before Serologic Screening in
Relatives of Patients With Celiac Disease as a Cost Containment Method. J
Clin Gastroenterol 2009;43:43–50
17) Niveloni S, Pedreira S, Sugai E, Vazquez H, Smecuol E, Fiorini A et
al. The natural history of gluten sensitivity: report of two new celiac
disease patients resulting from a long-term follow-up of nonatrophic,
first-degree relatives. Am J Gastroenterol 2000;95:463–8
18) Högberg L, Fälth-Magnusson K, Grodzinsky E, Stenhammar L. Familial
prevalence of coeliac disease: a twenty-year follow-up study. Scand J
Gastroenterol 2003;38:61–5
19) Pittschieler K, Gentili L, Niederhofer H. Onset of coeliac disease: a
prospective longitudinal study. Acta Paediatr 2003;92:1149–52
20) Verdu EF, Armstrong D, Murray JA. Between celiac disease and irritable
bowel syndrome: the "no man's land" of gluten sensitivity. Am J
Gastroenterol 2009;104:1587-94
Competing interests:
None declared
Competing interests: No competing interests