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Vol. 2/2003 Nr 3(4)
Endokrynologia Pediatryczna
Pediatric Endocrinology
Prevalence of positive celiac disease antibodies in children attending
a pediatric endocrinology clinic
Występowanie serologicznych wykładników choroby trzewnej u dzieci
z zaburzeniami endokrynologicznymi
1
Garine Lepejian, 1Douglas Rogers, 2Sarah Worley, 2Kathy Cotman
Section of Pediatric and Adolescent Endocrinology,
Department of Biostatistics and Epidemiology,
The Children’s Hospital, The Cleveland Clinic Foundation, Cleveland, Ohio USA
1
2
Address correspondence:
Douglas G. Rogers, M.D., The Cleveland Clinic, A-120, 9500 Euclid Ave, Cleveland, OH 44195, U.S.A.
Key words: celiac disease, type 1 diabetes mellitus, Down Syndrome, Turner Syndrome
Słowa kluczowe: choroba trzewna, cukrzyca typu 1, zespół Downa, zespół Turnera
STRESZCZENIE/
STRESZCZENIE/ABSTRACT
Introduction. Celiac disease (CD) is a disorder in which dietary gluten and related proteins trigger an immunologic
response leading to small bowel inflammation and autoantibody (Ab) production. The early diagnosis and treatment
of CD can prevent complications including malabsorption, poor growth, lymphoma and osteopenia. Anti-endomysial
IgA Ab by immunofluorescence has a reported sensitivity of at least 94% and specificity of 93% for diagnosis of CD.
A human recombinant anti-tissue transglutaminase ELISA has a reported sensitivity of at least 92% and specificity
of 95% for diagnosis of CD. Diagnosis of CD is confirmed by histopathologic exam of small bowel mucosa distal
to the duodenal bulb. The reported prevalence of CD in the U.S. is 0.4%. In patients with type 1 diabetes mellitus
(T1DM) the prevalence has been reported from 3.9% to 13.5%. Four percent of patients with Turner syndrome, 8%
with Down syndrome, and 7.7% with autoimmune thyroid disease are reported to have CD. Material and methods.
We determined the prevalence of positive CD Ab in our patients with one or more of the following disorders: T1DM,
Graves’ disease, Hashimoto’s disease, short stature, delayed onset of puberty. This was a retrospective study of 336
patients who presented to the pediatric endocrine clinic at The Cleveland Clinic Foundation with at least one of above
endocrine disorders, and who were screened for endomysial or transglutaminase IgA Ab. Confirmatory small bowel
biopsies were done on most patients with positive CD Ab. Chi-square of Fisher’s exact tests were used to compare
patients with the above endocrine disorders on the prevalence of positive CD Ab. Results. Eleven (6.6%) of 166 patients
with T1DM were positive for CD Ab. The CD Ab were significantly more prevalent only in patients with T1DM
(P = 0.008). We propose that all children with T1DM should be screened for CD Ab. Children with autoimmune
thyroid disease, short stature, or delayed onset of puberty do not need to be screened, unless they have another risk
factor for CD such as Down syndrome, Turner syndrome, or a family history of CD. In patients with T1DM, it is not
known when screening for CD Ab should begin, or how often screening should be repeated.
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Endokrynol. Ped., 2/2003;3(4):31-34
Wstęp. Choroba trzewna (CD) jest schorzeniem, w którym gluten i pokrewne białka obecne w pożywieniu, indukują odpowiedź immunologiczną przeciwko błonie jelita cienkiego oraz inicjują produkcję auto-przeciwciał
(Ab). Wczesna diagnostyka i leczenie CD może zapobiec powikłaniom do których należą: zespół złego wchłaniania, zaburzenia procesu wzrastania, chłoniaki i osteopenia. Badania oparte na określaniu miana przeciwciał przeciwko endomysium w klasie IgA, wykorzystujące technikę immunofluorescencyjną, charakteryzują się czułością rzędu 94% i specyficznością 93% w diagnostyce CD. Metoda ELISA z zastosowaniem przeciwciał przeciwko ludzkiej rekombinowanej tkankowej transglutaminazie charakteryzuje się czułością 92% i specyficznością 95%.
Diagnoza serologiczna uzupełniana jest badaniem histopatologicznym bioptatu śluzówki jelita cienkiego pobieranego dystalnie od opuszki dwunastnicy. W USA częstość występowania CD ocenia się 0.4%. U pacjentów z cukrzycą typu 1 (IDDM) częstość ta wynosi 3.9-13.5%, u pacjentów z zespołem Turnera -4%, z zespołem Downa 8%,
a u chorych z autoimmunologicznymi chorobami tarczycy -7.7%. Materiał. Ocenialiśmy częstość pojawiania się serologicznie dodatnich wyników sugerujących CD u naszych pacjentów z IDDM, chorobą Gravesa, Hashimoto, niskorosłością i opóźnionym dojrzewaniem płciowym. Nasza ocena była retrospektywna i obejmowała 336 pacjentów ze schorzeniami endokrynologicznymi oraz obecnością przeciwciała IgA przeciwko endomysium lub transglutaminazie. Metoda. U większości pacjentów z dodatnim wynikiem badania serologicznego dokonywano biopsji jelita cienkiego. Wnioskowanie statystyczne oparto na zastosowaniu testu Chi kwadrat lub testu Fishera. Wyniki.
11 pacjentów (6.6%) spośród chorujących na IDDM miało obecne przeciwciała typowe dla CD (CD Ab). Znaleźliśmy
dodatnią korelacją jedynie pomiędzy obecnością przeciwciał CD Ab a IDDM (p = 0.008), stąd proponujemy, aby dzieci z IDDM poddawać rutynowym badaniom przesiewowym w kierunku CD. Uważamy, iż takim badaiom nie muszą
być poddawane dzieci z autoimmunologicznymi schorzeniami tarczycy, niskorosłością lub opóźnionym dojrzewaniem,
chyba że istnieją u nich inne czynniki ryzyka CD takie jak zespołół Turnera, Downa i obciążający wywiad rodzinny.
Introduction & Background
Celiac disease (CD) is one of the most common
autoimmune disorders in humans [1]. It is unique
in that the environmental trigger is known and the
major histocompatability groups at risk have been
defined. Dietary gluten and related proteins trigger an immunologic response leading to small bowel inflammation and autoantibody production [2].
The two major haplotypes associated with CD are
DR3/DQ2 and DR4/DQ8 [1].
CD is a clinically variable disease with over 50%
of patients having no GI symptoms. For those who
have symptoms, dyspepsia, anorexia, weakness and
abdominal pain may be the only complaints. Other
features include glossitis, recurrent aphthous ulcers,
hair loss, vomiting, dysphagia, anemia, short stature and failure to thrive [1, 3]. CD, whether symptomatic or silent, if left untreated can lead to malabsorption, osteopenia, and rarely intestinal T-cell
lymphoma. Calcification of the cerebral cortex and
epilepsy has also been described [3].
The prevalence of CD in the U.S. is 0.4%, while in Finland the prevalence is 1% [1, 3]. The reported prevalence of CD in patients with Type 1 Diabetes Mellitus (T1DM) has ranged in different studies from 3.9% to 13.5% [4-8]. Four percent of patients with Turner Syndrome [9], 3.6% to 8% of patients with Down Syndrome [10, 11], and 7.7% of
patients with autoimmune thyroid disease are reported to have CD [12]. It has been recommended that
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all children with these disorders or problems with
growth should be screened for CD.
We determined the prevalence of positive celiac disease antibodies in our patients with certain
endocrine disorders to see if these recommendations are justified.
Methods
This was a retrospective study of 336 patients
who had one or more of the following endocrine disorders: T1DM, autoimmune thyroid disease (Graves or Hashimoto), osteoporosis, growth disorder
(short stature or delayed onset of puberty), Down
syndrome, Turner syndrome; and were screened
for IgA antibodies to tissue transglutaminase or
endomysium [5, 13, 14]. Anti-endomysial IgA Ab
by immunofluorescence has a reported sensitivity
of at least 94% and specificity of 93% for diagnosis of CD. A human recombinant anti-tissue transglutaminase ELISA has a reported sensitivity of at
least 92% and specificity of 95% for diagnosis of
CD [13, 14]. All patients had been seen between
June 2002 and July 2003. Confirmatory small bowel biopsies were done for most patients with positive antibody screening. Chi-square or Fisher’s
exact tests were used to compare patients with the
above endocrine disorders on the prevalence of positive CD antibodies. The institutional review board of the Cleveland Clinic Foundation approved
this study.
G. Lepejian et al. – Prevalence of positive celiac disease antibodies...
Results
CD antibodies were significantly more prevalent
only in T1DM (P = 0.008). Table 1 shows the positive CD antibody prevalence in our patients with the
studied endocrine disorders. Table 2 further characterizes those patients with T1DM.
Discussion
CD is more common than previously recognized and may be the most common autoimmune disease in some countries [1]. There is growing data
that suggests that early diagnosis and treatment can
prevent complications of CD [3]. The conventional
treatment is a gluten-free diet. In our population,
only T1DM was significantly associated with positive CD antibodies. Our numbers of patients with
Down syndrome or Turner syndrome were not large enough to reach a level of significance. However,
other studies have shown an increased prevalence of
positive CD antibodies among patients with Down
syndrome or Turner syndrome, and our data support
those findings.
Data suggest that the high prevalence of autoimmunity to tissue transglutaminase in patients with
T1DM could be due to the shared two major haplotypes associated with CD and T1DM: DR3/DQ2
and DR4/DQ8 [4]. Other possibilities include involvement of the gut in the pathogenesis of T1DM or
release of tissue transglutaminase from destroyed
pancreatic beta cells [6].
Our data suggest that routine screening for CD
antibodies in patients with T1DM, Down syndrome
or Turner syndrome is indicated. Further studies are
needed to determine when and how frequently these
patients should be screened for CD. Further studies
are also needed to see how patients with weakly positive CD antibodies should be evaluated.
Children being followed for growth concerns or
thyroid disease alone did not have positive CD antibodies above the expected background rate. We had
one patient with only pubertal delay who had positive CD antibodies, and this individual’s mother
had CD. Further studies are needed to determine the
usefulness of routine screening for CD in children
with short stature or pubertal delay. We do not recommend routine screening of patients who have
only autoimmune thyroid disease.
Table I. Prevalence of Positive Celiac Antibodies in the Pediatric Endocrine Clinic
Condition
Total
CD Ab +
Biopsy +
Biopsy -
Ab Prevalence
All T1DM
166
11
3
2
6.6%
27
0
0%
121
1
0.8%
Turner Syndrome
7
1
1
14.2%
Down Syndrome*
11
2†
1
18.1%
Osteoporosis
5
0
Thyroid disease
only
Growth disorder
only
0%
* All children also have thyroid disease.
† One positive patient also has T1DM.
Table 2. Prevalence of Positive Celiac Antibodies in Children with T1DM
Condition
Total
CD Ab +
Biopsy +
Biopsy -
Ab prevalence
T1DM only
155
8
2
1
5.2%
T1DM and thyroid disease
10
2
T1DM, thyroid disease and
Down syndrome
1
1
20 %
1
100%
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