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Coeliac disease in endocrine diseases of autoimmune origin

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Abstract

Abstract Coeliac disease (CD, sometimes called gluten-sensitive enteropathy or nontropical sprue) is an inflammatory disorder of the small intestine of autoimmune origin. It occurs in genetically predisposed people and is induced by a gluten protein, which is a component of wheat. The prevalence of histologically confirmed CD is estimated in screening studies of adults in the United States and Europe to be between 0.2% and 1.0%. The results of previous studies have indicated that the prevalence of CD is increased in patients with other autoimmune disorders such as: autoimmune thyroid diseases, type 1 diabetes mellitus, and Addison's disease. A coincidence of the above diseases constitutes autoimmune polyglandular syndrome (APS). The high prevalence of CD in APS is probably due to the common genetic predisposition to the coexistent autoimmune diseases. The majority of adult patients have the atypical or silent type of the disease. This is the main reason why CD so often goes undiagnosed or the diagnosis is delayed. CD, if undiagnosed and untreated, is associated with many medical disorders including haematological (anaemia), metabolical (osteopenia/osteoporosis), obstetric-gynaecological (infertility, spontaneous abortions, late puberty, early menopause), neurological (migraine, ataxia, epilepsy) as well as with an increased risk of malignancy, especially: enteropathy-associated T-cell lymphoma, small intestine adenocarcinoma, and oesophageal and oropharyngeal carcinomas. Early introduction of a gluten-free diet and lifelong adherence to this treatment decreases the risk of these complications.
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SZKOLENIE PODYPLOMOWE/POSTGRADUATE EDUCATION
Endokrynologia Polska/Polish Journal of Endocrinology
Tom/Volume 63; Numer/Number 3/2012
ISSN 0423–104X
Piotr Miśkiewicz MD, PhD, Department of Internal Medicine and Endocrinology, Medical University of Warsaw, ul. Żwirki i Wigury 61,
02–001 Warszawa, Poland, e-mail: p.miskiewicz@wp.pl
Coeliac disease in endocrine diseases of autoimmune origin
Celiakia w chorobach endokrynologicznych pochodzenia autoimmunologicznego
Piotr Miśkiewicz1, Anna Kępczyńska-Nyk1, Tomasz Bednarczuk1, 2
1Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw
2Endocrinology Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw
Abstract
Coeliac disease (CD, sometimes called gluten-sensitive enteropathy or nontropical sprue) is an inflammatory disorder of the small intestine
of autoimmune origin. It occurs in genetically predisposed people and is induced by a gluten protein, which is a component of wheat.
The prevalence of histologically confirmed CD is estimated in screening studies of adults in the United States and Europe to be between
0.2% and 1.0%. The results of previous studies have indicated that the prevalence of CD is increased in patients with other autoimmune
disorders such as: autoimmune thyroid diseases, type 1 diabetes mellitus, and Addison’s disease. A coincidence of the above diseases
constitutes autoimmune polyglandular syndrome (APS). The high prevalence of CD in APS is probably due to the common genetic
predisposition to the coexistent autoimmune diseases. The majority of adult patients have the atypical or silent type of the disease. This
is the main reason why CD so often goes undiagnosed or the diagnosis is delayed. CD, if undiagnosed and untreated, is associated with
many medical disorders including haematological (anaemia), metabolical (osteopenia/osteoporosis), obstetric-gynaecological (infertil-
ity, spontaneous abortions, late puberty, early menopause), neurological (migraine, ataxia, epilepsy) as well as with an increased risk of
malignancy, especially: enteropathy-associated T-cell lymphoma, small intestine adenocarcinoma, and oesophageal and oropharyngeal
carcinomas. Early introduction of a gluten-free diet and lifelong adherence to this treatment decreases the risk of these complications. (Pol
J Endocrinol 2012; 63 (3): 240–249)
Key words: coeliac disease, autoimmune polyglandular syndrome, Graves’ disease, autoimmune thyroid disease, type 1 diabetes, autoimmune
adrenal insufficiency
Streszczenie
Celiakia (inaczej: glutenozależna choroba trzewna, enteropatia glutenowrażliwa, sprue nietropikalna) jest enteropatią zap al ną jelita cienkiego
o podłożu autoimmunologicznym, spowodowaną trw ałą ni eto ler anc ją gl ute nu z aw art ego w zb ożach, występującą u os ób z pre dys poz ycj ą
genetyczną. Częstość potwierdzonej histopatologicznie celiakii w ogólnej populacji dorosłych, według wyników badań przesiewowych
przeprowadzonych w Europie oraz Stanach Zjednoczonych, wynosi 0,2–1,0%. Wyniki dotychczasowych badań suge ru ją, że ryzyko zachoro-
wania na celiakię je st k ilk akr ot nie większe u pacjentów z innymi chorobami autoimmunologicznymi, jak np.: choroby autoimmunologiczne
tarczycy (AITD), cukrzyca typu 1 (T1D) czy choroba Addisona. Powyższe choroby wchodzą w skład autoimmunologicznych zespołów
niedoczynności wielogruczołowej (APS). Jedną z p rzy czy n wi ększej częstości występowania celiakii w APS, w porównaniu z ogólną pop u-
lacją, jest prawdopodobnie wspólna predyspozycja genetyczna. U osób dorosłych zdecydowaną większość p rzy pad ków sta now ią postacie
atypowe i nieme. Wpływa to na opóźnioną i obniżoną wykrywalność choroby. Nierozpoznana i nieleczona celiakia może prowadzić do
wielu zaburzeń, w tym m.in.: hematologicznych (niedokrwistość), metabolicznych (osteopenia/osteoporoza), ginekologiczno-położniczych
(niepłodność, wzrost częstości samoistnych poronień, opóźnione dojrzewanie i wcześniejsza menopauza) i neurologicznych (migrena,
ataksja, padaczka). Nieleczona celiakia zwiększa również ogólne ryzyko zachorowania na złośliwe nowotwory, w tym przede wszystkim
na: chłoniaka jelita cienkiego, gruczolakoraka jelita cienkiego, gardła i przełyku. Skuteczne leczenie (dieta bezglutenowa), wprowadzone
wcześnie i kontynuowane przez całe życie, zmniejsza ryzyko wystąpienia wymienionych powikłań. (En dok ry nol Pol 2 012 ; 63 (3) : 24 0– 249 )
Słowa kluczowe: choroba trzewna, autoimmunologiczny zespół niedoczynności wielogruczołowej, choroba Gravesa i Basedowa,
autoimmunologiczna choroba tarczycy, cukrzyca typu 1, autoimmunologiczna niedoczynność nadnerczy
Case report
A 22 year-old female was admitted to the clinic for her
regular check-up. She had been diagnosed with Graves’
disease (GD) at the age of 15. She was treated with an-
tithyroid drugs from the age of 15 to the age of 20 and
twice underwent treatment with radioiodine (at the
age of 20). Before admission to hospital, she had been
taking 150 µg of levothyroxine. She was suffering from
recurrent constipation and moderate abdominal pain.
Additionally, she complained of a feeling of enamel
oversensitivity and severe migraines, which required
treatment with non-steroidal anti-inflammatory
drugs. For several years, the patient was diagnosed
with an iron deficiency and administered iron orally.
She denied having heavy menorrhagia. She pointed out
that the presence of autoimmune disorders ran in her
family (her father suffered from GD as well). Laboratory
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SZKOLENIE
PODYPLOMOWE
tests showed a normal TSH serum level (1.07 uIU/mL,
N: 0.2–4.0) a low ferritin level (6 ng/mL, N: 13–150),
a low iron level (36 ug/ml, N: 37–181), normal serum
Hb, folic acid, vitamin B12, calcium, phosphorus, total
proteins and albumin levels. Specific serological stud-
ies were performed revealing high levels of IgA tissue
transglutaminase antibodies (IgA TTG) (178.1 U/mL;
N: < 20.0) and IgA endomysial antibodies (IgA EMA)
(54.5 U/mL; N: < 20.0). An endoscopy of the upper di-
gestive tract was performed and a biopsy was obtained
from the descending part of the duodenum. Duodenal
mucosa showed atrophic changes with loss of folds
and contained visible fissures. Microscopic examina-
tion showed an increase in intraepithelial lymphocytes,
crypt hyperplasia and villous atrophy — Type III in
Marsh classification (Tab. I, Fig. 1). Coeliac disease (CD)
was diagnosed and a gluten-free diet was introduced.
The patient was invited for a check-up three months
after the introduction of a gluten-free diet, and neither
symptoms of digestive system disorders, nor migraines
and enamel oversensitivity were present. However, it
was observed that serum iron and ferritin concentra-
tions remained low. During following check-ups, the
dose of levothyroxine was gradually lowered to 125 µg,
with a normal serum TSH level. Iron supplements were
stopped and gradually blood iron and ferritin levels
stabilised. The patient regularly visits an endocrinologist
and a gastroenterologist.
Introduction
Coeliac disease (CD), also known as gluten-sensitive
enteropathy and nontropical sprue,, is a small bowel
disorder characterised by mucosal inflammation of
autoimmune origin caused by persistent intolerance to
gluten, a protein which is a component of cereal (rye,
wheat, barley). CD occurs in people with a genetic pre-
disposition [1]. The symptoms of CD were first described
by Dr. Samuel Gee in 1888, but the aetiology of the
symptoms remained unclear for many years [2]. In the
1940s, a paediatrician from Denmark, Wiliam K. Dicke,
recognised the association between diets which con-
tained gluten and the symptoms of CD [3]. In periods
of food shortages during the Second World War, there
were areas where people were poorly nourished and
where bread was replaced by a non-cereal substitute.
Dicke observed a recurrence of symptoms when bread
was reintroduced after the war. Initially, CD was consid-
ered to be a childhood disease, and the frequency of the
disease was estimated at about 1:4,000. After introducing
new, more sensitive and more specific diagnostic tests,
the recognisability of CD markedly increased. CD was
more and more frequently diagnosed in adults. Further
investigations revealed that the prevalence of CD is
more often seen in patients with other autoimmune
disorders such as autoimmune thyroid disease (AITD)
[4–13], type 1 diabetes (T1DM) [14–16], and Addison’s
disease [17–20]. The above-mentioned autoimmune
I II IIIa IIIb IIIc
Figure 1. Extent of small intestinal mucosal changes according to the Marsh histological damage score; the figure shows spectrum of
changes in mucosa of small intestine according to the Marsh classification and AGA. Histologically confirmed coeliac disease can be
diagnosed in cases IIIa, IIIb, IIIc (villous atrophy at different degree) [34]
Ryc ina 1 . Schemat przedstawiający zakres zmian błony śluzowej jelita cienkiego zgodnie z klasyfikacją Marsh; na rycinie przedstawiono
zakres zmian w obrębie błony śluzowej jelita cienkiego zgodnie z klasyfikacją Marsh i kryteriami Amerykańskiego Towarzystwa
Gastroenterologicznego. Histopatologicznie potwierdzoną celiakię można rozpoznać w przypadku zmian IIIa, IIIb, IIIc (zanik kosmków
o różnym stopniu zaawansowania) [34]
Table I. Histologic grading in coeliac disease (Marsh) [34]
Tabela I. Klasyfikacja zmian histopatologicznych w celiakii
(Marsh) [34]
Classification Description
Marsh 0 No changes in mucosal and villous architecture
Marsh I Normal mucosal and villous architecture
Increased numbers of intraepithelial
lymphocytes
Marsh II Similar to Marsh I but with enlarged crypts
(hyperplastic)
Marsh IIIa Partial villous atrophy
Marsh IIIb Subtotal villous atrophy
Marsh IIIc Total villous atrophy
Marsh IV Total villous atrophy and hypoplastic crypts
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Coeliac disease and other autoimmune disorders Piotr Miśkiewicz et al.
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diseases are part of the autoimmune polyglandular
syndrome (APS). The coexistence of autoimmune
diseases is probably connected to a common genetic
predisposition.
Epidemiology
The prevalence of histologically confirmed CD in the
general adult population in relation to screening re-
search from Europe (Italy, Holland, Germany, Great
Britain, Iceland, Greece) and the United States has
been estimated to be between 0.2 and 1.0% [21–27]
(Tab. II). The data concerning CD in Poland regards
mainly children and is based on classical symptoms
of the disease, which is the reason for underdiagnosis
(most research was performed in the 1980s and 1990s)
[28–33]. There have been no screening studies evaluat-
ing the frequency of CD in adults in Poland.
Clinical manifestations and types
of coeliac disease
Clinical symptoms of CD are characterised by a wide
spectrum within the clinical picture. In younger patients
(infants, young children), we often encounter the classi-
cal type of CD (chronic diarrhoea with hypoalbuminae-
mia, electrolyte abnormalities, abdominal pain) (Tab. III).
Diarrhoea occurs significantly less often in older chil-
dren and adults. Complaints in these groups are often
non-specific and less intensive (flatulence, temporary
abdominal pain) or even absent [34]. These are so called
atypical or silent types of the disease, which are difficult
to diagnose. Symptoms may actually concern all systems
within the human body (Tab. IV). With latent types of
CD in patients with genetic predispositions (genotype
HLA-DQ2 or DQ8), elevated IgA TTG and/or IgA EMA
levels are to be found and minimal changes (increased
intraepithelial lymphocytes of the intestine) or lack of
any histological changes can be seen in tissue samples
taken from the distal part of the duodenum. In order
to describe the variability of CD, it is often compared to
an iceberg. The tip above the water represents patients
with classical symptoms, but the greater part, which
is hidden, consists of asymptomatic patients or those
with atypical symptoms [35, 36] (Fig. 2). There are no
clearly marked borders between the different types of
CD because of its numerous clinical symptoms, and its
histological and immunological picture.
Table II. Prevalence of coeliac disease in different populations of healthy individuals
Ta b e l a I I . Badania przedstawiające częstość wys tępowania choroby trzewnej w różnych populacjach zdrowych dorosłych osób
Study Population Size of the study group (n) Coeliac disease [%]
Rostami et al., 1999 [25] Holland 1,000 0.3%
Volta et al., 2001 [27] Italy 3,483 0.5%
Henker an et al., 2002 [22] Germany 4,313 0.2%
Fasano et al., 2003 [21] USA 2,848 1.0%#
Sanders an et al., 2003 [26] UK 1,200 1.0%
Roka et al., 2007 [24] Greece 2,230 0.2%
Johannsson et al., 2008 [23] Island 813 0.7%
Population — group of individuals on whom the study was performed; the study group — number of individuals who underwent serologic tests specific
for coeliac disease; coeliac disease (%) — prevalence (%) of histologically confirmed coeliac disease in investigated population; #in Fasano’s study only
serological tests were estimated (only 20% of individuals underwent endoscopy and histological evaluation)
Table III. Types of coeliac disease [1, 34]
Tabela III. Kliniczne postacie celiakii [1, 34]
Types of coeliac disease Clinical symptoms Serological evaluation:
IgA EMA/IgA TTG
Histological evaluation
of small bowel biopsy
Classic disease Symptoms of malabsorption + +
Atypical/poor symptomatic Minor gastrointestinal complaints or other symptoms + +
Asymptomatic/silent No symptoms + +
Latent/potential No symptoms +
Serological evaluation: IgA EMA/IgA TTG (+) — elevated IgA endomysial antibodies and/or IgA tissue transglutaminase antibodies; histological
evaluation of the small intestine (+) — at least partial villous atrophy — Marsh III; (–) — no villous atrophy in histological examination
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Diagnosis of coeliac disease
Diagnosis of CD is based on serological tests and his-
tological evaluation of a small bowel biopsy. In some
doubtful situations, genetic tests can be performed
(CD occurs in genetically predisposed individuals with
HLA-DQ2 and/or DQ8). An approach to the diagnosis
of CD is summarised in Figure 3.
Serological evaluations
All diagnostic tests should be performed during
a gluten-rich diet. Nowadays, there are two tests of
high sensitivity and specificity: IgA TTG and IgA EMA,
which have equivalent diagnostic accuracy (Tab. V). IgA
EMA was discovered by a Polish scientist, Professor
Tadeusz Chorzelski, in 1983 [37]. Performing both of
these tests improves sensitivity by almost 100%. Due to
easier ambulatory procedures (ELISA, enzyme-linked
immunosorbent assays), some scientists recommend us-
ing the IgA TTG test first (the IgA EMA test is frequently
performed by a time-consuming indirect immunofluo-
rescence method). It is not advisable to use other serum
antibodies’ assays (antigliadin, antireticuline). Some
scientists recommend an evaluation of serum total anti
IgA level, and when the result is negative, tests for IgG
EMA and/or IgG TTG are recommended.
Histopathological examination
Patients positive with IgA EMA or IgA TTG should
undergo endoscopy of the upper digestive tract with
a small bowel biopsy (4–6 biopsies from the distal part
of the duodenum). A wide spectrum of histological
changes, ranging from increased intraepithelial lympho-
cytes to flat mucosal atrophy, contribute to histological
changes in CD, which can be described using the Marsh
classification (Tab. I) [34]. Diagnosis of CD is established
in patients who have at least partial villous atrophy
(Fig. 1). To avoid false diagnosis, the histological evalu-
ation should be performed in reference clinics.
Genetic evaluations
Antigen HLA-DQ2 is confirmed in 90–95%, and an-
tigen DQ8 in 5–10%, of patients with CD [38]. The
presence of HLA-DQ2 and/or DQ8 is necessary for the
development of symptoms of CD. However, genetic
evaluations are very rarely performed, and they are
restricted to situations in which other methods have
failed. A negative result of genetic evaluation excludes
a diagnosis of CD.
Table IV. Clinical symptoms of coeliac disease
Tabela IV. Objawy kliniczne celiakii
Organ abnormalities Symptoms
Digestive system Diarrhoea, constipation, distension, abdominal pain
Nervous system Ataxia, polyneuropathy, migraines, epilepsy
Reproductive disorders Women: delayed menarche, early menopause, higher rates of miscarriage, low birth weight
Men: hypogonadism, sexual dysfunction, low sperm quality
Haematological disorders Iron deficiency, vitamin B12 deficiency, folic acid deficiency, anaemia
Metabolic disorders Osteopenia, osteoporosis
Dermatologic disorders Dermatitis herpetiformis
Neoplasms Enteropathy-associated T-cell lymphoma-EATL, adenocarcinoma of small bowel, oropharynx and
oesophagus
Others Elevated transaminase levels, prevalence to liver diseases (like primary sclerosing cholangitis,
nonalcoholic fatty liver disease, liver cirrhosis and primary biliary cirrhosis), IgA deficiency, dental-enamel
hypoplasia, hyposplenism, psychiatric disorders
Figure 2. Iceberg showing wide spectrum of clinical symptoms
of coeliac disease (modified according to [35])
Rycina 2. Góra lodowa przedstawiająca spektrum objawów
klinicznych celiakii (zmodyfikowano na podstawie [35])
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Coeliac disease and other autoimmune disorders Piotr Miśkiewicz et al.
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Coeliac disease and autoimmune diseases
Previous studies have shown that patients suffering
from autoimmune diseases are more predisposed to CD
compared to the general population. Examples of auto-
immune diseases are: T1DM, AITD, and Addison’s dise-
ase. The frequency of autoimmune diseases associated
with CD is depicted in Table VI. Simultaneously, judg-
ing from other studies of patients with CD, it may be
stated that the frequency of other autoimmune diseases
in patients with CD is also above normal compared to
a healthy population. Therefore, in all cases regarding
patients with autoimmune disease and suspected of suf-
fering from CD, a proper diagnostic evaluation should
be performed. This often leads to the diagnosis of pa-
tients with CD of non-typical symptoms. The diagnosis
of CD and initiation of the correct therapy (gluten-free
diet) can prevent patients from suffering from many
disorders. Additionally, effective therapy can influence
the course and treatment of other autoimmune diseases
Figure 3. The diagnostic approach to coeliac disease (adapted from [70], up to date 19.2); *moderate or high probability: family history,
iron-deficiency anaemia of unknown origin, diarrhoea, failure to thrive in children, type 1 diabetes; IgA TTG: IgA tissue transglutaminase
antibodies; IgA EMA: IgA antiendomysial antibodies; antibodies: IgA EMA and/or IgA TTG; Consider 1: repeat IgA TTG, repeat biopsy
in reference clinic, multiply biopsy, histological evaluation by another pathologist, review adherence to gluten free diet; Consider 2: total
IgA measurement, perform genetic tests (HLA DQ2, -DQ8), consider other than coeliac disease causes of villous atrophy (cow milk
or other proteins intolerance, giardiasis, eosinophilic gastroenteritis, duodenitis, intestinal ischaemia, intestinal lymphoma, Crohn’s
disease, severe malnutrition)
Rycina 3. Schemat diagnostyczny celiakii (opracowano na podstawie [70], uptodate 19.2); *ryzyko średnie i duże: obciążający wywiad
rodzinny w kierunku celiakii, niedokrwistość z niedoboru żelaza o niejasnej etiologii, biegunka tłuszczowa, opóźnione wzrastanie
u dzieci, cukrzyca typu 1; IgA TTG — przeciwciała przeciwko tkankowej transglutaminazie w klasie IgA; IgA EMA — przeciwciała
przeciwendomyzjalne w klasie IgA; przeciwciała: IgA EMA i/lub IgA TTG: Rozważ 1: powtórzenie IgA TTG, powtórzenie biopsji
w referencyjnym ośrodku, wykonanie większej liczby wycinków, ocena wycinków przez drugiego histopatologa, sprawdzenie czy pacjent
przyjmował re gul arn ą die tę; Rozważ 2: p omi ar s tężenie całkowitego IgA, wykonanie badania genetycznego HLA DQ2, -DQ8, rozważenie
innej przyczyny atrofii kosmków (nietolerancja mleka krowiego oraz innych białek, giardioza, eozynofilowe zapalenie błony śluzowej
żołądka i jelit, zapalenie błony śluzowej dwunastnicy, niedokrwienie jelit, chłoniak jelita cienkiego, choroba Leśniowskiego-Crohna,
ciężkie niedożywienie)
Table V. Sensitivity and specificity of serological tests in diagnostics of coeliac disease (adapted from [34])
Tabela V. Czułość i specyficzność badań serologicznych w diagnostyce celakii (zmodyfikowano na podstawie [34])
Antibodies Sensitivity 95% Cl Specificity 95% Cl
IgA TTG 95.1% 91.8–98.1 98.3% 97.1–99.6%
IgA EMA 90.2% 86.3–92.5% 99.6% 98.4–99.9%
IgA TTG — IgA tissue transglutaminase antibodies; IgA EMA — IgA endomysial antibodies; CI — confidence interval
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which accompany CD (for example lowering doses of
levothyroxine in patients with hypothyroidism, and
lowering doses of hydrocortisone in patients with pri-
mary adrenal insufficiency).
Pathogenesis of the coincidence of coeliac disease
and other autoimmune diseases
CD can appear separately or be a part of APS. Ac-
cording to the definition, APS is a group of diseases
of autoimmune origin characterised by hypofunction
of a couple of endocrine glands [39, 40]. A common
genetic origin is the reason that a patient with one
autoimmune disease is more predisposed to other
autoimmune diseases. The occurrence of the symp-
toms of these diseases is usually not synchronised
in time. A patient diagnosed with one autoimmune
disease often shows a positive result with antibod-
ies characterised for another autoimmune disease,
although without yet displaying clinical symptoms or
organ failure. This can be called potential or silent APS
[41]. An example of this kind of syndrome is the state-
ment of presence of antibodies specific for CD (e.g.
IgA TTG), without any specific histological changes
in a patient with another autoimmune disorder (e.g.
GD). More detailed research, for example by using
an electron microscope, can confirm microvillous
atrophy in some of these patients [42]. It is confirmed
that some patients will develop the full histological
features of CD in the future.
We can define different types of APS, which depends
on the associated conditions of the diseases. Enthusiasts
of narrow classification classify APS into two groups
[43], while others classify APS into three [40] or even
four groups [44] (Tab. VII).
APS types are distinguished according to different
modes of inheritance. APS 1 is rare, usually appears
in childhood, is monogenic, and is connected to mu-
tations in an autoimmune-suppressor gene (AIRE,
autoimmune regulator). It is defined by the presence
of hypoparathyroidism, adrenal insufficiency and
chronic mucocutaneous candidiasis. Other APS types
are multigenic disorders and occur in adulthood [40].
A strong association with the HLA complex, mainly
DR3-DQ2 and DR4-DQ8, could be an explanation for
the coexistence of CD and other autoimmune disorders
[45–49]. It was stated in a course of self study that the
frequency of CD was significantly higher (p < 0.05) in
the subgroup of patients with Graves’ disease carrying
HLA DRB1*03 alleles [50].
Table VII. Classification of autoimmune polyendocrine syndromes (APS)
Tabela VII. Podział autoimmunologicznych zespołów niedoczynności wielogruczołowej (APS)
Authors APS-1 APS-2 APS-3 APS-4
Neufeld et al.,
1980 [44]
AD, candidiasis#,
hypoparathyroidism‡
(at least two present)
AD (always present)
plus AITD
and/or T1DM
AITD plus another AID
(except from AD and
hypoparathyroidism)
Combination of AID
not mentioned in the
previous groups
Eisenbarth et al.,
2004 [43]
AD, candidiasis#,
hypoparathyroidism‡
(at least two present)
AD, AITD, T1DM
(at least two present)
Lewiński 2005, [44] AD, candidiasis#,
hypoparathyroidism‡
(at least two present)
AD (always present)
plus: AITD†, AITD
and T1DM* T1DM
AITD, ABD, T1DM, vitiligo:
(at least two present)
APS-3A: AITD and T1DM
APS-3B: AITD and ABD
APS-3C: AITD plus other organ-
-specific AID (e.g. coeliac disease)
The table shows classification of APS and components of each type according to above-mentioned authors; #candidiasis — chronic candidiasis of
mucosa and skin; ‡hypoparathyroidism — hypoparathyroiditis of autoimmune origin; †Schmidt syndrome; *Carpenter syndrome; AD — Addison’s
disease; AITD — autoimmune thyroid disease; T1DM — type 1 diabetes; AID — autoimmune disease; ABD — Addison-Biermer disease
Table VI. Prevalence of coeliac disease in patients with other
autoimmune disorders and healthy volunteers (modified
according to [4–27])
Tabela VI. Częstość występowania celiakii u pacjentów
z innymi chorobami autoimmunologicznymi i u zdrowych
ochotników (zmodyfikowano na postawie [4–27])
Study group Prevalence of coeliac
disease (%)
Hashimoto’s thyroiditis 0–9.1
Graves’ disease 0–5.5
Addison’s disease 5.4–12.2
Type 1 diabetes mellitus in children 3.0–8.0
Type 1 diabetes mellitus in adults 2.0–5.0
Autoimmune hepatitis 2.9–6.4
Healthy volunteers 0.2–1.0
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Autoimmune disorders
associated with coeliac disease
Type 1 diabetes
The majority of studies released so far concern the pres-
ence of CD with another autoimmune disorder: T1DM.
Prevalence
Research was first performed by paediatricians over
30 years ago. At that time, only the classical form of
CD was diagnosed. Diagnosis was based on symptoms
such as steatorrhoea, malnutrition, and growth and
development disorders in children. The frequency
of CD in patients with T1DM was established at the
level of 1.0–1.5% [51] which was significantly under-
estimated (as it later turned out after the introduction
of serological assays as a diagnostic tool). In recent
investigations, where specific diagnostic tests are
used, the frequency of histologically confirmed CD in
patients with T1DM is estimated at the level of 2–5%
in adults and 3–9% in children [14–16]. According to
some researchers, the following criteria are connected
to a higher prevalence of CD in patients with T1DM:
young age [53], female gender [52], younger age at
diagnosis of T1DM [53].
Clinical manifestations
Among the clinical symptoms suggesting association
of CD with T1DM, apart from typical symptoms, there
may be episodes of hypoglycaemia caused by malab-
sorption. A gluten-free diet for patients with TD1 and
CD can reduce these episodes in some cases. There-
fore, changing the diet of these patients to one which
is gluten-free usually increases insulin requirements,
thus doses of insulin must be changed. We have to
remember that diarrhoea, a clinical feature of CD,
can also occur in association with bowel neuropathy
as observed in T1DM.
Recommendations for diagnostic evaluation
The Polish Diabetes Association, in its guidelines
from 2011, recommends CD screening in children and
young people with T1DM once a year [54]. The Ameri-
can Diabetes Association (ADA), in its guidelines
from 2011, recommends CD diagnosis when there is
an appearance of clinical symptoms, periodic screen-
ing studies of asymptomatic patients with T1DM
and diagnostic tests in all children with recently di-
agnosed T1DM [55]. However, the guidelines of the
National Institute of Health (NIH) from 2004 [56] and
the American Gastroenterological Association (AGA)
[34, 57] from 2006 recommend a diagnostic approach
to CD in patients with T1DM when the symptoms of
CD are present.
Autoimmune thyroid diseases
Studies of the presence of CD among patients with
autoimmune thyroid diseases (AITD) have concerned
mainly individuals with Hashimoto’s thyroiditis (HT).
Because of the different genetic factors of HT and GD,
these two diseases cannot be analysed as one group [58].
Prevalence
There were two studies performed concerning the fre-
quency of CD in patients with GD [4, 5]. In other investiga-
tions patients with GD have constituted only a small sub-
group of patients with AITD (from 18 to 100 individuals).
In these studies, elevated antibody levels, typical of CD,
were present in approximately 3.7% of patients (ranging
from 0 to 7.2%) and CD was finally diagnosed (histological
evaluation) in approximately 2.5% (ranging from 0% to
5.5%) [4–10, 13]. In self studies performed on 238 patients
with GD, an elevated level of antibodies specific to CD
(IgA TTG or IgA EMA) was confirmed in 5.9% of patients
and a histological diagnosis of CD was diagnosed in 3.4%
of patients [59]. In studies estimating the prevalence of
CD in patients with HT, an elevated level of autoantibod-
ies specific to CD was present in approximately 3.9% of
patients (ranging from 0% to 9.1%) [6, 7, 9–13]. Diagnosis
of CD was established in approximately 3.1% (ranging
from 0% to 9.1%) of patients. In all studies carried out so
far, no predisposition to CD in AIDT patients concerned
with age or gender has been observed. In a study in2010,
the frequency of autoimmune diseases in a group of 2,791
patients with GD and 491 patients with HT was 0.9% and
1.0% respectively [60]. The coexistence of CD and AITD
was assessed only according to a questionnaire, which was
probably the reason for the underestimation.
Clinical manifestations
Many patients with HT and GD suffering from CD have
atypical CD. Some symptoms typical of CD such as diar-
rhoea and weight loss can be incorrectly interpreted as
symptoms of hyperthyroidism in GD, which leads to
delayed diagnosis. One of the symptoms which indicate
the possibility of a coexistence of CD and AITD (HT or
GD after radical treatment) is related to situations con-
nected to hypothyroidism. In these cases, often a higher
dose of levothyroxine (up to 200 ug per day and more)
is required and a gluten-free diet leads, after some time,
to a reduction in doses of hormonal substitution.
Recommendations for diagnostic evaluation
Currently, there are no indications from the Polish En-
docrine Society concerning establishing a diagnosis of
CD in patients with HT and GD. The NIH (2004) [56]
and the AGA (2006) [4, 57] recommend a diagnostic
approach towards CD in patients with AIDT in case of
the appearance of CD symptoms.
247
Endokrynologia Polska/Polish Journal of Endocrinology 2012; 63 (3)
SZKOLENIE
PODYPLOMOWE
Other autoimmune disorders
Research projects concerning the presence of CD
among other autoimmune disorders are numerous and
are usually performed on small groups of patients. In
a couple of published studies regarding patients with
primary adrenal insufficiency, in various groups of 17
to 109 patients, a diagnosis of CD was established in
5.4% to 12.2% of patients [17, 20]. Authors focus on the
possibility of similar symptoms in both diseases, which
leads to a postponement in establishing a diagnosis
of CD (losing weight, abdominal pain, diarrhoea). In
numerous case reports, there is some data about the
coincidence of CD and primary hypoparathyroidism of
autoimmune origin [61–63]. It is important to remember
this, especially in patients with deep hypocalcaemia ac-
companied by the symptoms of tetany. As opposed to
this situation in which parathormone serum concentra-
tion is low, in patients with hypocalcaemia, connected
to malabsorption in CD, an elevation of serum PTH
concentration may occur.
There is some data regarding CD and its coexist-
ence with lymphocytic hypophysitis [64], alopecia
areata [65–67], and pernicious anaemia. It is essential to
remember that megaloblastic anaemia of B12 vitamin
deficiency can be caused by poor absorption in patients
with CD and the presence of autoantibodies in patients
with pernicious anaemia as well. As a result, when CD is
associated with pernicious anaemia there are indications
for a diagnostic evaluation of the presence of autoim-
mune features (autoantibodies to intrinsic factor).
Studies estimating the prevalence of autoimmune
diseases in patients with CD relate to a much larger
group of patients. Among these studies, the vast major-
ity concern AIDT and Addison’s disease. In a study of
14,021 patients with CD compared to a control group of
68,068, for the first time a significant increase in AITD
was diagnosed (HR = 2.9; 95% Cl = 2.0–4.2; p < 0.001)
[68]. In another study performed by the same authors
on the same group of patients with CD, a higher preva-
lence of Addison’s disease was observed compared to
a healthy control group (HR = 11.4; 95% Cl = 4.4–29.6;
p < 0.001) [69].
Recommendations concerning
the diagnostic approach to coeliac disease
in patients with autoimmune disorders
Recommendations concerning the diagnostic approach
to CD in patients with autoimmune disorders are am-
biguous and differ according to which autoimmune
disease is present, and the Society summarising the data.
At present, the most up-to-date and strict guidelines are
those formulated by the ADA. There are no guidelines
from Polish Societies, apart from the Polish Diabetes
Society. This probably stems from a lack of data con-
cerning the prevalence of CD in the Polish population
of patients with other than T1DM autoimmune disor-
ders. According to the present guidelines of the NIH
(2004) [56] (Tab. VIII) [34, 57], patients with autoimmune
disorders should undergo a diagnostic approach to CD
in the presence of any symptoms suggesting CD. With
relevance to atypical or even silent course of CD types,
it may lead to lower detectability.
It would require further clinical studies on larger
groups of patients with autoimmune disorders to
estimate the prevalence of CD in these patients, and
potential modification of the guidelines.
Remember!
CD is one of the most frequent diseases of autoim-
mune origin, diagnosed, on average, in one out of 100
Table VIII. Recommendations concerning the diagnostic approach to coeliac disease in adult patients based on NIH
recommendations [56]
Tabela VIII. Zalecenia dotyczące diagnostyki celiakii u dorosłych oparte na zaleceniach NIH [56]
Diagnostic approach to coeliac disease Diagnostic approach to coeliac
disease in symptomatic patients
Diagnostic approach to coeliac disease not
recommended
Malabsorption, isolated iron deficiency Family history of coeliac disease General population
Infertility Autoimmune thyroid disease Short history of symptoms from digestive system
Osteoporosis Sjögren’s syndrome Type 1 diabetes**
Ataxia and polyneuropathy Type 1 diabetes*
Arthritis of unknown origin Addison’s disease
Chronic liver disease of unknown origin Symptoms from digestive system
Dermatitis herpetiformis
Irritable bowel syndrome
*With symptoms of coeliac disease, **without symptoms of coeliac disease
248
Coeliac disease and other autoimmune disorders Piotr Miśkiewicz et al.
SZKOLENIE
PODYPLOMOWE
individuals. The results of studies indicate that there is
an increased prevalence of CD in patients with other
diseases of autoimmune origin. The coexistence of CD
with other autoimmune diseases is probably connected
to a common genetic predisposition.
The majority of adult patients suffer from atypical or
silent types of the disease, something which postpones
proper diagnosis. CD, if undiagnosed or untreated, can
lead to many medical disorders.
The diagnostic approach to CD is based on serologi-
cal evaluation (specific antibodies — IgA TTG and IgA
EMA of equivalent diagnostic accuracy). In many cases,
an evaluation of IgA TTG can be routinely considered
as a screening test. A patient with a positive serological
evaluation should undergo endoscopy with a biopsy of
the descending part of the duodenum.
Introducing a strict gluten-free diet in patients with
CD can decrease the risk of many of the medical disor-
ders mentioned above.
In patients with endocrinopathies of autoimmune
origin, in the diagnostic process of many symptoms
and diseases (for example iron deficiency, non-specific
abdominal symptoms, abnormal serum transaminases,
infertility), the coexistence of CD should always be
considered.
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... [5,26] The anti-tTG antibody has good sensitivity and specificity, occurring in more than 95% of patients with biopsy-proven CD. [28] The survey of the anti-endomysial antibody has the same accuracy of anti-tTG but is more expensive and observer-dependent, while the research of anti-gliadin antibodies, because they are less sensitive and specific, is not recommended for the screening of CD. [5] It is advisable to determine the level of serum IgA. [31] In individuals with deficiency of IgA, survey of anti-tTG IgG, anti-endomysial IgG, or anti-gliadin IGg antibodies can be done. [32] The patients who have suggestive serological screening should be referred for a biopsy of the small intestine to confirm the diagnosis of CD. [4,27,31] There is no consensus in the literature on the management of screening for CD in patients with T1DM. ...
... [31] In individuals with deficiency of IgA, survey of anti-tTG IgG, anti-endomysial IgG, or anti-gliadin IGg antibodies can be done. [32] The patients who have suggestive serological screening should be referred for a biopsy of the small intestine to confirm the diagnosis of CD. [4,27,31] There is no consensus in the literature on the management of screening for CD in patients with T1DM. [5,26] However, since diabetic patients have generally few or no symptoms associated to CD, some studies suggest the screening for CD at the time of diagnosis of T1DM, annually in the first 4 years of the diagnosis and every 2 years in the successive 6 years of follow-up. ...
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Context: Type 1 diabetes mellitus (T1DM) is caused by an immune-mediated destruction of pancreatic beta cells. Other autoimmune diseases can be observed in association with T1DM. The screening for celiac disease (CD) and Hashimoto's thyroiditis is necessary due to the increased prevalence of these pathologies in T1DM patients. Aims: This study aimed to investigate the prevalence of autoimmune markers for pancreatitis, thyroiditis, and CD in racially admixtured children and adolescents with T1DM. Settings and design: Cross-sectional clinic-based study. Methods: Seventy-one patients with T1DM (average: 11.6 ± 5.1 years). In all patients, the following antibodies were surveyed: Anti-glutamic acid decarboxylase (anti-GAD), immunoglobulin A (IgA) anti-transglutaminase (anti-tTG), Antithyroglobulin (AAT), anti-thyroid peroxidase (anti-TPO), and IgA. Statistical analysis used: The quantitative variables were expressed as a mean and standard deviation and the qualitative variables in contingency tables. Student's t-test and χ(2) tests were used to assess the differences between the groups. The level of significance was established as P < 0.05. Results: The prevalence of anti-GAD antibodies was 5.9%; anti-tTG IgA, 7.4%; anti-TPO, 11.8%; and AAT, 11.8%. Conclusions: Children and adolescents with T1DM have increased the prevalence of antithyroid and CD-related antibodies. The positivity for anti-GAD and antithyroid antibodies was less frequent than in other studies. The prevalence of anti-tTG antibodies was similar to the literature.
... [3][4][5][6][7] The association of celiac disease with PAS is also reported in few case reports. [8][9][10] It is quite interesting to note that the present case with PAS III is associated with empty sella and hypopituitarism, manifested by severe secondary adrenal insufficiency presenting with b a hypoglycemia, hyperprolactinemia and hypogonadism. Very few cases of PAS associated with empty sella have been reported in the literature. ...
... [3][4][5][6][7] The association of celiac disease with PAS is also reported in few case reports. [8][9][10] It is quite interesting to note that the present case with PAS III is associated with empty sella and hypopituitarism, manifested by severe secondary adrenal insufficiency presenting with hypoglycemia, hyperprolactinemia and hypogonadism. Very few cases of PAS associated with empty sella have been reported in the literature. ...
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... Uncontaminated Oat is considered to be a safer cereal for coeliac patients due to lower content of proline residue in its protein avenin [2]. Several attempts have been made to determine the role of cereal proteins in coeliac disease currently for patients suffering from this disease a strict gluten-free diet is often the recommended treatment [1][2][3][4][5]. ...
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A molecular dynamic (MD) modeling approach was applied to evaluate the effect of external electric field on gliadin protein structure and surface properties. Static electric field strengths of 0.001 V/nm and 0.002 V/nm induced conformational changes in the protein but had no significant effect on its surface properties. The study of hydrogen bond evolution during the course of simulation revealed that the root mean square deviation, radius of gyration and secondary structure formation, all depend significantly on the number hydrogen bonds formed. This study demonstrated that it is necessary to gain insight into protein dynamics under external electric field stress, in order to develop the novel food processing techniques that can be potentially used to reduce or eradicate food allergens.
... CD has also been associated with gynecologic disorders such as amenorrhea [10,23,31,33]. These may even be the only presenting features and are considered atypical clinical forms of CD [11,[13][14][15]34]. ...
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Because of the continuous increase in the prevalence of gluten-related disorders, selection of wheat 12 with a low content of immunogenic gluten epitopes could be an innovative alternative for prevention. 13 In this review, the focus is on literature data concerning the deallergenization tools of wheat, which are 14 mainly related to breeding approaches (classic and advanced) and processing operations (germination 15 and fermentation). Until now, no safe wheat genotype has been identified, whereas decreasing wheat 16 allergenicity is possible. On the other hand, the decrease of gluten or some of its epitopes can strongly 17 affect technological properties. Thus, obtaining celiac-safe gluten without affecting the technological 18 properties of wheat could be considered as a new challenge that scientists will be facing. Celiac-safe 19 wheat-based product development could be a great revolution in the market of foods for special 20 medical purposes. The present paper is aiming to: a) review the strategies and the approaches used, or 21 that can be used, for developing low allergenic wheat: their utilities and limits were also discussed and 22 b) screen the impact of gluten reduction or removal on the quality of wheat end-use products.
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The diagnosis of celiac disease (CD) in patients with different autoimmune diseases, including Graves' disease (GD) remains a challenge. The aim of our study was: (i) to assess the prevalence of CD in patients with GD in the Polish population; (ii) to evaluate the prevalence of CD in the subgroups of patients with GD divided on the basis of clinical and HLA typing criteria. The prospective study was conducted at an academic referral center. The study groups consisted of: (i) consecutive, euthyroid patients with GD (n=232) and (ii) healthy volunteers without autoimmune thyroid diseases (n=122). The diagnosis of CD was based on elevated IgA-TTG and small intestine biopsy findings. CD was diagnosed in 8 patients with GD (3.4%) and in 1 healthy volunteer (0.8%). The development of CD in patients with GD was strongly associated with HLADQ2 haplotype (as predicted from linkage disequilibria, 14.6% vs. 1.5%, P=0.009; OR=11.3; 95%CI 1.3-252.7): six patients with CD carried HLA-DRB1*03, one carried HLA-DRB1*04 allele and one HLA-DRB1*07/*11 genotype. Moreover multivariate analysis showed independent associations between CD and early onset of GD (P=0.014, OR=9.6), autoimmunity in family (P=0.029, OR=6.3) and gastroenterological symptoms (P=0.031, OR=8.1). The results of our study suggest that serological screening for CD may be considered in GD patients (i) with the HLA alleles typical for CD (ii) with an early onset of GD, (iii) with a family history of autoimmunity. Moreover in euthyroid GD patients with nonspecific gastrointestinal symptoms, the diagnosis of CD should be taken into account.
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Autoimmune polyglandular syndrome type 2 is defined as the occurrence of Addison's disease concomitantly with autoimmune thyroid disease and/or type 1 diabetes mellitus. An 11-year-old boy with Hashimoto's disease, Addison's disease, celiac disease and Langerhans islet cell autoimmunity is described in this case report. Treatment of an endocrine disease may also trigger the onset of another endocrine disease. This case report underlines the importance of early recognition and treatment of critical endocrine diseases as well as the necessity to investigate pediatric patients with autoimmune diseases for coexisting conditions. Furthermore, the role of psychological stress as an inducer of autoimmunity was also discussed.
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We present a case of autoimmune polyglandular syndrome type III (APS III) associated with Hashimoto's disease, type 1 diabetes mellitus, vitiligo and autoimmune urticaria. This rare genetic disorder occurs with unknown frequency in the Polish population. It is characterised by endocrine tissue destruction resulting in the malfunction of multiple organs.Several cases of APS III associated with organ-specific autoimmune diseases such as coeliac disease, hypogonadism and myasthenia gravis, as well as organ-nonspecific or systemic autoimmune diseases such as sarcoidosis, Sjögren syndrome, and rheumatoid arthritis have been described. To the best of our knowledge, we here describe the first case of APS III associated with autoimmune thyroiditis, type 1 diabetes mellitus, vitiligo and autoimmune urticaria in an adult patient. (Endokrynol Pol 2014; 65 (4): 320-323).
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In type 3 polyendocrine syndrome (PAS3), autoimmune thyroiditis occurs with other organ-specific autoimmune disease, but not with autoimmune adrenalitis. In this report we described a family from Pakistan in which mother and three daughters were affected by a PAS3. We studied a family from Pakistan: Father MMu age 44, mother KN aged 44, three daughters MM age 20, MH age 16 and MA age 14 and a son MU age 18. These subjects were tested for thyroids function, metabolic function, adrenal function, autoimmune disease. In this family the four females were shown hypothyroidism with presence of anti thyroid autoantibodies (AA) and high TSH serum concentration in association with the presence of anti transglutaminase AA. Moreover KN, MM and MH were positive for anti nuclear AA (granular pattern) and for antibodies against Saccaromyces cerdevisiae. MM was positive for AA against nuclear extractable antigens (SSA and SSB) too. No diabetes or pernicious anemia were observed. Adrenal and Pituitary function were normal. PAS 3C is an uncommon disease. In this family from Pakistan we observed a PAS3C in the four female members: mother and three daughters while father and son were unaffected.
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Background: Recent studies suggest that coeliac disease (CD) is one of the commonest, life-long disorders in Italy. The aims of this multicentre work were: (a) to establish the prevalence of CD on a nationwide basis; and (b) to characterize the CD clinical spectrum in Italy. Patients and methods: Fifteen centres screened 17201 students aged 6–15 years (68.6% of the eligible population) by the combined determination of serum IgG- and IgA-antigliadin antibody (AGA) test; 1289 (7.5%) were IgG and/or IgA-AGA positive and were recalled for the second-level investigation; 111 of them met the criteria for the intestinal biopsy: IgA-AGA positivity and/or AEA positivity or IgG-AGA positivity plus serum IgA deficiency. Results: Intestinal biopsy was performed on 98 of the 111 subjects. CD was diagnosed in 82 subjects (75 biopsy proven, 7 not biopsied but with associated AGA and AEA positivity). Most of the screening-detected coeliac patients showed low-grade intensity illness often associated with decreased psychophysical well-being. There were two AEA negative cases with associated CD and IgA deficiency. The prevalence of undiagnosed CD was 4.77 × 1000 (95% CI 3.79–5.91), 1 in 210 subjects. The overall prevalence of CD, including known CD cases, was 5.44 × 1000 (95% CI 4.57–6.44), 1 in 184 subjects. The ratio of known to undiagnosed CD cases was 1 in 7. Conclusions: These findings confirm that, in Italy, CD is one of the most common chronic disorders showing a wide and heterogeneous clinical spectrum. Most CD cases remain undiagnosed unless actively searched.
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Background: Coeliac disease (CD) is heterogenous in its clinical manifestation and pathological expression. Recent studies have reported an increase in prevalence of CD in children with insulin-dependent diabetes mellitus (IDDM), low stature and relatives of patient with CD. The purpose of the analysis was to determine the incidence rate of coeliac disease (CD) among the children from the region of Western Pomerania for the period of the last 22 years (1976-1998). Material and methods: The study involved 559 children stemming from 5 groups: group I - 232 children with chronic diarrhoea, group II - 7 children with Duhring disease, group III - 120 children with IDDM, group IV - 144 children with low stature, group V - 26 relatives, siblings-children with CD. CD was diagnosed in children with positive serological markers - antiendomysial antibody (EMA) and in the presence of villous atrophy in duodenum. Antigliadin antibodies (AGA) by ELISA test (Gilassay, Diamed) and EMA by indirect immunofluorescence test were estimated. Retrospective analysis of case history were performed in groups I and II. In groups III and IV three-stage screening was carried out performed: stage I - children with present AGA were isolated, stage II - in children with AGA EMA were determined, stage III - in children with EMA the duodenal mucosa was estimated. In group V stages 2 and 3 were carried aut. Results: At that period CD was diagnosed in 64 children, therein intestinal form - 46, extraintestinal (low stature) - 5 and asymptomatic - 13 children. Asymptomatic form of CD was diagnosed in children with Duhring disease, IDDM and siblings of children with CD. CD was most frequently diagnosed among children affected by Duhrings disease (1:1) and chronic diarrhea (1:6), rarely among siblings (1:26), children with diabetes mellitus (1:24) and low stature (1:29). Mean age of diagnosing CD in children with intestinal form was 5.6 years, and in children with low stature or asymptomatic form of CD it was twice larger - 11.2 and 12.2 years. Rate of CD (morbidity index - MI) for Western Pomerania region was 1:4979 (MI=2.00) (1976-1996). The highest incidence rate of CD (MI) was disclosed in the years 1982-1984 and 1985-1987 (1:4152 and 1:3619; MI=2.41 and 2.76), the lowest in the years 1994-1996 (1:8325; MI= 1.20). No case of CB was diagnosed in children born in 1997-1998 years. Conclusions: In relation to other regions of Poland the rate of intestinal form of CD in Western Pomerania region is found to be the lowest. The rate of CD in children with IDDM or low stature is the same in other regions of Poland.
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Attention is drawn to the different effects of different kinds of cereals and starches on patients with coeliac disease. The effect of wheat flour is unfavourable while that of wheat starch is harmless. The harmful effect is produced by a still unknown substance and not by starch. The substance in question is provisionally called the “wheat factor.” The effect of this factor is judged according to its ability to produce or aggravate anorexia, vomiting, diarrhoea and steatorrhoea. Several conclusions as to the significance of this factor are presented.
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This document presents the official recommendations of the American Gastroenterological Association (AGA) Institute on “Diagnosis and Management of Celiac Disease.” It was approved by the Clinical Practice and Economics Committee on August 21, 2006, and by the AGA Institute Governing Board on September 25, 2006.
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Common autoimmune disorders tend to coexist in the same subjects and to cluster in families. We performed a cross-sectional multicenter study of 3286 Caucasian subjects (2791 with Graves' disease; 495 with Hashimoto's thyroiditis) attending UK hospital thyroid clinics to quantify the prevalence of coexisting autoimmune disorders. All subjects completed a structured questionnaire seeking a personal and parental history of common autoimmune disorders, as well as a history of hyperthyroidism or hypothyroidism among parents. The frequency of another autoimmune disorder was 9.67% in Graves' disease and 14.3% in Hashimoto's thyroiditis index cases (P=.005). Rheumatoid arthritis was the most common coexisting autoimmune disorder (found in 3.15% of Graves' disease and 4.24% of Hashimoto's thyroiditis cases). Relative risks of almost all other autoimmune diseases in Graves' disease or Hashimoto's thyroiditis were significantly increased (>10 for pernicious anemia, systemic lupus erythematosus, Addison's disease, celiac disease, and vitiligo). There was relative "clustering" of Graves' disease in the index case with parental hyperthyroidism and of Hashimoto's thyroiditis in the index case with parental hypothyroidism. Relative risks for most other coexisting autoimmune disorders were markedly increased among parents of index cases. This is one of the largest studies to date to quantify the risk of diagnosis of coexisting autoimmune diseases in more than 3000 index cases with well-characterized Graves' disease or Hashimoto's thyroiditis. These risks highlight the importance of screening for other autoimmune diagnoses if subjects with autoimmune thyroid disease present with new or nonspecific symptoms.
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Patients with type 1 diabetes mellitus have an increase the risk of developing other autoimmune diseases, among them, autoimmune thyroid disease, mainly Hashimoto are more frequently observed. The aim of the study was to assess the prevalence of celiac disease and autoimmune thyroiditis in children and adolescents with type 1 diabetes mellitus. The study included 260 children (124 girls, 136 boys) aged 1.3-18 years (mean 11+/-4.01), the diabetes duration 3.99+/-3.7 years. Endomysial antibody (EMA) was measured and all patients with positive EMA had small-bowel biopsy. Antibodies against thyroperoxidase (a-TPO), thyroglobulin (a-Tg), TSH, fT4, HbA1c and ultrasound examination of thyroid glands were assessed. The prevalence of EMA was 10% (27/260) and 9% (25/260) had biopsy-proven celiac disease. The median age of T1DM at onset was significantly lower in patients with EMA than those without EMA 6.2+/-5.6 vs. 7.7+/-4.2 p=0.04. 20% of children diagnosed with type 1 diabetes at age <4 years had celiac disease p=0.001. The prevalence of thyroid antibodies was 29% (75/260). In the group with positive thyroid antibodies, in 28% (21/75) thyroid ultrasonography showed scattered hypoechogenicity and 23% (17/75) required treatment with thyroxine. Children with positive a-TPO had higher TSH level (2.87+/-2.1 vs. 1.95+/-0.9) p<0.01 and HbA1c level (8.32+/-1.64 vs. 7.59+/-1.67) p=0.03 than children without thyroid antibodies. More frequently thyroid antibodies were positive in girls than in boys. Out of five patients with T1DM, one is diagnosed with Hashimoto or celiac disease. Both diseases occurred independently. Autoimmune thyroid disease and celiac disease occur more frequently in children with T1DM, therefore screening at an onset and repeated measurements are recommended.