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A glance on celiac disease
1. A GLANCE ON
CELIAC DISEASE
Prof. Dr. Saad S Al Ani
Senior Pediatric Consultant
Head of Pediatric Department
Khorfakkan Hospital
Sharjah ,UAE
saadsalani@aol.com
2. 1. A previously healthy 8-year-old girl presents with a 3-
month history of persistent, intensely pruritic papules
distributed symmetrically on her
hands, thighs, elbows, and buttocks (Figure 1).
Thorough questioning may also reveal:
A. Negative review of systems
B. No relief from oral diphenhydramine
C. Positive family history of celiac disease
D. All of the above 2
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
3. 2. This 5-year-old boy presents with similar findings for 6
months duration (Figure 2). Skin biopsy to aid in the
diagnosis of this condition should be performed:
A. For histopathology and direct
immunofluorescence of the freshest lesion
B. For histopathology and direct
immunofluorescence of the most established lesion
C. For histopathology and tissue culture
D. For histopathology, tissue culture and viral cultures
3
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
4. 3. The diagnosis of dermatitis herpetiformis has
been made in this 9-year-old boy (Figure 3). The
most appropriate therapy includes:
A. Oral corticosteroids
B . Oral antihistamines and topical corticosteroids
C. Gluten-free diet and oral dapsone
D. Oral valacyclovir
4
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
5. LIGHT-SPOTS
Celiac disease is a multifactorial,
autoimmune disorder that occurs in
genetically susceptible individuals
5
Guandalini S, Setty M. Celiac disease. Curr Opin Gastroenterol. Nov 2008;24(6):707-12.
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
6. LIGHT-SPOTS (CONT.)
It is triggered by:
- Environmental factor
(gluten and related prolamins
present in wheat, rye, and barley)
- Autoantigen
( tissue transglutaminase)
6Husby S, Koletzko S, Korponay-Szabó IR, Mearin ML, Phillips A, Shamir R, et al. European
Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of
coeliac disease. J Pediatr Gastroenterol Nutr. Jan 2012;54(1):136-60.
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
7. The disease primarily affects the small
intestine, where it progressively leads to
flattening of the small intestinal mucosa
7
LIGHT-SPOTS (CONT.)
Guandalini S, Setty M. Celiac disease. Curr Opin Gastroenterol. Nov 2008;24(6):707-12.
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
8. Celiac disease develops only after
dietary exposure to the protein gluten
,which is found in wheat ,rye, and barley
8
LIGHT-SPOTS (CONT.)
Guandalini S, Setty M. Celiac disease. Curr Opin Gastroenterol. Nov 2008;24(6):707-12.
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
9. THE PREVALENCE OF CELIAC
DISEASE
Celiac disease affects 0.6 to 1.0% of
the population worldwide
Wide regional differences in Europe
0.3% in Germany
2.4% in Finland
for reasons that are unclear
o Also common in developing
countries, particularly in North Africa
and the Middle East
4/21/2014
9
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
10. THE PREVALENCE OF CELIAC
DISEASE (CONT.)
The frequency of celiac disease is
increasing in many developing
countries because of :
Westernization of the diet
Changes in wheat production &
preparation
Increased awareness of the disease
A combination of these factors
4/21/2014
10
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
http://blogs.nejm.org/now/index.php/celiac-disease
11. THE RISK FACTORS FOR CELIAC
DISEASE
Is increased among persons who have:
An affected first-degree relative (10 to 15%)
Type 1 diabetes (3 to 16%)
Hashimoto’s thyroiditis (5%)
Other autoimmune diseases
(Including autoimmune liver diseases, Sjogren’s
syndrome, and IgA nephropathy)
Down’s syndrome (5%)
Turner’s syndrome (3%)
IgA deficiency (9%)
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11
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
http://blogs.nejm.org/now/index.php/celiac-disease
12. GENETIC SUSCEPTIBILITY TO CELIAC
DISEASE
The genetic susceptibility to celiac
disease is conferred by well-identified
haplotypes in the human leukocyte
antigen (HLA) class II region (ie, DR3
or DR5/DR7 or HLA DR4).
12
[Best Evidence] Rubio-Tapia A, Kyle RA, Kaplan EL, et al. Increased prevalence and
mortality in undiagnosed celiac disease. Gastroenterology. Jul 2009;137(1):88-93.
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
13. 90% of patients
express the DQ2 heterodimer
7% of patients
express the DQ8 heterodimer
3% of patients
possess only half of the DQ2
heterodimer
13
GENETIC SUSCEPTIBILITY TO CELIAC
DISEASE (CONT.)
[Best Evidence] Rubio-Tapia A, Kyle RA, Kaplan EL, et al. Increased prevalence and
mortality in undiagnosed celiac disease. Gastroenterology. Jul 2009;137(1):88-93.
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
14. CLINICAL PRESENTATION
Celiac disease (CD) :
May occur without any symptoms
Minimally symptomatic celiac
disease is probably the most
common form of the
disease, especially in older children
and adults
14
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
16. POSSIBLE PRESENTATIONS OF
CELIAC DISEASE
1. Typical:
This presentation is primarily
characterized by GI signs and
symptoms
16
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Prof.Dr.SaadSAlAni
4/21/2014
17. POSSIBLE PRESENTATIONS OF
CELIAC DISEASE (CONT.)
2. Atypical:
GI signs and symptoms are minimal
or absent, and various extraintestinal
manifestations are present.
17
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
18. 3.Silent:
The small intestinal mucosa is
damaged, and celiac disease
autoimmunity can be detected with
serology; however, no symptoms
are present.
18
POSSIBLE PRESENTATIONS OF
CELIAC DISEASE (CONT.)
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
19. 4.Potential:
-Patients have a positive specific
autoimmune serology and may or
may not be symptomatic, but the
mucosa morphology is normal.
19
POSSIBLE PRESENTATIONS OF
CELIAC DISEASE (CONT.)
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
20. 4.Potential (Cont.):
-These individuals have genetic
compatibility with celiac disease
and full-blown celiac disease may
develop at a later stage in some or
all of these individuals.
20
POSSIBLE PRESENTATIONS OF
CELIAC DISEASE (CONT.)
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
21. 5.Latent:
Individuals with normal mucosal
morphology who “have had a gluten-
dependent enteropathy at some point
in their life.” This subset of patients
is the rarest of the group.
21
POSSIBLE PRESENTATIONS OF
CELIAC DISEASE (CONT.)
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
22. 22
CAUSATIVE FACTORS IN CELIAC DISEASE
Causative factors in celiac disease. HLA, human leukocyte antigen.
Di Sabatino A, Corazza GR: Coeliac disease, Lancet 373:1480-1490, 2009.)
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
23. GI SIGNS AND SYMPTOMS OF CELIAC
DISEASE
Infants and young children typically
present with:
Chronic diarrhea
Anorexia
Abdominal distension
Abdominal pain
Poor weight gain or weight loss
Vomiting 23
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
24. GI SIGNS AND SYMPTOMS OF
CELIAC DISEASE (CONT.)
Severely affected infants present with a
celiac crisis, which is characterized by:
Explosive watery diarrhea
Marked abdominal distension
Dehydration
Hypotension
Lethargy, often with profound electrolyte
abnormalities, including severe hypokalemia
24
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
25. GI symptoms in older children are
typically less evident and include:
Nausea
Recurrent abdominal pain
Bloating
Constipation
Intermittent diarrhea.
25
GI SIGNS AND SYMPTOMS OF
CELIAC DISEASE (CONT.)
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
26. EXTRAINTESTINAL MANIFESTATIONS
OF CELIAC DISEASE
The main extraintestinal manifestations of
celiac disease are as follows:
Dermatitis herpetiformis
Dental enamel hypoplasia
Aphthous ulcers
Delayed tooth eruption
26
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
30. Iron-deficiency anemia
Short stature and delayed puberty
Chronic hepatitis and
hypertransaminasemia
Arthritis and arthralgia
30
EXTRAINTESTINAL MANIFESTATIONS
OF CELIAC DISEASE (CONT.)
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
31. Osteopenia and osteoporosis
Neurological problems
Occipital calcifications and intractable
epilepsy
Gluten-induced ataxia
Psychiatric disorders
Subfertility or infertility
31
EXTRAINTESTINAL MANIFESTATIONS
OF CELIAC DISEASE (CONT.)
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
32. 1.Autoimmune conditions
Type 1 diabetes mellitus
Approximately 10% of patients
have typical findings of celiac
disease on duodenal biopsy samples.
Thyroiditis
Alopecia
32
Associated diseases
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
33. 2. Genetic syndromes
Down syndrome
The prevalence of Down syndrome in
celiac disease is 8-12%.
Most patients with Down syndrome who
have celiac disease have some GI
symptoms
About one third of these patients do not
have GI symptoms 33
Associated diseases (Cont.)
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
36. DIAGNOSIS
Serologic tests have a crucial role in
the diagnosis of celiac disease;
sensitivity of the IgA anti-TG2 is 61-
100% (mean, 87%), and specificity is
86-100% (mean, 95%).
Some 10% of patients whose disease
is diagnosed earlier than 2 yr of age
show absence of IgA anti-TG2.
36
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
37. DIAGNOSIS (CONT.)
The ultimate diagnosis of celiac
disease relies on the demonstration of
specific, though not
pathognomonic, histopathologic
abnormalities in the small bowel
mucosa
37
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
38. DIFFERENT GRADES OF SMALL INTESTINAL DAMAGE IN
COELIAC DISEASE
38
a-b normal villi
and pathological
increase of
intraepithelial
lymphocytes
(IELs)
c-d
mild/moderate
atrophy of villi
and pathological
increase of IELs
e-f total villous
atrophy and
pathological
increase of IELs
http://www.nature.com/cmi/journal/v8/n2/full/cmi201064a.html
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
49. Current criteria, the 2 requirements
mandatory for the diagnosis of celiac
disease are:
1. The finding of villous atrophy with
hyperplasia of the crypts and abnormal
surface epithelium, while the patient is
eating adequate amounts of gluten
2. A full clinical remission after withdrawal
of gluten from the diet.
European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)
49
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
DIAGNOSIS (CONT.)
50. CONT.
Circulating IgA celiac disease–
associated antibodies at the time of
diagnosis and their disappearance on a
gluten-free diet adds weight to the
diagnosis
50
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
51. A control biopsy to verify the
consequences of the gluten-free diet
on the mucosal architecture is
considered mandatory only in patients
with an equivocal clinical response to
the diet
51
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
CONT.
52. TREATMENT
The only treatment for celiac disease
is lifelong strict adherence to a
gluten-free diet
This requires a wheat-, barley-, and
rye-free diet.
52
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
53. TREATMENT (CONT.)
There is a consensus that all celiac
disease patients should be treated
with a gluten-free diet regardless of
the presence of symptoms
53
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
54. COMPLICATIONS
Lymphoma is the most common GI
malignancy in the pediatric
population
Predisposing conditions include:
- HIV/AIDS
- Agammaglobulinemia
- Long-standing celiac disease
54
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
55. Some of the researched concerning
celiac disease during the early2014
55
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
56. BMC Gastroenterol. 2014 Feb 13;14:28. doi: 10.1186/1471-230X-14-28.
Follow-up of pediatric celiac disease: value of antibodies in predicting mucosal healing, a prospective cohort study.
Vécsei E, Steinwendner S, Kogler H, Innerhofer A, Hammer K, Haas OA, Amann G, Chott A, Vogelsang H, Schoenlechner R, Huf W, Vécsei A1.
Abstract
BACKGROUND:
In diagnosing celiac disease (CD), serological tests are highly valuable. However, their role in following up children with CD after prescription of a gluten-free diet is unclear. This
study aimed to compare the performance of antibody tests in predicting small-intestinal mucosal status in diagnosis vs. follow-up of pediatric CD.
METHODS:
We conducted a prospective cohort study at a tertiary-care center. 148 children underwent esophohagogastroduodenoscopy with biopsies either for symptoms ± positive CD
antibodies (group A; n = 95) or following up CD diagnosed ≥ 1 year before study enrollment (group B; n = 53). Using biopsy (Marsh ≥ 2) as the criterion standard, areas under
ROC curves (AUCs) and likelihood-ratios were calculated to estimate the performance of antibody tests against tissue transglutaminase (TG2), deamidated gliadin peptide (DGP)
and endomysium (EMA).
RESULTS:
AUCs were higher when tests were used for CD diagnosis vs. follow-up: 1 vs. 0.86 (P = 0.100) for TG2-IgA, 0.85 vs. 0.74 (P = 0.421) for TG2-IgG, 0.97 vs. 0.61 (P = 0.004) for
DPG-IgA, and 0.99 vs. 0.88 (P = 0.053) for DPG-IgG, respectively. Empirical power was 85% for the DPG-IgA comparison, and on average 33% (range 13-43) for the non-
significant comparisons. Among group B children, 88.7% showed mucosal healing (median 2.2 years after primary diagnosis). Only the negative likelihood-ratio of EMA was low
enough (0.097) to effectively rule out persistent mucosal injury. However, out of 12 EMA-positive children with mucosal healing, 9 subsequently turned EMA-negative.
CONCLUSIONS:
Among the CD antibodies examined, negative EMA most reliably predict mucosal healing. In general, however, antibody tests, especially DPG-IgA, are of limited value in
predicting the mucosal status in the early years post-diagnosis but may be sufficient after a longer period of time.
CONCLUSIONS:
Among the CD antibodies examined, negative endomysium (EMA) most
reliably predict mucosal healing. In general, however, antibody
tests, especially deamidated gliadin peptide- IgA ( DPG-IgA) are of
limited value in predicting the mucosal status in the early years post-
diagnosis but may be sufficient after a longer period of time.
BMC Gastroenterol. 2014 Feb 13;14:28.
Follow-up of pediatric celiac disease: value of antibodies
in predicting mucosal healing, a prospective cohort study.
Vécsei E, Steinwendner S, Kogler H, Innerhofer A, Hammer
K, Haas OA, Amann G, Chott A, Vogelsang H, Schoenlechner
R, Huf W, Vécsei A1.
56
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
57. Childs Nerv Syst. 2014 Feb 25. [Epub ahead of print]
Prevalence of resistant occipital lobe epilepsy associated with celiac disease in children.
Dai AI1, Akcali A, Varan C, Demiryürek AT.
Abstract
PURPOSE:
Celiac disease (CD) is a chronic, inflammatory autoimmune disorder caused by intolerance to ingested gluten. Increased
frequency of CD has been reported in occipital lobe epilepsy. The aim of the present study is to investigate the frequency of CD
among children followed up due to epilepsy and diagnosed with epileptic activity in the occipital lobe in at least one
electroencephalography (EEG) test.
METHODS:
For this research, 90 pediatric epilepsy patients with epileptic activity in the occipital lobe were enrolled in the study group, while
the control group comprised of 100 healthy children. In addition to the EEG examination, tissue transglutaminase (tTG) antibody
was determined on duodenal biopsy.
RESULTS:
None of the healthy children in the control group was positive in terms of the tTG antibody test used to scan CD. In the group with
epileptic activity in the occipital lobe, two patients out of 90 were tTG antibody positive. The seroprevalence was 1/45 (2.22 %) in
this group. These two patients were diagnosed with CD based on the endoscopic duodenal biopsy. In these patients, the seizures
were uncontrollable through monotherapy.
CONCLUSIONS:
Our results showed that the prevalence of CD is observed to be higher than the normal population among the patients with
occipital lobe epilepsy. This type of seizure disorder seems to be more resistant to monotherapy, compared with other types of
occipital epilepsy. Therefore, screening for CD is recommended in children with resistant epileptic activity in the occipital lobe.
CONCLUSIONS:
Our results showed that the prevalence of CD is observed to be higher
than the normal population among the patients with occipital lobe
epilepsy. This type of seizure disorder seems to be more resistant to
monotherapy, compared with other types of occipital epilepsy.
Therefore, screening for CD is recommended in children with
resistant epileptic activity in the occipital lobe.
Childs Nerv Syst. 2014 Feb 25.
Prevalence of resistant occipital lobe epilepsy associated
with celiac disease in children.
Dai AI1, Akcali A, Varan C, Demiryürek AT.
57
AGlanceonCeliacdisease
Prof.Dr.SaadSAlAni
4/21/2014
58. Autoimmune Dis. 2014;2014:927190. 2014 Mar 3.
Exploring T cell reactivity to gliadin in young children with newly diagnosed celiac disease.
Liu E1, McDaniel K1, Case S1, Yu L1, Gerhartz B2, Ostermann N2, Fankhauser G2, Hungerford V2, Zou
C2, Luyten M2, Seidl KJ2, Michels AW1.
Abstract
Class II major histocompatibility molecules confer disease risk in Celiac disease (CD) by presenting gliadin
peptides to CD4 T cells in the small intestine. Deamidation of gliadin peptides by tissue transglutaminase
creates immunogenic peptides presented by HLA-DQ2 and DQ8 molecules to activate proinflammatory CD4
T cells. Detecting gliadin specific T cell responses from the peripheral blood has been challenging due to low
circulating frequencies and heterogeneity in response to gliadin epitopes. We investigated the peripheral T
cell responses to alpha and gamma gliadin epitopes in young children with newly diagnosed and untreated
CD. Using peptide/MHC recombinant protein constructs, we are able to robustly stimulate CD4 T cell clones
previously derived from intestinal biopsies of CD patients. These recombinant proteins and a panel of α- and
γ-gliadin peptides were used to assess T cell responses from the peripheral blood. Proliferation assays using
peripheral blood mononuclear cells revealed more CD4 T cell responses to α-gliadin than γ-gliadin peptides
with a single deamidated α-gliadin peptide able to identify 60% of CD children. We conclude that it is possible
to detect T cell responses without a gluten challenge or in vitro stimulus other than antigen, when measuring
proliferative responses.
We conclude that it is possible to detect T cell responses without a
gluten challenge or in vitro stimulus other than antigen, when
measuring proliferative responses.
Autoimmune Dis. 2014;2014:927190. 2014 Mar 3.
Exploring T cell reactivity to gliadin in young children
with newly diagnosed celiac disease.
Liu E1, McDaniel K1, Case S1, Yu L1, Gerhartz
B2, Ostermann N2, Fankhauser G2, Hungerford V2, Zou
C2, Luyten M2, Seidl KJ2, Michels AW1.
58
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59. PLoS One. 2014 Mar 4;9(3):e90552. doi: 10.1371/journal.pone.0090552. eCollection 2014.
Coeliac patients are undiagnosed at routine upper endoscopy.
Robson K1, Alizart M1, Martin J2, Nagel R3.
Abstract
BACKGROUND AND AIMS:
Two out of three patients with Coeliac Disease (CD) in Australia are undiagnosed. This prospective clinical audit aimed to determine how many CD patients would be
undiagnosed if duodenal biopsy had only been performed if the mucosa looked abnormal or the patient presented with typical CD symptoms.
METHODS:
All eligible patients presenting for upper gastrointestinal endoscopy (OGD) in a regional center from 2004-2009 underwent prospective analysis of presenting symptoms and
duodenal biopsy. Clinical presentations were defined as either Major (diarrhea, weight loss, iron deficiency, CD family history or positive celiac antibodies- Ab) or Minor Clinical
Indicators (CI) to duodenal biopsy (atypical symptoms). Newly diagnosed CD patients had follow up celiac antibody testing.
RESULTS:
Thirty-five (1.4%) new cases of CD were identified in the 2,559 patients biopsied at upper endoscopy. Almost a quarter (23%) of cases presented with atypical symptoms. There
was an inverse relationship between presentation with Major CI's and increasing age (<16, 16-59 and >60: 100%, 81% and 50% respectively, p = 0.03); 28% of newly diagnosed
CD patients were aged over 60 years. Endoscopic appearance was a useful diagnostic tool in only 51% (18/35) of CD patients. Coeliac antibodies were positive in 34/35 CD
patients (sensitivity 97%).
CONCLUSIONS:
Almost one quarter of new cases of CD presented with atypical symptoms and half of the new cases had unremarkable duodenal mucosa. At least 10% of new cases of celiac
disease are likely to be undiagnosed at routine upper endoscopy, particularly patients over 60 years who more commonly present atypically. All new CD patients could be
identified in this study by performing pre-operative celiac antibody testing on all patients presenting for OGD and proceeding to biopsy only positive antibody patients and those
presenting with either Major CI or abnormal duodenal mucosa for an estimated cost of AUS$4,629 and AUS$3,710 respectively.
CONCLUSIONS:
Almost one quarter of new cases of CD presented with atypical
symptoms and half of the new cases had unremarkable duodenal
mucosa. At least 10% of new cases of celiac disease are likely to be
undiagnosed at routine upper endoscopy,
PLoS One. 2014 Mar 4;9(3):e90552.
Coeliac patients are undiagnosed at routine upper
endoscopy.
Robson K1, Alizart M1, Martin J2, Nagel R3.
59
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60. J Pediatr Gastroenterol Nutr. 2014 Mar 31. [Epub ahead of print]
Mucosal Healing in Children With Treated Celiac Disease.
Ghazzawi Y1, Tapia AR, Murray JA, Absah I.
Abstract
OBJECTIVES::
Limited data suggest complete mucosal healing in treated children with celiac disease (CD), but recent data from adult endoscopic biopsies have shown substantial
numbers with persistent mucosal injury. We aimed to assess the rate of mucosal healing and indications for repeat small-bowel (SB) biopsy in children with CD.
METHODS::
We retrospectively reviewed records of children (age 1-18 years) with CD who underwent a second SB biopsy. All were seen at Mayo Clinic (Rochester, Minnesota) from
January 1997 through June 2013.
RESULTS::
Forty children were identified (14 male); average age at diagnosis was 8.5 years. Indications for second small bowel (SB) biopsy were abdominal pain (n = 20), diarrhea
(n = 7), constipation (n = 5), non-celiac-related concern (n = 2), follow-up (n = 5), and persistent serology (n = 1). Average time between biopsies was 24 months (range, 4-120
months). Histology on the second biopsy showed complete healing (n = 25), intraepithelial lymphocytes (n = 9), and persistent villous atrophy (n = 6). Of these 3 patients with
partial villous atrophy, and 3 with complete villous atrophy. Persistent villous atrophy was observed in 2/20 patients with abdominal pain and 1/7 with diarrhea. All patients
with persistent constipation (n = 5) had complete resolution.
CONCLUSION::
Mucosal healing in children with CD may not be complete as previously assumed. Abdominal pain was the most common indication for repeating the SB biopsy.
Persistence of abdominal pain, diarrhea and constipation was poorly associated with persistence of mucosal injury.
CONCLUSION::
MUCOSAL HEALING IN CHILDREN WITH CD MAY NOT BE COMPLETE AS
PREVIOUSLY ASSUMED. ABDOMINAL PAIN WAS THE MOST COMMON
INDICATION FOR REPEATING THE SB BIOPSY. PERSISTENCE OF
ABDOMINAL PAIN, DIARRHEA AND CONSTIPATION WAS POORLY
ASSOCIATED WITH PERSISTENCE OF MUCOSAL INJURY.
J Pediatr Gastroenterol Nutr. 2014 Mar 31.
Mucosal Healing in Children With Treated Celiac
Disease.
Ghazzawi Y1, Tapia AR, Murray JA, Absah I.
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61. Aliment Pharmacol Ther. 2014 Mar 24. doi: 10.1111/apt.12707. [Epub ahead of print]
The effects of oats on the function of gut microflora in children with coeliac disease.
Tjellström B1, Stenhammar L, Sundqvist T, Fälth-Magnusson K, Hollén E, Magnusson KE, Norin E, Midtvedt T, Högberg L.
Abstract
BACKGROUND:
Faecal short chain fatty acids (SCFAs) are produced by the gut microflora. We have previously reported high faecal SCFA levels in children with coeliac disease (CD), indicating alteration in gut microfloral metabolism. Data accumulated
over recent decades by us and others suggest that wheat-free oats can safely be included in a gluten-free diet (GFD). However, concerns have been raised with respect to the safety of oats in a subset of coeliacs.
AIM:
To describe faecal SCFA patterns in children with newly diagnosed CD treated for 1 year with a GFD with or without oats.
METHODS:
This report is part of a randomised, double-blind study on the effect of a GFD containing oats (GFD-oats) vs. a standard GFD (GFD-std). Faecal samples were received from 34 children in the GFD-oats group and 37 in the GFD-std
group at initial diagnosis and/or after 1 year on a GFD. Faecal SCFAs were analysed.
RESULTS:
The GFD-std group had a significantly lower total faecal SCFA concentration at 12 months compared with 0 months (P < 0.05). In contrast, total SCFA in the GFD-oats group remained high after 1 year on the GFD. The children in the
GFD-oats group had significantly higher acetic acid (P < 0.05), n-butyric acid (P < 0.05) and total SCFA concentration (P < 0.01) after 1-year diet treatment compared to the GFD-std group.
CONCLUSIONS:
Our results indicate that oats do affect the gut microflora function, and that some coeliac children receiving oats may develop gut mucosal inflammation, that may present a risk for future complications.
CONCLUSIONS:
Our results indicate that oats do affect the gut microflora function, and
that some coeliac children receiving oats may develop gut mucosal
inflammation, that may present a risk for future complications.
Aliment Pharmacol Ther. 2014 Mar 24
The effects of oats on the function of gut microflora in
children with coeliac disease.
Tjellström B1, Stenhammar L, Sundqvist T, Fälth-Magnusson
K, Hollén E, Magnusson KE, Norin E, Midtvedt T, Högberg L.
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62. Dig Dis Sci. 2014 Apr 6.
Clinical Utility of Celiac Disease-Associated HLA Testing.
Pallav K1, Kabbani T, Tariq S, Vanga R, Kelly CP, Leffler DA.
Abstract
BACKGROUND:
Negative predictive value (NPV) of celiac disease (CD)-related human leukocyte antigens (HLA) DQ2 and DQ8 approaches 100 % in individual patients.
However, studies evaluating its exclusionary utility in patient groups are lacking.
AIM:
We aim to assess the performance of HLA testing when applied to patient groups with varying characteristics and propose evidence-based recommendations for its
clinical use.
METHODS:
Demographic and clinical information was recorded in patients undergoing HLA testing. Using predetermined criteria, patients were classified as CD, non-CD, or
indeterminate. Diagnostic yield of HLA testing was defined as the percentage of patients in whom CD could be excluded based on negative HLA test.
RESULTS:
Two hundred and fifty-six patients underwent testing for CD-related HLA DQ2 and DQ8. 102 (100 non-CD, 2 CD) patients tested HLA negative for a 98 % NPV and
39 % diagnostic yield. Diagnostic yield was highest (60 %) in patients with intraepithelial lymphocytosis plus normal IgA tissue transglutaminase antibody (IgA-tTG)
and lowest in patients with positive IgA-tTG plus villous atrophy (0 %). CD was diagnosed in two HLA-negative patients, who carried half of DQ2.5 trans genotype.
CONCLUSIONS:
Diagnostic yield of CD-related HLA testing varies widely depending on clinical indication. HLA testing is a practical and valuable test for most patients in whom initial
evaluation for CD is inconclusive. A negative HLA result usually obviates the need for further celiac testing including endoscopy and gluten challenge. Rarely, in
patients reported as HLA negative, half of HLA DQ2.5 (cis or trans) is sufficient for development of CD.
HLA testing is a practical and valuable test for most patients in
whom initial evaluation for CD is inconclusive.
A negative HLA result usually obviates the need for further
celiac testing including endoscopy and gluten challenge
CONCLUSIONS:
Dig Dis Sci. 2014 Apr 6.
Clinical Utility of Celiac Disease-Associated HLA Testing.
Pallav K1, Kabbani T, Tariq S, Vanga R, Kelly CP, Leffler DA.
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63. Pediatr Neurol. 2014 May;50(5):479-81. doi: 10.1016/j.pediatrneurol.2014.01.021. Epub 2014 Jan 11.
Prevalence of celiac disease in children with idiopathic epilepsy in southeast Turkey.
Işıkay S1, Kocamaz H2.
Abstract
BACKGROUND:
We examined the prevalence of celiac disease in children with idiopathic epilepsy.
METHODS:
Patients were screened for celiac disease using the immunoglobulin A anti-tissue transglutaminase antibody. Upper
gastrointestinal endoscopy and small intestinal biopsy were offered to all antibody-positive patients. The control group consisted of
400 healthy children.
RESULTS:
A total of 600 patients (332 boys, 268 girls; 8 months-15 years; 9.40 ± 4.09 years) were studied. In 38 patients, the diagnosis was
childhood partial epilepsy with occipital paroxysms. Six of the 38 patients with childhood partial epilepsy with occipital paroxysms
(15.7%) had positive immunoglobulin A anti-tissue transglutaminase antibody. The frequency of biopsy-proven celiac disease was
15.7% (6/38) among children with childhood partial epilepsy with occipital paroxysms. None of the control patients had positive
immunoglobulin A anti-tissue transglutaminase antibody results.
CONCLUSIONS:
These findings suggest that the prevalence of celiac disease in children with partial epilepsy with occipital paroxysms may be
higher than with other types of epilepsies. It may be reasonable to screen individuals with this type of epilepsy for celiac disease.
CONCLUSIONS:
These findings suggest that the prevalence of celiac disease in children
with partial epilepsy with occipital paroxysms may be higher than with
other types of epilepsies. It may be reasonable to screen individuals with
this type of epilepsy for celiac disease.
Pediatr Neurol. 2014 May;50(5):479-81.
Prevalence of celiac disease in children with idiopathic
epilepsy in southeast Turkey.
Işıkay S1, Kocamaz H2.
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64. 1. A previously healthy 8-year-old girl presents with a 3-
month history of persistent, intensely pruritic papules
distributed symmetrically on her hands, thighs, elbows,
and buttocks (Figure 1). Thorough questioning may also
reveal:
A. Negative review of systems
B. No relief from oral diphenhydramine
C. Positive family history of celiac disease
D. All of the above 64
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65. 2. This 5-year-old boy presents with similar findings for 6
months duration (Figure 2). Skin biopsy to aid in the
diagnosis of this condition should be performed:
A. For histopathology and direct
immunofluorescence of the freshest lesion
B. For histopathology and direct
immunofluorescence of the most established lesion
C. For histopathology and tissue culture
D. For histopathology, tissue culture and viral cultures 65
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66. 3. The diagnosis of dermatitis herpetiformis has been
made in this 9-year-old boy (Figure 3). The most
appropriate therapy includes:
A. Oral corticosteroids
B . Oral antihistamines and topical corticosteroids
C. Gluten-free diet and oral dapsone
D. Oral valacyclovir
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67. CONCLUSION
Ratio between patients with diagnosed
and with undiagnosed disease may be
as high as 1 : 7
Case finding by liberal use of anti-
endomysium or anti-TG2
antibodies, followed by confirmatory
jejunal biopsy, is more cost effective in
primary care than mass screening is.
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68. The diagnosis of celiac disease involves:
1. Serologic testing (generally for IgA
anti–tissue transglutaminase antibodies)
2. Upper endoscopy with biopsy for
confirmation in most patients.
http://blogs.nejm.org/now/index.php/celiac-disease/
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CONCLUSION (CONT.)
69. Patients with celiac disease should
follow a lifelong, strict gluten-free diet.
http://blogs.nejm.org/now/index.php/celiac-disease/
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CONCLUSION (CONT.)
70. Monitoring with periodic visits for
assessment of :
- Symptoms
- Growth
- Physical examination
- Adherence to the gluten-free diet.
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CONCLUSION (CONT.)