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A GLANCE ON CELIAC DISEASE Prof. Dr. Saad S Al Ani Senior Pediatric Consultant Head of Pediatric Department Khorfakkan Hospital Sharjah ,UAE [email protected]
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A GLANCE ON CELIAC DISEASE
Prof. Dr. Saad S Al Ani
Senior Pediatric Consultant
Head of Pediatric Department
Khorfakkan Hospital
Sharjah ,UAE
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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
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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
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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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LIGHT-SPOTS
Celiac disease is a multifactorial, autoimmune disorder that occurs in genetically susceptible individuals
Guandalini S, Setty M. Celiac disease. Curr Opin Gastroenterol. Nov 2008;24(6):707-12.
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LIGHT-SPOTS (CONT.)
It is triggered by: - Environmental factor (gluten and related prolamins present in wheat, rye, and barley) - Autoantigen ( tissue transglutaminase)
Husby 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.
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The disease primarily affects the small intestine, where it progressively leads to flattening of the small intestinal mucosa
LIGHT-SPOTS (CONT.)
Guandalini S, Setty M. Celiac disease. Curr Opin Gastroenterol. Nov 2008;24(6):707-12.
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Celiac disease develops only after dietary exposure to the protein gluten ,which is found in wheat ,rye, and barley
LIGHT-SPOTS (CONT.)
Guandalini S, Setty M. Celiac disease. Curr Opin Gastroenterol. Nov 2008;24(6):707-12.
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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 unclearo Also common in developing countries,
particularly in North Africa and the Middle East
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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
http://blogs.nejm.org/now/index.php/celiac-disease
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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%)
http://blogs.nejm.org/now/index.php/celiac-disease
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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).
[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.
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90% of patients express the DQ2 heterodimer 7% of patients express the DQ8 heterodimer 3% of patients possess only half of the DQ2 heterodimer
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.
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CLINICAL PRESENTATION
Celiac disease (CD) : May occur without any symptomsMinimally symptomatic celiac disease is probably the most common form of the disease, especially in older children and adults
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POSSIBLE PRESENTATIONS OF CELIAC DISEASE
1. Typical: This presentation is primarily characterized by GI signs and symptoms
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POSSIBLE PRESENTATIONS OF CELIAC DISEASE (CONT.)
2. Atypical: GI signs and symptoms are minimal or absent, and various extraintestinal manifestations are present.
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3.Silent: The small intestinal mucosa is damaged, and celiac disease autoimmunity can be detected with serology; however, no symptoms are present.
POSSIBLE PRESENTATIONS OF CELIAC DISEASE (CONT.)
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4.Potential: -Patients have a positive specific autoimmune serology and may or may not be symptomatic, but the mucosa morphology is normal.
POSSIBLE PRESENTATIONS OF CELIAC DISEASE (CONT.)
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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.
POSSIBLE PRESENTATIONS OF CELIAC DISEASE (CONT.)
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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.
POSSIBLE PRESENTATIONS OF CELIAC DISEASE (CONT.)
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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.)
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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
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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
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GI symptoms in older children are typically less evident and include:
Nausea Recurrent abdominal pain Bloating Constipation Intermittent diarrhea.
GI SIGNS AND SYMPTOMS OF CELIAC DISEASE (CONT.)
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EXTRAINTESTINAL MANIFESTATIONS OF CELIAC
DISEASEThe main extraintestinal manifestations of
celiac disease are as follows: Dermatitis herpetiformis Dental enamel hypoplasia Aphthous ulcers Delayed tooth eruption
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DERMATITIS HERPETIFORMIS
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DENTAL ENAMEL HYPOPLASIA
http://www.uiowa.edu/~c090247/ENAMEL_HYPOPLASIA.pdf
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Aphthous ulcers
en.wikipedia.org/wiki/Mouth_ulcer
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Iron-deficiency anemiaShort stature and delayed pubertyChronic hepatitis and hypertransaminasemiaArthritis and arthralgia
EXTRAINTESTINAL MANIFESTATIONS OF CELIAC
DISEASE (CONT.)
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Osteopenia and osteoporosis
Neurological problems Occipital calcifications and intractable
epilepsy Gluten-induced ataxia
Psychiatric disorders Subfertility or infertility
EXTRAINTESTINAL MANIFESTATIONS OF CELIAC
DISEASE (CONT.)
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1.Autoimmune conditions Type 1 diabetes mellitus Approximately 10% of patients
have typical findings of celiac
disease on duodenal biopsy samples. Thyroiditis Alopecia
Associated diseases
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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
Associated diseases (Cont.)
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2. Genetic syndromes (Cont.)
Turner syndrome Williams syndrome
Associated diseases (Cont.)
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http://huntgatherlove.com/content/disease-civilization-or-disease-only-properly-diagnosed-civilization
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DIAGNOSISSerologic 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.
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DIAGNOSIS (CONT.)
The ultimate diagnosis of celiac disease relies on the demonstration of specific, though not pathognomonic, histopathologic abnormalities in the small bowel mucosa
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DIFFERENT GRADES OF SMALL INTESTINAL DAMAGE IN COELIAC DISEASE
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
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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)
DIAGNOSIS (CONT.)
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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
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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
CONT.
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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.
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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
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COMPLICATIONS
Lymphoma is the most common GI malignancy in the pediatric population
Predisposing conditions include: - HIV/AIDS
- Agammaglobulinemia
- Long-standing celiac disease
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Some of the researched concerning celiac disease during the early2014
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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.
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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. AbstractPURPOSE: 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.
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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.
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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. AbstractBACKGROUND 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.
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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. AbstractOBJECTIVES:: 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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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. AbstractBACKGROUND: 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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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. AbstractBACKGROUND: 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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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. AbstractBACKGROUND: 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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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
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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
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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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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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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/
CONCLUSION (CONT.)
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Patients with celiac disease should follow a lifelong, strict gluten-free diet.
http://blogs.nejm.org/now/index.php/celiac-disease/
CONCLUSION (CONT.)
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Monitoring with periodic visits for assessment of :
- Symptoms - Growth - Physical examination - Adherence to the gluten-free diet.
CONCLUSION (CONT.)
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