Presentation and Evaluation of Celiac Disease
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1 Presentation and Evaluation of Celiac Disease C. CUFFARI, MD, FRCPC, FACG, AGAF The Johns Hopkins Hospital Baltimore MD.
2 Main Points Celiac disease is not rare (1 in ) It can present in many ways: IBS or non-specific GI symptoms, iron deficiency anemia, depression, osteopenic bone disease, abnormal LFTs, dyspepsia, DH, recurrent miscarriages, microscopic colitis Associated with autoimmune diseases Screening with ttg IgA is best Confirm diagnosis with duodenal biopsy Cornerstone of treatment is avoidance of gluten Prognosis overall appears very good
3 Celiac Disease: Overview Gluten Induced Enteropathy AKA: Celiac Sprue, Non-tropical sprue Permanent, genetically determined auto-immune illness initiated by cereal prolamines (gluten/gliadin); antibody to ttg (screening) Mucosal Lesion causes intestinal malabsorption. Biopsy of small Intestine is gold standard for diagnosis Histologic and clinical improvement on gluten withdrawal.
4 Celiac Disease: Prevalence USA (OLMSTEAD Co) 1/4,600 N. IRELAND 1/122 ARGENTINA 1/170 EUROPE 1/ USA (BALTIMORE) 1/250
5 Genetic Factors: HLA + Other Genes Plus Environmental Factors Increased frequency of HLA haplotypes DR3-DQ2 DR5/7-DQ2 DR4-DQ8 70% concordance in MZ twins 10-15% prevalence in first degree relatives Other factors involved since most with these haplotypes do not get celiac sprue Other genetic factors - genes on chromosomes 5, 16,?6 Environmental factors - Infectious agents Cytokines released during infection - Affecting APCs (e.g., dendritic cells) Cross-reactive amino acid sequences - Adenovirus, H. pylori SC
6 Celiac Disease Pathogenesis Gluten: Prolamin: albumin globulin gliadin glutinin rye, barley, oats* Olsen. Gastroenterology 1999;A914
7 Celiac Disease Genetic basis (DQ2/DQ8) Abnormal Permeability Gluten ingestion T-cell mediated Antibodies
8 Pathogenesis of Celiac Disease Kagnoff, J Clin Invest, 117:41, 2007
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13 PRESENTATION OF CELIAC DISEASE Anemia (13%) Diarrhea (36%) Diarrhea Incidental Endoscopy Screening Bone Disease Anemia Other Bone disease (5%) Screening (8%) Incidental at EGD (4%) PG
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15 CAUSES OF SCALLOPING OF DUODENAL MUCOSA Tropical sprue HIV enteropathy Opportunistic infections Giardiasis Amyloid Crohn s disease Systemic mastocytosis
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17 Changing Picture of Celiac Disease Classical form less prevalent now Other presentations are being increasingly recognized: Irritable Bowel Syndrome Anemia Osteoporosis Obstetrical problems Neuropsychiatric manifestations Related autoimmune conditions Microscopic colitis
18 Celiac Disease: Asymptomatic and Latent Forms Asymptomatic: - No apparent symptoms or associated diseases May be first or second degree relatives of Patients with biopsy proven celiac disease picked up at mass screenings Latent: Positive serology Negative small bowel biopsies Positive biopsies later in life.
19 Ventura et al. Gastroenterology 2009;117:297 Celiac Disease: Prevalence of Autoimmune Disease N (909) Type I Diabetes 3.9% Dermatitis Herpet. 3.5% Epilepsy 1.5% Alopecia 1.3% CTD 1.3% Thyroiditis 1.2% AIH 1.1% psoriasis 0.9%
20 Case: Silent Celiac Disease in Patients with Co-morbid Conditions 12 year old female with Type 1 diabetes, no GI symptoms and a positive serology for celiac disease: Endoscopy: Duodenitis Scalloping of the folds Biopsy: To confirm the diagnosis of celiac disease in patients with comorbid conditions and nonspecific duodenitis.
21 Case: Associated Illnesses 20 year old patient with Diabetes: bone pain muscle weakness Osteomalacia Pseudofractures High alk. phosphatase Low Vitamin D
22 Clinical Presentations: Musculoskeletal Enamel defects of permanent teeth Osteopenia/Osteoporosis Osteomalacia, rickets Related autoimmune conditions RA, SLE, Sjogren s syndrome, psoriasis Idiopathic short stature Delayed bone age Clubbing SC
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24 Associated Hepatobiliary Conditions Primary sclerosing cholangitis Autoimmune cholangitis Primary biliary cirrhosis Elevated transaminases (aminotransferases) Evaluation of unexplained elevated AST, ALT should include celiac screening Ludvugsson et al, Clin Gastroenterol Hepatol, 5:63, 2007 SC
25 Clinical Presentations: Neuropsychiatric Hyperactivity - attention deficit disorder Irritability Cognitive deficits Cerebral calcifications Fatigue Seizures Peripheral neuropathy Ataxia Myelopathy Schizophrenia Depression Migraines SC
26 Other Associated Conditions Oral aphthae Microscopic colitis Down s syndrome Turner s syndrome IgA deficiency IgA nephropathy Many others postulated,? real SC
27 ROLE OF SEROLOGICAL TESTING IN CELIAC DISEASE Triage patients for biopsy Monitoring adherence to diet Screening high risk groups
28 Serologic Tests Test Sensitivity Specificity AGA IgA < 80% in 50% > 80% in most AGA IgG variable non-specific EMA IgA 96-97% ME, 90% HUV 100% ME, HUV ttg IgA 90% GP, 98%HR 95% GP, 98% HR ttg IgG 40% 98% SC Rostom et al, Gastroenterology, 128:S38, 2005
29 SELECTIVE IgA DEFICIENCY Occurs in 1.5%-2.5% of celiac patients X general population Lack EMA, anti-ttg, IgA AGA Elevated IgG antibodies (AGA, EMA, anti-ttg) Identical clinically
30 Relatives: Who and How to Screen? Index case has proven celiac disease Relative is interested in being screened Relative is willing to undergo diagnostic testing and treatment Relative will derive benefit from treatment If relative is symptomatic, approach is diagnostic not screening SC
31 CELIAC DISEASE Common (high risk groups) Increased rate of diagnosis (use of serologies IgA, EMA, ttg (IgA, IgG) IgA deficient- ttg, anti-gliadins (IgG) DQ2DQ8 Easy to treat? surveillance: compliance nutritional co-morbidities
32 REASONS FOR CASE SEEKING AND STRICT ADHERENCE TO THE DIET Prevention of ill health anemia, osteoporosis Elderly with CD are often extremely ill Increased mortality Vs general population Increased incidence of malignancy Occurrence of autoimmune disorders
33 Refractory Celiac Disease 80-90% ingesting gluten or wrong Dx Type 1 refractory: Respond to oral or topical steroids (budesonide or beclamethasone) Type 2: Pre-malignant condition:50% develop Enteropathy Associated T-cell Lymphoma (ETAL) within 5 yrs of Dx 3X Rel Risk in un-rxed CD for ETAL CD on GFD >5yrs:No incr. risk ETAL or GI Cancer Ulcerative Jejuno-Ileitis (? Relation to ETAL) (Bayless, et al. NEJM 1967) ML
34 Prognosis Generally good prognosis Small increase in death rate returns to baseline in first few years after diagnosis Increased mortality in malabsorptive presentations, if diagnosis delayed, and in those poorly compliant with diet Main cause of excess death is lymphoma Ulcerative jejuno-ileitis, can be fatal
35 Summary Celiac disease is not rare (1 in ) It can present in many ways: Iron deficiency anemia, depression, osteopenic bone disease, abnormal LFTs, non-specific or IBS-like GI symptoms, dyspepsia, DH, recurrent miscarriages, microscopic colitis Associated with autoimmune diseases Screening with ttg IgA is best Confirm diagnosis with duodenal biopsy Cornerstone of treatment is avoidance of gluten Prognosis overall appears very good
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