Celiac Disease Flashcards
1
Q
celiac disease
A
- The cause of CD unexplained until after World War II
- Dutch pediatrician, Willem K. Dicke, noted affected children with a wasting syndrome showed clinical improvement in during periods of food shortages when bread was in short supply
- Symptoms recurred when bread was reintroduced after the war.
- Controlled experiments by Dr Dicke, et al, after WWII determined that celiac disease was triggered by ingestion of proteins found in three “toxic cereals”: wheat, barley, and rye
2
Q
epidemiology of celiac disease
A
- Until the 1990s, CD was thought to occur mainly among White Europeans
- CD is now recognized in diverse populations
- The highest prevalence is in Western Europe (0.3-1.0%) and countries to which Europeans migrated (Australia and North America)
- Prevalence rates similar to Europe have been found in Saharan Africa, and the Middle East especially Iran, Pakistan and Northern India where the HLA-DR3-DQ2 haplotype is prevalent
- Celiac disease has also been reported in Latin America (Brazil, Argentina, and Chile, with the latter including native South American Indians)
- Very rare among pure Chinese, Japanese, and Afro-Americans, and Sub-saharan Africans
3
Q
pathogenesis of celiac disease
A
- Wheat, rye, and barley contain an alcohol-extractable disease-activating protein component termed gluten
- “Gluten” is a complex mixture of hundreds of related, but distinct, proteins
- Gluten is a mixture of two main protein families: gliadin and glutenin both of which can trigger a toxic T-cell response
- Gluten proteins have extraordinary levels of proline and glutamine
- The high proline content of glutens renders these proteins resistant to proteolytic digestion by gastric, pancreatic, or brush border enzymes.
- An intact 33- amino acid peptide (residues 55-88) results from this incomplete enzymatic digestion
- Tissue transglutimase (tTG), the target auto-antigen of anti-endomycial antibodies, deaminates the glutamine residues into negatively charged glutamic acid residues increasing binding to HLA-DQ2 and DQ8
- This leads to a complex immune cascade resulting in damage to mucosa of the small bowel
4
Q
pathophysiology
A
- Genetics play a key role in pathogenesis
- CD does not develop unless a person has alleles for HLA-DQ2 or DQ8. (Intestinal antigen-presenting cells with the DQ2 or DQ8 alleles have a high affinity for negatively charged amino acids in bound proteins)
- 5-15% prevalence in first-degree relatives and 70-85% concordance in monozygotic twins
- Environmental factors also important (Twin studies, Protective effect of breast feeding, Early introduction of gluten no longer thought to be a factor, Recurrent intestinal infections (rotavirus), Lower prevalence in smokers (O.R. 0.37, p<0.006))
- There is a gradient of severity of disease from the duodenum (most severe) to the distal intestine
- Length of small intestine involved and severity of mucosal injury varies from patient to patient
- The small intestine has considerable functional reserve so the severity of the proximal mucosal changes do not necessarily correlate with the severity of clinical symptoms such as diarrhea, and malabsorption
5
Q
clinical presentation
A
- Celiac disease has a highly variable clinical expression potentially affecting multiple organ systems
- Estimates that >2/3’s have no or minimal GI symptoms (Silent and Latent CD)
- Others may present in atypical fashion such as unexplained iron deficiency, abnormal liver function, IBS
- Females predominate (2.9:1)
- The mean age of diagnosis is 46.4 years
- 20% diagnosed after age 60
- The mean delay between onset of symptoms and diagnosis is 11 years (Columbia Medical Center Celiac Center: 1138 CD patients)
6
Q
classic GI manifestations
A
- Malabsorption (Diarrhea, Flatulence/bloating/distension, Weight Loss – in their extremities, Abdominal pain, Anorexia)
- Iron deficiency anemia
- Osteopenia
7
Q
presentation
A
- Classic: (25%) - Diarrhea, steatorrhea, weight loss
- Monosymptomatic (50%) - Anemia, diarrhea, lactose intolerance
- Non-GI (25%) - Infertility, bone disease, short stature, abnormal LFTS, neurologic disease, chronic fatigue
- Acute abdomen (rare) - Intussusception, small bowel lymphoma, SB carcinoma, perforation
8
Q
evolving presentation of CD
A
- 770 patients, 599 of them female, diagnosed with CD between 1998 and 2007
- 610 pts,(79%), had symptoms when they were diagnosed.
- Most of their symptoms were not the typical diarrhea and weight loss, but rather “non-classical” issues like bloating, osteoporosis and anemia.
- Diarrhea was a symptom in just 27%.
- Classical symptoms became less common over the years, decreasing from 47% of patients during the first 10 years to 13% in the last five.
- “A high proportion of celiac disease patients did not show any gastrointestinal symptom, but they displayed extra-intestinal manifestations such as iron-deficiency anemia, unexplained osteoporosis, abnormalities of liver-function tests and recurrent miscarriages,”
- The most common illness associated with celiac was thyroid disease.
- Only half the patients had severe mucosal changes on duodenal biopsy.
- 40% of people diagnosed with celiac are overweight at their time of diagnosis.
- Only 4-5% are underweight.
9
Q
Iron deficiency resistant to oral iron
A
- Although folate and cobalamin deficiency are known complications of celiac disease, the most common nutritional anemia associated with celiac disease is iron deficiency.
- Iron deficiency anemia was reported in up to 46% of patients with subclinical celiac disease in one study, and its prevalence was higher in adults than in children
- Up to 4% of adults with newly-diagnosed iron deficiency anemia have celiac disease
- Between 5-8% of unexplained iron deficiency (no visible pathology on endoscopy) have CD
- A characteristic feature is CD-associated iron deficiency anemia that is often refractory to oral iron replacement
10
Q
cancer risk with celiac disease
A
- The Finnish register comprised of 32,439 adult celiac patients was linked with the Finnish Cancer Registry, which covers over 98% of diagnosed malignancies from 2002–2011,
- The SIRs for non-Hodgkin lymphoma (NHL; 1.94; 1.62–2.29), small-intestinal cancer (4.29; 2.83–6.24), colon cancer (1.35; 1.13–1.58), and basal cell carcinoma of the skin (1.13; 1.03–1.22) were increased, (NHL incidence: 0.0008/year, Small bowel cancer: 0.00016/year)
- The SIRs for lung cancer (0.60; 0.48–0.74), pancreatic cancer (0.73; 0.53–0.97), bladder cancer (0.53; 0.35–0.77), renal cancer (0.72; 0.51–0.99), and breast cancer (0.70; 0.62–0.79) were decreased.
11
Q
how is celiac disease diagnosed
A
Up to 98% of patients with celiac disease in the US may be undiagnosed
12
Q
under-diagnosis of CD
A
- A 2012 Mayo Clinic analysis of CD prevalence estimates roughly 1.8 million Americans have celiac disease, but around 1.4 million of them are unaware that they have it.
- The 2010 prevalence of diagnosed CD at Mayo clinic is 17/100,000, but the estimated prevalence of a positive tTG is 1%, or 1000/100,000
- Estimate 983/1000 undiagnosed = 98%
- Meanwhile, 1.6 million people in the United States are on a gluten-free diet even though they haven’t been diagnosed with celiac disease
13
Q
diagnosis of celiac disease
A
- No one test can definitively diagnose or exclude celiac disease in every individual
- Tests must be performed while the patient is on a gluten-containing diet
- IgA anti-human tissue transglutimase (tTG) is the preferred single test for the detection of CD in patients over the age of 2 (The sensitivity of the for untreated CD is about 95%, The specificity is also 95% or greater)
- Duodenal biopsies indicated for strong suspicion even in the presence of negative antibodies
- Total IgA should be checked, since selective IgA deficiency is 10-15 times more common in CD than the general population (2-3% of CD)
- Crypts are like pseudocysts
14
Q
antibody tests dependent on ingestion of gluten
A
- Antibodies directed against gliadin or its deamidated products as well as the self-antigen tTG are dependent on the ingestion of gluten.
- The reduction or cessation of dietary gluten leads to a decrease in the levels of all these celiac-associated antibodies to normal concentrations
- A weakly positive individual may become negative within weeks of strict adherence to GFD
- After 6–12 months of adhering to a GFD, 80% of subjects will test negative by serology
- By 5 years, more than 90% of those adhering to the GFD will have negative serologies
15
Q
CD serology
A
- Duodenal biopsies should be taken in all patients with positive CD serology
- Negative celiac serology does not rule out the possibility of CD, especially Marsh IIIa or milder disease
- Consider CD in patients with iron deficiency, folate deficiency, malabsorption, unexplained weight-loss, idiopathic elevation of LFTs, refractory “functional” symptoms
