Celiac Disease Flashcards
What is celiac disease?
Gluten-sensitivity enteropathy
Autoimmune condition that causes INFLAMMATION OF THE SMALL BOWEL
Gluten is the trigger, but the MAIN agent it is DEAMIDATED GLUTEN –> GLIADIN
Gluten is a storage protein of wheat, rye and barley, often hidden in every day foods, medications, etc
What’s the problem if a disease attacks the small bowel?
Small bowel has many functions, mainly to ABSORB NUTRIENTS:
IRON for O2 transport on RBCs (duodenum)
B12 –> RBC/nerve function (ileum)
Vitamin K –> coagulation factors (upper)
Calcium/Vit D –> Bone formation, nerve fxn
Water absorption too!
Main pathologic feature?
VILLOUS ATROPHY/FLATTENING, Increased inflammatory cells, LARGER, DEEPER, DISTORTED Crypts (hyperplastic crypts)
Pathophysiology of Celiac
Normally, small bowel mucosa is impermeable to gluten peptides
In Celiac –> Gluten cross the subepithelial area due to TIGHT JUNCTION malfunctions
Tissue transglutaminase (TG2) acts in the subepithelail space to DEAMIDATE gluten to GLIADIN
Gliadin displays high affinity for receptors on APCs –> Gliadin is more toxic than gluten
APCs present cross-linked proteins to CD4+ T Cells and this triggers the inflammatory process –> Intraepithelial lymphocytes and myofibroblasts are activated –> T cells interact with B cells to form antibodies (auto-antibodies)
Autoantibodies –> Gliadin AutoAb; TG2 AutoAb; Endomysial AutoAb
These cause destruction!
Epidemiology
1% of general population (3 million US)
Risk factors –> 1st degree relative (5%), 2nd degree (2.5%)
Associated conditions –> Type 1 DM, Thyroid disorders, primary biliary cirrhosis, Turner’s syndrome, IgA deficiency, Down Syndrome
MOST PEOPLE GO UNDIAGNOSED –> Undiagnosed : Diagnosed = 7 : 1
Avg delay in diagnosis is 11 years! Often misdiagnosed as irritable bowel syndrome, lactose intolerance, chronic fatigue syndrome, etc
Not all present with GI symptoms!
Celiac “Iceberg”
Top of the iceberg is the minority –> identifiable disease (positive serology, inflamed small bowel, symptoms)
Middle = “silent” disease –> positive serology, inflamed small bowel, LACKS symptoms
Bottom = MAJORITY = LATENT –> positive serology, normal small bowel, LACKS symptoms
Signs and Symptoms of Celiac
Manifests at any age in any number of ways
Classical signs –> Diarrhea, cramps, bloating, flatus, vomiting, fatty stools, malabsorption/failure to thrive, anemia, osteoporosis, neurological disorders
Subclinical –> chronic fatigue, IBS, mild anemia, lab abnormalities, oral ulcers, glossitis
Atypical signs –> neuropsych, seizure, depression, arthritis, dermatitis herpetiformis, osteoporosis, hyposplenism, kidney disease, heart disease
Dermatitis Herpetiformis –> Main dermatological manifestation –> Pruritic, papules, vesicles, increased risk of folliculitis, infections, herpes, should improve with gluten-free diets
Women’s Health Issues –> delayed puberty, delayed menarche, early menopause, infertility, recurrent fetal loss, low birth weight for newborns, pre-term births
Celiac and Cancer Risk
Slightly elevated
Intestinal T-cell lymphoma is the most concerning, but extremely rare –> BUT, we treat latent and mild CD still to protect agains the development of cancer!
NHL and GI carcinomas even more rare
Improved diet decreases risk to that of normal population after 15 years
Diagnosing Celiac
Serology –> antibodies to what? GLIADIN, TG2, ENDOMYSIUM
Receptors HLA-DQ2 and DQ8 confer INCREASED AFFINITY TO GLIADIN –> 99% of patients with CD will have them, but only 30% with this genotype will have CD (sensitive, not specific)
Serology not enough for diagnosis –> positive serology or negative serology with high suspicion of disease, should get an upper endoscopy to look at the small bowel (look for scalloping and flat folds)
Appearance alone not enough –> MARSH’S CRITERIA (increased IELs, crypt hyperplasia, villous atrophy)
After diagnosis –> check for nutrient deficiencies, scan for osteoporosis (bone density scan), check thyroid
Treating Celiac
REMOVE GLUTEN FROM THE DIET –> tough to do! Lots of shit has gluten
Goals of treatment –> healing the small bowel mucosa, recovering GI and extra-intestinal fxn, preventing nutritional deficiencies, improving reproductive health, decreasing cancer risk, improving QOL
See improvements within 2-6 weeks if compliant; serologic improvement in 4-6 wks; small bowel takes long time to fully recover, if at all
Refractory Disease
Those not responsive to a diet free of gluten PROBABLY are non-compliant/don’t know
2 main categories of true refractory disease
Those that do not initially respond to the diet (Type 1) –> characterized by polyclonal populations of intraepithelial lymphocytes and can be treated by CHRONIC, LOW-DOSE Steroids
Initially respond, then become refractory (Type 2) –> MONOCLONAL population of IELs and are therefore at risk for LYMPHOMA –> weight loss, fatigue, malaise, fevers; NO RESPONSE TO STEROIDS
Ulcerative Jejunitis
Most common in MIDDLE AGED CELIAC
Presents with fatigue, anorexia, weight loss, abdominal pain, diarrhea, fever
Chronic, benign-appearing ulcers in the jejunum
Small bowel obstruction results from intestinal structuring
1/3 of patients DIE FROM COMPLICATIONS
Resection of the ulcerated areas can improve prognosis
Intestinal Lymphoma
Enteropathy associated T cell lymphoma can result from REFRACTORY or LONG STANDING, UNTREATED CELIAC
Can present similar to ulcerative jejunitis due to LARGE, ULCERATED MASSES
Complications include ASCITES (fluid in the peritoneal cavity), perforation, obstruction
10% 5 year survival :(
