Definition
A.Celiac disease, previously known as celiac sprue, is an immune-mediated disorder triggered by ingestion of gluten, a storage protein contained in three grains: wheat, barley, and rye. Patients with celiac disease are unable to tolerate gliadin, the alcohol soluble fraction of gluten. The disease primarily affects the small intestine in those genetically susceptible. Onset of symptoms depends on the amount of gluten in the diet. Dietary nonadherence is the chief cause of persistent or recurrent symptoms. (See Appendix B: Dietary Recommendations, Gluten-Free Diet.
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B.Celiac disease is a common cause of chronic malabsorption due to injury to the small intestine resulting in loss of absorptive surface area and decrease in digestive enzymes, leading to impaired absorption of fat-soluble vitamins, iron, and potentially vitamin B12 and folic acid.
C.A substantial number of patients are misdiagnosed as having irritable bowel syndrome (IBS) for years prior to the diagnosis of celiac disease.
D.The complications from celiac disease include osteopenia, osteoporosis, infertility, short stature, delayed puberty, anemia, and gastrointestinal (GI) malignancies and non-Hodgkin’s lymphoma (NHL).
Incidence
A.Celiac disease can occur at any stage of life. Its prevalence is approximately 1% of the general population in North America. The highest incidence (5%) is noted in the sub-Saharan African population. The true incidence is undetermined due to asymptomatic disease and under diagnosis.
B.Newly diagnosed patients with celiac disease should inform their first-degree family members of their increased risk of celiac disease and the American College of Gastroenterology (ACG) recommendation for screening.
C.Celiac disease is strongly associated with autoimmune conditions, including type 1 diabetes, Addison’s disease, and thyroiditis as well as genetic syndromes, including Down syndrome, Williams syndrome, and Turner syndrome.
D.Liver disease and Crohn’s disease (CD) share widespread risk factors. Liver disorders such as autoimmune hepatitis, elevation of liver enzyme levels, primary biliary cirrhosis, nonspecific hepatitis, primary sclerosing cholangitis (PSC), and nonalcoholic fatty liver disease (NAFLD) have been reported in patients with CD.
Pathogenesis
A.Both immune and genetic factors play a role in the intestinal reaction to gluten ingestion. After the gluten fragment is ingested and absorbed, broken into fragments by tissue transglutaminase, an immune complex is formed in genetically prone individuals. The formation of the complex then stimulates both cellular and humoral immunity, leading to production of autoantibodies, which attack enterocytes causing atrophy, and inflammatory cytokines, which cause mucosal inflammation and villous atrophy. Celiac disease primarily affects the mucosal layer of the small intestine. The classic celiac lesion is noted in the proximal small intestine.
B.Hallmark histological findings include presence of intraepithelial lymphocytes in the jejunum, duodenum, or both; crypt hyperplasia; villous atrophy.
The Marsh Classification is used to describe the progressive histological stages of celiac disease. Note: Marsh 1 and Marsh 2 may be seen in sow’s and cow’s milk allergies.
Marsh 0: Preinfiltrative stage (normal).
Marsh 1: Infiltrative lesion (increased intraepithelial lymphocytes).
Marsh 2: Hyperplastic lesion (type 1 plus hyperplastic crypts).
Marsh 3: Destructive lesion (type 2 plus villous atrophy of progressively more severe degrees [termed 3a, 3b, and 3c]).
Marsh 4 (atrophic–hypoplastic): Total villous atrophy, crypt hypoplasia.
Predisposing Factors
A.Female gender.
B.Infectious diarrheal episode or other intestinal disease (e.g., rotavirus).
C.Genetic disorders:
1.Down syndrome (8%–12%).
2.Type 1 diabetes (10%).
3.Turner’s syndrome (2%–10%).
4.Williams syndrome (8.2%).
D.Strong hereditary component (10% in first-degree relatives; 2% in second-degree relatives).
E.The introduction of gluten before 4 months of age is associated with an increased development of disease.
F.Autoimmune thyroid disorders (Hashimoto thyroiditis and Graves’ disease).
G.Selective immunoglobulin A (IgA) deficiency.
Common Complaints
A.Asymptomatic.
B.Chronic diarrhea or explosive watery diarrhea.
C.Foul-smelling voluminous stools.
D.Anorexia.
E.Abdominal distention/bloating/flatulence.
F.Abdominal pain.
G.Poor weight gain or weight loss.
H.Vomiting.
I.Steatorrhea (malabsorption of ingested fat).
Other Symptoms
A.Behavioral changes, including irritability.
B.Dehydration.
C.Lethargy.
D.Constipation.
E.Failure to thrive (FTT).
F.Short stature and delayed puberty.
G.Dermatitis herpetiformis/skin disorders.
H.Arthritis.
I.Seizures.
J.Weakness and fatigue.
K.Dental enamel hypoplasia of permanent teeth.
L.Iron deficiency anemia unresponsive to treatment.
M.Bruising/bleeding tendency.
N.Osteopenia/osteoporosis.
O.Hair loss.
P.Lactose intolerance.
Q.Aphthous stomatitis.
Subjective Data
A.Review the onset, duration, course, type of symptoms, and aggravating or alleviating factors.
B.Review the patient’s weight history.
C.Evaluate family history for celiac disease or members with similar histories.
D.Review current medications and drug history, especially antibiotic, laxative, and herbal products.
E.Review bowel habits and note changes: constipation, diarrhea, anorexia, and/or food intolerance.
F.Review the patient’s tolerance to lactose products.
Physical Examination
A.Check vital signs, including height and weight. Follow serial changes in body mass index (BMI).
B.Inspect:
1.Observe general overall appearance.
2.Oral examination to evaluate glossitis, dry mucosal membranes (dehydration), and the presence of oral aphthae.
3.Examine the skin for the presence of dermatitis herpetiformis, a blistering rash involving the scalp, neck, elbows, knees, and buttocks.
4.Evaluate the abdomen for the presence of bloating and protuberant potbelly.
5.Evaluate the patient’s weight loss, including muscle wasting.
C.Auscultate:
1.Auscultate for bowel sounds.
D.Percuss abdomen.
E.Palpate:
1.Palpate the abdomen for masses, rebound tenderness, and peritoneal signs:
a.Before palpating the abdomen, ask the patient to bend his or her knees and place hands at sides to help with relaxation of the wall musculature.
2.Perform a rectal examination, including testing stool for occult blood.
Diagnostic Tests
Screening of the general population for celiac disease in asymptomatic persons is not recommended by the U.S. Preventive Services Task Force. However, screening of high-risk populations such as those patients with a positive family history is recommended.
The confirmation of a diagnosis of celiac disease is based on the combination of findings from the medical history, physical examination, serology, and upper endoscopy, with histological analysis of multiple biopsies of the duodenum. All testing should be performed while patients are following a gluten-rich diet.
A.Endoscopy for duodenal biopsies is the standard and a critical component for diagnosing celiac disease.
B.Screening and monitoring test for celiac disease (see Table 14.1 for celiac disease tests and possible results):
1.Tissue transglutaminase antibody (tTG), IgA class—95% sensitive, 95% specific:
a.Primary test ordered to screen for celiac disease.
b.Used for monitoring and evaluating the effectiveness of treatment.
c.Antibody levels should fall when gluten is removed from the diet.
2.Total IgA—IgA deficiency is more common in patients with celiac disease.
3.Anti-tTG antibodies, immunoglobulin G (IgG).
4.Deamidated gliadin peptide antibodies (anti-DGP, IgA).
5.Anti-gliadin antibodies (AGA) IgA.
6.IgA endomysial antibody (EMA)—less frequently ordered, measures same as the anti-tTG.
7.Antireticulin antibody (ARA)—rarely ordered.
8.Anti-F-actin—ordered if the disease has been diagnosed; evaluates the severity of intestinal damage. May be used for monitoring.
C.Complete blood count (CBC) and electrolytes.
D.Aspartate transaminase (AST) and alanine transaminase (ALT)—liver enzymes normalize on a gluten-free diet.
E.Prothrombin time (PT) may be prolonged with malabsorption of vitamin K.
F.C-reactive protein (CRP).
G.Erythrocyte sedimentation rate (ESR).
H.Total protein.
I.Albumin.
J.Calcium.
K.Iron, transferrin and ferritin.
L.Vitamin B12, folate levels, and vitamin D.
M.Stool culture, ova, and parasites.
N.Fecal fat.
O.Bone density (bone mineral density improves on gluten-free diet).
P.Human leukocyte antigen (HLA) haplotypes.
Q.Colonoscopy if bloody stools or symptoms of colitis.
R.Sweat test to exclude cystic fibrosis (CF).
S.Radiograph, including barium swallow study with a small bowel follow through, is usually nonspecific and is not indicated.
Differential Diagnoses
A.Celiac disease.
B.Microscopic colitis.
C.Food allergies.
D.Inflammatory bowel disease (IBD):
1.CD.
2.Ulcerative colitis (UC).
E.Immunodeficiency disorders.
F.Gastroenteritis (viral or bacterial).
G.Parasites.
H.Fungal infection.
I.IBS.
J.Malabsorption.
K.Lymphomas of the small intestine.
L.Pancreatic exocrine dysfunction.
Plan
A.Lifelong adherence to a gluten-free diet is the only accepted treatment for celiac disease:
1.Gluten-free dietary instructions should be given and reinforced.
2.Reinforce the need to read all food labels.
3.Stress that wheat-free is not the same as gluten-free.
B.The American College of Gastroenterology (ACG) recommends a referral to a registered dietitian to receive a thorough nutritional assessment and education on a gluten-free diet. A gluten-free diet should be maintained for life. Numerous apps are available for download to smartphones to aid the patient in dietary selections.
C.Monitor for nutritional deficiencies including iron, B vitamins, and vitamin D. Substitute flours are not fortified with B vitamins. Supplement with iron, folate, and vitamin B12 as needed.