Topic Editor: Robert Giles, MBBS, BPharm
Review Date: 9/28/2012
Definition
Celiac disease (CD) is an immune-mediated enteropathic condition caused by ingestion of gluten in genetically sensitive individuals. Patients with CD have chronic intestinal inflammation which leads to villous atrophy, epithelial damage, and a functionally diminished absorptive surface.
Description
- Celiac Disease (CD) is a chronic intestinal disease associated with maldigestion and malabsorption of most food nutrients
- Patients suffering from CD cannot tolerate wheat gluten and similar substances, such as barley and rye
- Clinical manifestations vary remarkably by patient age, and by duration and extent of disease
- In the classical form of celiac disease, patients present with failure to thrive and diarrhea. Some patients may have only subtle symptoms (atypical celiac disease) or may be asymptomatic (silent celiac disease)
- Depending on the symptoms present the different states of CD are:
- Clinically overt CD or Symptomatic CD: Typical gastrointestinal symptoms (diarrhea, weight loss, abdominal pain and discomfort) and signs of malabsorption. On histologic examination, there will be changes such as villous atrophy and hypertrophic crypts
- Silent CD or Asymptomatic CD: Typical histological changes, but without any evident signs and symptoms
- Atypical CD: Typical histological changes and extraintestinal findings, immunoglobulin (IgA) nephropathy and neurological symptoms
- Latent CD/potential CD: This classification includes patients who have a genetic predisposition, but have normal histology with no atrophy or crypt hyperplasia. These patients may have more subtle findings, such as increased count of Intestinal Intraepithelial Lymphocytes (IELs), and positive endomysium antibody (EMA) or a positive tissue trans-glutaminase (tTG) antibody. Such individuals may develop clinically evident CD later in life
- Refractory CD: Is present when there is persistent or recurrent malabsorptive symptoms despite strictly avoiding a gluten-free diet. On histology, these patients continue to demonstrate villous atrophy
- CD is linked with human leukocyte antigen (HLA) DQ2 and DQ8 haplotypes
- Interactions among environmental, genetic, and immunological factors lead to CD pathogenesis
- Lifelong gluten-free diet is the only effective treatment to normalize antibodies and maintain intestinal mucosa integrity
Epidemiology
Incidence/ prevalence
- The prevalence of celiac diseases is ~1% of the general population
- In the at-risk group, prevalence is 1:22 in first-degree relatives, and1:39 in second-degree relatives
Age
- The prevalence of CD is slightly higher in children than in adults (
2 yrs) - Seropositive prevalence for undetected CD was noted to be 1.2% in one large population-based study of people aged 45–76 years
- Two recent studies (2010/11) indicate prevalence at 0.8% in older adults
Gender
- In practice more females than males are diagnosed with CD. However, the underlying prevalence by gender appears equal in population studies
Race
- Celiac disease is more common in people of European descent.
- Increased incidence has been observed in the US, Africa, and Asia
Risk factors
- Atopic Dermatitis
- First degree relatives with CD
- Monozygotic twin with CD
- Autoimmune thyroiditis
- Autoimmune hepatitis
- Dermatitis Herpetiformis
- Diabetes, type 1
- Down, Turner, orWilliams syndromes
- Selective IgA deficiency
- Sjogren syndrome
Etiology
- Genetic factors and immunological responses to an environmental factor (gliadin) result in CD. It is an autoimmune disease due to inappropriate T-cell–mediated immune response directed toward consumed gluten in a genetically predisposed individual who carries either a HLA-DQ2 or HLA-DQ8 gene. Alcohol-soluble gliadin in wheat, barley, and rye products interact with the mucosa of the small intestine, which results in an inflammatory cascade characterized by infiltration of the lamina propria and the epithelium, along with chronic inflammation and villous atrophy
- The appearance of symptoms of celiac disease in children at risk is related to the timing of introduction of gluten into an infant's diet. There is continued debate and conflicting evidence as to whether introducing solids earlier or later increases the risk of developing CD
History
- Clinical manifestations vary remarkably by patient age, as well as duration and extent of disease
- Gastrointestinal symptoms in infants and children include diarrhea and abdominal distention
- Extraintestinal manifestations are less common in infants and children
- Symptoms related to malnutrition include short stature, anemia, defects in dentition, failure to thrive, or developmental delay
- Adult patients present with gastrointestinal symptoms such as abdominal pain, flatulence, weight loss, diarrhea and steatorrhea
- Extraintestinal features among adults include
- Anemia (iron, vitamin B12 and folate deficiency)
- Arthritis
- Bleeding and hematoma (vitamin K deficiency)
- Bone symptoms due to osteoporosis, vitamin D, or calcium deficiency
- Fatigue and weight loss (impaired absorption of most nutrients)
- Hormonal disorders, such as infertility and delayed menarche
- Muscle cramps (magnesium and calcium deficiency)
- Neurologic symptoms such as motor weakness, paresthesias with sensory loss, ataxia, myelopathy and seizures
- Skin disorders, including dermatitis herpetiformis
Physical Findings on examination
- Abominal findings of a protuberant and tympanic abdomen
- Anemia (clinically pallor)
- Aphthous stomatitis
- Atopic dermatitis
- Bulky, greasy stools
- Dehydration
- Dental enamel hypoplasia in up to 30% of untreated patients
- Edema
- Failure to thrive and growth delay in infants and children
- Muscle wasting may be present
- Peripheral neuropathy
Blood test findings
- Serum electrolytes and biochemistry: May see hypokalemia, hypocalcemia, hypomagnasemia, metabolic acidosis, and/or hypocholesterolemia
- Complete blood count (CBC): Decreased hemoglobin (anemia)
- Iron studies: Consistent with iron deficiency
- Prothrombin time (PT): Elevated PT suggesting malabsorption of vitamin K
- Serologic tests:
- Serologic tests are used in the diagnosis and screening of at risk populations
- Serological tests will be negative if a strictly gluten free diet has been adhered to. Patients should be encouraged to eat at least one gluten containing meal every day for up to six weeks before serological testing
- IgA Tissue Transglutaminase (IgA tTG): Recommended first line investigation
- IgA Endomysial Antibodies (IgA EMA): Recommended if IgA tTG is equivocal or unavailable (higher specificity but poorer sensitivity)
- Test for IgA deficiency if serology is negative and clinical suspicion is high
- If IgA deficiency is confirmed use IgG tTGA +/- IgG EMA
- Human leukocyte antigen(HLA) typing: Positive HLA-DQ2 or -DQ8. Testing is not recommended in the initial diagnosis of CD
- Liver function test (LFT):
- Elevated transaminases and alkaline phosphatase may be observed in autoimmune liver diseases
- Hypoalbuminemia, hypoproteinemia
Other laboratory test findings
- Stool testing: Presence of fat indicates fat malabsorption
Radiographic findings
- Radiographic barium study: Barium meal test may diagnose untreated celiac disease or exclude complications
Other diagnostic test findings
- Capsule endoscopy: May reveal macroscopic features of villous atrophy or ulceration
- Intestinal biopsy:
- Gold standard for diagnosis of CD. Perform if serology positive or suspicion still high despite negative serology
- Histologic changes indicate minor or total villous atrophy with decreased villous-to-crypt ratio and crypt hyperplasia with increased mitosis and increased plasma cell and lymphocyte infiltration in the lamina propria
- Patients should be encouraged to continue a normal (gluten containing) diet prior to biopsy
General treatment items
- The principle treatment for celiac disease is total lifelong avoidance of dietary gluten, present in wheat, rye and barley. Gluten may unknowingly be consumed in a wide variety of foods therefore referral to a dietician/nutritionist is recommended
- Patients may suffer from iron, folate, B12, calcium, and vitamin D deficiencies. Thus, they should be screened and treated with dietary supplements as needed
- Critically ill patients who present with acute celiac crisis, and patients with refractory celiac disease may also require treatment with corticosteroids (prednisone), and other immunosuppressant agents, including azathioprine and cyclosporine
- Parenteral nutrition can be considered in patients who do not respond to immunosuppressant therapy
Medications indicated with specific doses
- Prednisone: Used in refractory patients only. Initially high dose therapy before reduction to the minimal dose needed to maintain remission
Dietary or Activity restrictions
- Lifelong elimination of gluten-containing grain products such as wheat, rye, and barley
- Use of oat in celiac disease is controversial due to possible cross contamination with other cereals. The American Dietetic Association does not endorse the use of oats in celiac disease. Newly diagnosed patients should initially avoid oats, and only after complete resolution of symptoms may reintroduce it to their diet in small quantities
