Basics
Description
- Celiac disease (CD) is a systemic immune-mediated disorder caused by a permanent sensitivity to gluten in genetically susceptible individuals.
- "Gluten"¯ is the collective term for specific alcohol-soluble proteins (called prolamines) that are found in wheat, rye, and barley.
- "Classic CD"¯ refers to children who present predominately with malabsorptive symptoms including diarrhea, abdominal pain, vomiting, and abdominal distention in the setting of suboptimal growth and irritability.
- "Silent CD"¯ defines a minority of people with CD who have no identifiable symptoms but have consistent intestinal mucosal lesions and elevated serum antibodies.
- A rare, but serious, manifestation of CD is termed "celiac crisis"¯ and consists of severe watery diarrhea, electrolyte disturbances, dehydration, hypotension, and lethargy.
- Patients with positive serologic testing but normal intestinal histology are referred to as "potential CD."¯ Some, but not all, of these patients are thought to develop CD overtime on a gluten-containing diet.
Pathophysiology
- In people with CD, ingestion of gluten leads to an enteropathy of the small intestine characterized by mucosal inflammation and villous atrophy.
- Generation of unique serologic autoantibodies and development of a diverse spectrum of signs and symptoms also occur.
- Elimination of gluten, via implementation of a strict gluten-free diet (GFD), leads to intestinal healing, normalization of elevated antibody levels, and resolution of related symptoms.
Epidemiology
- CD is present in approximately 1% of the U.S. population, but only a small proportion have been diagnosed.
- Average age at diagnosis of pediatric CD in the United States is approximately 9 years old.
- Females are more affected than males.
Genetics
- There is increased prevalence in patients with 1st-degree relatives with CD (10-15%).
- HLA-DQ2 and HLA-DQ8 haplotypes are "necessary but not sufficient"¯ for CD.
- 90+% of CD patients carry HLA DQ2, 5% carry HLA-DQ8.
- High negative predictive value for negative DQ2/DQ8 testing
- Low positive predictive value (30% of general population in North America is HLA-DQ2 positive)
- Numerous other genes have been identified as increasing CD susceptibility.
- A family or personal history of autoimmune disease is also associated with CD.
Commonly Associated Conditions
- Autoimmune thyroiditis
- Type 1 diabetes mellitus
- Sj ¶gren syndrome
- Selective IgA deficiency
- Williams syndrome
- Down syndrome
- Turner syndrome
Diagnosis
- The range of signs and symptoms secondary to CD is broad. Malabsorptive symptoms such as diarrhea and weight loss are more commonly seen in early childhood. Other more subtle gastrointestinal (GI) symptoms in pediatric CD can be recurrent intermittent abdominal pain, intermittent diarrhea, constipation, and nausea.
- Extraintestinal manifestations of CD may be more prominent, especially in the older child. Atypical"¯ or "nonclassic"¯ symptoms can include the following:
- Aphthous stomatitis
- Arthritis/arthralgias
- Delayed puberty
- Dental enamel hypoplasia
- Dermatitis herpetiformis (a pruritic blistering symmetric rash)
- Elevated transaminases
- Elevated pancreatic enzymes
- Fatigue
- Iron deficiency anemia
- Neuropsychiatric symptoms (including headaches, cognitive impairment, neuropathy, epilepsy and ataxia)
- Osteopenia
- Short stature
- Thyroiditis
- Vitamin deficiencies
- Awareness of the wide range of clinical presentation and the high prevalence of CD coupled with a careful history and physical exam is essential to making the diagnosis of CD.
- Obtaining celiac-specific serologic markers is also integral to making the diagnosis.
- Currently, small bowel biopsies remain the gold standard and are required for confirmation of CD.
- Treatment with a GFD should not be initiated before confirmation of disease.
History
- Review the patient's stooling pattern as well as symptoms of abdominal pain, nausea/ vomiting, low appetite, and bloating/distension.
- Investigate extraintestinal manifestations of CD including fatigue, arthralgias, recurrent oral sores, unusual rashes, and headaches.
- Attention to family history of CD, long-standing undiagnosed GI symptoms, and autoimmune diseases
Physical Exam
- Focus on growth patterns:
- Some patients may have short stature or suboptimal weight gain as the only manifestation of CD.
- Many children with CD have normal growth or even overweight status.
- Assess pubertal development.
- Although patients with classic CD often have a distended abdomen with wasted buttocks, most patients do not have clear physical signs of CD.
- Observe for dental enamel defects, oral sores, or dermatitis herpetiformis.
Diagnostic Tests & Interpretation
All evaluation for CD should be done while a patient is consuming gluten regularly. Testing for the disease while on a GFD can lead to false-negative results. Both serologic testing and histopathologic changes can normalize with gluten removal.
Initial Lab Tests
- Total IgA quantification is essential. IgA deficiency is associated with CD and can contribute to false-negative results.
- Celiac serologic markers with high specificity and sensitivity
- Tissue transglutaminase antibody IgA (tTG IgA): best general screening test
- Endomysial antibody IgA (EMA IgA): more subjective and expensive than tTG IgA
- Celiac serologic markers with low specificity and sensitivity
- Antigliadin IgA and IgG (AGA IgA, AGA IgG) are NOT recommended for screening.
- New serologic markers: Deamidated gliadin peptide antibody IgG is a newer test with high sensitivity and specificity that may be useful to obtain in cases of IgA deficiency.
- Nonspecific testing to screen for associated nutritional deficiencies
- Vitamin levels
- CBC
- Iron panel
- Bone densitometry
- Tests of absorption (fecal fat, D-xylose uptake)
Endoscopic Evaluation
- Small bowel biopsies obtained by esophagogastroduodenoscopy (EGD) is required in most cases to confirm CD.
- It is recommended to obtain multiple small bowel biopsies during endoscopy due to the patchy distribution of lesions.
- The duodenal bulb, in addition to the duodenum, should be biopsied.
- The current recommendation is to obtain a small bowel biopsy on a gluten-containing diet.
Pathologic Findings
CD has a number of cardinal histopathologic findings on small bowel biopsy:
- Increased intraepithelial lymphocytosis
- Villous atrophy (partial, subtotal, or total)
- Crypt hyperplasia
- Infiltration of lamina propria with excess lymphocytes (CD4 T cells mainly) and plasma cells
Differential Diagnosis
- Presumed infectious causes:
- Giardiasis
- Rotavirus, parasites
- Chronic gastroenteritis
- Postenteritis enteropathy
- Intractable diarrhea of infancy
- Tropical sprue
- Intestinal bacterial overgrowth
- Immunodeficiency syndromes (HIV)
- Presumed noninfectious:
- Milk or soy protein intolerance
- Protein-calorie malnutrition
- Eosinophilic gastroenteritis
- Autoimmune enteropathy
- Graft-versus-host disease
- Collagenous sprue
- Peptic duodenitis
- Immunodeficiency syndromes
- Crohn disease
- Congenital enteropathies (microvillus inclusion disease, tufting enteropathy)
- Bowel ischemia
- Radiation
- Chemotherapy
Treatment
- Current treatment of CD consists of a strict, lifelong gluten-free diet (GFD).
- Elimination of all wheat, rye, and barley is essential, with close care to avoid cross-contamination during the preparation and serving of food.
- Oats, unless specifically certified as gluten free, should also be avoided, as they are standardly contaminated with wheat.
- Consultation with a specialized dietitian with expertise in the GFD is recommended for all cases.
Medication
There are no medications currently available to treat CD. However, people on a gluten-free diet should take a multivitamin. It is imperative to confirm that all medications are also GF.
It may be appropriate to consider recommending the following:
- Calcium and vitamin D
- Iron for iron deficiency anemia
- In patients with symptoms of lactose intolerance, lactase enzyme replacement
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Close clinical monitoring of patients with newly diagnosed CD is important. Patients should be seen several times within the 1st year of diagnosis to monitor symptom response to the GFD, adherence to the GFD, and patient/family coping with the lifestyle changes associated with the GFD. After the 1st year, yearly follow-up is recommended.
- Special attention should be paid to growth at each visit. Catch-up growth is typically noted within the 1st year on the GFD.
- Monitor for other autoimmune disease, especially thyroiditis and diabetes mellitus, with targeted history and exam.
- Assessing for adequate calcium intake and vitamin D deficiency is also recommended to optimize bone health. Bone density in children with CD typically normalizes on a GFD. Bone densitometry can be considered but, in most cases, is recommended after a year on a GFD.
- tTG levels typically normalize within a year on the GFD and, coupled with clinical status, can be helpful in assessing response to the GFD. Obtaining a tTG IgA is recommended after 6 months on a GFD and then on a yearly basis.
- Repeat endoscopic evaluation is not currently recommended in patients who respond clinically to a GFD and who have normalization of tTG IgA. However, repeat endoscopic evaluation in cases of clinical nonresponse to the GFD or persistent serologic elevation should be considered.
Prognosis
In patients with CD, it is strongly recommended to remain on a GFD for life. In patients on a strict GFD, there is lower risk for malignancies and other complications associated with CD. However, increased risk of other autoimmune diseases seems to persist.
Complications
- Adults with CD have increased risk of intestinal lymphoma and other GI malignancies. This risk is magnified in suboptimally treated CD.
- Other complications include the following:
- Osteopenia/osteoporosis
- Infertility
- Development of other autoimmune disorders.
- Nutritional deficiencies
- Refractory CD is a diagnosis of exclusion that is defined by persistent symptoms and villous atrophy on a strict GFD.
- Refractory CD is rare in children but affects up to 5% of adults with CD, most of whom harbor an abnormal clonal intraepithelial T-lymphocyte population
- Complications of refractory sprue: "Cryptogenic enteropathy-associated T-cell lymphoma,"¯ ulcerative jejunoileitis, and collagenous sprue.
- Treatment: immunosuppressives including corticosteroids, azathioprine, cyclosporine, and total parenteral nutrition, in addition to GFD
Additional Reading
- Fasano A, Catassi C. Clinical practice. Celiac disease. N Engl J Med. 2012;367(25):2419-2426. [View Abstract]
- Hill ID, Dirks M, Liptak G, et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2005;40(1):1-19. [View Abstract]
- Leffler DA, Schuppan D. Update on serologic testing in celiac disease. Am J Gastroenterol. 2010;105(12):2520-2524. [View Abstract]
- Olsson C, Hernell O, H ¶rnell A, et al. Difference in celiac disease risk between Swedish birth cohorts suggests an opportunity for primary prevention. Pediatrics. 2008;122(3):528-534. [View Abstract]
Codes
ICD09
ICD10
SNOMED
- 396331005 Celiac disease (disorder)
- 197478000 Congenital celiac disease (disorder)
FAQ
- Q: Is biopsy confirmation necessary if my patient is already doing better on a GFD?
- A: Yes. Referral to a pediatric gastroenterologist who can obtain small bowel biopsy is recommended in almost all cases of suspected pediatric CD.
- Q: Are oats included in the gluten-containing cereal group?
- A: Strictly speaking, wheat, rye, and barley are more closely related in their development from the primitive grains than are oat, rice, corn, sorghum, and millets, which do not activate CD. Gluten-free means a diet devoid of all wheat, rye, and barley. Several studies have shown that ingestion of oats did not cause histologic or clinical deterioration. However, it is important to use a brand of oats that has been tested and demonstrated to not be contaminated with gluten.