What is the appropriate workup for celiac disease (CD) in a patient with anemia?

From the Guidelines

A celiac disease workup for anemia should begin with serologic testing, specifically anti-tissue transglutaminase (tTG) IgA antibodies and total serum IgA, as recommended by recent guidelines 1. These tests should be performed while the patient is on a gluten-containing diet to avoid false negatives. If tTG IgA is positive or if the patient has IgA deficiency (which occurs in about 2-3% of celiac patients), additional testing with deamidated gliadin peptide (DGP) IgG antibodies is recommended. Patients with positive serologic tests should be referred for an upper endoscopy with multiple duodenal biopsies to confirm the diagnosis. It's essential to note that patients should continue consuming gluten until the biopsy is completed. For anemia evaluation in suspected celiac disease, a complete blood count, iron studies (ferritin, iron, TIBC), vitamin B12, and folate levels should be checked, as celiac disease can cause malabsorption of these nutrients. HLA-DQ2 and DQ8 genetic testing may be helpful in certain cases, particularly when serology results are equivocal. This comprehensive approach is necessary because celiac disease is an autoimmune condition triggered by gluten that damages intestinal villi, leading to malabsorption of nutrients including iron, which commonly presents as iron deficiency anemia. Key considerations in the workup and management include:

• The importance of a gluten-containing diet during diagnostic testing to ensure accurate serology and histology results 1
• The potential for seronegative celiac disease, particularly in older patients or those with IgA deficiency, which may require alternative diagnostic approaches 1
• The role of clinical chemistry analysis and dietetic evaluation in monitoring patients with established celiac disease on a gluten-free diet 1
• The need for a holistic clinical assessment, including consideration of quality of life and potential complications, in managing celiac disease 1

From the Research

Celiac Disease Workup for Anemia

• Celiac disease is an immune-mediated disorder that can cause anemia, among other symptoms, in genetically susceptible individuals exposed to gluten-containing grains 2.
• The condition can develop at any age and presents with a variety of manifestations, including diarrhea, weight loss, abdominal pain, bloating, malabsorption, and failure to thrive 2.
• Adult patients with celiac disease often present with nonclassic symptoms, such as anemia, osteoporosis, transaminitis, and recurrent miscarriage 2.

Diagnostic Tests for Celiac Disease

• Immunoglobulin A tissue transglutaminase serologic testing is the recommended initial screening for all age groups 2, 3.
• Esophagogastroduodenoscopy with small bowel biopsy is recommended to confirm the diagnosis in most patients, including those with a negative serologic test for whom clinical suspicion of celiac disease persists 2.
• Genetic testing for human leukocyte antigen alleles DQ2 or DQ8 may be performed in select cases 2.
• Serum immunoglobulin A antibodies to tissue transglutaminase (tTG-ab) have been reported to correlate closely with IgA antiendomysial antibodies (EMA) and are highly sensitive and specific markers of celiac disease 3.

Laboratory Testing for Celiac Disease

• Laboratory testing, in particular TTG-IgA, plays a central role in the diagnosis and has an accuracy comparable to histology 4.
• Diagnostic algorithms utilizing laboratory testing are critical for the development of novel strategies to improve diagnosis 4.
• Tests for serum transglutaminase and endomysial antibodies do not detect most patients with celiac disease and persistent villous atrophy on gluten-free diets 5.

Monitoring Patients with Celiac Disease

• The clinical follow-up of celiac disease usually includes a repeat TTG-IgA examination 4.
• Patients with celiac disease who do not respond to a gluten-free diet should have the accuracy of the diagnosis confirmed, have their diet reassessed, and be evaluated for coexisting conditions 2.
• A subgroup of patients with celiac disease on a gluten-free diet has complete normalization of intestinal biopsies, intestinal permeability defects, and antibody levels, while others may have abnormal TTG antibodies and intestinal permeability with zonulin levels that correlate with IP 6.