Diagnosis and Management of Celiac Disease

INTRODUCTION The American College of Gastroenterology is releasing an update to their guidelines on the diagnosis and management of celiac disease (CD) (1). Changes to the guidelines include an updated diagnostic algorithm, screening guidance, management suggestions, dietary/treatment recommendations, and vaccination advice. We offer a case-based approach to highlight some of these important updates. DIAGNOSIS Mrs B is a 39-year-old woman with a history of appendectomy who presented to our gastroenterology clinic for positive celiac serology. She was screened for CD using a case-finding strategy after her sister was diagnosed (Recommendation 7A). She had no gastrointestinal symptoms and was following a regular diet. Her health history revealed no associated conditions such as iron deficiency anemia, irritable bowel syndrome, bone fractures, elevated liver enzymes, or thyroid disease. Her tissue transglutaminase IgA (TTG IgA) antibody was >250 units (normal range 0–14). At her initial clinic visit, we recommended she undergo esophagogastroduodenoscopy with duodenal biopsies (Recommendation 1A) to confirm her diagnosis. Patients with negative serology but a high pretest probability of disease should also be referred for duodenal biopsy (i.e., if this patient had unexplained iron deficiency or malabsorption symptoms). The patient's esophagogastroduodenoscopy revealed decreased folds and scalloping in her duodenum (Figures 1a and 2a). Biopsies were obtained from the bulb (2) and distal duodenum (4) because histological changes in CD can be patchy (2,3). One piece of tissue was obtained per pass in an attempt to improve specimen orientation, and water immersion was performed to inspect the villi (Figure 2a). Pathology showed duodenal mucosa with intraepithelial lymphocytosis, crypt hyperplasia, and villous blunting morphologically consistent with CD (Figure 3a). She was instructed to follow a strict gluten-free diet (GFD) and was referred to our dietitian for education.Figure 1.: Before and after endoscopic appearance in a clinical case patient. (a) Before. Gross endoscopic appearance at the time of diagnosis revealing scalloped mucosa and flattened villi. (b) After. Gross endoscopic appearance after 2 years on gluten-free diet revealing a normal duodenum.Figure 2.: Before and after villi appearance in a clinical case patient. (a) Before. Water immersion at the time of diagnosis showing a lack of villi. (b) After. Water immersion after 2 years on gluten-free diet showing healthy villi.Figure 3.: Pathology. (a) Before. Histopathology slide at the time of diagnosis with hematoxylin and eosin (H&E) stain. Pathology images by Erica Savage, MD, Cleveland Clinic. (b) After. Histopathology slide at the time of follow-up with H&E stain. Pathology images by Erica Savage, MD, Cleveland Clinic.PATIENT MONITORING Physician and dietitian care with assessments of health, dietary compliance, serology status, associated conditions, and complications coupled with appropriate preventive care measures form the cornerstones of CD patient monitoring in the office. Mrs B was followed with periodic clinic visits with multiple in the first year after diagnosis and regular appointments thereafter. General goals of monitoring include control of symptoms, facilitation of adherence to the GFD (she engaged in dietitian follow-up), monitoring for seroconversion, and assessment for complications and comorbidities of CD (Table 1).Table 1.: Checklist for follow-up careIn her introductory visit with the dietitian, she received instruction on the lifelong GFD. This visit included a systematic discussion of gluten-free foods and how to incorporate them into a well-balanced diet. The dietitian reviewed the safety of gluten-free oats and their permissibility in her diet as per guidelines (Recommendation 5) (4). Initially, she was overwhelmed with the lifestyle overhaul and the downstream personal, family, professional, and social effects. She asked for tips to avoid gluten cross-contact and methods to test whether contamination occurs because she did not experience symptoms. These new guidelines currently do not support the routine use of a gluten detection device to sample food or biospecimens (urine or stool) given insufficient evidence that these technologies enhance dietary adherence, improve quality of life, nor distinguish between significant and trivial exposures (Recommendation 3) (5). A dietitian interview remains the standard of care for assessing dietary adherence, and she was encouraged to continue dietitian follow-up for questions and concerns. Follow-up gastroenterology visits focused on overall health, disease monitoring, and preventive care. She inquired about the use of vitamins or other supplements such as probiotics to aid in the management of her CD. At this time, no adjuvant therapies are recommended beyond the GFD. Although the microbiome may play an important role in CD, overall, there is insufficient evidence for or against the use of probiotics (Recommendation 4). Issues with supplements include lack of regulation and possibility of gluten contamination which should be considered (6). Supplements should be recommended if micronutrient deficiencies are identified. Tissue transglutaminase was monitored every 3 months and then 6 months, and she seroconverted transitioning from positive to negative serology over time (Figure 4). We surveyed for comorbid autoimmune diseases and checked thyroid-stimulating hormone and liver enzymes, which were normal. Baseline micronutrients that can be low in CD were checked; vitamin B12, zinc, folate, ferritin, and vitamin D were normal. A dual-energy x-ray absorptiometry scan was performed to assess her bone health and was within normal limits for age. We discussed the increased risk of pneumococcal infections in patients with CD and the benefit of vaccination given its safety and efficacy (Recommendation 6) (7). She received Prevnar 20 during one of her gastroenterology clinic visits in addition to yearly influenza vaccinations and COVID-19 vaccines per our clinic's recommendations.Figure 4.: Serology progression over time. Trajectory from the clinical case in the text.INTESTINAL HEALING Normal CD serology levels and symptoms do not consistently predict intestinal healing (8). The healing rate is variable with a median time of 3 years, and a 1-year biopsy is too soon for many (8). We reviewed the slight increase in risk of lymphoproliferative disorders and bone disease in CD with persistent atrophy and elected for a follow-up biopsy after 2 years on the GFD (Recommendation 2). (9,10) The duodenum was normal endoscopically and showed recovery of villi on histology (Figures 1b, 2b, and 3b). Without a change in symptoms or serology, she will not need further duodenal biopsies and her prognosis is excellent. Intestinal healing is the overall goal of GFD therapy; now that this important clinical end point was achieved, we turned our attention to those surrounding the patient. SCREENING FAMILY MEMBERS First-degree family members should strongly consider screening. We advocate for this given the increased frequency of CD, which grows when multiple family members are affected (11,12). Our patient has 2 siblings—her sister was the index case and the other sibling was subsequently screened and diagnosed using a case-finding strategy per guidelines (Recommendation 7A). She also has 4 children who qualify for evaluation. All of her kids were screened with TTG IgA, including the child younger than 2 years (Recommendation 8A). The TTG IgA is the recommended serology test for screening patients, regardless of their age (13). Her 5-year-old son had a TTG IgA level >10× upper limit of normal and a positive endomysial antibody in a successive sample. After discussion with the pediatrician about risks and benefits, a nonbiopsy diagnosis was elected given the high degree of elevation and positive combination testing (Recommendation 1B) (14). Her son had mild growth delay and iron deficiency, which quickly resolved with GFD and oral iron supplementation. For her other children who screened negative, they may consider repeat serologic testing in the future or genetic testing to understand whether they carry a permissive genotype. The strategy of family member screening was responsible for Mrs B's diagnosis and helped identify multiple relatives with CD. CONCLUSION CD, although a common disease, is often misdiagnosed, underdiagnosed, or not managed at all after diagnosis. These updated guidelines if followed correctly should improve these shortcomings. Although no treatment outside the GFD is currently recommended, we are hopeful that technology and therapy currently under research will be incorporated into future guidelines. CONFLICTS OF INTEREST Guarantor of the article: Alberto Rubio-Tapia, MD. Specific author contributions: Writing of the initial draft of the manuscript: C.J.K. and D.A.; editing of the manuscript: C.J.K., D.A., and A.R.-T.; supervision and guarantor: A.R.-T. Financial support: None to report. Potential competing interests: None to report.