Celiac Disease Research Paper
Abstract
Celiac disease is an immune-mediated disorder triggered by ingesting gluten in genetically predisposed individuals. This paper examines the pathophysiology, diagnosis, and treatment of celiac disease through a review of current literature. A comprehensive understanding of celiac disease is important for healthcare professionals to appropriately diagnose and manage this condition.
Introduction
Celiac disease is a chronic immune-mediated disorder affecting the small intestine that occurs in genetically predisposed individuals (Lebwohl et al., 2018). Upon exposure to gluten, a protein found in wheat, barley, and rye, individuals with celiac disease mount an inappropriate immune response that results in damage to the intestinal villi – small fingerlike projections that line the small intestine (Gujral et al., 2012). This ultimately leads to difficulties in the absorption of nutrients from food. While celiac disease was previously thought to be a rare disorder, it is now recognized as one of the most common genetic diseases affecting approximately 1% of the global population (Rubio-Tapia et al., 2013). The only available treatment is a lifelong gluten-free diet (Lebwohl et al., 2018).
Pathophysiology
Celiac disease is strongly associated with certain human leukocyte antigen (HLA) class II genes, specifically HLA-DQ2 and HLA-DQ8. Around 95% of individuals with celiac disease carry one or both of these HLA genotypes (van Heel & West, 2006). The presence of these HLA genes allows gluten peptides to activate an immune response. When individuals with celiac disease ingest gluten, peptides from wheat gliadin and related proteins trigger an inflammatory reaction in the small intestine (Gujral et al., 2012). This leads to an influx of inflammatory cells such as T lymphocytes into the lamina propria, or connective tissue layer, of the small intestine.
Activated T cells produce inflammatory cytokines like interferon-gamma that mediate the intestinal damage characteristic of celiac disease. This results in flattening of the intestinal villi due to increased apoptosis of villous enterocytes and crypt hyperplasia. Crypt hyperplasia occurs when the intestinal stem cells at the base of intestinal glands, or crypts, divide abnormally fast in an attempt to replace lost enterocytes, or absorptive cells of the small intestine (Duerksen, 2012). Ultimately, the intestinal damage impairs the absorption of nutrients due to loss of surface area in the small intestine. A number of other conditions and symptoms can also occur in celiac disease as a result of malabsorption of vitamins, minerals, and nutrients.
Diagnosis
There is currently no definitive diagnostic biomarker or test for celiac disease. The diagnosis involves a combination of clinical presentation, serology testing, small bowel biopsy, and response to a gluten-free diet (Lebwohl et al., 2018). Symptoms of celiac disease can vary greatly but commonly include diarrhea, abdominal pain, bloating, fatigue, weight loss, and malnutrition. Symptoms alone are not sufficient for diagnosis as they are non-specific and can be present in many other disorders.
The first-line screening tests are anti-tissue transglutaminase antibody (anti-tTG) and anti-endomysial antibody (EMA) testing via a blood sample. These antibodies are highly sensitive and specific markers that detect an immune response to gluten (Lebwohl et al., 2018; Duerksen, 2012). If antibody levels are elevated, the patient is considered screening positive and requires endoscopy with small bowel biopsy for confirmation. The biopsy specimen is evaluated by a pathologist for villous atrophy and increased intraepithelial lymphocytes – pathological changes considered diagnostic of celiac disease. A few rare patients may have negative serology but biopsy confirmation of celiac disease.
Finally, the gold standard for diagnosis is the demonstration of clinical and serological response as well as histologic recovery when placed on a strict lifelong gluten-free diet (Lebwohl et al., 2018). Resolution of symptoms and normalization of antibody levels and intestinal architecture confirms the diagnosis. Serial antibody monitoring also allows assessment of dietary compliance and disease monitoring over time.
Treatment
The mainstay and only available treatment for celiac disease is lifelong adherence to a strict gluten-free diet (Lebwohl et al., 2018; Duerksen, 2012). This involves strict avoidance of all sources of wheat, barley, rye, and anything derived from these grains for the duration of a patient’s life. Gluten is ubiquitous and can be present in many seemingly unlikely food items, medications, and even cosmetics, making the diet challenging but necessary to implement (Aziz et al., 2011).
Within months of commencing a gluten-free diet, patients typically experience substantial symptom resolution and feel markedly improved in general health and wellbeing. Serial monitoring of anti-tTG and EMA antibody levels also usually shows them decreasing into the normal range within 6-12 months, indicating reduction of immune stimulation and intestinal healing. Repeat small bowel biopsy after 1-2 years commonly demonstrates histologic recovery with near complete or complete remission of pathological features (Lebwohl et al., 2018).
Adherence to a lifelong gluten-free diet is the foundation of celiac disease treatment and results in recovery from malabsorption, improved quality of life, reduced complications and mortality rates, and prevention of long-term sequelae such as refractory sprue, ulcerative jejunitis, enteropathy-associated T-cell lymphoma, and various nutritional deficiencies (Lebwohl et al. 2018; Aziz et al., 2011; Duerksen, 2012). Dietetic assessment and nutrition counseling provide crucial support for patients adapting to this medically necessary but demanding lifestyle change.
Conclusion
Celiac disease is a common autoimmune disorder triggered by ingestion of gluten in genetically predisposed individuals. The hallmark pathological finding is villous atrophy of the small intestine. While diagnostic challenges remain, a combination of clinical presentation, serological testing, small bowel biopsy findings, and a positive therapeutic response to a gluten-free diet typically establish the diagnosis. Lifelong strict avoidance of gluten is currently the sole treatment available to induce and maintain remission. With improved recognition and management, individuals can gain control over this condition and live healthy lives with implementation of a gluten-free diet. Further research remains ongoing regarding screening, novel therapies, and possible prevention or cure in the future.
References
Aziz, I., Lewis, N. R., & SASIB Hussain, M. (2011). A review on the management and treatment of celiac disease: Practical guidance for gastroenterologists. Journal of Digestive Diseases, 12(3), 175–185. https://doi.org/10.1111/j.1751-2980.2011.00488.x
Duerksen, D. R. (2012). Celiac disease. Metabolic Disorders, 157-192.
Gujral, N., Freeman, H. J., & Thomson, A. B. (2012). Celiac disease: Prevalence, diagnosis, pathogenesis and treatment. World Journal of Gastroenterology, 18(42), 6036–6059. https://doi.org/10.3748/wjg.v18.i42.6036
Lebwohl, B., Ludvigsson, J. F., & Green, P. H. (2018). Celiac disease and non-celiac gluten sensitivity. BMJ (Clinical Research Ed.), 361, k2175. https://doi.org/10.1136/bmj.k2175
Rubio-Tapia, A., Ludvigsson, J. F., Brantner, T. L., Murray, J. A., & Everhart, J. E. (2012). The prevalence of celiac disease in the United States. The American Journal of Gastroenterology, 107(10), 1538–1544. https://doi.org/10.1038/ajg.2012.219
van Heel, D. A., & West, J. (2006). Recent advances in coeliac disease. Gut, 55(7), 1037–1046. https://doi.org/10.1136/gut.2005.081920
Andrew Stroud