Gluten-Associated Medical Problems

Gluten has become a topic of significant scientific and clinical interest in recent years. Although media attention has contributed to increased public awareness of gluten, it has also contributed to the proliferation of inconsistent or misleading information. From a medical perspective, gluten is relevant due to its association with a range of well-characterized disorders. This activity aims to categorize gluten-related conditions based on established scientific evidence, with a focus on their clinical relevance. Gluten (derived from Latin meaning "glue") is a composite of storage proteins termed as "prolamins" and "glutelins," which are stored along with starch in various grains. Gluten is found in wheat, barley, rye, certain hybrid and ancient grains (such as spelt, Khorasan, and emmer), as well as in their derivatives (such as malt). Gluten imparts elasticity to dough, helping it maintain structure and producing a light, chewy texture when baked. Gluten accounts for approximately 80% of the total protein content in traditional bread, whereas pasta contains a lower percentage of protein. Gluten is also commonly found in imitation meats, beer, soy sauce, ice cream, and ketchup, often due to the addition of gluten-based stabilizing agents. Cross-contamination of food products with gluten is a common occurrence. Additionally, some nonfood items, such as hair products and cosmetics, may contain gluten. Gluten is associated with various medical conditions, including celiac disease, non-celiac gluten sensitivity (NCGS), gluten ataxia, and dermatitis herpetiformis. Aretaeus of Cappadocia described a nonspecific entity in 250 CE, termed , derived from the Greek term , which refers to the abdomen. In 1856, Francis Adams translated this into English, using the term "coeliacs" or "celiacs." The first comprehensive modern description of celiac disease was provided by British physician Samuel Gee in 1888. He emphasized the importance of dietary management, stating that " and "." In 1908, another British physician, Carnegie Brown, published a book that described peripheral neuritis in patients with celiac disease. He also mentioned “sprue” and ataxia, although confirmation of these diagnoses was challenging due to the limited diagnostic tools and clinical evidence available at the time. World War II brought widespread devastation and famine, leading to malnutrition and illness across much of the world. However, during this time, a unique clinical observation emerged—some individuals with celiac disease experienced significant improvement in their symptoms. In the Netherlands, wartime shortages of wheat and other grains resulted in a significant reduction in gluten consumption, which was accompanied by notable clinical improvements in affected patients. In 1950, Dutch pediatrician Willem-Karel Dicke formally demonstrated that eliminating wheat, rye, and oats from the diet resulted in dramatic symptom relief in children with celiac disease. Mortality rates from the condition declined during the war but rose again after gluten-containing foods were reintroduced. This trend reversed once gluten was identified as the offending dietary component, and the adoption of a gluten-free diet (GFD) led to a renewed decline in mortality. The development of small bowel biopsy techniques in the 1950s and 1960s enabled the definitive diagnosis of celiac disease. AK Taylor published an immunological study linking celiac disease to circulating antibodies in 1961. Although initially considered a food allergy, celiac disease was later recognized as an autoimmune disorder, with a strong association to the human leukocyte antigen DQ2 (HLA-DQ2). In 1966, researchers observed enteropathy in 9 of 12 patients with dermatitis herpetiformis, and in the same year, they identified an association between celiac disease and neurological disorders. In the 1980s, the journal coined the term "non-celiac gluten sensitivity." Although this condition was prevalent in Europe, it was less frequently identified in North America. Alessio Fasano, a physician experienced in treating celiac patients in Europe, later moved to Boston to work at Massachusetts General Hospital. There, he demonstrated that the condition was also present in the United States. His 2003 article in the helped raise awareness and laid the foundation for further research into gluten-related disorders. During the 2000s and 2010s, a combination of medical studies and popular media coverage linked celiac disease to a wide range of conditions, contributing to a growing public perception of gluten as harmful. This perception led to the widespread vilification of gluten, even among individuals without a diagnosed gluten-related disorder. In response to increasing consumer demand, the U.S. Food and Drug Administration established regulations in 2013 requiring standardized labeling for gluten-free products. The resulting surge in interest fueled the growth of the gluten-free market, which reached an estimated value of $4.7 billion by 2020. The popularity of GFDs also spurred the rapid expansion in related consumer products, including gluten-free foods, cookbooks, mobile applications, and dedicated restaurant offerings. This activity reviews the 4 main gluten-associated medical conditions—celiac disease, dermatitis herpetiformis, NCGS, and gluten ataxia. This activity also provides information on the etiology, prevalence, diagnosis, and management of this condition. Please refer to StatPearls' companion resources, "Protein Intolerance," "Celiac Disease," "Ataxia," and "Wheat Allergy," for more information.