The clinical picture of untreated celiac disease varies from asymptomatic to severe. Gastrointestinal symptoms are the result of intestinal inflammation and include nausea, vomiting, stomach pain, bloating, and chronic diarrhea and are accompanied by weight loss and, in children, growth failure. The damage to the lining of the proximal small intestine produces maldigestion and malabsorption of carbohydrates, lactose, fats, and proteins and deficiencies of micronutrients such as fat-soluble vitamins, iron, and vitamin B12. The classic clinical picture of a stunted child with a large belly and flat buttocks who has steatorrhea is rare. Oligosymptomatic or monosymptomatic manifestations such as growth failure, anemia, or nonspecific gastrointestinal symptoms, including constipation, are now more common than the classic clinical features. The consequences of mal absorption include iron-deficiency anemia, which may not resolve with oral iron supplementation, and bone disease with osteoporosis. Extraintestinal symptoms, including dermatitis herpetiformis and other organ-specific effects, may occur in the absence of gastrointestinal symptoms, and celiac disease can manifest with a wide variety of extra gastrointestinal symptoms (Table 1).
Table1. Extragastrointestinal Manifestations of Celiac Disease.
Other less common manifestations of celiac disease may include seizures associated with occipital lobe calcifications, myocarditis, and pulmonary hemosiderosis, as well as an increased risk of spontaneous abortion. Celiac disease is associated with an increased risk of gastrointestinal cancer, especially cancer affecting the small intestine, the esophagus, or both. Gastrointestinal and nongastrointestinal lymphoproliferative dis ease is more common among patients who receive a diagnosis later in life, occurring particularly in the first year after diagnosis. Refractory celiac disease is a condition that does not respond to a gluten-free diet. Refractory celiac disease type I is a condition without malignant potential, whereas refractory celiac disease type II has clonal aberrations that can progress to enteropathy-associated T-cell lymphoma, a rare condition that arises from the development of aberrant lymphocytes in the context of long-standing inflammation and is often preceded by refractory celiac disease. Simple immunohistochemical staining for intraepithelial lymphocytes that maintain cytoplasmic staining of CD3 but lack surface staining of CD8 may suggest refractory celiac disease type II. Confirmation requires molecular testing and flow cytometry to determine aberrancy. The presence of clonality alone is not enough to make this diagnosis.
