Prevalence and Pathophysiology of Celiac Disease

Celiac disease, or gluten-sensitive enteropathy, is an intestinal disorder in which the ingestion of gluten (a protein found in grains such as wheat, rye, and barley) incites an autoimmune reaction in the small intestine.1 Celiac disease prevalence rates have increased over the past few decades to approximately 0.7% in the overall US population, with the highest rate (1.0%) found in non-Hispanic White individuals.2

Rates also vary by geographic location, with higher rates found in northern latitudes of the United States compared with southern latitudes.2-4 Additionally, celiac disease is more common in women than in men.2,4,5

The pathophysiology of celiac disease is multifactorial and complex, and includes an inherent environmental component (ie, gluten exposure) and a strong genetic component, namely expression of human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 heterodimers.1,3


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Not all patients with HLA-DQ2/DQ8 alleles develop celiac disease. In fact, only 3% of the approximately 25% to 35% of people with HLA-DQ2 or HLA-DQ8 develop celiac disease; however, nearly all patients who develop these disease have one of the HLA genotypes.3,6,7

There is also a familial component to celiac disease, and patients with a positive family history have a higher risk of developing the disease.6 A recent retrospective study found a high prevalence of celiac disease ­­­(44%) in first-degree relatives of patients diagnosed with the disease.8

Although gluten exposure and HLA-DQ2/DQ8 are major contributors to the development of celiac disease, the pathophysiology is multifactorial and complex. Many other environmental factors and genetic factors have been implicated, such as feeding patterns in infancy (eg, timing and quantity of wheat exposure in infancy), rotavirus infections, and exposure to persistent organic pollutants.6,9,10

Presentation of Celiac Disease: Classic and Nonclassic Forms

Clinical manifestations of celiac disease are extremely varied and may be affected by the extent of the disease, patient age, and the presence of other comorbid conditions.6 The classic features of celiac disease include intestinal symptoms, such as chronic diarrhea, steatorrhea, weight loss, flatulence, and abdominal pain.11 Patients may complain of changes in the caliber of their stool, such as watery stools, fatty/greasy stools, and stools with foul odor. Although these GI symptoms are commonly associated with celiac disease, the majority of patients present with nonclassic symptoms or are asymptomatic (Figure 1).4,11

Figure 1. Classic and nonclassic symptoms of celiac disease.4,11

In the nonclassic presentation, many patients only experience extraintestinal symptoms, such as iron-deficiency anemia, arthritis, fatigue, and dermatitis herpetiformis.6,12 Women may experience reproductive problems, such as amenorrhea and infertility.5,13 This phenomenon has been coined the “celiac iceberg,” in which the tip of the iceberg represents patients with classic disease and the deeper, larger hidden portion underneath represents all of the patients with atypical or silent forms of the disease.6,12

Patients with either GI or extraintestinal symptoms can present with constitutional symptoms, such as fatigue and weight loss.13 Physical examination findings typically correlate with the patient’s symptoms. For instance, an abdominal examination might reveal a distended abdomen with hyperactive bowel sounds because of excessive gas. If patients have iron-deficiency anemia, they may present with pallor of the mucous membranes and nail beds. Dermatitis herpetiformis, an erythematous vesiculopapular rash associated with celiac disease, may be present on the extensor surfaces of the patient’s extremities.13

Patients with nonclassic presentations are more likely to experience longer delays in diagnosis.14 In a retrospective chart review of 101 patients with a biopsy-proven diagnosis of celiac disease, the average delay in diagnosis was 2.3 months in patients with classic GI symptoms compared with 42 months in patients with nonclassic symptoms (P <.001).13

The delay in diagnosis is significant given the natural history of celiac disease. Over time, untreated celiac disease can cause enterocyte destruction and atrophy of the villi of the small intestine (Figure 2), impeding absorption of nutrients and leading to iron-deficiency anemia, certain vitamin deficiencies, and steatorrhea.1,15 Untreated celiac disease also can lead to long-term complications, such as osteoporosis, malignancy, and infertility.13  Therefore, it is of vital importance that healthcare providers are aware of both the classic and extraintestinal manifestations of celiac disease to promptly diagnose patients and start effective treatment.

Figure 2. Photomicrographs of a hematoxylin and eosin-stained paraffin section of a duodenal mucosal biopsy sample taken from a patient with refractory celiac disease showing subtotal villous atrophy and increased inflammatory cell infiltrates of the lamina propria compartment (original magnification 100x).
From Sedda S.15

This article originally appeared on Clinical Advisor