Diagnostic criteria

Histopathologic abnormalities of the small bowel mucosa were first described by Paulley in surgical resection specimens of intestines in 1954. Villous atrophy was a characteristic feature observed in patients with celiac disease (CD), which is now a recognized component of the histologic triad for diagnosing CD. In earlier times, the histopathologic diagnosis of CD was based exclusively on detecting villous atrophy in small bowel biopsies. The recognition of milder degrees of injury in the small bowel mucosa of patients with CD was an important step forward in expanding the histopathologic manifestations of CD. In the 1990s, Marsh described and classified the histologic patterns of small intestinal mucosal injury, the spectrum ranging from normal villous architecture with increased intraepithelial lymphocytes (IELs) as the sole abnormality to total villous atrophy with crypt hyperplasia and increased lamina propria inflammation. The Marsh classification was composed of 4 categories (types 1–4) representing progressive states of mucosal injury, which was modified by Oberhuber in 1999. The Oberhuber classification subdivided the type 3 lesion (flat mucosa) into 3 groups based on the severity of villous atrophy; mild to moderate (partial) villous atrophy (type 3A), marked (subtotal) villous atrophy (type 3B) and completely flat mucosa (total) villous atrophy (type 3C). The modified Marsh-Oberhuber classification is currently used by many pathologists.

In recent years, the diagnostic approach to CD has changed, because of a better understanding of the clinical manifestations of CD and the availability of more sensitive and specific serologic tests, as well as high-resolution HLA typing for disease susceptibility alleles. Most importantly, the presence of total villous atrophy is no longer necessary for diagnosing CD, provided the established spectrum of histopathologic features of CD is present. Nevertheless, small bowel mucosal biopsy remains the gold standard for diagnosing CD. All serologic tests and small bowel biopsies need to be performed while the patient is on a gluten-containing diet. According to the US National Institutes of Health consensus statement, serologic testing is recommended as the first step in pursuing a diagnosis of CD. Duodenal biopsy is recommended in individuals with a positive celiac antibody test, when serologic results are nondiagnostic and in individuals at risk for CD who have suggestive clinical symptoms, such as first-degree relatives of CD and patients with iron-deficient anemia, cryptogenic hypertransaminitis, and CD-associated autoimmune disorders. With positive serology and a biopsy showing characteristic findings of intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy, a presumptive diagnosis of CD can be made. Definitive diagnosis requires symptom resolution on commencing a gluten-free diet (GFD). A repeat biopsy to show normalized histology after a GFD is no longer required for diagnosing CD, although it is often used to document healing.