An Update on Celiac Disease Histopathology and the Road Ahead

Abstract

Context.—Celiac disease (CD) is a common immune-mediated disorder that occurs in genetically predisposed individuals (carriers of HLA-DQ2 and DQ8 haplotypes) on consumption of wheat (gluten). It is characterized by inflammation of the small-intestinal mucosa and myriad gastrointestinal and systemic manifestations. Celiac disease is common in the general population (prevalence, 0.5%–1%). Currently, small-bowel biopsy is considered the gold standard for diagnosing CD. However, the role of serologic testing in the diagnosis of CD has evolved, from being a supportive test to supplanting intestinal biopsies in certain patient populations. Objective.—To summarize key aspects of histopathologic assessment, discuss the benefit of standardized pathology reports, impact of the site and number of small-bowel biopsy samples on diagnosis, and recommendations regarding serologic testing. Data Sources.—Literature review of publications on CD and experience with histopathologic review of biopsies at the Department of Pathology and Cell Biology, Columbia University Medical Center, New York-Presbyterian Hospital, New York. Conclusions.—Intraepithelial lymphocytosis in the context of villous atrophy is considered a characteristic histologic finding of CD; however, it is a rather nonspecific finding. A growing list of publications has also indicated that the detection of intraepithelial lymphocytosis in the absence of villous atrophy has rather low specificity for CD. Therefore, communication between pathologists and gastroenterologists is paramount, as is knowledge regarding the pertinent clinical and laboratory data, in distinguishing between CD and other disorders with similar histopathologic and clinical manifestations.

Celiac disease and its histopathology

“…Delayed puberty, infertility, protein deficiencies and elevated liver enzyme levels are also seen. 2,10,13 Celiac disease is also found to be associated with diabetes mellitus type 1. They also have increased risk Crypt hyperplasia.…”

“…10,11 The prevalence ranges from 10% to 13% in first degree relatives and a high rate of concordance (70 to 75%) in monozygotic twins compared to dizygotic twins. 3,6,10,12 The incidence is higher in wheat eating populations such as Western Europe and North America while the incidence continues to rise in Eastern societies, possibly as a result of western style eating habits.…”

“…10,11 The prevalence ranges from 10% to 13% in first degree relatives and a high rate of concordance (70 to 75%) in monozygotic twins compared to dizygotic twins. 3,6,10,12 The incidence is higher in wheat eating populations such as Western Europe and North America while the incidence continues to rise in Eastern societies, possibly as a result of western style eating habits. 2 Clinical presentation varies from full blown malabsorption with weight loss, diarrhea and steatorrhea to more subtle symptoms such as folate or iron deficiency anemia, flatulence, episodic diarrhea, loose stools, neurological problems, osteoporosis and vitamin K and D deficiencies in as many as 50% of patients.…”

“…Elimination of gliadin stops the direct mucosal injury and eliminates the substrate necessary to form the neopeptide that propagates immunologically mediated damage. 9,10 A diverse population of immune mediators contribute to CD including macrophages, plasma cells, CD4+T helper cells, CD8+ cytotoxic T cells and natural killer cells. 3 The inflammatory cascade produces inflammatory cytokine, proteinases and other tissue damaging mediators which damages the mucosa leading to characteristic histopathological findings.…”

Diagnostic challenges in celiac disease

“…1 In these patients mild histological changes, such as increased intraepithelial lymphocytes (IELs) can be present. 11 Because lesion distribution in CD is often uneven, villous atrophy may be localized solely in duodenal bulb or distal parts of jejunum, thus missed by biopsy. Therefore, if this condition persists, repeated biopsy or capsule endoscopy might be necessary.…”