Can severe celiac disease (CD) cause pathological alterations on tissue biopsy outside of the duodenum?

From the Guidelines

Severe celiac disease can cause pathological alterations outside of the duodenum, but the primary site of damage is the small bowel, particularly the duodenum.

Pathological Alterations

• The disease is characterized by villous atrophy, intra-epithelial lymphocytosis, and crypt hyperplasia of the small bowel 1.
• The presence of these alterations in the duodenum is a key diagnostic criterion for celiac disease, and biopsy of the duodenum is a critical component of the evaluation 1.

Extra-Intestinal Symptoms

• While the primary site of damage is the small bowel, celiac disease can also cause extra-intestinal symptoms, such as diarrhea, weight loss, and anemia 1.
• However, these symptoms are not necessarily a direct result of pathological alterations outside of the duodenum, but rather a consequence of malabsorption and inflammation in the small bowel.

Diagnosis and Biopsy

• Diagnosis of celiac disease is based on serology and duodenal biopsy, and the analysis of biopsy specimens is crucial for establishing the diagnosis 1.
• Multiple biopsies from the bulb and distal duodenum are recommended to confirm the diagnosis, as the disease can be patchy and mucosal changes can be hampered by Brunner's glands or peptic changes 1.

From the Research

Pathological Alterations in Celiac Disease

• Celiac disease (CD) is a chronic intestinal disease caused by intolerance to gluten, characterized by immune-mediated enteropathy, associated with maldigestion and malabsorption of most nutrients and vitamins 2.
• The diagnosis of CD is based upon the combination of raised serum anti-tissue transglutaminase or anti-endomysial antibodies and the presence of histological alterations of variable degree in the duodenal mucosa 3, 4.
• Severe CD can cause pathological alterations outside of the duodenum, as it can affect other intestinal areas, including the colon 5.
• A study found that gluten-dependent immunological activation affects more intestinal tracts with different degrees of involvement, suggesting that the organ culture of colonic biopsies could represent a new tool to opportunistically detect CD 5.
• The exact cause of CD is unknown but is thought to be primarily immune mediated (tissue-transglutaminase autoantigen); often the disease is inherited 2.

Tissue Biopsy Outside of the Duodenum

• Duodenal biopsy remains the gold standard in the diagnosis of CD, with the recognition of the spectrum of histological changes and classification of mucosa damage based on updated Corazza-Villanacci system 4.
• However, other studies suggest that CD can also affect other areas of the intestine, including the colon, and that tissue biopsy outside of the duodenum may be useful in diagnosis 5.
• A study found that EMA and anti-tTG were detected in sigmoid culture supernatants of CD patients, suggesting that the organ culture of colonic biopsies could be a useful tool in diagnosis 5.

Implications of Pathological Alterations

• Severe CD can cause significant clinical and histological impairment, including growth retardation in untreated children and atypical symptoms like infertility or neurological symptoms 2.
• Management of CD consists of lifelong withdrawal of dietary gluten, which leads to significant clinical and histological improvement 2.
• However, complete normalization of histology can take years, highlighting the importance of early diagnosis and treatment 2.