What is the most definitive investigation to diagnose coeliac disease?

The most definitive investigation to diagnose coeliac disease is a duodenal biopsy. This procedure involves obtaining a tissue sample from the lining of the duodenum, which is the first part of the small intestine. Examination of this biopsy under a microscope can reveal characteristic changes associated with coeliac disease, such as villous atrophy and crypt hyperplasia.

These histological findings provide clear evidence of damage caused by gluten ingestion, making duodenal biopsy the gold standard for diagnosis. Other diagnostic methods, such as blood tests, can aid in the initial assessment by identifying specific antibodies associated with coeliac disease. However, these tests do not provide the definitive diagnosis that a biopsy does, as they can sometimes yield false positives or negatives. Endoscopy is often performed to obtain the biopsy but is not considered a diagnostic test on its own. Skin biopsies are relevant for a related condition known as dermatitis herpetiformis, which can occur with coeliac disease, but they are not used for diagnosing the disease itself. Thus, the duodenal biopsy is essential for accurately diagnosing coeliac disease.