We viewed with great interest the e-video and case description by Xu and colleagues regarding confocal laser endomicroscopy (CLE) in protein-losing enteropathy (PLE) [1]. While CLE is an exciting novel technique, we would like to address some aspects in this recent publication that we view critically.

First, we would like to address some specificity and technical issues. The presence of leakiness of fluorescence into the lumen using CLE has been reported repeatedly in disorders of gut–brain interaction: patients without PLE but instead with irritable bowel syndrome or functional dyspepsia [2] [3] [4]. One group found that gaps per 1000 epithelial cells in the duodenum correlated with intestinal permeability in patients with functional dyspepsia [4]. While this is intriguing, there is currently no uniform way to assess leakiness using CLE. Several analysis methods, both quantitative and semiquantitative, have been put forward with up to 24% spontaneous fluorescence leakage [2]. To the best of our knowledge, normal reference values, along with validation and reproducibility of these findings, are currently lacking. Additionally, CLE only records a very small surface of the mucosa, raising the question of how many spots should be investigated to get a true representation of the whole small bowel.

Furthermore, PLE is a syndrome with a broad differential diagnosis. To evaluate the potential benefit of CLE in the diagnosis of PLE, α1-antitrypsin clearance should be added as the best reference – mere clinical response to immunosuppression does not confirm the presence of PLE [5].

These limitations, along with the fact that this observation was made in one single case, leads us to disagree with the authors’ conclusion that CLE would be the “perfect tool” for diagnosing PLE. While CLE may offer exciting possibilities, its role and specificity in assessing intestinal permeability require further investigation. To classify it as the perfect tool for diagnosing PLE is certainly premature.

Article published online:
30 January 2024

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