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  • Review Article
  • Published:

NERD: an umbrella term including heterogeneous subpopulations

Nature Reviews Gastroenterology & Hepatology volume 10, pages 371–380 (2013)Cite this article

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Abstract

Nonerosive reflux disease (NERD) represents the more common phenotypic presentation of GERD and comprises patients who have typical symptoms without any mucosal breaks at endoscopy. However, these patients are markedly heterogeneous from a pathophysiological point of view and should be correctly classified by means of 24 h impedance–pH testing, which enables detection of both acidic and weakly acidic reflux and correlation with symptoms. This technique is able to identify two subsets of NERD (that is, patients with an excess of acid or with a hypersensitive oesophagus to both acid and weakly acidic reflux) and patients with functional heartburn (who do not have any kind of reflux underlying their symptoms and must be excluded from the realm of GERD). The mechanisms of symptom generation are not clear in patients with NERD, but the presence of microscopic oesophagitis, including the dilation of intercellular spaces, seems to have a relevant role. Patients with NERD in whom acid is the main pathogenetic factor respond successfully to PPI therapy, while those with hypersensitive oesophagus to weakly acidic reflux need to be treated with reflux inhibitors or surgery, although the experience in this field is very scant. Patients with functional heartburn should undergo therapy with pain modulators, but large placebo-controlled trials are necessary.

Key Points

  • Nonerosive reflux disease (NERD) represents the more common phenotypic presentation of GERD and includes patients who are heterogeneous from a pathophysiological and clinical point of view

  • 24 h impedance–pH testing has enabled subdivision of patients with NERD into several subgroups according to their oesophageal acid exposure time and symptom association analysis to acid and/or weakly acidic reflux episodes

  • This technique has identified a new subgroup of patients with NERD who have hypersensitive oesophagus to weakly acidic reflux, which contributes to narrowing down the population of patients with functional heartburn

  • The mechanisms of symptom generation are not completely understood in patients with NERD, but the presence of microscopic oesophagitis seems to have a relevant role

  • Treatment of NERD is based on the use of PPIs, which are successful in patients in whom acid has a pathogenetic role; pain modulators can be used in patients with hypersensitive oesophagus

  • Patients with functional heartburn should be treated with pain modulators, but clinical trials aimed at assessing the efficacy of these drugs in this well-defined group are lacking at this time

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Figure 1: Endoscopic and impedance–pH testing categorization of patients with GERD.16,35,38
Figure 2: Proposed diagnostic algorithm to distinguish patients with nonerosive reflux disease (NERD) from those with functional heartburn.
Figure 3: Treatment options for patients with NERD and functional heartburn.

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35128, Padua, Italy

    Edoardo Savarino

  2. Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Viale Benedetto XV 6, 16132, Genoa, Italy

    Patrizia Zentilin & Vincenzo Savarino

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  1. Edoardo Savarino
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Savarino, E., Zentilin, P. & Savarino, V. NERD: an umbrella term including heterogeneous subpopulations. Nat Rev Gastroenterol Hepatol 10, 371–380 (2013). https://doi.org/10.1038/nrgastro.2013.50

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