We appreciate the positive and constructive commentary by Kumar and Katz concerning the potential of oesophageal biopsies to distinguish patients with non-erosive reflux disease (NERD) from patients with functional heartburn (FH).[1, 2]
Kumar and Katz very appropriately point out that sensitivity and specificity of the proton pump inhibitor (PPI) test are fair to moderate, and symptom quality and severity in our study cannot differentiate between NERD and FH. If PPIs fail to alleviate heartburn, pH studies or combined pH-impedance analysis after a normal upper endoscopy is recommended to confirm or rule out NERD or FH. However, sensitivity and specificity of reflux monitoring with a high day-to-day variability are low and may require additional or repeated testing. For that reason, we investigated the additional value of oesophageal biopsies to reflux monitoring in the differential diagnosis and management of refractory heartburn.
Before general recommendation for routine histology, Kumar and Katz recommend validating a standardised biopsy protocol, scoring system and the need of specially trained pathologists. There have been several studies addressing the characterisation of microscopic oesophagitis in the diagnosis of gastro-oesophageal reflux disease (GERD).[6-10] These studies included several morphological changes, including basal cell hyperplasia, papillary elongation and infiltration of immune cells, in addition to dilated intercellular spaces. We agree that a welltrained pathologist is needed. The interobserver agreements among expert pathologists showed excellent kappa values (0.84–0.88).[8, 11] Already in 2004, an independent working group of international pathologists aimed to standardise the histological assessment for general application in clinical practice after a training phase.
With nearly identical histological assessment as used in our study, Savarino et al. recently reported a similar differentiation of NERD from patients with FH based on microscopic changes of oesophageal mucosa. Sensitivity and specificity are moderate, but these results should encourage more prospective studies. We fully agree with Kumar and Katz that oesophageal biopsies cannot be recommended for the routine diagnosis of GERD, but in cases of PPI-refractory heartburn, oesophageal biopsies analysed by a trained pathologist are a valid and simple tool for better definition and differentiation of the subgroup with FH in addition to reflux monitoring.