I thank Professor Guntinas-Lichius for the important point that larnygopharyngitis due to reflux is also an indication for PPI. Many of these patients have typical reflux symptoms along with laryngitis and thus an uncontroversial indication for PPI. For those who have laryngitis without any typical symptoms of reflux esophagitis, the reflux finding score (RFS) has been developed and has been found to be well correlated with the laryngoscopic structural findings (1). There have been very few prospective, randomized, placebo-controlled trials of PPI for this indication. The indication was uncontroversial in the patients studied, all of whom had abnormal esophageal pH values; it is, therefore, surprising that laryngitis did not improve more than it actually did under PPI treatment (2). It seems that, for many patients with chronic hoarseness or irritative cough, acid reflux really is not the cause. There is certainly nothing to be said against trial treatment with PPI for a period of no longer than four weeks.
I cannot agree with Dr. Kraus’ statement that there are many cases of severe magnesium deficiency under long-term treatment with PPI. A study published last year, based on a large number of patients, revealed that, in the absence other risk factors for hypomagnesemia, such as chronic renal failure, diarrhea, diuretics, or cancer, treatment with PPI alone hardly confers any risk (3). I would therefore not recommend routine serum magnesium measurement in patients taking PPI over the long term, unless they have other predisposing factors for hypomagnesemia.
Professor Steffen cites the important study by Ahrens et al. from Greifswald that confirms a statement I made in the article (4), to the effect that PPI are too often given without any clear-cut indication. He addresses a further important point as well: which patients should be given PPI to prevent so-called stress ulcers? Acid suppression with an H2-blocker combined with the muscarinic receptor antagonist pirenzepine was a standard treatment in intensive care units for many years, until this was called into question when a study showed that intubated patients receiving H2-blockers were at an elevated risk of pneumonia with Gram-negative bacteria (5). It was probably for this reason that the manufacturers of PPI drugs had no interest in conducting a placebo-controlled trial to determine whether even stronger acid suppression with PPI might be indicated to prevent ulcers in intubated patients. Even though the risk of pneumonia was later found to have been overestimated, there has still not been any trial that would definitively tell us which intensive-care patients should be treated with acid suppression—a matter that has taken on a different aspect in recent years, with the dropping prevalence of Helicobacter pylori and the shrinking percentage of patients with a history of ulcer. The available recommendations are based on low-level evidence, often derived merely from clinical observations rather than from trials that were designed to answer specific questions.
Prof. Dr. med. Joachim Mössner
Klinik und Polklinik für Gastroenterologie und Rheumatologie
Department für Innere Medizin, Neurologie und Dermatologie
Universitätsklinikum Leipzig, AöR
Conflict of interest statement
Prof. Mössner directed and participated in clinical trials concerning the efficacy of lansoprazole, esomeprazole, pantoprazole, and omeprazole. Until 2009, he received financial support for clinical trials and honoraria for lectures at satellite symposia and continuing medical education events supported by the pharmaceutical industry, namely by the Altana Nycomed, AstraZeneca, Eisei, and Takeda companies. He has received reimbursement of meeting participation fees and travel expenses from AstraZeneca.
|1.||Belafsky PC, Postma GN, Koufman JA: The validity and reliability of the reflux finding score (RFS). Laryngoscope 2001; 111: 1313–7 CrossRef MEDLINE|
|2.||Lam PK, Ng ML, Cheung TK, Wong BY, Tan VP, Fong DY, Wei WI, Wong BC: Rabeprazole is effective in treating laryngopharyngeal reflux in a randomized placebo-controlled trial. Clin Gastroenterol Hepatol 2010; 8: 770–6 CrossRef MEDLINE|
|3.||Sharara AI, Chalhoub JM, Hammoud N, Harb AH, Sarkis FS, Hamadeh G: Low Prevalence of Hypomagnesemia in Long-term Recipients of Proton Pump Inhibitors in a Managed Care Cohort. Clin Gastroenterol Hepatol 2016; 14: 317–21 CrossRef MEDLINE|
|4.||Mössner J: The indications, applications, and risks of proton pump inhibitors—a review after 25 years. Dtsch Arztebl Int 2016; 113: 477–83 VOLLTEXT|
|5.||Driks MR, Craven DE, Celli BR, Manning M, Burke RA, Garvin GM, Kunches LM, Farber HW, Wedel SA, McCabe WR: Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. The role of gastric colonization. N Engl J Med 1987; 317: 1376–82 CrossRef MEDLINE|