Proton Pump Inhibitor–induced Hyperhidrosis: Important but Not Recognized

ABSTRACT Objective: To discuss the prevalence of hyperhidrosis, its association with proton pump inhibitor (PPI) use, and possible underlying mechanism(s) accounting for PPI-induced hyperhidrosis. Methods: We describe 2 patients who presented with hyperhidrosis while on PPI therapy, review the literature regarding PPI-associated hyperhidrosis, discuss a potential mechanism, and provide recommendations for hyperhidrosis evaluation in the setting of PPI use. Results: A 62-year-old man (case 1) presented with hyperhidrosis. Biochemical workup was nondiagnostic except for elevated chromogranin A (CgA) levels. He had been taking lansoprazole. Since PPI therapy can increase CgA levels, lansoprazole was discontinued. CgA levels decreased by 2 weeks, and hyperhidrosis resolved within 4 weeks. Symptoms recurred once PPI therapy was restarted. An 83-year-old man (case 2) presented with hyperhidrosis. He had been on omeprazole for 9 months. Omeprazole was held before performing extensive biochemical workup. Hyperhidrosis resolved after 5 days and recurred within 3 days of re-introducing omeprazole. Omeprazole was switched to ranitidine, and hyperhidrosis resolved within 1 month. Conclusion: PPI-induced hyperhidrosis is an uncommon side effect, and a mechanism has not been described. CgA is a precursor of several bioactive peptides, and levels increase while on PPIs. Expression of CgA has been identified on sweat glands and ducts. Elevated CgA levels may play a functional role in PPI-induced hyperhidrosis, but this remains to be demonstrated. In the absence of an apparent cause of hyperhidrosis in a patient on PPI therapy, a trial off PPI should be considered prior to embarking on costly and extensive workup. Abbreviations: CgA = chromogranin A; ECL = enterochromaffin-like; GERD = gastroesophageal reflux disease; PPI = proton pump inhibitor