Prospective comparative study: metabolomics profiles of exudate and serum for patients with and without venous ulcer wound itch

Introduction: Itch is an unpleasant sensation that elicits the desire to scratch and can cause great distress, particularly in persons with venous ulcers. This pilot study explored the difference in metabolic profiles for wound exudate and serum in patients with or without venous ulcer wound itch. Methods: Patient information, wound assessment, and itch sensation ratings were recorded. Wound fluid and blood were collected for metabolomics assays. High-resolution mass spectrometry coupled with liquid chromatography and 1-dimensional proton nuclear magnetic resonance spectrometry were used to profile wound fluid and serum samples. Results: Patients (N=21) were included (ages: 32–91 y) with venous ulcers that itched (n=10) or did not itch (n=11). Metabolomic profiling discovered a previously unreported biochemical pathway for glycine, serine, and threonine metabolism in both serum and wound fluid significantly associated with itch. Using wound exudate, we developed diagnostic algorithms capable of discriminating between patients who itched and those who did not, with an area under the curve (95% confidence interval)=0.705 (0.461–0.948). Discussion: Our results demonstrate that the glycine-serine-threonine pathway is the most significantly altered metabolic pathway associated with venous ulcer itch. This pathway may serve as a biomarker for itch in patients with venous ulcers and help to identify itch before scratching further exasperates the ulcer. Studies with larger patient numbers are critically required to validate these findings. Our results may lead to novel therapeutic targets for the prophylactic treatment of itch.