{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T23:52:10Z","timestamp":1772927530296,"version":"3.50.1"},"reference-count":144,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health (Ricerca Corrente)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Inborn errors of glutathione metabolism may cause high anion gap metabolic acidosis due to pyroglutamic acid accumulation. Since 1988, cases of this acidosis have been reported in individuals without these defects. Methods: Given the poorly characterized predisposing factors, presentation, management, and prognosis of acquired pyroglutamic acidosis, we conducted a systematic review using the National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar databases. Results: A total of 131 cases were found. Most patients were females (79%), adults (92%) aged 51 years or older (66%) with pre-existing conditions (74%) such as undernutrition, alcohol-use disorder, or kidney disease, and had an ongoing infection (69%). The clinical features included diminished consciousness (60%), Kussmaul breathing (56%), and nausea or vomiting (27%). At least 92% of patients were on paracetamol therapy for &gt;10 days at an appropriate dose, 32% on a \u03b2-lactamase-resistant penicillin, and 2.3% on vigabatrin. Besides severe anion gap acidosis, patients also presented with hypokalemia (24%) and kidney function deterioration (41%). Management involved discontinuing the offending drug (100%), bicarbonate (63%), acetylcysteine (42%), and acute kidney replacement therapy (18%). The fatality rate was 18%, which was higher without acetylcysteine (24%) compared to with it (11%). Conclusions: Acquired pyroglutamic acidosis is a rare, potentially fatal metabolic derangement, which usually occurs after paracetamol use, frequently combined with a \u03b2-lactamase-resistant penicillin or vigabatrin. This condition predominantly affects adults, especially women with factors like undernutrition, alcohol-use disorder, or kidney disease, often during infection. Increased awareness of this rare condition is necessary.<\/jats:p>","DOI":"10.3390\/jcm13195781","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T06:39:35Z","timestamp":1727678375000},"page":"5781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Drug-Related Pyroglutamic Acidosis: Systematic Literature Review"],"prefix":"10.3390","volume":"13","author":[{"given":"Tessa","family":"Scafetta","sequence":"first","affiliation":[{"name":"Family Medicine Institue, Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orsolya","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Family Medicine Institue, Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6900 Lugano, Switzerland"},{"name":"Department of Anesthesia, H\u00f4pital du Valais, 1951 Sion, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3829-4254","authenticated-orcid":false,"given":"Gregorio P.","family":"Milani","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Clinical Sciences and Community Health, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7676-3379","authenticated-orcid":false,"given":"Gabriel","family":"Bronz","sequence":"additional","affiliation":[{"name":"Family Medicine Institue, Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8391-5462","authenticated-orcid":false,"given":"Sebastiano A. G.","family":"Lava","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology Unit, Department of Pediatrics, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland"},{"name":"Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9line","family":"Betti","sequence":"additional","affiliation":[{"name":"Pediatric Emergency Department, University Children\u2019s Hospital Zurich, 8032 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Vanoni","sequence":"additional","affiliation":[{"name":"Pediatric Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland"},{"name":"Faculty of Biomedical Sciences, Universit\u00e0 Della Svizzera Italiana, 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario G.","family":"Bianchetti","sequence":"additional","affiliation":[{"name":"Family Medicine Institue, Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro B.","family":"Far\u00e9","sequence":"additional","affiliation":[{"name":"Family Medicine Institue, Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"Camozzi","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, H\u00f4pital du Valais, 1951 Sion, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.emc.2014.01.002","article-title":"Approach to metabolic acidosis in the emergency department","volume":"32","author":"Rice","year":"2014","journal-title":"Emerg. 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