{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:23:53Z","timestamp":1787009033621,"version":"build-2736575974"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to review existing literature regarding the association between haemophagocytic lymphohistiocytosis (HLH) and trimethoprim\/sulfamethoxazole and examine the risk of HLH using data from the FDA Adverse Event Reporting System (FAERS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a literature review to identify studies investigating the link between trimethoprim\/sulfamethoxazole and HLH. Additionally, we performed an active-comparator restricted disproportionality analysis (ACR-DA) in FAERS (2004Q1\u20132023Q4) for trimethoprim\/sulfamethoxazole compared to amoxicillin\/clavulanate and azithromycin. We calculated reporting odds ratios (ROR), adjusted ROR (accounting for age category and indications for respiratory and urinary tract infections), proportional reporting ratios and information components (IC25), to identify potential safety signals for HLH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our literature review identified five case reports of HLH linked to trimethoprim\/sulfamethoxazole, showing a male predominance of 80% and a median age of 39\u2005years. Symptoms appeared 2 to 14\u2005days after initiating treatment, with fever being the first symptom reported in all patients. The disproportionality analysis indicated that reports of HLH associated with trimethoprim\/sulfamethoxazole were approximately 3 to 14 times more frequent than those for amoxicillin\/clavulanate (ROR, 3.08; 95% CI, 1.67\u20135.68) and azithromycin (ROR, 13.89; 95% CI, 5.88\u201332.82), with most reports submitted by other healthcare professionals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Trimethoprim\/sulfamethoxazole may be linked to an increased risk of HLH. Further pharmacoepidemiologic research is necessary to confirm these findings and inform the safe clinical use of trimethoprim\/sulfamethoxazole.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf231","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T07:46:15Z","timestamp":1751355975000},"page":"2421-2427","source":"Crossref","is-referenced-by-count":6,"title":["Trimethoprim\/sulfamethoxazole and risk of haemophagocytic lymphohistiocytosis (HLH): a literature review and disproportionality analysis using individual case safety reports from FAERS"],"prefix":"10.1093","volume":"80","author":[{"given":"Rinko","family":"Lau","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Western University , London, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasti","family":"Sadeghi","sequence":"additional","affiliation":[{"name":"Department of Biology, Western University , London, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Ahmadi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Western University , London, ON ,","place":["Canada"]},{"name":"ICES Western , Kidney Dialysis and Transplantation Research Program, London, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niaz","family":"Chalabianloo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Western University , London, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Preyra","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Western University , London, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6847-0699","authenticated-orcid":false,"given":"Mohammad Ali","family":"Omrani","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Western University , London, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4682-6564","authenticated-orcid":false,"given":"Flory T","family":"Muanda","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Western University , London, ON ,","place":["Canada"]},{"name":"Department of Epidemiology and Biostatistics, Western University , London, ON ,","place":["Canada"]},{"name":"ICES Western , Kidney Dialysis and Transplantation Research Program, London, ON ,","place":["Canada"]},{"name":"Lawson Health Research Institute, London Health Sciences Centre , London, ON 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