Research Article: Observational Study Diagnosis and outcomes of fever of unknown origin cases with an erythrocyte sedimentation rate of 100 mm/h or more: An International ID-IRI (Infectious Diseases – International Research Initiative) Observational Retrospective Cohort Study Elbahr, Umran MDa,*; Erdem, Hakan MDb; Ben Yahia, Wissal MDc; Baymakova, Magdalena Petrova MD, PhDd; Letaief, Amel MDe; Poposki, Kostadin MDf; Grgić, Svjetlana MDg; Sanlidag, Gamze MDh; Miftode, Ionela-Larisa MDi; Marino, Andrea MDj; Miftode, Egidia Gabriela MDi; Amer, Fatma MDk; Oncu, Serkan MDl; Hasanoglu, Imran MDm; Wegdan, Ahmed Ashraf MDn; Eser, Fatma MDm; Guner, Hatice Rahmet MDm; Kaya Kalem, Ayse MDm; Cosentino, Federica MDj; Kolovani, Entela MDo; Tahmaz, Alper MDp; Sonmezer, Meliha Cagla MDq; Arapovic, Jurica MDg; Ceylan, Mehmet Resat MDr; Kayaaslan, Bircan MDm; Hakamifard, Atousa MDs; Önder, Taylan MDt; Eser-Karlidag, Gulden MDu; Tehrani, Hamed Azhdari MDv; Addepalli, Syam Kumar MDw; Kumari, Hema Prakash MDw; Kumar, Meela Ranjith MDx; Sayana, Suresh Babu MDy; Sipahi, Oguz Resat MDa,h Author Information aInfectious Diseases Department, Bahrain Oncology Center, King Hamad University Hospital, Muharraq, Bahrain bDepartment of Infectious Diseases and Clinical Microbiology, Turkish Health Sciences University, Gulhane School of Medicine, Ankara, Türkiye cInternal Medicine Department, Farhat Hached University Hospital, Ibn El Jazzar Medical School, University of Sousse, Sousse, Tunisia dDepartment of Infectious Diseases, Military Medical Academy, Sofia, Bulgaria eInfectious Diseases Department, Farhat Hached University Hospital, Ibn El Jazzar Medical School, University of Sousse, Sousse, Tunisia fFaculty of Medicine, University Clinic for Infectious Diseases and Febrile Conditions, Skopje, Republic of North Macedonia gInfectious Diseases Department, University Clinical Hospital Mostar, Mostar, Bosnia and Herzegovina hDepartment of Infectious Diseases and Clinical Microbiology, Ege University Faculty of Medicine, Bornova, Izmir, Türkiye iSt. Parascheva Clinical Hospital of Infectious Diseases, Iasi, Romania jDepartment of Clinical and Experimental Medicine, Unit of Infectious Diseases, ARNAS Garibaldi Hospital, University of Catania, Catania, Italy kDepartment of Medical Microbiology and Immunology, Zagazig University, Faculty of Medicine, Zagazig, Egypt lDepartment of Infectious Diseases and Clinical Microbiology, Adnan Menderes University, School of Medicine, Aydin, Türkiye mDepartment of Infectious Diseases and Clinical Microbiology, Ankara City Hospital, Ankara, Türkiye nDepartment of Medical Microbiology and Immunology, Fayoum University, Faculty of Medicine, Fayoum, Egypt oUniversity Hospital Center “Mother Theresa,” Infectious Disease Clinic, Tirana, Albania pDepartment of Infectious Diseases and Clinical Microbiology, Antalya Training and Research Hospital, Antalya, Türkiye qDepartment of Infectious Diseases and Clinical Microbiology, Hacettepe School of Medicine, Hacettepe University, Ankara, Türkiye rDepartment of Infectious Diseases and Clinical Microbiology, Harran University, School of Medicine, Sanliurfa, Türkiye sInfectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran tDepartment of Infectious Diseases and Clinical Microbiology, Onsekiz Mart University, School of Medicine, Canakkale, Türkiye uDepartment of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Elazig Fethi Sekin City Hospital, Elazig Türkiye vDepartment of Hematology and Medical Oncology, Shahid Beheshti University of Medical Sciences, Tehran, Iran wDepartment of Microbiology, GITAM Institute of Medical Sciences and Research, Visakhapatnam, Andhra Pradesh, India xDepartment of Pharmacology, Government Medical College & Government General Hospital, Suryapet, Telangana, India yDepartment of Pharmacology, Government Medical College and General Hospital, Bhadradri Kothagudem, Telangana, India. Received: 10 December 2024 / Received in final form: 17 May 2025 / Accepted: 5 June 2025 The authors have no funding and conflicts of interest to disclose. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. How to cite this article: Elbahr U, Erdem H, Ben Yahia W, Baymakova MP, Letaief A, Poposki K, Grgić S, Sanlidag G, Miftode I-L, Marino A, Miftode EG, Amer F, Oncu S, Hasanoglu I, Wegdan AA, Eser F, Guner HR, Kaya Kalem A, Cosentino F, Kolovani E, Tahmaz A, Sonmezer MC, Arapovic J, Ceylan MR, Kayaaslan B, Hakamifard A, Önder T, Eser-Karlidag G, Tehrani HA, Addepalli SK, Kumari HP, Kumar MR, Sayana SB, Sipahi OR. Diagnosis and outcomes of fever of unknown origin cases with an erythrocyte sedimentation rate of 100 mm/h or more: An International ID-IRI (Infectious Diseases – International Research Initiative) Observational Retrospective Cohort Study. Medicine 2025;104:29(e43341). *Correspondence: Umran Elbahr, Infectious Diseases Department, Bahrain Oncology Center, King Hamad University Hospital, Muharraq 24343, Bahrain (e-mail: drumran_08@hotmail.com). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Medicine 104(29):p e43341, July 18, 2025. | DOI: 10.1097/MD.0000000000043341 Open Abstract Plain Language Summary Herein, we aimed to analyze the final diagnosis in a well-defined cohort of fever of unknown origin (FUO) cases whose erythrocyte sedimentation rate (ESR) was 100 mm/h or more during the admission. The subgroup of the FUO patients with an ESR of 100 mm/h or more during the FUO evaluation, was extracted from the study database of a previously published multicenter study (European Journal of Clinical Microbiology & Infectious Diseases. April 15, 2023;42 (4):387–98). Data for 139 patients (17.6%, 139/788 of the original cohort) who fulfilled the study inclusion criteria, were obtained from 29 centers from 11 countries. Infections, neoplasms, and noninfectious inflammatory diseases were found to be the reason of fever in [n = 74 (53.2%)], [n = 14 (10%)], and [n = 13 (9.3%)] of 139 patients, respectively. Regardless of the diseases subgroup top 6 diseases that were determined to be the reasons of FUO were tuberculosis [n = 15 (10.8%)], HIV/AIDS [n = 13 (9.3%)], urinary tract infection [n = 9 (6.5%)], infective endocarditis [n = 9 (6.5%)], lymphoma [n = 9 (6.5%)], and abscess [n = 9 (6.5%)]. The most common infectious diseases were tuberculosis (15/74, 20.2%), HIV/AIDS (13/74, 17.5%), and infective endocarditis (9/74, 12.1%), along with urinary tract infection [n = 9 (6.5%)] and abscess [n = 9 (6.5%)]. The most common noninfectious inflammatory diseases were adult onset Still disease (3/13, 23%) and giant cell arteritis, also known as temporal arteritis (3/13, 23%), and followed by polyarteritis nodosa (2/13, 15.3%). The most common neoplasm was lymphoma (9/14, 64.2%), followed by lung cancer (2/14, 14.2%). Reason of fever could not be defined in (29/139, 20.8%) patients. The invasive procedures were performed in (64/139, 46%) patients. Gender, age > 50 or not, and income level (high–middle–low) of the participating country were not associated with a significant difference in the final diagnosis category of the FUO case (P > .05). To the best of our knowledge, this is the first study evaluating the FUO in the subgroup of cases with extreme ESR elevation and infectious diseases comprised the most cause of the FUO in this particular subgroup.