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.

HIV-associated hemophagocytic lymphohistiocytosis (HLH) is mainly due to infections caused by viruses, fungi, and, to a lesser extent, bacteria, often with fatal results. Case presentation: A 15-year-old pediatric patient from another institution was admitted to our hospital with a fever of unknown origin (FUO). Clinical analysis and laboratory studies diagnosed HIV infection. The approach to an FUO in a patient with AIDS is much more complex due to the search for common etiologies and opportunistic infections. In this case, disseminated histoplasmosis, pulmonary tuberculosis, pneumocystosis, and ehrlichiosis were diagnosed, prompting an urgent and comprehensive approach to prevent mortality. Due to the multiple infections, HLH was triggered. An early intervention with trimethoprim (TMP)-sulfamethoxazole (SMX), liposomal amphotericin B, doxycycline, and quadruple antiphimic therapy to suppress infections, in conjunction with the early administration of HLH treatment, favored the survival of this patient.

Fever of unknown origin (FUO) was first described by Dr. Petersdorf and Dr. Beesom in 1961.[1] FUO was defined as a temperature of 101F (38.3 C) or higher with a minimum duration of 3 weeks without an established diagnosis despite at least 1 week's investigation in the hospital. This definition was later changed to accommodate technological advances allowing for sophisticated outpatient evaluations, increasing numbers of immunocompromised individuals including those with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), and more complex treatment options becoming available. The revised definition proposed by Durack and Street in 1991 divided cases into four distinct subclasses: classic FUO, nosocomial FUO, neutropenic FUO, and HIV-related FUO. [2] A comprehensive history and physical examination can aid in diagnosis and direct diagnostic testing. Recommended investigations for work-up include complete blood count (CBC) with differential, 3 sets of blood cultures (from different sites, several hours apart, and before initiation of antibiotic therapy, if indicated), chest radiograph, complete metabolic panel (including hepatitis serologies if LFTs are abnormal), urinalysis with microscopy and urine culture, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibodies (ANA), rheumatoid factor (RA), cytomegalovirus IgM antibodies or virus detection in blood, heterophile antibody test, tuberculin skin test, HIV testing and computed tomography (CT) scan of the abdomen.[3] Over 200 malignant/neoplastic, infectious, rheumatic/inflammatory, and miscellaneous disorders can cause FUO.[4] Clinicians often order non-clue-based imaging and specific testing early in the FUO workup, which may be misleading and is certainly not economical.[4] Despite extensive workup and diagnostic advances, up to 51% of FUO cases remain undiagnosed.[5][6] In modern medicine, FUO remains one of the most challenging diagnoses. It is important to note that immunocompromised and HIV patients may require an entirely different approach in diagnosing and treatment of recurrent fevers. This article focuses on FUO in immunocompetent adult patients.[3]

Although acute HIV-induced HLH is rare in literature, HIV is an important differential diagnosis in patients with HLH. In our study, a 33-year-old previously healthy male patient was admitted with fever of unknown origin, lymphadenopathy, generalized edema, transaminitis, acute renal failure, oliguria, myalgias, night sweats, unintentional weight loss, and leukopenia. Disease course was indicative of a viral-like prodrome of roughly 2-month duration. At an outside hospital, full viral work-up (including EBV, CMV, HIV antibodies, hepatitis panel) was negative. HIV p24 antigen assay was not available at the outside facility. Outside liver chemistry and lymph node biopsy were suggestive of HLH. HLH was confirmed via serum ferritin, white cell receptor, and cytokine studies. Repeat viral and rheumatologic studies revealed a positive p24 antigen with indeterminant HIV antibody. We demonstrate efficacy of a specific treatment plan as well as importance of p24 antigen studies in patients with HLH and/or the HIV window-period, adding to available literature/documentation of a rare disease process.

Fever was a common symptom in patients with Human Immunodeficiency Virus (HIV) infection in the early phases of the epidemic. Fever of Unknown Origin (FUO) was frequent in HIV-patients and conditions causing FUO were often opportunistic conditions. The HIV-epidemic continues to expand, but access to effective antiretroviral therapy is also expanding, resulting in a growing number of HIV-infected patients less likely to be severely immunocompromised and less likely to present opportunistic conditions. Yet part of newly diagnosed patients continue to present with advanced HIV-infection and are still at high risk of opportunistic conditions. This epidemiological evolution strongly influences the spectrum of conditions causing fever and FUO in HIV-patients. While some patients with HIV-associated fever and FUO may still be suffering from opportunistic conditions classically associated with HIV-related FUO, many others will have causes of fever that are similar to the non-HIV-infected population or to classical FUO. Strategies for diagnosis and treatment of fever and its causes in HIV-infected patients need to take into account this evolution.

A bone marrow (BM) aspiration and biopsy is often believed to be a much needed diagnostic procedure in the work up of patients with fever of unknown origin (FUO), especially in the setting of AIDS. Is it worthwhile to proceed with this invasive diagnostic method? The usefulness of a BM aspiration or biopsy to assist in the diagnosis of FUO or prolonged fever in AIDS patients has been reported previously to range from 4% to 40%. The purpose of this study was to assess the usefulness of a BM aspiration and biopsy in diagnosing the cause of FUO in patients with AIDS and to identify the utility of the procedure for the diagnosis of malignancies/other hematological disorders resulting in the FUO. In this study, comprising of 30 patients, we have tried to find the diagnostic yield of bone marrow examination in finding the etiology of "FUO associated with HIV infection". Though similar studies have been reported in the literature but it is lacking from eastern India. The majority of BM examination in this series revealed infections followed by hematological disorders. Our study showed the diagnostic yield of bone marrow examination in "HIV associated FUO" to be 26.7%. It was found to be positive in 33.3% of the patients, who had the final diagnosis of an infective etiology and 100% of the patients, who had a final diagnosis of an underlying hematological etiology.