Pyrexia of unknown origin (PUO) remains a diagnostic challenge, particularly when associated with lymphadenopathy, multisystem involvement and positive autoimmune serology. Distinguishing between infectious, inflammatory and malignant causes is often difficult, especially when advanced imaging demonstrates findings suggestive of lymphoma. A previously healthy man in his late 40s presented with a 10-day history of intermittent fever, myalgia, joint stiffness and pleuritic chest pain. During admission, he developed photophobia, mild neck stiffness, progressive upper and lower limb pain and weakness resulting in impaired mobility. Investigations demonstrated marked systemic inflammation with a C-reactive protein (CRP) of 235 mg/L and an erythrocyte sedimentation rate (ESR) of 105 mm/hr despite a normal white cell count (WCC). Extensive microbiological investigations including blood cultures, cerebrospinal fluid analysis, bacterial and fungal molecular testing, tuberculosis screening and viral polymerase chain reaction (PCR) testing were negative apart from detectable Epstein-Barr virus (EBV) DNA and positive EBV IgM serology. Autoimmune screening revealed positive ANA, anti-Ro52, anti-Ro60 and anti-La antibodies with low complement C4. Cardiac magnetic resonance imaging (MRI) confirmed acute myopericarditis. Positron emission tomography-computed tomography (PET-CT) demonstrated fluorodeoxyglucose (FDG)-avid supra- and infradiaphragmatic lymphadenopathy with splenic involvement highly suspicious for lymphoma. However, excisional cervical lymph node biopsy demonstrated reactive lymphoid hyperplasia without evidence of malignancy. Clinical improvement began approximately during the second week after admission and occurred without immunosuppressive therapy.

We describe a patient who has both fibrous dysplasia (FD) and monoclonal gammopathy of undetermined significance (MGUS). The simultaneous occurrence of these two pathological conditions is rare, and it is necessary to distinguish whether the bones are being affected by FD or multiple myeloma. The patient's problems began with a non-healing tooth extraction, raising suspicion of osteomyelitis. Later, he was also examined for fever of unknown origin, as he had elevated inflammatory markers, low-grade fever, and headaches. According to skeletal scintigraphy, the patient had a craniofacial skeleton affected by FD. Given the presence of IgG lambda type MGUS, it was necessary to rule out transformation of MGUS into multiple myeloma. PET/CT examination with the radiopharmaceuticals sodium fluoride (18F-NaF) and fluorodeoxyglucose (18F-FDG) was used to differentiate this. In the craniofacial skeleton area, the CT image corresponded to FD, and these lesions showed significant NaF accumulation. 18F-FDG accumulation was less pronounced, and none of the lesions with a high 18F-NaF uptake had an osteolytic character, which is indicative of skeletal involvement by FD rather than multiple myeloma. The patient was treated with denosumab, with an initial administration at 28-day intervals and a planned extension of the intervals to 3 months after stabilization of the condition. Immediately after the first denosumab injection, the headaches caused by craniofacial skeletal involvement due to FD disappeared. In the coexistence of MGUS and FD, it is necessary to precisely determine whether the bones are affected by FD or multiple myeloma by using PET/CT imaging and radiopharmaceuticals 18F-NaF and 18F-FDG. The text provides an overview of the drug treatment of FD from a 2026 perspective.

This article details the diagnosis and treatment of an elderly male patient with VEXAS syndrome who came with fatigue and fever.The patient thereafter developed several clinical manifestations，including macrocytic anemia，tracheal and bronchial wall thickening，polyarthritis，rashes，and elevated levels of inflammatory markers.The final clue for subsequent genetic testing came from the bone marrow smear，which showed vacuolar degeneration in the cytoplasm of immature granulocytes.The UBA1 gene testing showed the mutation c.121A>C （p.Met41Val），which confirmed the diagnosis of VEXAS syndrome.Following glucocorticoid therapy，the patient's clinical conditions were significantly ameliorated.However，the patient's recurrence of fever and anemia months after discontinuing glucocorticoid medication was consistent with the repeated relapses described in VEXAS syndrome.The whole diagnostic process for the patient suggests that in clinical settings，thorough integration of clinical clues is crucial for making an appropriate diagnosis.To accomplish precision therapy，clinicians must retain an open mind and actively participate in multidisciplinary collaboration.

Background/Objectives: The objective of this study is to evaluate the efficacy and safety of maintaining antimicrobial (AM) therapy or adjusting AM therapy during episodes of febrile neutropenia (FN) catalogued as a fever of unknown origin (FUO) in children with cancer. Methods: This is a prospective, multicenter, noninferiority, randomized study, approved by ethics committee, in children with episodes of FN in eight hospitals in Chile. Microbiological and molecular samples were drawn at admission. Patients with FUO (negative bacterial and viral study with no clinical focus suggesting infection) and favorable evolution during the first 48-72 h of AM therapy were randomized 1:1 to maintain or adjust treatment, reducing the number and spectrum of AMs. The primary endpoint was the percentage of episodes with an uneventful resolution; the secondary endpoints were the re-adjustment of AM therapy, days of fever/hospitalization/AM therapy, days of vancomycin and meropenem per 1000 days of neutropenia, number of AMs after randomization, pediatric intensive care unit (PICU) admission, sepsis, and death. Results: A total of 266 of 939 FN episodes recruited between March 2021 and January 2024 were catalogued as FUO, of which 231 had a favorable evolution at 48-72 h and were randomized, 111 to maintain and 120 to adjust AM therapy. Both groups presented the same percentage of uneventful resolution, with 106 (96%) in the group that maintain AM therapy and 114 (95%) in the adjusted group (p = 1.00); relative risk 1.01, (95%CI 0.95-1.06); absolute risk difference 0.01, (95%CI -0.05-0.06). Conclusions: The main finding of this study demonstrates that adjusting antimicrobial therapy appears safe in carefully selected FUO cases with a favorable early evolution, during episodes of FN catalogued as FUO in children with cancer. These findings open an opportunity to new AM stewardship strategies in this population, with a possible future impact on AM resistance.

Acute cholangitis classically presents with fever, jaundice, and right upper quadrant pain, but atypical or subacute disease may present as pyrexia of unknown origin (PUO) and remain unrecognized until vascular complications develop. We report a 45-year-old man referred for weight loss, malaise, and suspected non-cirrhotic portal hypertension after upper gastrointestinal endoscopy showed esophageal varices despite a normal FibroScan. Detailed history revealed intermittent fever for 2 months. Laboratory evaluation demonstrated marked systemic inflammation, with leukocytosis, neutrophilia, ferritin 1095 ng/mL, and C-reactive protein > 200 mg/L, together with a cholestatic-hepatitic liver enzyme pattern and preserved liver synthetic function. Blood and urine cultures were negative. Initial ultrasonography showed bile duct dilatation without a definite obstructing lesion, delaying diagnosis. Subsequent magnetic resonance cholangiopancreatography and contrast-enhanced computed tomography demonstrated biliary abnormality with portal vein thrombosis and periportal collateralization, consistent with septic pylephlebitis, cavernous transformation, and portal biliopathy secondary to occult cholangitis. The patient was treated with intravenous broad-spectrum antibiotics and anticoagulation, with clinical improvement and partial portal vein recanalisation on follow-up ultrasonography at 3 months. This case highlights that occult cholangitis should be considered in patients with PUO and cholestatic liver biochemistry, even in the absence of classic biliary symptoms, and that early cross-sectional biliary imaging may allow timely recognition of pylephlebitis before chronic portal hypertensive and biliary sequelae become established.

A 72-year-old woman with fever, confusion, and upper extremity superficial venous thrombosis was admitted. Despite screening for infectious, neurologic, and autoimmune causes, no diagnosis was established. Generalized lymphadenopathy was found afterwards. An excised lymph node biopsy with immunohistochemical analysis revealed aggressive B-cell lymphoma.

Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disorder characterized by fever, rash, arthritis, and hyperferritinemia, often presenting as a diagnostic challenge due to its nonspecific manifestations. We report the case of a 35-year-old previously healthy male who presented with a 20-day history of pruritic erythematous skin lesions, high-grade fever, severe odynophagia, and symmetric inflammatory polyarthritis. Laboratory evaluation revealed leukocytosis with neutrophilia, elevated acute-phase reactants, liver enzyme abnormalities, and hyperferritinemia (1,050 ng/mL). Infectious, autoimmune, and neoplastic causes were excluded. During hospitalization, the patient developed chest pain with electrocardiographic changes and elevated troponin levels, consistent with acute pericarditis. Skin biopsy demonstrated nonspecific inflammatory dermatitis. A diagnosis of AOSD was established based on clinical findings and Yamaguchi criteria. Initial treatment with systemic corticosteroids resulted in partial improvement; however, early relapse required escalation to tocilizumab, achieving complete clinical remission at two months. This case highlights the importance of considering AOSD in patients with fever of unknown origin and elevated inflammatory markers, as well as the role of early targeted therapy in improving outcomes.

Fever of unknown origin (FUO) poses significant challenges for clinicians due to the myriad of possible etiologies, exhaustive evaluation requirements, diagnostic delays, patient and family frustration, and prolonged hospital stays. Defined as a fever lasting more than three weeks without a diagnosis despite one week of inpatient evaluation, this clinical phenomenon could result from infectious, autoimmune, neoplastic, or miscellaneous etiologies. We report the case of an elderly woman with FUO who was diagnosed with oncocytic carcinoma of thyroid origin on cervical lymph node biopsy. Interestingly, the biopsy was taken from a cervical node that was detected incidentally on neuroimaging. Oncocytic thyroid cancers, also known as Hürthle cell carcinomas, are differentiated but aggressive thyroid neoplasia. These rare tumors often present as thyroid nodules, detected incidentally during imaging or as palpable thyroid swellings. This case report highlights the clinical and diagnostic challenges in patients with FUO and reports an exceedingly rare presentation of oncocytic thyroid cancer as FUO. Additionally, it emphasizes the diagnostic utility of imaging and the need to follow even subtle diagnostic clues when evaluating patients with FUO.