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.

Strongyloidiasis is an intestinal parasitic disease caused by Strongyloides stercoralis, a soil-transmitted nematode. It is a common infection in Southeast Asia, including India, and is related to poor sanitation, rural residence, barefoot walking, and occupational exposure to soil. We report a case of a 71-year-old male farmer from rural Gorakhpur, Eastern Uttar Pradesh, who presented with intermittent watery diarrhoea for 2 years and tenesmus for 15 days. He was admitted with a diagnosis of fever of unknown origin. Routine stool microscopy revealed motile rhabditiform larvae of Strongyloides stercoralis, which were identified by their characteristic morphology, including a short buccal capsule and prominent genital primordium. Haematological examination revealed mild anaemia and eosinophilia. No other ova, cysts, or trophozoites were observed in the stool samples. The patient was treated with 200 µg/kg/day ivermectin for 2 days and showed clinical improvement. This case highlights the importance of routine stool microscopy in patients with chronic gastrointestinal complaints, especially in elderly patients from rural agricultural backgrounds.

Background: Fever of unknown origin (FUO) remains a major diagnostic challenge due to its heterogeneous etiologies and nonspecific clinical manifestations. Although metagenomic next-generation sequencing (mNGS) represents a promising diagnostic tool, its clinical utility in adult patients with FUO remains incompletely characterized. Methods: In this study, we retrospectively analyzed adult FUO patients who underwent mNGS testing at Peking Union Medical College Hospital between March 2022 and April 2024. Clinically meaningful diagnostic contribution was determined according to the final clinical diagnosis following multidisciplinary adjudication. Diagnostic performance, pathogen spectrum, therapeutic impact, specimen type, and predictors of clinically meaningful mNGS results were evaluated. Results: A total of 127 FUO patients were included in the study. Infectious diseases accounted for 53.5% of final diagnoses, followed by noninfectious inflammatory diseases (11.0%), malignancies (10.2%), and undiagnosed conditions (19.7%). mNGS made a clinically meaningful diagnostic contribution in 31.5% (40/127) of patients, despite an overall positivity rate of 56.7% (72/127), and showed a higher sensitivity than conventional culture for infectious etiologies (69.1% vs. 16.9%), though with a lower specificity (57.6% vs. 96.0%). Diagnostic contribution varied significantly by specimen type, with drainage fluid/abscess samples showing the highest diagnostic yield (90.9%). Lower white blood cell count was independently associated with clinically meaningful mNGS results (OR 0.87, 95% CI 0.77-0.98). Conclusions: mNGS provides clinically meaningful diagnostic value in adult patients with FUO, particularly for identifying occult infectious etiologies. Lesion-directed sampling, whenever feasible, and careful interpretation of sequencing results in the clinical context are essential to maximize the diagnostic utility of this approach. A lower white blood cell count was independently associated with clinically meaningful mNGS results, although this finding requires validation in larger prospective studies.

In Japan, general medicine (GM) has been recognized as a unique specialty addressing the needs of an aging society with complex comorbidities. GM physicians act as essential "gatekeepers," managing initial evaluations for diverse conditions and facilitating collaboration among various medical departments. This case study presents the critical nature of this role when clinical suspicion encounters diagnostic limitations. A young pathologist presented with recurrent fever. She expressed concern regarding possible occupational exposure during an autopsy and pathological specimen preparation performed months earlier on a deceased patient with an undetermined infection. Although the autopsy revealed widespread necrotizing granulomatous lesions associated with yeast-like fungi, the hospital's central laboratory was unable to identify the species. The GM physician used a professional network to consult an infectious disease specialist, who subsequently engaged a fungal expert. The pathogen was identified as Histoplasma capsulatum via PCR sequencing. However, the patient's subsequent test for histoplasma antibodies was negative, and a causal relationship between the recurrent fever and potential histoplasma exposure could not be established. Histoplasmosis is extremely rare in Japan and is typically associated with international travel. However, the deceased patient in this case had no recent history of overseas travel. Because laboratory assays for this high-risk fungus are not currently covered by the Japanese health insurance, such cases may remain undiagnosed. This report demonstrates that a general physician's ability to establish and coordinate specialist networks is crucial for resolving complex diagnostic challenges and ensuring the safety of healthcare workers.

Molecular and microscopy-based diagnostic capacity is often insufficient or unavailable in places where infectious disease burdens are highest, such as in West Africa. Rapid diagnostic testing (RDT) can provide quick and affordable diagnoses of common infections but is an imperfect solution due to limitations around detecting and dealing with false-negative and false-positive results. An alternative to RDT is unbiased metagenomic sequencing for pathogen surveillance. Here, we present data from unbiased metagenomic sequencing used to identify causes of undiagnosed febrile illness in Jos, Plateau State, Nigeria. Proof of concept for this approach has been demonstrated by several groups who have identified epidemic and endemic viral diseases like Lassa fever, yellow fever, and chikungunya. We show that unbiased deep sequencing and metagenomic analysis can be used to identify RNA viruses in clinical samples. We sequenced RNA from sera of patients (n = 343), many of whom were acutely febrile (76%), in a survey of clinics in Jos. We detected five human-infecting viruses in 39 (11 %) specimens. Among these were hepatitis B virus, human pegivirus, and several anelloviruses. While most of the viruses identified are unlikely to cause clinical symptoms in the patients we sampled, their presence demonstrates the validity of our approach. Additionally, our sequencing data allowed us to identify genetic material from potentially pathogenic bacteria, another possible etiological agent of febrile illness.

Toxoplasma gondii infection in cats is mostly subclinical. Systemic disease usually occurs in immunocompromised individuals. This report describes an unusual systemic toxoplasmosis, presenting as parasitic arthritis in an adult 14-year-old neutered male indoor domestic shorthair cat, with no identifiable cause of immunosuppression, and referred for lethargy, anorexia, and fever. Laboratory abnormalities included non-regenerative anemia, thrombocytopenia, increased serum amyloid A concentration, and polyclonal hypergammaglobulinemia. With persistent discomfort on palpation of the pelvic region and hind limb joints, synovial fluid was aspirated from the left carpus, elbow, and tarsus, and cytological analysis supported inflammatory polyarthritis. Additionally, the elbow joint fluid showed free crescent-shaped organisms, morphologically resemblingT. gondii tachyzoites. Serum anti-T. gondii IgG titer was initially 1:256 (cut-off titer, 1:50), although this was insufficient to confirm active infection. Whole-blood T. gondii polymerase chain reaction (PCR) was negative. The cat markedly improved with amoxicillin-clavulanate, enrofloxacin, clindamycin and supportive treatment. Two weeks later, serum anti-T. gondii IgG titer increased fourfold (1:1024), confirming seroconversion and active systemic toxoplasmosis. The infection likely triggered secondary immune-mediated thrombocytopenia (sIMT) and hemophagocytic syndrome, which improved following antibiotic therapy. T. gondii-associated immune thrombocytopenic purpura is reported in humans, but to our knowledge, never in cats. This case highlights the diagnostic value of synovial fluid cytology and seroconversion in feline systemic toxoplasmosis. Negative blood PCR test should not exclude active infection. Toxoplasmosis should be considered in cats presenting with fever of unknown origin, polyarthritis, or unexplained hyperglobulinemia, regardless of the immune status or lifestyle.