Kikuchi Disease is a rare, self-limiting autoinflammatory pathology, traditionally presenting with fever and cervical lymphadenopathy. Generalised lymphadenopathy remains an underreported presentation of this disease in the literature. We present the case of a 28-year-old woman who presented with fever of unknown origin along with unilateral cervical lymphadenopathy. PET-CT revealed generalised lymph node involvement with high tracer uptake values, creating the classic picture of lymphoma. Histopathology and immunohistochemistry analysis finally helped establish the diagnosis of Kikuchi disease. The non-specific presentation of this disease, coupled with its self-resolving nature, poses a significant diagnostic dilemma, underscoring the importance of a thorough workup and a high degree of clinical suspicion to guide accurate diagnosis.

Fever is one of the most common reasons for presentation to the emergency department and requires a structured approach due to unfamiliar patients, time pressure, and the risks of both over- and underdiagnosis. This review article outlines practical strategies for the initial assessment and management of patients presenting with fever in the emergency setting, with a particular focus on the early recognition of potentially life-threatening risk constellations in line with the "fever-plus principle".

Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome characterized by excessive immune activation and cytokine storm. While primary HLH is genetic and typically presents in childhood, secondary HLH is acquired and often triggered by malignancy, autoimmune disorders, or infections. Acute cytomegalovirus (CMV) infection is a known trigger, although it is rarely the primary cause in immunocompetent adults. We present the case of a healthy 33-year-old female presenting with three weeks of high-grade fever and flank pain following treatment for a presumed urinary tract infection. Despite multiple courses of antibiotics, her symptoms persisted. Evaluation revealed hepatitis, cytopenias, and splenomegaly. Testing confirmed acute CMV infection with a relatively low viral titer. However, the patient met the diagnostic criteria for HLH with a high H-score. She was successfully treated with antivirals, corticosteroids, and intravenous immunoglobulin (IVIG). This case highlights the necessity of considering HLH in the differential diagnosis of fever of unknown origin (FUO) and underscores that even mild CMV viremia can precipitate life-threatening HLH in immunocompetent adults.

Fever of unknown origin remains a diagnostic frontier, with research predominantly focused on the underlying disease spectrum. However, this focus largely overlooked issues between previous diagnostic criteria-the "quantitative" or "qualitative" definitions-and the critical role of evaluating the patient. This review synthesizes mounting evidence that the qualitative criteria are a central, yet underappreciated, driver of an effective and efficient clinical evaluation process for the ambulatory adult immunocompetent population. With input from infectious disease physicians, rheumatologists, and oncologists with expertise in this area, we chart the complex landscape of this widely recognized and potentially devastating condition, revealing key recommendations from a modified Delphi consensus panel and the Society of Nuclear Medicine and Molecular Imaging that offer changes beyond earlier definitions and management. By recentering the conversation around this updated approach, we argue for a paradigm shift for modern clinical practice and future research.

A 69-year-old male with acute myeloid leukemia (AML) undergoing chemotherapy developed erythematous skin lesions at sites of prior intravenous access, along with fever and elevated inflammatory markers. Initially suspected of having resistant cellulitis or disseminated infection, his condition did not improve despite broad-spectrum antibiotics. Skin biopsy confirmed Sweet syndrome, and the patient showed rapid clinical improvement following corticosteroid therapy, with resolution of fever and skin lesions within 72 hours. This case underscores the importance of considering Sweet syndrome in neutropenic patients with unexplained fever and skin lesions, as early recognition and treatment can prevent unnecessary antibiotic use and ensure timely continuation of chemotherapy.

Abacavir (brand name Ziagen) is used in the treatment of human immunodeficiency virus (HIV) infection. Abacavir is a nucleoside (and nucleotide) reverse transcriptase inhibitor (NRTI), and is used in combination with other medications as part of highly active antiretroviral therapy (HAART) (1). Hypersensitivity reactions associated with abacavir can be severe and potentially fatal. Symptoms include fever, rash, vomiting, and shortness of breath. They typically appear within the first 42 days of treatment (11 days median onset). HLA-B*57:01 significantly increases the risk of hypersensitivity reactions when abacavir is administered. Approximately 6% of Caucasians and 2-3% of African Americans carry this allele in the human leukocyte antigen B (HLA-B) gene. The HLA-B gene plays an important role in how the immune system recognizes and responds to pathogens, and mediates hypersensitivity reactions. HLA-B*57:01 has been found to be associated with abacavir hypersensitivity across different ethnicities, including Caucasians, Hispanics, and individuals of African origin (2, 3). Screening for the HLA-B*57:01 allele before starting abacavir therapy is recommended for all patients according to the FDA drug label for abacavir (Table 1). Even if previously tolerated, screening should happen before restarting abacavir therapy if HLA-B*57:01 status is unknown. Abacavir is contraindicated in HLA-B*5701-positive patients, and in patients with a prior hypersensitivity reaction to abacavir. Dosing guidelines from the professional societies, Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP), also recommend that HLA-B*57:01 screening should be performed prior to initiation of abacavir therapy and an alternate drug be administered for patients with the allele (Table 2, Table 3)(1, 3-5).

Adult-onset still's disease (AOSD) is a rare systemic inflammatory disorder characterized by quotidian fever, inflammatory arthritis, rash, and markedly elevated serum ferritin levels. Due to its nonspecific presentation and the need to exclude infectious, autoimmune, and malignant etiologies, diagnosis remains challenging. We report a case of a middle-aged patient presenting with prolonged high-grade fever, diffuse abdominal pain, polyarthralgia, and generalized pruritus. Extensive investigations ruled out infectious and autoimmune causes. Markedly elevated inflammatory markers and hyperferritinemia supported the diagnosis of AOSD. The patient showed significant clinical improvement with corticosteroids and methotrexate therapy. This case highlights the importance of considering AOSD in patients with fever of unknown origin and hyperferritinemia after exclusion of other causes.

We aimed to evaluate the diagnostic process and etiological spectrum of inflammation of unknown origin (IUO) and fever of unknown origin (FUO). Retrospectively, 8821 patients were evaluated between 2010 and 2024. 168 patients with IUO and 88 with FUO were included in the study. The demographic, clinical, and laboratory characteristics and diagnostic spectra of the IUO and FUO groups were compared. The diagnostic contribution, sensitivity, specificity, and positive and negative predictive values of computed tomography and 18F-FDG PET/CT were calculated. The median age (59 vs 46.7 years; P < .001) and the proportion of males (57.1% vs 40.9%; P = .014) were higher in the IUO. The most common symptom in all patients was arthralgia (78.5%). Weight loss and sore throat were more common in the FUO (P = .012 and P = .004, respectively). c-reactive protein and erythrocyte sedimentation rate levels were similar in both groups. Noninfectious inflammatory diseases (NIID) were the most common cause (31%), followed by neoplasms (18%), infections (11%), and miscellaneous diseases (7%). Infections were significantly more prevalent in the FUO (19.3% vs 6%, P < .001), whereas neoplasms were more commonly observed in the IUO (20.8% vs 12.5%, P = .099). In NIID, vasculitis occurred more frequently in the IUO, whereas adult-onset Still's disease was more prevalent in the FUO (P < .001). 18F-FDG PET/CT contributed 52.1% of cases, with 85% sensitivity and 17% specificity. Infections were common in FUO, whereas patients with IUO were older at presentation, more likely to be male, and had a higher frequency of neoplasms. Among NIIDs, vasculitis was predominant in the IUO, while adult-onset Still's disease was more prominent in the FUO.

Objectives: To assess whether [[99m]Tc]Tc-UBI 29-41 SPECT/CT combined with a standardized target-to-liver ratio can reliably support clinical decision-making in patients with difficult-to-diagnose bacterial infections and to establish a reproducible diagnostic threshold applicable across four infectious scenarios. Methods: This prospective diagnostic accuracy study, conducted following STARD guidelines, included 156 consecutive patients (346 lesions) with clinical suspicion of infected arthroplasty, spondylodiscitis, osteomyelitis, or fever of unknown origin. Target-to-liver total count ratios were calculated from SPECT/CT images. Diagnostic performance was assessed using bootstrap-resampled ROC analysis, Fagan nomograms, and penalized logistic regression. Results: All four conditions showed good discriminatory capacity (AUC: 0.965-0.979). At a cutoff ratio ≥ 1.5, specificities exceeded 95% and negative predictive values were ≥97.8% across all subgroups. Post-test probability after a negative scan decreased to 2-3% in every condition, consistent with clinically meaningful rule-out capability across all four scenarios. Penalized logistic regression confirmed significant associations between elevated ratios and confirmed infection (OR: 22.02-245.53; all p ≤ 0.003). Conclusions: [[99m]Tc]Tc-UBI 29-41 SPECT/CT with target-to-liver ratio analysis provides clinically meaningful diagnostic support across four distinct infectious scenarios, with particular strength as a rule-out test. A threshold of ≥1.5 offers a standardized, potentially reproducible criterion that may guide clinical decisions and reduce reliance on invasive confirmatory procedures. Prospective multicentre validation is warranted to establish this bacteria-specific approach as a practical complement to existing diagnostic algorithms.