Leprosy is a chronic infectious disease that mainly affects the skin and peripheral nerves, it can also invade deeper tissues and organs, including mucous membranes, lymph nodes, testes, eyes, and internal organs. Severe cases can result in deformities and disabilities. We encountered the case of a 39-year-old male with unexplained fever, headache and rash. The patient\'s lesions were taken for histopathological examination and slit skin smear analysis. Further, the patient was detected of Mycobacterium leprae (M.leprae) nucleic acid sequences in the cerebrospinal fluid (CSF) and plasma, and M.leprae gene targets in the skin lesion tissue and blood. The patient was eventually diagnosed with multibacillary leprosy and type II leprosy reaction. These results suggest the possibility of bacteremia in patients with leprosy to some extent, and observation implies the potential invasion of CSF by M.leprae or its genetic material.

We introduce a 16-year-old female who presented with tender cervical lymphadenopathy, prolonged fever, and hypothyroidism. After excluding common causes of fever of unknown origin, a surgical biopsy of cervical lymph nodes revealed Kikuchi-Fujimoto disease. The patient showed improvement with a short-term course of NSAIDs. An increased titre of thyroperoxidase antibody led to a diagnosis of Hashimoto\'s thyroiditis during stable condition. This report underscores the importance of considering Kikuchi-Fujimoto disease in the differential diagnosis of prolonged fever of unknown origin with lymphadenopathy and highlights the association with Hashimoto\'s thyroiditis, advocating for vigilance regarding hypothyroidism in long-term follow-up after Kikuchi-Fujimoto disease recovery.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder caused by abnormal histiocytes and T cell activation. In adults, it is predominantly associated with infections, cancers, and autoimmune diseases. Relapsing polychondritis (RP), another rare disease, is diagnosed based on symptoms without specific tests, featuring cartilage inflammation characterized by swelling, redness, and pain, rarely inducing HLH.
METHODS: A 74-year-old woman visited the emergency room with a fever of 38.6 °C. Blood tests, cultures, and imaging were performed to evaluate fever. Results showed increased fluorescent antinuclear antibody levels and mild cytopenia, with no other specific findings. Imaging revealed lymph node enlargement was observed; however, biopsy results were inconclusive. Upon re-evaluation of the physical exam, inflammatory signs suggestive of RP were observed in the ears and nose, prompting a tissue biopsy for confirmation. Simultaneously, persistent fever accompanied by cytopenia prompted a bone marrow examination, revealing hemophagocytic cells. After finding no significant results in blood culture, viral markers, and tissue examination of enlarged lymph nodes, HLH was diagnosed by RP. Treatment involved methylprednisolone followed by azathioprine. After two months, bone marrow examination confirmed resolution of hemophagocytosis, with normalization of hyperferritinemia and pancytopenia.
CONCLUSIONS: Thorough physical examination enabled diagnosis and treatment of HLH triggered by RP in patients presenting with fever of unknown origin.

We present a case of a 56-year-old female with rheumatoid arthritis (RA) who has been on methotrexate for 9 years and has been complaining of high-grade fever for the past 1 month with no localizing signs and symptoms. She was thoroughly evaluated before being labeled as pyrexia of unknown origin. Histoplasmosis was suspected after bone marrow aspiration smear examination. The presence of histoplasma antigen in the urine confirmed our diagnosis. Fever responded after 2 weeks of liposomal amphotericin B and patient discharged in stable condition on tablet itraconazole.

UNASSIGNED: Fever of unknown origin is quite common in everyday clinical practice, and the approach is challenging. Prolonged fever as the sole manifestation of craniopharyngioma has been rarely reported in literature.
UNASSIGNED: Herein, we report a case of adamantinomatous craniopharyngioma presented as fever of unknown origin in a 51-year-old woman, initially misdiagnosed as atypical subacute thyroiditis.
UNASSIGNED: During the work up, the patient complained about bitemporal hemianopsia. Thus, she underwent a pituitary Magnetic Resonance Imaging, which revealed a mixed mass originating from the pituitary stalk and compressing the optic chiasm. The mass was surgically excised, and the histology confirmed the diagnosis of adamantinomatous craniopharyngioma. The patient remained afebrile post-surgery. We hypothesize that the craniopharyngioma caused an abnormality of thermoregulatory mechanisms due to infiltration of the hypothalamus.

Fever of unknown origin (FUO) remains a formidable diagnostic challenge in the field of medicine. Numerous studies suggest an association between FUO and genetic factors, including chromosomal abnormalities. Here, we report a female patient with a 4.5 Mb Xp microdeletion, who presented with recurrent FUO, bacteremia, colitis, and hematochezia. To elucidate the underlying pathogenic mechanism, we employed a comprehensive approach involving single cell RNA sequencing, T cell receptor sequencing, and flow cytometry to evaluate CD4 T cells. Analysis of peripheral blood mononuclear cells revealed augmented Th1, Th2, and Th17 cell populations, and elevated levels of proinflammatory cytokines in serum. Notably, the patient exhibited impaired Treg cell function, possibly related to deletion of genes encoding FOPX3 and WAS. Single cell analysis revealed specific expansion of cytotoxic CD4 T lymphocytes, characterized by upregulation of various signature genes associated with cytotoxicity. Moreover, interferon-stimulated genes were upregulated in the CD4 T effector memory cluster. Further genetic analysis confirmed maternal inheritance of the Xp microdeletion. The patient and her mother exhibited X chromosome-skewed inactivation, a potential protective mechanism against extensive X chromosome deletions; however, the mother exhibited complete skewing and the patient exhibited incomplete skewing (85:15), which may have contributed to emergence of immunological symptoms. In summary, this case report describes an exceptional instance of FUO stemming from an incompletely inactivated X chromosome microdeletion, thereby increasing our understanding of the genetics underpinning FUO.

UNASSIGNED: Fever of unknown origin (FUO) has long been a cause for concern among clinicians, and its spectrum has evolved with progress in medicine. This study aimed to investigate the distribution of causes of FUO in China between 2013 and 2022 to facilitate the clinical understanding of the etiology of FUO.
UNASSIGNED: Case series of FUO in China published between 2013 and 2022 were retrieved from PubMed, Wanfang Data, and CNKI databases and retrospectively analyzed. The rates of different causes of FUO were calculated, and these data were compared with previously published distributions of causes of FUO in China.
UNASSIGNED: The causes of FUO with the highest rates from the 51 identified case series (n = 19,874) were infectious, autoimmune, and neoplastic diseases (59.6%, 14.3%, and 7.9%, respectively). A comparison of a subset (43 case series subdivided by disease category, n = 16,278) with previously reported data revealed an increased rate of FUO attributed to infectious diseases in the past decade, with a significantly higher rate attributed to bloodstream infections (10.0% vs. 4.8%) and a significantly lower rate attributed to tuberculosis (9.3% vs. 28.4%), compared with the rates from the previous period. In contrast, the rates of FUO attributed to both autoimmune and neoplastic diseases decreased, with significantly decreased rates attributed to adult-onset Still\'s disease among autoimmune diseases (4.6% vs. 8.5%) and lung cancer among neoplastic diseases (0.6% vs. 1.6%).
UNASSIGNED: Despite an overall increase in the rate attributed to infectious diseases, that attributed to tuberculosis has decreased. The rates attributed to both autoimmune and neoplastic diseases have also decreased.

Febrile neutropenia (FN) is a complication in approximately 90% of autologous stem cell transplant (SCT) patients. Guidelines support early broad-spectrum antibiotics (BSA) to prevent morbidity and mortality. However, in patients who are clinically stable and deemed to have a fever of unknown origin, the optimal duration of BSA is unknown. Accumulating evidence suggests that de-escalation of BSA in select patients may decrease duration of BSA exposure without compromising clinical outcomes such as infection, recurrent fever, and readmission. With this, a de-escalation protocol was implemented at Vanderbilt University Medical Center (VUMC) to identify autologous SCT patients who may benefit from early de-escalation of BSA. The objectives of this study were to analyze the impact of early empiric antibiotic de-escalation on the duration of BSA as well as its impact on the incidence of recurrent fever and documented infection in autologous SCT patients. This was a single-center, retrospective study evaluating patients older than 18 years of age who underwent autologous SCT and experienced an episode of FN from January 2018 to December 2022 at VUMC (N = 195). The protocol was initiated on January 1, 2020, to de-escalate BSA back to prophylaxis in stable neutropenic patients determined to have a fever of unknown origin. The primary outcome was the number of BSA days within 30 days. Secondary clinical outcomes included recurrent fever, documented infection, readmission, 30-day mortality, and 90-day non-relapsed mortality (NRM). Outcomes were compared across pre- and postprotocol groups with a Wilcoxon rank sum test, Pearson chi-square test, or regression analysis as appropriate. The median BSA duration was 4.7 and 2.7 days in the pre- and postprotocol groups, respectively (P < .001). Recurrent fever (14.2% versus 16.0%, P = .726), documented infection (1.7% versus 6.7%, P = .068), and readmission (13.3% versus 22.7%, P = .091) within 30 days were not significantly different between the two groups. Neither 30-day mortality (0.8% versus 1.3%, P = .736) nor 90-day NRM (0.8% versus 1.3%, P = .736) differed. The implementation of an early de-escalation protocol for autologous SCT patients who develop FN was associated with a reduction in duration of BSA compared to the preprotocol group without a significant difference in readmission, recurrent fevers, and documented infections. This study adds to existing evidence that early de-escalation of BSA in FN patients with a fever of unknown origin who are afebrile and clinically stable is safe and reduces unnecessary antibiotic use.

Diagnosing neoplastic fever requires excluding identifiable causes, making it a diagnostic challenge. Fever as a primary manifestation of pancreatic adenocarcinoma is uncommon with few cases reported in the literature. Here we present an unusual case of metastatic pancreatic adenocarcinoma primarily manifesting as pyrexia of unknown origin. A 63-year-old Sri Lankan male, a non-smoker who was diagnosed with diabetes, hypertension and dyslipidaemia presented with a history of fever, anorexia and weight loss for 2 months. Despite the completion of treatment for positive serology for paratyphi, his symptoms and inflammatory markers remained elevated while the rest of the infectious screening was negative. On further evaluation, the patient was found to have a hypodense distal pancreas with ring-enhancing multiple liver lesions on imaging. Histology confirmed pancreatic adenocarcinoma with liver metastasis. Atypical liver metastases may present with evidence of ring enhancement in computed tomography imaging; thus, the biopsy is mandatory for diagnosis and decision-making. Usually, tumours of the pancreatic tail are resectable but if they are associated with liver metastatic disease, surgical resection is not recommended because it is not potentially curative. Therefore, in the context of metastatic pancreatic adenocarcinoma, palliative chemotherapy and pharmacological management of fever are required.

A 53-year-old otherwise healthy man was referred to our hospital with a fever of unknown origin, headache, and arthralgia. Four days earlier, he had a fever with chills. Treatment with antibiotics and acetaminophen proved ineffective, with the patient subsequently developing headache and joint pain. Blood analysis revealed elevated inflammatory markers, liver impairment, and severe thrombocytopenia (platelet count, 19,000/μL). Subsequent tests revealed elevated levels of anti-cytomegalovirus IgM and IgG. Based on these findings, the patient was diagnosed with severe thrombocytopenia associated with cytomegalovirus infection. Platelet counts increased spontaneously without antiviral therapy. Forty-five days after the initial visit, the symptoms improved, and blood tests revealed resolution of the inflammatory findings, with the platelet count recovering to 155,000/μL. Although the disease may resolve spontaneously, cytomegalovirus infection should be considered as a differential diagnosis in case of severe thrombocytopenia in immunocompetent adults.