Adult-onset Still's disease masquerading as acute coronary syndrome: a case report and review of the literature.

INTRODUCTION: Adult-onset Still's disease is a rare systemic autoinflammatory disease. We present a case of a young man with a constellation of symptoms and myopericarditis as a complication of this disease. CASE: A 36-year-old Hispanic man with no significant past medical history developed a quotidian fever pattern following an upper respiratory tract infection. He initially presented with chest pain concerning for myocardial infarction and underwent cardiac catheterization, which revealed non-obstructive coronary artery disease. He was found to have myopericarditis, significant neutrophilic leukocytosis, and hyperferritinemia. He improved on high-dose corticosteroids but developed steroid-induced psychosis, and 4 months from symptom onset, he finally received tocilizumab, which eventually induced remission without adverse reactions. DISCUSSION: Adult-onset Still's disease should be considered in a patient with fevers of undetermined origin. Due to its multisystemic involvement, adult-onset Still's disease is often a diagnosis arrived at after an extensive cardiac, hematologic, malignant, and infectious workup. Imaging, laboratory testing, and bone marrow biopsy were necessary to rule out alternative etiologies of this patient's presentation. Steroids are the mainstay of treatment because they are easily affordable, although the high risk of adverse effects makes them less desirable. Interleukin-1 inhibitors (anakinra or canakinumab) and interleukin-6 inhibitor tocilizumab are the steroid-sparing biologic agents of choice but are cost-prohibitive. CONCLUSION: Adult-onset Still's disease should be considered in the differential diagnoses of fever of undetermined origin. Early identification and initiation of treatment are critical to faster recovery and prevention of progression to severe complications. Steroids remain the standard first-line therapy and should be followed by disease-modifying steroid sparing drugs. The social determinants of health may preclude their timely initiation and should alert providers of proactive ways to avoid further delays.

Summary: Appropriate Use Criteria for the Use of Nuclear Medicine in Fever of Unknown Origin.

The diagnostic work-up of patients with fever of unknown origin (FUO) begins with a thorough history and physical examination, complete blood count with differential, chest x-ray, urinalysis and culture, electrolyte panel, liver enzymes, erythrocyte sedimentation rate, and C-reactive protein level. Additional imaging procedures, including nuclear medicine tests, are generally used as second-line procedures, with 18F-FDG PET and PET/CT assuming increasingly important roles in the diagnostic work-up. The Society of Nuclear Medicine and Molecular Imaging, the Infectious Diseases Society of America, and the American College of Nuclear Medicine convened an autonomous expert work group to comprehensively review the published literature for nuclear imaging in adults and children with FUO and establish appropriate use criteria (AUC). This process was performed in accordance with the Protecting Access to Medicare Act of 2014, which requires that all referring physicians consult AUC by using a clinical decision support mechanism before ordering advanced diagnostic imaging services. The complete findings and discussions of the work group were published on January 8, 2023, and are available at https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=15666 The AUC in the final document are intended to assist referring health care providers in appropriate use of nuclear medicine imaging procedures in patients with FUO. The work group noted limitations in the current literature on nuclear medicine imaging for FUO, with the need for well-designed prospective multicenter investigations. Consensus findings from published data and expert opinions were used to create recommendations in common clinical scenarios for adults and children. Included in the complete document is a discussion of inflammation of unknown origin (IUO), a recently described entity. In view of the fact that the criteria for FUO and IUO are similar (except for fever > 38.3°C [100.9°F]) and that the most common etiologies of these 2 entities are similar, it is the expert opinion of the work group that the recommendations for nuclear medicine imaging of FUO are also applicable to IUO. These recommendations are included in the full guidance document. This summary reviews rationale, methodology, and main findings and refers the reader to the complete AUC document.

Performance and value of 18F­FDG PET/CT in patients with fever of unknown origin.

Fever of unknown origin (FUO) is a common clinical and diagnostic challenge. The main aim of the present study was to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET)/CT in patients who present with FUO. Overall, 105 consecutive patients (61 men and 44 women) with a mean age of 51±35 years with FUO underwent 18FDG PET/CT scans. The performance of 18FDG PET/CT in determining the etiology of FUO was assessed. According to the PET/CT results, patients were classified into four groups: Group 1, patients with true-positive results (n=51; 49%), in whom abnormal 18FDG uptake identified the final diagnosis; group 2, patients with false-positive results (n=24; 23%), in whom 18FDG uptake was not consistent with the final diagnosis; group 3, patients with true-negative results (n=10; 9.5%), in whom the 18FDG uptake was normal and no final disease was established; and group 4, patients with false-negative results (n=20; 19%), in whom 18FDG uptake was normal and disease was finally established. Of the 51 patients with true-positive PET/CT results, 51% had infections, 35% had malignancies and 14% had inflammatory processes. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 72, 29, 68, 33 and 58%, respectively. In conclusion, the present results demonstrated that 18FDG PET/CT established the final diagnosis of FUO in the majority of patients (72%). These results support the use of 18FDG PET/CT in the initial evaluation and management of patients with FUO.

Something Seems Fishy: Hepatic Abscess Due to Foreign Body Ingestion in a Pediatric Patient.

Pediatric hepatic abscesses are uncommon in children. They are usually preceded by intra-abdominal infections or caused by acute or chronic biliary disease. Cases of hepatic abscesses secondary to foreign body ingestion are even rarer but are most reported in countries such as China, where ingestion of fish and chicken bones is common. We report a rare case of an adolescent patient who developed a hepatic abscess after ingestion of a fishbone foreign body. He presented to the emergency department with emesis, abdominal pain, and subjective fevers of unknown etiology. Initial imaging of the abdomen was pertinent for a heterogeneous hepatic mass with evidence of fluid collection, concerning for malignancy. Subsequent incision and drainage then confirmed fluid collection to be pus. However, his cryptogenic hepatic abscess was not responsive to broad-spectrum intravenous antibiotics. After imaging was re-reviewed and repeated, a 4.3 cm thin curvilinear hyperdensity was identified embedded in the liver parenchyma. Eventually, the patient underwent exploratory laparoscopy where a fishbone foreign body was removed. To our knowledge, this is one of the few reported pediatric cases of hepatic abscess formation caused by a foreign body ingestion. Hepatic abscesses that do not resolve with antibiotics and ultrasound-guided drainage via catheter should prompt reassessment of other uncommon etiologies, specifically migrated foreign bodies as a rare but important differential diagnosis. Compared to pyogenic hepatic abscesses, hepatic abscesses secondary to foreign bodies require expedited surgical intervention for source control; thus, timely recognition and prompt intervention are crucial to minimize morbidity and mortality.

Kikuchi-Fujimoto disease co-occuring with Hashimoto thyroiditis: A case report and literature review.

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.

Three-Month History of Lymphadenopathy Caused by Bartonella henselae in a 13-Year-Old Following a Dog Scratch.

We reported the case of a 13-year-old immunocompetent boy presenting with a right cervical neck mass. He complained of fatigue, back pain, coughing, and a right neck mass persisting for three months. He did not have a fever, but his parents reported he had lost 20 lbs. in the past six months without any change in diet or appetite. They are also very concerned about the risk of malignancy. During the initial work-up, there was no abnormality in the complete blood count. During the follow-up visit 10 days later, he complained of new-onset dysphagia and throat pain. The mass was about 5 cm on the right neck, poorly mobile, and mildly tender to palpation. It looks significantly different compared to the first visit. Blood serology tests were indicated, and titers of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and toxoplasma were not reactive. However, serology detected that IgM and IgG titers to Bartonella henselae were ≥1:20 and ≥1:1024, respectively. A fine needle aspiration (FNA) of the mass on the same day revealed lymphoid proliferation. Afterward, the patient was treated with amoxicillin-clavulanic acid for two weeks. After three weeks, the mass almost disappeared, and the patient reported a remarkable improvement in symptoms. This case report is a helpful reminder that B. henselae should be suspected on the differential diagnoses in a case of lymphadenopathy associated with non-specific symptoms such as fatigue, back pain, and weight loss.

Hemophagocytic Lymphohistiocytosis Associated With T-cell Lymphoma in Pregnancy: Diagnostic Conundrum Unveiled.

Hemophagocytic lymphohistiocytosis (HLH) during pregnancy is a rare and often misdiagnosed disease. The clinical manifestations are non-specific, contributing to a high maternal mortality rate. This case report details the presentation of a 31-year-old pregnant woman with high-grade fever initially treated as an infection-related condition. The diagnostic challenge arose from the rarity of HLH, its variable clinical presentation, and the lack of specificity in clinical and laboratory findings. Despite numerous tests and escalation of therapies, the patient, unfortunately, succumbed to HLH associated with T-cell lymphoma. This case report aims to raise awareness of HLH, emphasizing its challenging definition. Malignancy-associated HLH is not uncommon, and early identification and treatment are paramount to prevent progressive tissue damage, organ failure, and mortality. The atypical presentation of HLH as a clinical manifestation of T-cell lymphoma underscores the need for vigilance in diagnosing this potentially fatal syndrome.

Hemophagocytic lymphohistiocytosis triggered by relapsing polychondritis: A case report.

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. CASE SUMMARY: 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. CONCLUSION: Thorough physical examination enabled diagnosis and treatment of HLH triggered by RP in patients presenting with fever of unknown origin.

Fever of Unknown Origin (FUO) Criteria Influences Diagnostic Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Criteria classifying fever of unknown origin (FUO) patients remains subject to discrepancies. A minimal standardized set of investigative tests serves as the foundation for the qualitative criteria, whereas quantitative incorporates the length of evaluation (7 or 3 days). A systematic review of studies would help physicians anticipate the frequency of illness types that could influence management. METHODS: Prospective studies published in Medline (PubMed), Embase, Scopus, and Web of Science databases from January 1, 1997 to July 31, 2022, were included. A meta-analysis estimated associated pooled proportions between these criteria and diagnostic outcomes adjusted to the International Classification of Diseases, 10th edition (ICD-10) definitions. RESULTS: Five qualitative studies corresponded to an increase of 15.3% (95% CI: 2.3%-28.3%, P = .021) in undiagnosed FUO proportions compared to eleven quantitative studies. Quantitative studies had 19.7% (95% CI: 6.0%-33.4%, P = .005) more in adjusted infectious disease proportions than qualitative studies. No significant differences in proportions between FUO defining criteria were noted for adjusted noninfectious inflammatory disorders (P = .318), oncology (P = .901), non-inflammatory miscellaneous disorders (P = .321), diagnostic evaluation process, gross national income (GNI), or World Health Organization (WHO) geographic region. CONCLUSIONS: Use of either qualitative or quantitative FUO criteria was associated with a statistically significant risk of over- or under-estimating infectious diseases and undiagnosed illnesses when using an ICD-10 adjusted FUO five-category system. Clinicians should anticipate differences depending on which criteria are used. While further research is warranted, qualitative criteria provide the best framework for study comparisons.

Evaluating Antibiotic De-escalation for Autologous Stem Cell Transplant Patients With Febrile Neutropenia in a Real-World Clinical Setting.

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.

Fever of unknown origin: A 12-year case series in Colombia.

BACKGROUND: Fever of unknown origin (FUO) is a diagnostic challenge with highly heterogeneous causes. Its etiology can change according to the studied regions, and the chance of reaching a diagnosis depends on available resources. The aim of this study is to describe the clinical characteristics, etiology and the usefulness of diagnostic aids in cases of FUO managed over 12 years in a Colombian reference center. METHODOLOGY: Single-institution retrospective case series. All cases of FUO between 2006 and 2017 were identified with the help of an electronic medical record search software. Cases of adults with fever for more than three weeks who remained undiagnosed after three days of hospitalization are described. RESULTS: Of 1,009 cases evaluated, 112 cases met the inclusion criteria (median age 43 years, 66% men). The etiologies identified were infectious (31.2%), inflammatory (20.5%), neoplastic (14.3%), and miscellaneous (2.7%) diseases. 31.2% remained without etiological diagnosis. The most frequent conditions were tuberculosis (17%), Hodgkin's lymphoma (7.1%), systemic lupus erythematosus (6.3%), disseminated histoplasmosis, and adult Still's disease. Contrast tomography and biopsies were the studies that most frequently supported or confirmed the final diagnosis. CONCLUSIONS: This series of contemporary Latin American cases suggests that the categories of FUO etiologies are similar to those reported in studies from developed countries, with tuberculosis being the most frequent cause in our setting. Our results highlight the importance of tomography-guided invasive studies in the diagnostic approach to FUO.

Atypical hepatic metastases of pancreatic adenocarcinoma unveiled through persistent and unresolved pyrexia: Case report.

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.

Severe thrombocytopenia caused by cytomegalovirus infection in an immunocompetent adult: A case report.

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.

Metagenomic next-generation sequencing in patients with fever of unknown origin: A comprehensive systematic literature review and meta-analysis.

Metagenomic Next-Generation Sequencing (mNGS) holds promise in diagnosing fever of unknown origin (FUO) by detecting diverse pathogens. We systematically reviewed the literature to evaluate mNGS's accuracy, clinical efficacy, and limitations in FUO diagnosis. Nine studies revealed mNGS's positivity rate ranging from 66.7% to 93.5% for bacterial bloodstream infections and systemic infections. Meta-analysis of three studies involving 857 patients, including 354 with FUO, showed a sensitivity of 0.91 (95% CI: 0.87-0.93) and specificity of 0.64 (95% CI: 0.58-0.70). Despite lower specificity, mNGS demonstrated a higher Diagnostic Odds Ratio (DOR) of 17.0 (95% CI: 4.5-63.4) compared to conventional microbiological tests (CMTs) at 4.7 (95% CI: 2.9-7.6). While mNGS offers high sensitivity but low specificity in identifying causative pathogens for FUO, its superior DOR suggests potential for more accurate diagnoses and targeted interventions. Further research is warranted to optimize its clinical application in FUO management.

Distribution of the causes of fever of unknown origin in China, 2013-2022.

Background and Objectives: 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. Materials and Methods: 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. Results: 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%). Conclusion: 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.

The Diagnostic Yield of [18F]FDG-PET/CT in a Heterogeneous In-Patient Population with Suspected Infection or Inflammation Is Comparable to Findings in Patients with Classic Fever of Unknown Origin.

INTRODUCTION: Suspected infection or inflammation of unknown origin in in-patients remains challenging. Literature on [18F]FDG-PET/CT is abundant in classic fever of unknown origin (FUO), but evidence is complex and may not always reflect clinical reality. This study explores the application of [18F]FDG-PET/CT in a diverse clinical population of in-patients with suspected infection not defined by stringent FUO-criteria. METHODS: Retrospective chart review of consecutive in-patients who underwent [18F]FDG-PET/CT in the workup of suspected infection or inflammation from 1 July 2022 to 31 December 2022 was conducted. We evaluated indications, diagnostic yield, and clinical impact of [18F]FDG-PET/CT, and compared the findings of [18F]FDG-PET/CT and stand-alone CT. Univariate logistic regression assessed associations between [18F]FDG-PET/CT outcome and clinical parameters. Receiver operating characteristic curve (ROC) analysis evaluated diagnostic performance. RESULTS: 77 patients met the inclusion criteria. [18F]FDG-PET/CT established a diagnosis in 35% of cases, ruled out focal infection in 26%, and thus was helpful in 61% of patients. It prompted 72 additional examinations resulting in seven incidental diagnoses, including two cancers. Antibiotic treatment was changed in 26% of cases. Regression analysis found white blood cell counts (WBC) associated with true positive outcomes. [18F]FDG-PET/CT was compared to stand-alone CT findings, and was concordant in 69% of cases. CONCLUSIONS: Results were comparable to findings in more classic FUO. [18F]FDG-PET/CT was clinically helpful in 61% of cases but also prompted many additional examinations with relatively few clinically important findings. WBC count was a predictor of true positive outcome. CT and [18F]FDG-PET/CT were discordant in 31%, of cases, especially in cases of endocarditis and spondylodiscitis.

An Unusual Case of Fever in Paralytic Ileus.

Still's disease is frequently a condition of exclusion for patients with an unidentified cause of fever. Accompanying symptoms typically include fever, arthralgia, and a transient skin rash. The underlying pathophysiology indicates an autoimmune origin. Diagnosis is primarily clinical, often utilizing the Yamaguchi criteria. The case in question involves a 19-year-old male presenting with high-grade fever and paralytic ileus. The patient received intravenous glucocorticoids and cyclophosphamide, resulting in a rapid clinical improvement. During the follow-up, tofacitinib was initiated based on the clinical response observed.

Recommendations for Updating Fever and Inflammation of Unknown Origin From a Modified Delphi Consensus Panel.

Background: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are syndromes commonly used as medical diagnoses. Since the existing literature has a mixture of diagnostic approaches, developing consensus-based recommendations would be helpful for clinicians, researchers, and patients. Methods: A modified Delphi process was performed from October 2022 to July 2023, involving 4 rounds of online surveys and 2 live video conferences. The panel comprised international experts recruited based on peer-reviewed published publications and studies. Results: Among 50 invited experts, 26 (52.0%) agreed to participate. Twenty-three panelists completed round 1 of the survey, 21 completed rounds 2 and 3, 20 completed round 4, and 7 participated in round 5 live video discussions. Of the participants, 18 (78.3%) were academic-based clinicians and researchers, 5 (21.7%) practiced in a community-based hospital, and 6 (26.1%) were female. Consensus was reached on 5 themes: (1) incorporating epidemiologic factors, such as geographic location and travel history; (2) updated criteria for classifying FUO or IUO; (3) initial evaluation approaches; (4) a classification system for diagnoses; and (5) recommendations for judicious limitation of empiric therapies. Experts strongly disagreed with using 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography as part of the diagnostic criteria for FUO. There were mixed opinions about the importance of the temperature measurement site, the 3-week minimum illness criterion, the need for a standard definition of relapsing fevers, and the use of similar evaluation strategies for FUO and IUO. Conclusions: These Delphi-generated consensus-based recommendations offer potential improvements compared with earlier definitions and a guide for clinical practice and future research.

Spider Bite Presenting as Fever, Macrophage Activation Syndrome and a Skin Ulcer.

Introduction: Fever of unknown origin (FUO) refers to a condition of prolonged increased body temperature, without identified causes. The most common cause of FUO worldwide are infections; arthropod bites (loxoscelism) should be considered in view of the spread of the fiddleback spider. Loxoscelism can present in a cutaneous form (a necrotic cutaneous ulcer) or in a systemic form with fever, haemolytic anaemia, rhabdomyolysis and, rarely, macrophage activation syndrome (MAS). For this suspicion, it is important to have actually seen the spider. Case description: A 71-year-old man was admitted to our department because of intermittent fever, arthralgia and a necrotic skin lesion on his right forearm that appeared after gardening. Laboratory tests were negative for infectious diseases, and several courses of antibiotics were administered empirically without clinical benefit. Whole-body computed tomography showed multiple colliquative lymphadenomegalies, the largest one in the right axilla, presumably of reactive significance. A shave biopsy of the necrotic lesion was performed: culture tests were negative and histological examination showed non-specific necrotic material, so a second skin and lymph node biopsy was performed. The patient developed MAS for which he received corticosteroid therapy with clinical/laboratory benefit. Cutaneous and systemic loxoscelism complicated by MAS was diagnosed. Subsequently, the second biopsy revealed morphological and immunophenotypic findings consistent with primary cutaneous anaplastic large cell lymphoma (PC-ALCL). Conclusions: Skin lesions and lymphadenomegalies of unknown origin should always be biopsied. It is very common to get indeterminate results, but this does not justify not repeating the procedure to avoid misdiagnosis. LEARNING POINTS: In case of necrotic skin lesions with fever, malignancy (and in particular cutaneous lymphoma) should always be considered.Misdiagnosis of loxoscelism is common. Definitive diagnosis requires the identification of the responsible spider.It is frequent to obtain inconclusive results from biopsies, but this does not justify not repeating the procedure to avoid misdiagnosis.

Fever of unknown origin revealing testicular nocardiosis: a case report and literature review.

BACKGROUND: Nocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the most frequent sites of nocardiosis. Testis is a highly unusual location for nocardiosis. CASE PRESENTATION: We report the case of an immunocompromised 75-year-old-man admitted for fever of unknown origin. He presented with skin lesions after gardening and was first suspected of Mediterranean spotted fever, but he did not respond to doxycycline. Then, physical examination revealed new left scrotal swelling that was compatible with a diagnosis of epididymo-orchitis. The patient's condition did not improve despite empirical antibiotic treatment with the onset of necrotic scrotal abscesses requiring surgery. Nocardia brasiliensis yielded from the removed testis culture. High-dose trimethoprim-sulfamethoxazole and ceftriaxone were started. Multiple micro-abscesses were found in the brain and spinal cord on imaging studies. After 6 weeks of dual antibiotic therapy for disseminated nocardiosis, slight regression of the brain abscesses was observed. The patient was discharged after a 6-month course of antibiotics and remained relapse-free at that time of writing these lines. Trimethoprim-sulfamethoxazole alone is meant to be pursued for 6 months thereafter. We undertook a literature review on previously reported cases of genitourinary and urological nocardiosis; to date, only 36 cases have been published with predominately involvement of kidney, prostate and testis. CONCLUSIONS: To the best of our knowledge, this is the first case of Nocardia brasiliensis simultaneously infecting skin, testis, brain and spinal cord in an immunocompromised patient. Knowledge on uncommon forms of nocardiosis remains scarce. This case report highlights the difficulty of diagnosing atypical nocardiosis and the importance of prompt bacteriological sampling in case of empirical antibiotics failure.