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Background: While petechiae can be a sign of a serious underlying condition, the majority are benign. Frequently, an underlying cause is not identified despite extensive diagnostic testing. Petechiae may be caused by CMV infection which is rarely considered in the differential diagnostic process. Most immunocompetent adults with primary CMV infection are asymptomatic or develop a mononucleosis-like syndrome with fever and mild hepatitis. Case report: We report the case of a 30-year-old man who presented to an out-of-hours general physician consult with intermittent fever for three weeks. Examination showed petechiae on the upper extremities. Initial laboratory data revealed lymphocytosis and elevated liver enzyme tests. Further testing showed positive CMV throat swab and CMV/EBV immunoglobulin M and G. His symptoms resolved gradually without any treatment. Why should an emergency physician be aware of this?: This report shows that primary CMV infection can be a cause of petechiae. Emergency physicians should keep in mind that although uncommon, immunocompetent adults can experience acute symptomatic CMV infections characterized by an extended disease course and testing may avoid unnecessary and extensive diagnostic workup and repeated hospital contacts.

Background: Fever of unknown origin (FUO) in developing countries is an important dilemma and further research is needed to elucidate the infectious causes of FUO. Methods: A multi-center study for infectious causes of FUO in lower middle-income countries (LMIC) and low-income countries (LIC) was conducted between January 1, 2018 and January 1, 2023. In total, 15 participating centers from seven different countries provided the data, which were collected through the Infectious Diseases-International Research Initiative platform. Only adult patients with confirmed infection as the cause of FUO were included in the study. The severity parameters were quick Sequential Organ Failure Assessment (qSOFA) ≥2, intensive care unit (ICU) admission, vasopressor use, and invasive mechanical ventilation (IMV). Results: A total of 160 patients with infectious FUO were included in the study. Overall, 148 (92.5%) patients had community-acquired infections and 12 (7.5%) had hospital-acquired infections. The most common infectious syndromes were tuberculosis (TB) (n=27, 16.9%), infective endocarditis (n=25, 15.6%), malaria (n=21, 13.1%), brucellosis (n=15, 9.4%), and typhoid fever (n=9, 5.6%). Plasmodium falciparum, Mycobacterium tuberculosis, Brucellae, Staphylococcus aureus, Salmonella typhi, and Rickettsiae were the leading infectious agents in this study. A total of 56 (35.0%) cases had invasive procedures for diagnosis. The mean qSOFA score was 0.76±0.94 {median (interquartile range [IQR]): 0 (0–1)}. ICU admission (n=26, 16.2%), vasopressor use (n=14, 8.8%), and IMV (n=10, 6.3%) were not rare. Overall, 38 (23.8%) patients had at least one of the severity parameters. The mortality rate was 15 (9.4%), and the mortality was attributable to the infection causing FUO in 12 (7.5%) patients. Conclusions: In LMIC and LIC, tuberculosis and cardiac infections were the most severe and the leading infections causing FUO.

Many clinical conditions can cause fever of unknown origin (FUO) in children, but the etiological diagnosis remains challenging despite the variety of inspection methods available at present. This study aims to investigate the effectiveness of droplet digital polymerase chain reaction (ddPCR) in identifying pathogens in children with FUO as a novel application. A 7-month-old boy failed to obtain etiology evidence for his disease through various tests. After collecting peripheral blood for ddPCR analysis, Staphylococcus aureus and Escherichia coli were detected, and Sanger sequencing confirmed the pathogens. During the disease, the child developed septic arthritis and osteomyelitis in the femur. Despite the patient's fever being removed, his limb activity improving, and inflammatory biomarkers decreasing, avascular necrosis of the femoral head remained after targeted antibiotic treatment and surgery. If the patient had undergone ddPCR analysis at an early stage, it may be possible to avoid sequelae. ddPCR helps identify pathogens in the diagnosis of children with FUO and could be a promising complementary tool.

Objectives: Clinicians often face the challenge of differentially diagnosing febrile patients who are suspected of infectious diseases, since the clinical manifestations of infection and cancer may overlap. A single test that can detect both pathogens and tumor could provide timely and accurate diagnostic clues to aid the treatment and management of these patients. Methods: We enrolled eight patients to evaluate the utility of metagenomic Next-Generation Sequencing for simultaneously detecting pathogens and neoplasms using body fluids and tissue samples. Patients were selected by the following criteria: 1) Tumor was not considered upon hospitalization, but mNGS testing indicated neoplasm; 2) Tumor was not excluded, but microbial infection was primarily suspected according to initial clinical assessment. Results: We detected potential pathogens in five patients, three of whom had progressed into critical infections. Moreover, abnormal chromosomal copy numbers were identified in all patients that indicated presence of neoplasms, which were pathologically confirmed. Conclusions: Although copy number variations do not render a definitive cancer diagnosis, it can prompt clinicians to conduct more focused diagnostic testing for cancer, potentially saving time and cost. As a result, integrating copy number analysis with pathogen detection in mNGS may help establish rapid and accurate diagnosis for febrile patients.

Background: Intravascular large B-cell lymphoma (IVLBCL) is rare and fatal when diagnosed late in the disease course. Random skin biopsy (RSB) is useful for early diagnosis, but criteria for its application are not well established. Objective: To develop an IVLBCL-probability scoring system for stratifying patients and investigate its feasibility and capability for RSB application. Methods: A retrospective cohort of 77 consecutive patients with suspected IVLBCL who underwent RSB was included in this study. All patients were classified into 3 IVLBCL-probability groups according to the IVLBCL-probability scoring system comprising the following 4 components: general symptoms, organ-specific symptoms, serum soluble-interleukin-2 receptor levels, and serum lactate-dehydrogenase levels. Results: The high (score 7-10), intermediate (score 4-6) and low (score 1-3) IVLBCL-probability groups contained 32, 30, and 15 patients, respectively. All 5 patients with IVLBCL were stratified into the high IVLBCL probability group. Accuracies in the diagnosis of IVLBCL were 100%, 100%, and 93.8% for the low, intermediate, and high IVLBCL-probability groups. The positive detection rate in the high IVLBCL-probability group increased to 9.4% from 3.9% across all groups. Conclusions: The newly-developed IVLBCL-probability scoring system has good capability for stratification of patients and could allow limiting application of RSB for diagnosis only to high-probability groups.

In malignant mesotheliomas, cases involving the peritoneum as the primary site are rare, accounting for approximately 10% of all mesothelioma cases. We report a case of medical-type peritoneal mesothelioma leading to death 2 months after the onset of fever of unknown origin, along with a review of the literature. A 76-year-old man presented with a fever of unknown origin over 4 weeks. Thoracoabdominal computed tomography (CT) scan showed increased mesenteric adipose tissue density. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scan showed diffuse hyperaccumulation in the mesentery and hyperaccumulation in the intraperitoneal and parasternal lymph nodes. A thoracoscopic biopsy of the parasternal lymph nodes revealed metastatic peritoneal mesothelioma. The treatment plan was discussed with him and his family, and the best supportive care was provided. 2 months later, he died from multiple organ failure. Underlying malignant tumors cause 38% of mesenteric panniculitis cases. Symptoms accompanied by lymphadenopathy within the area of mesenteric panniculitis are highly suggestive of malignancy. Peritoneal mesothelioma can be classified as (1) classical, which is accompanied by abdominal pain, ascites, and abdominal masses; (2) surgical, which is accompanied by hernia incarceration and intestinal occlusion; and (3) medical, wherein systemic symptoms, such as fever and weight loss, are primarily observed. The medical-type peritoneal mesothelioma, wherein systemic symptoms are primarily observed, has a poorer prognosis than the other types. FDG-PET/CT is an effective diagnostic modality for peritoneal mesothelioma and typically shows diffuse hyperaccumulation along the peritoneal surface.

Objective: Thyrotoxicosis from local invasion of the thyroid gland by an extrathyroidal malignancy is rare. We describe a patient with thyrotoxicosis secondary to invasion of the thyroid gland by an oropharyngeal squamous cell carcinoma (OPSCC). To our best knowledge, this has not been reported. Case Report: A 62-year-old Indian man with histologically proven, p16-negative, cT3N3bM0 (stage IVb) posterior OPSCC was admitted for elective gastrostomy. Biochemical thyroid profile was normal before admission, and there was no thyroid invasion radiologically. The patient developed persistent fever and tachycardia associated with an elevated white cell count and C-reactive protein. This was treated as sepsis, and antibiotic therapy was initiated for 17 days without response. An extensive septic workup did not reveal any infection. A subsequent neck computed tomography revealed rapid progression of the OPSCC, with the invasion of bilateral thyroid lobes. Thyroid function tests revealed primary hyperthyroidism. Antibodies indicative of Graves’ disease were negative. A tracheostomy was performed due to impending airway compromise. The patient showed minimal clinical improvement with medical management, and thyroid function continued to worsen. He died due to cardiorespiratory collapse due to tumor progression, new-onset atrial fibrillation, and poor underlying cardiac function. Discussion: We report a rare observation of thyrotoxicosis secondary to thyroid gland invasion by OPSCC. This highlights the need for a high index of suspicion of malignancy-induced hyperthyroidism and evaluation of thyroid function early in febrile/tachycardic patients with locoregionally advanced head and neck SCCs. Urgent oncological treatment may be necessary to control thyrotoxicosis.

Tularemia is a rare zoonotic disease caused by the two predominant subspecies of Francisella tularensis, namely subspecies tularensis and subspecies holarctica. The latter is less virulent than the former, is endemic in Europe, and usually has a mild disease course, although respiratory involvement and bacteraemia can occur. Tularemia in Belgium is rare, but the incidence seems to be increasing. It therefore seems prudent to raise awareness among clinicians for this potentially severe disease. We report the first case of pneumonic tularemia with bacteraemia from Belgium, and want to recommend including Francisella tularensis in the differential diagnosis of pneumonia when an unfavorable evolution is seen with standard treatment.

Objective: To develop and validate a diagnostic score to identify adult-onset Still's disease (AOSD) in fever of unknown origin (FUO). Methods: A single center, retrospective case-control study of inpatients with FUO from January 2018 to December 2021. Using clinical and laboratory data from 178 cases with AOSD and 486 cases with FUO, we developed an AOSD/FUO (AF) score with a Bayesian Model Averaging approach. AF score and Yamaguchi's criteria were evaluated by sensitivity, specificity, accuracy, and positive/negative predictive value for diagnosis of AOSD in developmental and validation samples. Results: Persistent pruritic eruptions (PPEs) in patients with rashes was higher in AOSD group than FUO group (52.3% vs 7.4%; P

COVID-19 can damage the endothelial cells of every organ in the body and lead to vasculopathy and vasculitis. It has been shown that various types of vasculitis could be a new manifestation of COVID-19. Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic necrotizing vasculitis that affects small vessels. Here we report our experience with a 42-year-old man with a 3-weeks history of fever of unknown origin after two months from COVID-19 recovery presented with loss of appetite, loss of weight, and paresthesia in his lower extremities. After required evaluations including nerve biopsy, EGPA was diagnosed for him.

Hemophagocytic lymphohystiocytosis is an extremely life-threatening immune deregulatory syndrome. It is characterized by pathologic activation of immune cells, leading to excessive cytokine production, multiorgan failure, and potentially, death. A 28-year-old primigravida at 32 weeks and 3 days of gestation presented with newly-diagnosed preeclampsia with severe features, fever, and fetal tachycardia. She was delivered by cesarean delivery. After delivery, she had a fever of unknown origin, with evidence of a hyperinflammatory state. Extensive infectious work-up was significant for positive Epstein-Barr Virus. A bone marrow biopsy demonstrated hemophagocytosis. She was diagnosed with Epstein-Barr-Virus-associated hemophagocytic lymphohystiocytosis and was treated with immunosuppression and chemotherapy. Hemophagocytic lymphohistiocytosis is a rare, life-threatening immune dysregulatory syndrome with both genetic and extragenic triggers that can occur in the postpartum period. Rituximab is an effective add-on therapy to conventional treatment.

Introduction: It is important to predict adverse outcomes in febrile children with hematology/oncology diseases. Procalcitonin (PCT) is a promising biomarker for the prediction of infection severity, but further studies have revealed its performance in excluding adverse outcomes of infection. IL-6 and IL-10 were reported to have a close association with those infection outcomes. The aim of the study was to investigate the performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal PCT., Methods: This was a retrospective study conducted in a tertiary children's hospital in China over the past ten years. Inflammatory biomarkers, including IL-6, IL-10, PCT and C-reactive protein (CRP), were detected at the onset of infection. Separate analyses were conducted in patients with neutropenia and without neutropenia., Results: In total, 5987 febrile cases were enrolled. For patients with neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with bloodstream infection (BSI), gram-negative bacteremia (GNB) and severe sepsis (SS), but only IL-6 and IL-10 were predictive of GNB and SS. For patients without neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with BSI, GNB and SS, but no biomarkers were predictive of adverse outcomes. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis in patients with neutropenia., Conclusions: IL-6 and IL-10 could be predictors for GNB and SS in febrile patients with neutropenia and had some association with unfavorable outcomes in febrile patients without neutropenia. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Although acute HIV-induced HLH is rare in literature, HIV is an important differential diagnosis in patients with HLH. In our study, a 33-year-old previously healthy male patient was admitted with fever of unknown origin, lymphadenopathy, generalized edema, transaminitis, acute renal failure, oliguria, myalgias, night sweats, unintentional weight loss, and leukopenia. Disease course was indicative of a viral-like prodrome of roughly 2-month duration. At an outside hospital, full viral work-up (including EBV, CMV, HIV antibodies, hepatitis panel) was negative. HIV p24 antigen assay was not available at the outside facility. Outside liver chemistry and lymph node biopsy were suggestive of HLH. HLH was confirmed via serum ferritin, white cell receptor, and cytokine studies. Repeat viral and rheumatologic studies revealed a positive p24 antigen with indeterminant HIV antibody. We demonstrate efficacy of a specific treatment plan as well as importance of p24 antigen studies in patients with HLH and/or the HIV window-period, adding to available literature/documentation of a rare disease process.

Resumen: Introducción: Los parechovirus humanos (HPeV) son virus de la familia Picornaviridae, recientemente descritos, a los que se atribuyen cuadros de fiebre sin foco (FSF), sepsis clínica, gastroenteritis, meningitis o encefalitis fundamentalmente en lactantes pequeños. Nuestro objetivo fue describir la epidemiología y las características clínicas de las infecciones por HPeV en nuestro medio. Pacientes y métodos: Estudio multicéntrico prospectivo, llevado a cabo en 12 hospitales a nivel nacional, entre 2013-2015, en niños 3 meses. Todos los pacientes presentaron fiebre, el 45% irritabilidad, el 18,6% exantema y el 14% diarrea. No se observa ninguna alteración específica en las pruebas bioquímicas. El diagnóstico final más frecuente fue FSF (61%) seguido de sepsis clínica (29%). Aunque un 29% de los niños precisaron ingreso en cuidados intensivos, solo un paciente presentó secuelas. Conclusiones: Los HPeV circulan en nuestro país, afectando fundamentalmente a lactantes < 2 meses y se asocian a FSF y sepsis clínica, con un predominio en primavera y verano. Sería de interés implementar las técnicas moleculares de diagnóstico en todos los hospitales para reconocer y manejar adecuadamente estas infecciones. Abstract: Introduction: Human parechovirus (HPeV) is one of the recently described picornaviridae viruses that have been associated with fever of unknown origin (FUO), clinical sepsis, gastroenteritis, meningitis, or encephalitis in very young infants. The aim of this study is to describe the epidemiology and clinical features of these viruses. Patients and methods: A prospective multicentre 3-year study was conducted in 12 hospitals in Spain. Out of 850 specimens examined, 47 were positive (5.52%), with HPeV-3 being the most frequent (29 cases). Infections occurred throughout the year, but mainly in May and July, and a biennial distribution was observed. More than half (57%) were neonates, and only 2 children were older than 3 months. Fever was present in all children, with irritability in 45%, rash in 18.6%, and diarrhoea in 14%. The results of biochemical tests were all in normal range. The most common final diagnosis was FUO (61%), followed by clinical sepsis (29%). Up to 29% of infants were admitted to the intensive care unit, but only one patient had sequelae. Results: Out of 850 specimens examined, 47 were positive (5.52%) for HPeV, with HPeV-3 being the most frequent (29 cases). Infections occurred throughout the year, but mainly in May and July, and a biennial distribution was observed. More than half (57%) were neonates, and only 2 children were older than 3 months. Fever was present in all children, with irritability in 45%, rash in 18.6%, and diarrhoea in 14%. The results of biochemical tests were all in normal range. The most common final diagnosis was FUO (61%), followed by clinical sepsis (29%). Up to 29% of infants were admitted to the intensive care unit, but only one patient had sequelae Conclusions: HPeV circulates in our country, mainly during spring and summer, and affects young infants with a FUO and clinical sepsis. Molecular diagnostic techniques in all hospitals could help in improving the management of patients with these infections.

Objective: Fever of unknown origin (FUO) is a diagnostic challenge. This study aimed to assess the efficacy of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and gallium-67 single-photon emission computed tomography/computed tomography (67Ga SPECT/CT) in diagnosing FUO. Methods: A total of 68 patients with FUO underwent 18F-FDG PET/CT and 67Ga SPECT/CT from January 2013 through May 2016. Images were read independently. The imaging results were compared with the final diagnosis and categorized as helpful for diagnosis or non-contributory to diagnosis in the clinical setting. Associations between categorical variables were evaluated with the chi-square test or Fisher’s exact test. Results: Ten of the 68 patients were excluded. An infectious underlying disease was found in 23 patients. A malignant disorder was the cause of FUO in 10 patients. Non-infectious inflammatory disease was found in 11 patients. Adrenal insufficiency was the cause of FUO in two patients. The cause of FUO was not found for 12 patients. A high false-positive rate of 44% (7/16) was observed for 18F-FDG PET/CT, while a high false-negative rate of 55% (23/42) was observed for 67Ga SPECT/CT. 18F-FDG PET/CT studies depicted all 67Ga-avid lesions. The sensitivity (79% vs. 45%) and clinical contribution (72% vs. 55%) of 18F-FDG PET/CT in diagnosing FUO were significantly higher than those of 67Ga SPECT/CT (p

Background: Patients with persistent fevers of undetermined etiology often undergo extensive evaluation without a diagnosis. Autoinflammatory syndromes may not always be considered in the differential, as these are rare entities, there are no consensus clinical criteria and genetic testing can only capture a few of these diseases. We aimed to describe the experience and value of an undiagnosed diseases program in the evaluation and management of patients who present with persistent fevers., Methods: A retrospective analysis was performed on eleven patients who presented with persistent fevers to the Undiagnosed Diseases Program (UDP) at University of Alabama at Birmingham. All patients received extensive testing prior to referral and were seen by multiple subspecialists. The primary outcome of complete remission was resolution of episodes of fever and malaise in response to empiric biological anti-inflammatory treatment., Results: All patients received genetic testing and further diagnostic evaluation by the UDP. Even without confirmed genetic testing, they were empirically started on anti-inflammatory therapies (including colchicine, IL-1 inhibitors, IL-6 inhibitors). Ten patients have achieved complete remission on empiric treatment. Three patients were given formal diagnoses. No patients have had any major adverse events from therapy., Conclusions: This is a pilot study suggesting the role for empiric treatment trials of biologics for patients with suspected autoinflammatory diseases. As the differential diagnosis of patients with persistent fevers is broad, and the diagnosis of autoinflammatory diseases often comes with some degree of uncertainty, evaluation by a center with expertise in diagnosing these conditions can help determine which patients should have empiric trials of biologics., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Southern Society for Clinical Investigation. All rights reserved.)

A mycotic aneurysm is an infection of the vessel wall which can be bacterial, fungal, or viral in origin. It is invariably a fatal infectious disease if appropriate treatment is not done. We describe the case of a forty-six years male who presented with complaints of high-grade fever and lower back pain with worsening symptoms with the passage of the illness. An infrarenal lobulated abdominal aortic aneurysm was confirmed by CT angiography. He underwent aneurysmorrhaphy and metronidazole was started following the culture report (Bacteroides fragilis). He was discharged successfully from the hospital., (Copyright © 2022 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Hemophagocytic syndrome (HPS) may be primary or secondary to malignancies, infections, autoimmune diseases, or drugs. In most cases, HPS occurs at the same time as the diagnosis of underlying malignancy or when it relapses. In rare situations, the neoplastic disease can be occult, even for more than a decade. We report the case of a 28-year-old woman admitted because of HPS. Treatment with etoposide for fulminant HPS was effective. Four months later, she was admitted again because of newly developed subcutaneous nodules and cellulitis-like skin lesions over her legs. Excisional biopsy of subcutaneous nodule showed subcutaneous panniculitis-like T-cell lymphoma. After etoposide, solumedrol, cytosine arabinoside, and cisplatin regimen chemotherapy, both skin lesions and subcutaneous nodules disappeared. In conclusion, for patients presenting with HPS and cellulitis-like skin lesions, occult lymphoma should be considered, which might not be diagnosed for months, even years. Adequate treatment, including steroid and chemotherapy against malignant lymphoma, should be started as soon as possible for patients with fulminant HPS because of its fatal course. [J Formos Med Assoc 2007;106(2 Suppl):S55-S59]

OBJETIVO: quando a queixa febre é única ou preponderante, em criança atendida em consultório ou ambulatório, é recomedado selecionar aquelas que requerem investigação mais apurada, determinar os exames mais indicados para triagem, detectar os casos que exigem intervenção imediata e saber lidar com o sintoma febre e a ansiedade que ela provoca. FONTES DE DADOS: levantamento bibliográfico no Medline e em artigos previamente selecionados por sua importância. SÍNTESE DE DADOS: a febre pode acarretar alguns efeitos danosos e outros benéficos, nenhum de grande monta. A anamnese deve enfocar faixa etária, intensidade da febre, tremores de frio, alterações evidentes do apetite e do comportamento (estado infeccioso), outros sintomas localizatórios e duração do episódio febril. Os exames de triagem são hemograma, VHS, proteína C-reativa, exame de urina (leucócitos e bacterioscópico), eventualmente liquor e hemocultura. O tratamento da febre pode ser feito com antitérmicos, às vezes, completado com meios físicos (banho, compressas) para reduzir o desconforto. CONCLUSÃO: a criança com febre exige do pediatra conhecimentos técnicos que se aplicam a todos os casos, e empatia, para individualizar a conduta.OBJECTIVE: to determine how to select a child who requires in depth laboratory investigation, defining the most appropriate laboratory screening tests, and to detect the individual who requires immediate therapy, when fever is the main symptom presented by the child seen in an outpatient clinic, or at the physician's office. Additionally, this review aims at providing suggestions on how to deal with fever, and with the anxiety it causes. SOURCES OF DATA: bibliographic review using Medline database and previously selected manuscripts. SUMMARY OF THE FINDINGS: fever may cause both negative and positive outcomes, none of major consequence. Age group, fever magnitude and duration, shivering, appetite decrease or behavioral changes (toxemia), and other localizing symptoms should be investigated through the patient's medical history. Laboratory screening tests should include complete blood count, erythrocyte sedimentation rate, C-reactive protein, urinalysis (white cells count and gram stain of the sediment), and in some cases, lumbar puncture and blood culture. The treatment should include antipyretic medications and, occasionally, physical methods (cool baths, sponging) in order to reduce discomfort caused by the fever. CONCLUSIONS: children with fever request both scientific expertise, as well as empathy from the pediatrician, so that they can receive individualized therapy.

We report, to the best of our best knowledge, the oldest individual to ever be diagnosed with Familial Hemophagocytic Lymphohistiocytosis (FHL) Type 2 from homozygous c.1349C>T (p.T450M) missense variants in the PRF1 gene. This rare case advanced in complexity with a simultaneous diagnosis of Chronic Active Epstein-Barr Virus (CAEBV) - a distinct clinical entity from acute EBV infections and a well-described trigger of Hemophagocytic Lymphohistiocytosis (HLH). This is, to the best of our knowledge, the only individual to ever be diagnosed with CAEBV in the setting of this specific variant and the oldest to be diagnosed with a coexisting perforin variant. This case provides understanding of EBV, human genetics, and lymphoproliferative disorders while adding a unique differential diagnosis to adults who present with fever of unknown origin and diffuse lymphadenopathy without evidence of malignancy. This report explores the diagnosis and treatment of both HLH and CAEBV, encouraging discussion regarding current clinical management and future research needs., Competing Interests: Conflicts of interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Portal vein thrombosis (PVT) is well recognized as a complication of hepatic cirrhosis and is likely to be suspected in patients with hypercoagulable syndromes, however, it is rarely recognized as a possibility in otherwise healthy patients with Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infection. We report a case of a healthy 27-year-old man with fever and weight loss who was found to have PVT in the setting of acute EBV and CMV infection., Case Report: A 27-year-old man with no known medical history presented to the emergency department (ED) for fever for 18 days. Patient reported daily high fevers associated with chills, night sweats, generalized myalgia, nausea with appetite loss, and unquantified weight loss. Vital signs showed temperature of 100.5°F. Patient reported discomfort upon palpation of abdomen on physical examination. There was no lymphadenopathy, cardiac murmur, rash, or jaundice. Laboratory tests revealed titers diagnostic of acute EBV and CMV infection with elevated liver function tests and leukocytosis with lymphocyte predominance (white blood cell count 15,400/μL; 43% atypical lymphocytes). Computed tomography of the abdomen/pelvis with i.v. contrast showed a filling defect in the anterior portal vein. The patient was admitted with the ED diagnosis of PVT secondary to viral infection and was initiated on anticoagulation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although rarely considered, CMV has been associated with PVT in up to 6% of cases, and EBV infection has been implicated as well. Emergency physicians should be aware of this potentially serious complication of these common viral infections and consider imaging modalities to rule out thrombosis, if appropriate., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to detect the seroprevalence of Crimean-Congo haemorrhagic fever virus (CCHFV) in patients with fever of unknown origin (FUO) in endemic (Kyzylorda) and non-endemic (Almaty) oblasts of Kazakhstan., Methods: Paired serum samples from 802 patients with FUO were collected. Serum samples were investigated by ELISA to detect IgG and IgM antibodies against CCHFV. Sera with suspected acute infection were further investigated by RT-PCR to detect the viral RNA., Results: IgG antibodies were detected in 12.7% of the sera from both oblasts. Acute infection was shown by IgM ELISA in four patients from Kyzylorda, with only one developing severe CCHF. Viral RNA was found by RT-PCR in the other three patients' sera. Phylogenetic analysis of partial L and S segments revealed CCHFV genotype Asia 2 and a possible reassortment between the genotypes Asia 1/Asia 2. Animal husbandry, such as working with cattle and horses, was significantly associated with CCHFV seropositivity., Conclusions: The antibodies and viral RNA detected in sera indicate that mild or even asymptomatic CCHFV infections are presented in Kazakhstan. This study describes the circulation of CCHFV in the so far non-endemic Almaty oblast for the first time. In conclusion, physicians treating patients with FUO in Kazakhstan should be aware of mild CCHF., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)