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Biological false-positive reactions to non-treponemal syphilis tests occur under various conditions, including in patients with infectious mononucleosis. However, false-positive treponemal test results are rarely reported. We present three cases of Epstein-Barr virus-associated infectious mononucleosis that exhibited concurrent false-positive results in both treponemal and non-treponemal tests, effectively imitating syphilis serology. Notably, the false-positive treponemal test results were transient and persisted for more than 6 months before reverting to negative. This is atypical for true Treponema pallidum infection (syphilis), in which treponemal tests usually remain positive for life. This case series highlights the potential for misdiagnosis and emphasizes the importance of careful interpretation of syphilis serology results in the context of infectious mononucleosis. This is particularly important when typical syphilis symptoms are absent, as in our patients. The similarity in the clinical manifestations between infectious mononucleosis and syphilis, including sore throat, lymphadenopathy, rash, and hepatitis, further complicates the diagnostic process. Clinicians should consider recent Epstein-Barr virus-associated infectious mononucleosis when interpreting positive syphilis serology, especially in young adults presenting with mononucleosis-like symptoms. Follow-up serological testing is useful to avoid unnecessary treatment and potential patient mismanagement., Competing Interests: Declaration of competing interest The author declares no competing interest associated with this article., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (EBV-HLH) and infectious mononucleosis (IM) are characterized by fever, hepatomegaly, and splenomegaly, but HLH has a 50% lethality rate. Therefore, this study aimed to compare the laboratory findings in differentiating EBV-HLH children from IM children who have fever, hepatomegaly, or splenomegaly. A total of 131 IM patients and 29 EBV-HLH pediatric patients with fever, hepatomegaly, or splenomegaly were enrolled in our study. The clinical traits and laboratory findings were analyzed, and a predictive regression analysis was also performed. EBV-HLH patients had a lower set of diagnostic markers, which included fibrinogen (FIB), white blood cells (WBC), hemoglobin (Hb), and platelet (PLT), compared to IM patients. Triglyceride (TG) and ferritin were elevated obviously in EBV-HLH patients compared to IM patients. CD4 dim CD8 + T cells are highly activated T cells. EBV-HLH patients experienced a significant decrease in the absolute number and ratio of CD4 dim CD8 + T cells (CD4 dim CD8 + T#, CD4 dim CD8 + T%) compared to IM patients in our study. The AUC of CD4 dim CD8 + T # in the diagnosis of EBV-HLH was 0.920 with a sensitivity of 86.2% and a specificity of 90.1%. A logistic regression analysis was developed to improve sensitivity. The results revealed that lower levels of Hb, FIB, and CD4 dim CD8 + T cells were risk factors for EBV-HLH. The regression model for separating EBV-HLH from EBV-IM had an AUC of was 0.996 with a sensitivity of 100% and a specificity of 95.3%. The ratio and absolute number of CD4 dim CD8 + T cells were decreased in IM and EBV-HLH patients. EBV-HLH can be identified in IM patients with fever, hepatomegaly, or splenomegaly by detecting Hb, FIB, and the absolute number of CD4 dim CD8 + T cells., Competing Interests: Declarations. Ethics approval: The study was approved by the local ethics committee of Hunan Children’s Hospital (Code: HCHLL-2024–471). Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Castleman's disease (CD), also called angiofollicular lymphoid hyperplasia, is a rare lymphoproliferative illness with two unique variants: unicentric disease and multicentric disease (MCD). The multicentric variant is rare and presents as a systemic illness with symptoms like peripheral lymphadenopathy, splenomegaly, anaemia and systemic inflammatory symptoms. Given the vague and systemic presentation, this variant can be difficult to differentiate from infection and other autoimmune diseases. Here, we discuss the case of a middle-aged female who presented to the hospital with a 2 week history of systemic symptoms, including cough, fever, weight loss and painful lymphadenopathy at the neck and posterior auricular region. Initially, the patient was treated for presumed upper respiratory infection in the setting of Epstein-Barr virus (EBV); however, an excisional biopsy of the cervical lymph node confirmed the diagnosis of MCD. In this case, we highlight the diagnostic dilemma of MCD, especially in association with EBV., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Aim: Kikuchi-Fujimoto disease (KFD) rarely affects pediatric patients and is characterized by prolonged fever and cervical lymphadenopathy. The diagnosis of KFD remains challenging and often requires an invasive biopsy. Low serum alkaline phosphatase levels have frequently been observed in patients with KFD; however, the clinical significance of low serum alkaline phosphatase levels remains unclear., Methods: This retrospective study included pediatric patients aged < 16 years who were pathologically or clinically diagnosed with KFD and infectious mononucleosis between April 2016 and March 2023. Serum alkaline phosphatase levels were analyzed employing age- and sex-specific reference intervals. Clinical and laboratory data were evaluated to determine their association with serum alkaline phosphatase levels., Results: Thirty patients with KFD and 23 patients with infectious mononucleosis were included in the study. Seventeen patients with KFD (56.7%) had serum alkaline phosphatase levels below the 2.5th percentile of the age- and sex-specific reference intervals. Serum alkaline phosphatase levels were significantly lower in patients with KFD than in those with infectious mononucleosis. Clinical and other laboratory findings were not significantly different between patients with KFD with or without a decline in serum alkaline phosphatase levels., Conclusion: A decrease in serum alkaline phosphatase levels, particularly when assessed as a percentage of age- and sex-specific reference intervals, may be a valuable and noninvasive supportive feature of KFD in pediatric patients., (© 2025 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a severe hyperinflammatory disorder induced by overactivation of macrophages and T cells. This study aims to identify the risk factors for the progression from infectious mononucleosis (EBV-IM) to EBV-HLH, by analyzing the laboratory parameters of patients with EBV-IM and EBV-HLH and constructing a clinical prediction model. The outcome of this study carries important clinical value for early diagnosis and treatment of EBV-HLH., Methods: A retrospective analysis was conducted on 60 patients diagnosed with EBV-HLH and 221 patients diagnosed with EBV-IM at our hospital between November 2018 and January 2024. Participants were randomly assigned to derivation and internal validation cohorts in a 7:3 ratio. LASSO regression and logistic regression analyses were employed to identify risk factors and construct the nomogram., Results: Ferritin (OR, 213.139; 95% CI, 8.604-5279.703; P=0.001), CD3 - CD16 + CD56 + % (OR, 0.011; 95% CI, 0-0.467; P=0.011), anti-EBV-NA-IgG (OR, 57.370; 95%CI, 2.976-1106.049; P=0.007), IL-6 (OR, 71.505; 95%CI, 2.118-2414.288; P=0.017), IL-10 (OR, 213.139; 95% CI, 8.604-5279.703; P=0.001) were identified as independent predictors of EBV-HLH. The prediction model demonstrated excellent discriminatory capability evidenced by an AUC of 0.997 (95% CI,0.993-1.000). When visualized using a nomogram, the ROC curves for the derivation and validation cohorts exhibited AUCs of 0.997 and 0.993, respectively. These results suggested that the model was highly stable and accurate. Furthermore, calibration curves and clinical decision curves indicated that the model possessed good calibration and offered significant clinical benefits., Conclusions: The nomogram, which was based on these five predictors, exhibited robust predictive value and stability, thereby can be used to aid clinicians in the early detection of EBV-HLH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Wu, Wang, Liu, Zhu, Huang, Chen and Lv.)

Objective: To investigate the diagnostic value of peripheral blood lymphocyte testing in children with infectious mononucleosis (IM)., Methods: A total of 135 children with IM as the IM group and 100 healthy volunteers as the healthy group were included in this retrospective study. Peripheral blood lymphocyte subsets marked as CD3+, CD4+, CD8+, CD16 + CD56+, and CD19 + in the peripheral blood were quantified using flow cytometry. Statistical analysis was performed using the chi-square test, Kruskal-Wallis test, AUROC curve, and Kappa consistency test to assess the diagnostic value of these markers in IM., Results: The AUROC curve for CD8 + cells and for CD4+/CD8 + ratios both achieved a value of 1 with the sensitivity and specificity of 100% (P<0.001). The Kappa coefficients were 1 for CD8+, CD4+/CD8 + ratios and the combined EBV analysis, indicating a 100% consistency with the clinical diagnosis. Significant differences were also observed in the CD3+, CD4+, CD16 + CD56+, and CD19 + lymphocyte subsets between the IM group and the healthy group (P<0.05)., Conclusion: The evaluation of CD8 + and CD4+/CD8 + ratios in peripheral blood lymphocytes represents a significant advancement in the diagnosis of IM. Peripheral blood lymphocyte testing offers a reliable, sensitive, and specific diagnostic tool to enhance the clinical management of children with IM., Competing Interests: Declarations Consent for publication Not Applicable. Human research ethics approval The study was approved by the Medical Ethics Committee of the Suqian First Hospital and Xuzhou Medical University (2019-SL-0014) and conducted in accordance with the Declaration of Helsinki. All patients’ parents or legal guardians were informed with the study and the signed consent forms were obtained. Consent to participate statement All patients’ parents or legal guardians were informed with the study and the signed consent forms were obtained. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Sialadenitis has rarely been reported in patients with infectious mononucleosis (IM). Our patient was a 22-year-old man who presented with bilateral swelling of the parotid and submandibular glands, a fever, malaise, and splenomegaly. Laboratory tests revealed an increased percentage of atypical lymphocytes in the leukocyte fraction. Serological testing for antibodies against Epstein-Barr virus (EBV) revealed an acute infection pattern. The patient was diagnosed with sialadenitis associated with IM caused by EBV infection. With symptomatic treatment, the salivary gland swelling completely resolved within a week. This case suggests that EBV-induced IM should be included in the differential diagnosis of diffuse sialadenitis with elevated atypical lymphocyte counts.

Large diagnostic panels allow for pathogens with high or low likelihood of causing attributable illness to be tested simultaneously. Infectious mononucleosis (IM) due to primary infection with Epstein-Barr virus (EBV) is a common cause of acute febrile illness (AFI) in case series from high-income countries, though its contribution to AFI in tropical low-income settings is unclear. As part of a case-control study using multiplex quantitative polymerase chain reaction (qPCR) diagnostics, we set out to determine if primary EBV infection was an underrecognized cause of AFI in the Peruvian Amazon. Presence of EBV DNA in whole-blood samples was equally prevalent among febrile cases and afebrile controls (34.6% [247/714] versus 35.7% [248/695]) and was not correlated with classic IM symptoms. Given the clear lack of clinical significance of the whole-blood PCR results, additional testing was pursued to ascertain the true prevalence of IM among cases of AFI in this population. The presence of EBV DNA in plasma, a marker of active EBV-related processes, was detected in 7% (5/68). Anti-EBNA-1 IgG, a late marker of prior infection, was tested via ELISA and detected in 4/5 of the plasma-positive patients, thereby excluding an acute primary EBV infection in all but one patient. Infectious mononucleosis due to primary infection with EBV was not an important etiology of AFI in the Peruvian Amazon, despite high rates of initial test positivity.

Background: Bilateral optic neuritis associated with optic disc swelling is a common feature of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, extensive deep retinal haemorrhages have not been described in the context of MOG-associated optic neuritis. Here, we report a case of infectious mononucleosis with marked binocular peripapillary and perivascular haemorrhages as well as extensive deep retinal haemorrhages in the presence of MOGAD., Case Report: A 39-year-old Chinese woman presenting with subacute binocular vision reduction with no light perception was diagnosed with MOGAD. Fundus examination revealed the presence of binocular peripapillary and perivascular haemorrhages as well as extensive deep retinal haemorrhages with severe optic disc swelling greater in the right eye than in the left and dilated and tortuous retinal venules. The patient tested positive for the Epstein-Barr virus (EBV) antigen (595 U/mL) and the EBV capsid antigen (>750 U/mL). She had a fever and right upper quadrant abdominal pain, and a doctor determined splenomegaly 1 week before the onset of orbital pain and decreased vision acuity. Medical history and laboratory tests indicated the presence of concurrent infectious mononucleosis. Other investigational indicators of retinal haemorrhages, including hypertension, diabetes mellitus, vascular disease, systemic lupus erythematosus, metabolic disease, and renal or liver dysfunction, were absent., Discussion: This case suggests that retinal haemorrhage is a possible complication of infectious mononucleosis in the presence of MOGAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Sun, Wei, Xu and Zhou.)

Epstein-Barr virus (EBV) is a major cause of infectious mononucleosis (IM), characterized by fever, fatigue, sore throat, lymphadenopathy, atypical lymphocytosis, and elevated liver enzymes. However, ascites is a rare complication associated with IM. We present a rare case of IM with ascites and peritonitis in a patient who underwent a peritoneal biopsy. A 20-year-old woman presented with fatigue and abdominal distension. Laboratory examination revealed atypical lymphocytes in peripheral blood (54%) and elevated liver enzymes. EBV serological tests revealed a recent primary infection (EBV VCA IgM 1:160). Computed tomography revealed moderate ascites and peritonitis. Adenocarcinoma was suspected based on the ascites' cytology. Considering possible complications of IM and adenocarcinoma, a laparoscopic biopsy was performed. Histological findings of biopsy specimens from the peritoneum, omentum, and fimbria of the fallopian tube demonstrated severe inflammatory cell infiltration and focal aggregation of large EBV-encoded RNA-1 (EBER1)-positive B cells, mimicking EBV-positive polymorphous B-cell lymphoproliferative disorder. Furthermore, intracytoplasmic inclusion bodies of Chlamydia trachomatis were observed by immunohistochemistry. Real-time polymerase chain reaction detected C. trachomatis in cervical secretions. Two months after laparoscopy, ascites decreased, and the diagnosis was IM-associated peritonitis with C. trachomatis infection. IM should be considered as a differential diagnosis in young patients with ascites., (© 2024 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Objective: To develop a prediction model based on peripheral blood signs to distinguish between infectious mononucleosis and chronic active EBV infection., Methods: Retrospective data was collected for 60 patients with IM (IM group) and 20 patients with CAEBV infection (CAEBV group) who were hospitalized and diagnosed at the General Hospital of Tianjin Medical University between December 2018 and September 2022. The analyses used were univariate and LASSO (least absolute shrinkage and selection operator) logistic regression., Results: Univariate analyses revealed that both IM and CAEBV-infected patients displayed overlapping and intersecting clinical manifestations, such as fever, sore throat, enlarged lymph nodes, and enlargement of the liver and spleen, and that in contrast to inflammatory responses in peripheral blood, CAEBV-infected patients had more severe inflammatory responses. Nine biomarkers-HGB, lymphocyte count, percentage of lymphocytes, ALB, fibrinogen, CRP, IFN-, IL-6, and EBV-DNA load-were subsequently selected by LASSO logistic regression modeling to serve as discriminatory models., Conclusions: Our investigation offers a solid foundation for diagnosing IM and CAEBV infection using the LASSO logistic regression model based on the significance and availability of peripheral blood indicators. Infected patients with CAEBV require early medical attention., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Jin hua Yuan, Chong jie Pang, Shuang Long Yuan.)

Epstein-Barr virus (EBV) typically infects B cells in infectious mononucleosis (IM), but a rare case shows EBV infection in T cells. Seven cases of lymphoproliferative disorder caused by EBV-positive cytotoxic T/natural killer (NK) cell proliferation in the lymph nodes, termed IM with transient EBV infection of T and NK cells (EBV + T/NK cells in IM), are reported here. The purpose of the study is to describe clinicopathological features of EBV + T/natural killer (NK) cells in IM of the lymph node. We retrospectively analysed seven cases of Chinese children and young people adults with EBV + T/NK cells in IM. We used morphological observation, immunohistochemical staining, EB virus in situ hybridisation detection, and analysis of T-cell receptor gene rearrangement. The patients were healthy prior to illness, experiencing sudden onset occurring in all the patients, with high fever as the first symptom, followed by lymphadenopathy and hepatosplenomegaly. Diagnosis occurred < 1.5 months of symptom onset. Most lymphocytes in lesions expressed CD3 and Granzyme B or TIA-1 and lacked CD5. CD56 was expressed in numerous cells in 5 of the 7 cases. EBV-encoded RNA (EBER) was detected in medium-to-large-sized cells (50-100 cells per cell/high-power field). T-cell receptor (TCR) gene rearrangement was seen in six cases, with monoclonal rearrangement in four cases. Treatment was conservative treatment but not chemotherapy. Four received anti-HLH therapy and others anti-inflammatory treatment. All patients survived with relapse after long-term clinical observation and follow-up. EBV + T/NK cells in IM can elicit malignant features that mimic T/NK-cell lymphoma pathologically and benign features mimicking IM clinically. These findings indicate that EBV + T/NK cells in IM could serve as valuable diagnosis. Additional clinical information, including age of onset (children and young people), nature of onset (sudden), disease course (short), symptoms (systemic), EBV infection status (acute), and lymph node involvement, is crucial for accurate diagnosis and prognostic evaluation., (© 2024. The Author(s).)

Objective: This study aims to enhance the management of Epstein-Barr Virus (EBV) infections by analyzing the correlation between laboratory indicators and clinical manifestations in children, thereby proposing more precise diagnostic and treatment strategies., Methods: In this retrospective study included 163 pediatric patients with EBV infections treated at the Children's Hospital of Soochow University from December 2017 to December 2019. Data collected through retrospective analysis included gender, age, clinical symptoms, signs, liver function tests, T-cell subset distribution, EBV-DNA copy numbers in plasma, and treatment outcomes. Patients were grouped based on EBV-DNA copy numbers in plasma and hospital stay duration to compare clinical indicators across different groups., Results: The dichotomous results of EBV-DNA copy numbers in plasma showed that the two groups of children were significantly different in the number of days of fever (p = .0022), platelet count (p = .0212), ALT (p = .001), immunoglobulin IgM (p = .0039), IgG (p = .0195), TBiL (p = .025), LDH (p = 0.0001), and length of hospital stay (p < .001) were significantly different, indicating that EBV-DNA copy numbers in plasma may be correlated with these characteristic variables. The dichotomous results of the length of hospital stay showed that the two groups were significantly increased in tonsil enlargement (p = .0024), platelet count (p = .0059), LDH (p = .0394), and ferritin (p = .0106) and EBV-DNA copy numbers in plasma (p = 0.0361) were significantly different, This suggests a potential correlation between EBV-DNA copy numbers in plasma and these clinical indicators., Conclusion: Variations in platelet counts and lactate dehydrogenase (LDH) levels in children with EBV infections may serve as indicators of clinical outcomes., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Rationale: Splenic infarction usually occurs in patients with underlying illnesses such as thromboembolic disorders and infiltrative hematologic diseases. Herein, we report a rare case of splenic infarction in a previously healthy boy diagnosed with infectious mononucleosis (IM). Splenic infarction is a rare complication of IM and its incidence is unknown. This case report summarizes the clinical characteristics, treatment options, and anticipated time for recovery from splenic infarction in IM., Patient Concern: A16-year-old boy presented to our clinic with complaints of fever, sore throat, and general sweakness for 7 days. The patient was diagnosed with IM due to an Epstein-Barr virus infection. Two days later, the patient developed severe abdominal pain in the left upper quadrant and returned to our ER for further evaluation., Diagnosis: IM complicated with splenic infarction., Interventions: Contrast-enhanced CT confirmed the diagnosis of splenic infarction. This patient was admitted for supportive treatment and close medical monitoring. Surgical., Outcomes: The patient recovered well with conservative treatment., Lessons: IM is most often seen in adolescents and young adults. Splenic infarction is a rare complication of IM, particularly in patients who do not usually have any underlying predisposing medical conditions. Contrast-enhanced CT is the imaging modality of choice in suspected cases. Early recognition and treatment of splenic infarction in patients with IM can help prevent potentially life-threatening events. Patients should be advised to avoid sports that may precipitate splenic rupture. However it is still unknown when it is safe for patients to resume sports. In our case, 6 weeks after the splenic infarction, the patient generally felt well with complete resolution of objective symptoms and splenomegaly, and resumed sports without experiencing any adverse events., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Previous investigations into multiple sclerosis (MS) risk factors predominantly relied on retrospective studies, which do not consider different follow-up times and assume a constant risk effect throughout lifetime., Objective: We aimed to evaluate the impact of genetic and early life factors on MS diagnosis by employing a time-to-event analysis in a prospective cohort., Methods: We used the UK Biobank data, considering the observation period from birth up to 31 December 2022. We considered genetic risk, using a multiple sclerosis polygenic risk score (MS-PRS), and various early life factors. Tobacco smoking and infectious mononucleosis diagnosis were also considered as time-varying variables along the follow-up. Using a Cox proportional hazards model, we examined the associations between these factors and MS diagnosis instantaneous risk., Results: We analyzed 345,027 participants, of which 1669 had an MS diagnosis. Our analysis revealed age-dependent effects for sex (females vs males) and higher MS-PRS, with greater hazard ratios observed in young adults., Conclusion: The age-dependent effects suggest that retrospective studies could have underestimated sex and genetic variants' risk roles during younger ages. Therefore, we emphasize the importance of a time-to-event approach using longitudinal data to better characterize age-dependent risk effects., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The Epstein-Barr virus (also known as EBV), responsible for infectious mononucleosis, is a virus that infects the majority of the world's population. Infection occurs in several forms, most often asymptomatic, or as a fever accompanied by pharyngitis and lymphadenopathies. A rare complication of infectious mononucleosis is acute acalculous cholecystitis, an inflammation of the gallbladder characterized by ischaemia and severe cholestasis. The diagnosis of this pathology is made by imaging, but determining the cause may be tricky. We present here the case of acute acalculous cholecystitis in a 21-year-old woman. This case highlights a rare complication of EBV infection that is probably under-diagnosed, and demonstrates the usefulness of interpreting liver tests and leukocyte count in association with imaging findings.

Purpose of Review: Infectious mononucleosis (IM) is an infectious disease that presents clinically in only a small percentage of individuals despite almost universal infection with the causative agent. Here, we review the latest concepts in the clinical presentation, epidemiology, and host response of this disease., Recent Findings: Several recently published papers/reviews describe IM as a condition caused by one of several etiologic agents including, cytomegalovirus (HHV-5), Roseola virus (HHV-6) and Toxoplasmosis amongst others; this review focuses on IM as solely caused by the human herpes virus 4 (HHV-4). Since the initial discovery of the virus in the 1960s and its subsequent discovery as the primary etiologic agent for IM it has been associated with several human cancers and autoimmune disorders. Recent published findings show a correlation between HHV-4 and the autoimmune disorder, multiple sclerosis (MS), suggesting earlier IM could possibly act as a causative factor. Considering the important links being made with IM to so many cancers and autoimmune disorders it is surprising that a standard investigative procedure has yet to be determined for this disease. A standard approach to the investigation of IM would ensure more cases are diagnosed, particularly atypical cases, this would benefit epidemiological studies, and more immediately help practitioners distinguish viral from bacterial throat infections, enabling them to treat accordingly., Summary: The understanding of the latest concepts in clinical presentation, epidemiology and host response to IM would benefit greatly from the introduction of a standard procedure for its investigation and diagnosis., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Epstein-Barr virus (EBV) is a nonhepatotropic virus. It causes mild self-limiting illness characterized by fever, oral ulcer, diarrhea, lymphadenopathy, and hepatosplenomegaly. Rarely it causes acute liver failure (ALF). EBV-related ALF (EBV-ALF) accounts for 0.2% of all ALF cases. The prognosis of EBV-ALF is dismal, and it can affect both immunocompromised and immunocompetent individuals. We performed a partial autopsy on a 30-year-old immunocompetent individual with infectious mononucleosis and ALF. The autopsy showed characteristic histomorphology of EBV-ALF in the form of centrizonal confluent hepatocytic necrosis, portal mixed inflammatory infiltrate, sinusoidal lymphocytosis, numerous hemophagocytic figures, and tissue Epstein-Barr encoded RNA-in situ hybridization (EBER-ISH) positivity. Extensive hemophagocytosis was noted in the liver, spleen, lymph node, and bone marrow. Other features include T-zone expansion of lymph nodes and spleen, interstitial pneumonia pattern in the lungs, and exanthematous skin changes. EBV-DNA polymerase chain reaction from the postmortem blood sample yielded 70,200 copies/µL. The index case highlights the uncommon occurrence of EBV-ALF, its histomorphological features, and its putative pathogenesis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The goal was to study the difference of virological, immunologic, and inflammatory indicators between Epstein-Barr associated infectious mononucleosis (EBV-IM) and EBV associated hemophagocytic lymphohistiocytosis (EBV-HLH) and to explore the evaluation indicators for monitoring the therapeutic efficacy of EBV-HLH., Methods: Twenty children with EBV-IM (IM group) and 10 children with EBV-HLH (HLH group) were selected. Virology indicators were detected; the absolute count of lymphocyte, and lymphocyte subsets were detected; the levels of immunoglobulin and ferritin were assayed., Results: Compared to the IM group, the HLH group showed a decrease in EBV-specific VCA-IgM antibody levels (U = 29.0, p = 0.006) and an increase in EBV-specific NA-IgG antibody levels (U = 17.0, p = 0.001), while there was no significant difference in EB-DNA loads (t = 0.417, p = 0.680). The counts of lymphocytes, and various lymphocyte subsets in the HLH group were lower than those in the IM group. Inflammatory markers in the HLH group were significantly higher than those in IM group. Dynamic monitoring of virological, immunological, and inflammatory indicators in HLH patients during treatment showed that EBV DNA gradually decreased in patients with good prognosis. Inflammatory indicators significantly decreased and returned to normal, lymphocyte count significantly increased and returned to normal during treatment. However, patients with poor prognosis showed rebound increase in EBV DNA and inflammatory indicators in the later stage of treatment, while lymphocyte count further decreased with the recurrence of the disease., Conclusions: Exhausted and damaged immune function in host by persistent stimulation of EB viral antigen is one of the main pathogeneses of EB-HLH. Lymphocyte count and serum ferritin level are effective indicators to monitor the therapeutic efficacy during the treatment to HLH.

Purpose: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease characterized by substantial fatigue, postexertional malaise, unrefreshing sleep, and orthostatic intolerance, among other symptoms. Specific risk factors for the development of ME/CFS have not been adequately characterized. It has been suggested that ME/CFS is a connective tissue disorder and that joint hyperflexibility is a risk factor for the development of ME/CFS., Methods: The goal of this study was to examine whether joint hyperflexibility is a risk factor for the development of ME/CFS after infectious mononucleosis (IM). This study was part of a prospective cohort study. College students were studied for the development of IM and were followed up for the development of ME/CFS 6 months later. Participants in the cohort for the present study included 53 students who met criteria for ME/CFS 6 months after IM and 66 recovered control subjects who had modified Beighton scores (a measure of joint hyperflexibility) available., Findings: No connection was found between joint hyperflexibility and the development of ME/CFS after IM. Differences in joint hyperflexibility (as measured by using the modified Beighton score) in the ME/CFS group and the control group were not statistically significant. Female subjects had significantly higher Beighton scores compared with male subjects., Implication: After IM, no relationship was found between joint hyperflexibility and the development of ME/CFS., Competing Interests: Declaration of competing interest None of the authors have any associations that may pose a conflict of interest (including but not limited to pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding) for at least the 2 years before manuscript submission. The sponsor had no role in study design, in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cold agglutinin syndrome (CAS) is a hemolytic anemia mediated by antibodies, mainly IgM, whose maximum activity occurs at 4 °C. It happens secondary to infectious, autoimmune or neoplastic diseases, due to the formation of antibodies that cross-react against erythrocyte antigens, particularly of the I system. Here, we describe a case of CAS associated to Epstein-Barr virus (EBV) reactivation in a patient with primary human immunodeficiency virus (HIV) infection., Clinical Case: 22-year old man with no medical history, hospitalized due to mononucleosis and anemic syndrome. Hemoglobin of 3.7 g/dL and elevation of lactate dehydrogenase were documented. In the peripheral blood smear it was observed spherocytosis, polychromasia and nucleated erythrocytes. EBV infection was confirmed with serology and viral load, as well as seronegative HIV infection with positive viral load. The C3d monospecific direct antiglobulin test was positive and an irregular antibody screening revealed the presence of an anti-I antibody. The patient received transfusion support and conservative treatment, with remission of the symptoms 2 weeks after admission., Conclusions: Cold agglutinin syndrome is a rare, potentially fatal complication of infectious mononucleosis, which should be considered in the face of findings suggestive of hemolysis in order to initiate support measures in a timely manner., (Licencia CC 4.0 (BY-NC-ND) © 2024 Revista Médica del Instituto Mexicano del Seguro Social.)

Background: Infectious mononucleosis is common among adolescents and young adults. Although the majority of cases resolve spontaneously, life-threatening manifestations, and complications have been recognised., Objective: The purpose of this article is to familiarize clinicians with the clinical manifestations, evaluation, diagnosis, and management of infectious mononucleosis., Methods: A search was conducted in October 2022 in PubMed Clinical Queries using the key terms "infectious mononucleosis" OR "Epstein-Barr virus" OR "EBV". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the aforementioned search was used in the compilation of the present article., Results: Infectious mononucleosis, caused by Epstein-Barr virus, most commonly affects adolescents and adults aged 15 to 24 years. Epstein-Barr virus is transmitted primarily in saliva. Infectious mononucleosis is characterized by a triad of fever, tonsillar pharyngitis, and lymphadenopathy. Fatigue may be profound but tends to resolve within three months. Periorbital and/or palpebral edema, typically bilateral, occurs in one-third of patients. Splenomegaly and hepatomegaly occur in approximately 50% and 10% of cases, respectively. A skin rash, which is usually widely scattered, erythematous, and maculopapular, occurs in approximately 10 to 45% of cases. Peripheral blood leukocytosis is observed in most patients; lymphocytes make up at least 50% of the white blood cell differential count. Atypical lymphocytes constitute more than 10% of the total lymphocyte count. The classic test for infectious mononucleosis is the demonstration of heterophile antibodies. The monospot test is the most widely used method to detect the serum heterophile antibodies of infectious mononucleosis. When confirmation of the diagnosis of infectious mononucleosis is required in patients with mononucleosis-like illness and a negative mono-spot test, serologic testing for antibodies to viral capsid antigens is recommended. Infectious mononucleosis is a risk factor for chronic fatigue syndrome. Spontaneous splenic rupture occurs in 0.1 to 0.5% of patients with infectious mononucleosis and is potentially life-threatening. Treatment is mainly supportive. Reduction of activity and bed rest as tolerated are recommended. Patients should be advised to avoid contact sports or strenuous exercise for 8 weeks or while splenomegaly is still present. Most patients have an uneventful recovery., Conclusion: Infectious mononucleosis is generally a benign and self-limited disease. Prompt diagnosis is essential to avoid unnecessary investigations and treatments and to minimize complications. Splenic rupture is the most feared complication. As avoiding exposure to EBV is almost impossible, the most effective way to prevent EBV infection and infectious mononucleosis is the development of an effective, safe, and affordable EBV vaccine that can confer life-long immunity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

To improve the diagnosis of atypical lymphocytes and reduce the misdiagnosis rate,we analyzed the medical records of 2 cases with cell morphology suggestive of atypical lymphocytes.One case was diagnosed with infectious mononucleosis and the other with aggressive NK cell leukemia.The purpose of this paper is to emphasize that the diagnosis of atypical lymphocytes based only on morphological interpretation of cells may be incorrect,which should be combined with clinical symptoms,signs,imaging examination,cell immunophenotype,and disease outcome.

SummaryRhabdomyolysis is characterised by muscle breakdown which causes myoglobin light chain release and can result in renal injury. While some of the most common causes of rhabdomyolysis are trauma related, others include toxins, autoimmune processes or viral aetiologies. We present the case of a 20s-year-old man, with no significant medical history, who presented to the emergency department with a 1-week history of weakness, myalgias, nausea, vomiting and subjective fevers. A review of systems and physical exam were otherwise unremarkable, including being negative for sore throat, dysphagia and lymphadenopathy. On presentation, the patient was noted to have dark urine with a creatine kinase value of 452 458 U/L and an elevated creatinine at 7.23 mg/dL. The patient denied any trauma or increased physical activity. His toxin screen and autoimmune workup were negative. The patient's serological workup was significant for acute Epstein-Barr virus (EBV) infection, without additional viral coinfection or mononucleosis. During his hospitalisation course, the patient was managed with supportive care including haemodialysis. The patient made a full renal recovery and was discharged with scheduled outpatient follow-up. This case highlights the recognition of an acute EBV infection causing rhabdomyolysis in the absence of mononucleosis or concomitant infection., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Infectious mononucleosis (IM) is a common infectious disease in children mainly caused by Epstein-Barr virus (EBV) infection, followed by abnormal immune response, and resulting in serious complications. However, there are few clinical analyses of immune responses in children with IM at different stages., Methods: This study combined EBV serological test and EBV DNA test to diagnose the infection status of children with IM, and the infection status was divided into primary acute IM infection (AIM), primary late IM infection (LIM) and reactivation IM infection (RIM)., Results: The results revealed that the absolute numbers of leukocytes and CD8 + T lymphocytes in primary IM infection were significantly higher than those in reactivation infection, while the frequencies of CD4 + T lymphocytes and B cells were significantly lower than those in reactivation infection. In addition, the activities of ALT, AST, α-HBDH and LDH in liver function indicators in primary infection were significantly increased compared with reactivation infection. Similarly, the EBV DNA levels of the primary infection were significantly higher than that of the reactivation infection., Conclusion: There are differences in immune response at different stages of infection, which can provide guidance for effective treatment in children with IM infection., (© 2023 John Wiley & Sons Ltd.)

Background and Aim: Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and infectious mononucleosis (EBV-IM) share mimic symptoms in the early stages of childhood development. We aimed to examine the clinical features and laboratory indices of these two diseases in children and uncover unique indicators to assist pediatricians in identifying these diseases early., Methods: We collected clinical data from 791 pediatric patients diagnosed with EBV-IM or EBV-HLH, compared the clinical traits and laboratory biomarkers presented in the two groups, and constructed predictive models based on them., Results: Patients with EBV-IM had greater ratios of cervical lymphadenopathy, eyelid edema, and tonsillitis, whereas individuals with EBV-HLH were more likely to have hepatomegaly and splenomegaly. When using the criteria of interleukin (IL)-10 > 89.6 pg/mL, interferon (IFN)-γ > 45.6 pg/mL, ferritin > 429 μg/L, D-dimer > 3.15 mg/L and triglycerides > 2.1 mmol/L, the sensitivity was 87.9%, 90.7%, 98.1%, 91.1% and 81.5% to predict EBV-HLH, while the specificity was 98.4%, 96.3%, 96.5%, 94.1% and 80.6%, respectively. A logistic regression model based on four parameters (IL-10, ferritin, D-dimer, and triglycerides) was established to distinguish EBV-HLH patients from EBV-IM patients, with a sensitivity of 98.0% and a specificity of 98.2%., Conclusions: IL-10, IFN-γ, ferritin and D-dimer levels are significantly different between EBV-HLH and EBV-IM. Predictive models based on clinical signs and laboratory findings provide simple tools to distinguish the two situations., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Epstein-Barr virus (EBV), also known as human herpesvirus 4, is one of the most common pathogenic viruses in humans. EBV mononucleosis always involves the spleen and as such it predisposes to splenic rupture, often without a trauma, and splenic infarction. Nowadays the goal of management is to preserve the spleen, thereby eliminating the risk of post-splenectomy infections., Methods: To characterise these complications and their management, we performed a systematic review (PROSPERO CRD42022370268) following PRISMA guidelines in three databases: Excerpta Medica, the United States National Library of Medicine, and Web of Science. Articles listed in Google Scholar were also considered. Eligible articles were those describing splenic rupture or infarction in subjects with Epstein-Barr virus mononucleosis., Results: In the literature, we found 171 articles published since 1970, documenting 186 cases with splenic rupture and 29 with infarction. Both conditions predominantly occurred in males, 60% and 70% respectively. Splenic rupture was preceded by a trauma in 17 (9.1%) cases. Approximately 80% (n = 139) of cases occurred within three weeks of the onset of mononucleosis symptoms. A correlation was found between the World Society of Emergency Surgery splenic rupture score, which was retrospectively calculated, and surgical management: splenectomy in 84% (n = 44) of cases with a severe score and in 58% (n = 70) of cases with a moderate or minor score (p = 0.001). The mortality rate of splenic rupture was 4.8% (n = 9). In splenic infarction, an underlying haematological condition was observed in 21% (n = 6) of cases. The treatment of splenic infarction was always conservative without any fatal outcomes., Conclusions: Similarly to traumatic splenic rupture, splenic preservation is increasingly common in the management of mononucleosis-associated cases as well. This complication is still occasionally fatal. Splenic infarction often occurs in subjects with a pre-existing haematological condition.

The heterophile antibody (also known as the Monospot) test is a useful screening tool for infectious mononucleosis (IM) resulting from primary Epstein-Barr virus (EBV) infection. However, up to 10% of patients with IM are heterophile negative. Heterophile-negative patients who have lymphocytosis or atypical lymphocytes on peripheral blood smear should be further tested for EBV serologies, which include testing for specific IgM and IgG antibodies against viral capsid antigens, early antigens and EBV nuclear antigen proteins. A diagnostic dilemma arises when the patient has clinical and laboratory features of IM, but is both heterophile negative and seronegative for IM, as illustrated in this case presentation. To avoid missed diagnoses of IM, misdiagnosis of mononucleosis-like illnesses and unnecessary testing, knowledge of test characteristics and the evolving course of EBV serologies is important to assure and inform both the physician and the patient., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

A 28-year-old patient is admitted in the emergency department for management of localized pain in the left hypochondrium and left flank that appeared 48 hours before his visit to the emergency room. At the same time, the patient describes the presence of fever, odynophagia and myalgia present for 8 days. The clinical examination highlights the presence of multiple upper cervical and submandibular bilateral and soft adenopathies of about 1.5 cm. There is also an abdominal defense at the level of the left hypochondrium and the left flank. The exploration will attest the presence of a primary EBV infection associated with a splenic rupture complicated by hemoperitoneum without hemodynamic repercussions. This clinical case illustrates the presence of a rare and potentially fatal complication following a very common disease, infectious mononucleosis.

Background: The typical presentation of Epstein-Barr virus infectious mononucleosis includes fever, pharyngitis, measles-like rash, jaundice, and enlarged lymph nodes, liver, or spleen. A painless bilateral swelling of the upper eyelid, sometimes with drooping of the lateral aspect, may also occur. This sign, referred to as Hoagland sign, is not or only marginally mentioned in reviews and textbooks., Methods: Between 2019 and 2021, two of us evaluated all subjects with a positive acute Epstein-Barr virus serology for the typical signs of mononucleosis and for the possible existence of the Hoagland sign., Results: During the mentioned period, the diagnosis of mononucleosis was made in 26 (14 females and 12 males) subjects aged from 9.0 to 33 years. The initial presentation included fever in 24, enlarged cervical lymph nodes in 23, pharyngitis in 21, a palpable liver in 7, a palpable spleen in 7, jaundice in 2, and a measles-like rash in 2 cases. The Hoagland sign was noted in 14 cases. Patients with and without Hoagland sign did not significantly differ with respect to age and sex., Conclusions: The Hoagland sign is an easily identifiable clinical sign that is common and likely helpful early in the course of Epstein-Barr virus infectious mononucleosis. There is a need to expand awareness of this sign among physicians., (© 2022. The Author(s).)

Background: Individual symptoms and signs of infectious mononucleosis (IM) are of limited value for diagnosis., Objective: To develop and validate risk scores based on signs and symptoms with and without haematologic parameters for the diagnosis of IM., Design and Setting: Data were extracted from electronic health records of a university health centre and were divided into derivation (9/1/2015-10/31/2017) and a prospective temporal internal validation (11/1/2017-1/31/2019) cohort., Method: Independent predictors for the diagnosis of IM were identified in univariate analysis using the derivation cohort. Logistic regression models were used to develop 2 risk scores: 1 with only symptoms and signs (IM-NoLab) and 1 adding haematologic parameters (IM-Lab). Point scores were created based on the regression coefficients, and patients were grouped into risk groups. Primary outcomes were area under the receiver operating characteristic curve (AUROCC) and classification accuracy., Results: The IM-NoLab model had 4 predictors and identified a low-risk group (7.9% with IM) and a high-risk group (22.2%) in the validation cohort. The AUROCC was 0.75 in the derivation cohort and 0.69 in the validation cohort. The IM-Lab model had 3 predictors and identified a low-risk group (3.6%), a moderate-risk group (12.5%), and a high-risk group (87.6%). The AUROCC was 0.97 in the derivation cohort and 0.93 in the validation cohort., Conclusion: We derived and internally validated the IM-NoLab and IM-Lab risk scores. The IM-Lab score in particular had very good discrimination and have the potential to reduce the need for diagnostic testing for IM., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Infectious mononucleosis is a relatively common acute presentation to the ENT department. There is an expected derangement in the liver function test results in most patients. There is no guidance regarding follow up, and practice varies. This study aimed to evaluate the utility of liver function tests and abdominal ultrasound in infectious mononucleosis., Methods: This was a retrospective study of all adult patients admitted under ENT with infectious mononucleosis over a five-year period., Results: A total of 153 patients were included; 80 per cent had abnormal liver function test results at presentation. Around 50 per cent had at least one liver function test assessment following discharge. Median (interquartile range) time to resolution of liver function test results was 32 days (20-50 days); maximum time was 10 months. Six patients had in-patient abdominal ultrasound: all showed a normal liver and biliary tree. No patient developed any liver disease sequelae., Conclusion: The findings suggest that serial assessment of liver function is not required in immunocompetent adults with subclinical derangement in liver function.

Objectives: Infectious mononucleosis (IM) is a clinical syndrome that is characterised by lymphadenopathy, fever and sore throat. Although generally not considered a serious illness, IM can lead to significant loss of time from school or work due to profound fatigue, or the development of chronic illness. This study aimed to derive and externally validate clinical prediction rules (CPRs) for IM caused by Epstein-Barr virus (EBV)., Design: Prospective cohort study., Setting and Participants: 328 participants were recruited prospectively for the derivation cohort, from seven university-affiliated student health centres in Ireland. Participants were young adults (17-39 years old, mean age 20.6 years) with sore throat and one other additional symptom suggestive of IM. The validation cohort was a retrospective cohort of 1498 participants from a student health centre at the University of Georgia, USA., Main Outcome Measures: Regression analyses were used to develop four CPR models, internally validated in the derivation cohort. External validation was carried out in the geographically separate validation cohort., Results: In the derivation cohort, there were 328 participants, of whom 42 (12.8%) had a positive EBV serology test result. Of 1498 participants in the validation cohort, 243 (16.2%) had positive heterophile antibody tests for IM. Four alternative CPR models were developed and compared. There was moderate discrimination and good calibration for all models. The sparsest CPR included presence of enlarged/tender posterior cervical lymph nodes and presence of exudate on the pharynx. This model had moderate discrimination (area under the receiver operating characteristic curve (AUC): 0.70; 95% CI: 0.62-0.79) and good calibration. On external validation, this model demonstrated reasonable discrimination (AUC: 0.69; 95% CI: 0.67-0.72) and good calibration., Conclusions: The alternative CPRs proposed can provide quantitative probability estimates of IM. Used in conjunction with serological testing for atypical lymphocytosis and immunoglobulin testing for viral capsid antigen, CPRs can enhance diagnostic decision-making for IM in community settings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Question: Infectious mononucleosis (IM) is a common viral infection year round, and we see patients with it in our family medicine clinic frequently. With fatigue, fever, pharyngitis, and cervical or generalized lymphadenopathy causing prolonged illness and school absences, we always look for treatments that will shorten the duration of symptoms. Does treatment with corticosteroids benefit these children?, Answer: Current evidence points to small and inconsistent benefits when using corticosteroids for symptom relief in children with IM. Corticosteroids alone or in combination with antiviral medications should not be given to children for common symptoms of IM. Corticosteroids should be reserved for those with impending airway obstruction, autoimmune complications, or other severe circumstances., (Copyright © 2023 the College of Family Physicians of Canada.)

Background: Fever is a common symptom in children with infectious mononucleosis (IM). However, the significance of the duration of a fever is poorly understood. This study aimed to analyze the risk factors for persistent fever in children with IM., Methods: Patients diagnosed with IM (aged <18 years; except those with concomitant hematological malignancies or tumor diseases) in a high-volume academic hospital in 2019 were reviewed from a prospectively maintained database. Children with transient fever (≤7 days) were compared with those with persistent fever (>7 days). The risk factors for persistent fever in children with IM were examined using binary logistic regression. Furthermore, the predictive ability of these risk factors was assessed and presented using a receiver operating characteristic (ROC) curve., Results: Of the 184 children included in this study, 131 (71.96%) belonged to the transient fever group and 53 (28.04%) belonged to the persistent fever group (median age: 49 and 64 months, respectively; p = 0.093). Statistical significance was observed in hepatomegaly, alanine aminotransferase level, blood triglyceride level, and blood Epstein-Barr virus polymerase chain reaction (EBV-PCR) copy number (all p < 0.05). Binary logistic regression revealed that high blood triglyceride level was the risk factor for persistent fever in children with IM. High blood triglyceride level predicted persistent fever duration with an area under the ROC curve of 0.73 and an optimal cutoff value of 1.315 mmol/L., Conclusion: High blood triglyceride level was the risk factor for persistent fever in children with IM. Thus, children with elevated levels of blood triglycerides need additional care. To diagnose IM, a blood EBV-PCR is more useful than a throat-swab EBV-PCR., (© 2023 Japan Pediatric Society.)

Infectious mononucleosis is a viral syndrome characterized by fever, pharyngitis, and posterior cervical lymphadenopathy. It is usually caused by Epstein-Barr virus and most often affects adolescents and young adults 15 to 24 years of age. Primary transmission is through close personal contact with a person who is infected, particularly their saliva. Cost-effective, efficient initial laboratory testing for acute infectious mononucleosis includes complete blood count with differential (to assess for greater than 40% lymphocytes and greater than 10% atypical lymphocytes) and a rapid heterophile antibody test. The heterophile antibody test has a sensitivity of 87% and specificity of 91% but can have a false-negative result in children younger than five years and in adults during the first week of illness. The presence of elevated liver enzymes increases clinical suspicion for infectious mononucleosis in the setting of a negative heterophile antibody test result. Epstein-Barr viral capsid antigen-antibody testing is more sensitive and specific but more expensive and takes longer to process than the rapid heterophile antibody test. Treatment of infectious mononucleosis is supportive; routine use of antivirals and corticosteroids is not recommended. Current guidelines recommend that patients with infectious mononucleosis not participate in athletic activity for three weeks from onset of symptoms. Shared decision-making should be used to determine the timing of return to activity. Immunosuppressed populations are at higher risk of severe disease and significant morbidity. Epstein-Barr virus infection has been linked to nine types of cancer, including Hodgkin lymphoma, non-Hodgkin lymphoma, and nasopharyngeal carcinoma, and some autoimmune diseases.

Background: Ordering a serologic test for infectious mononucleosis (IM) in all young patients with sore throat is costly and impractical. The test threshold to determine when to order a diagnostic test for IM based on the patient's symptoms has not been previously studied., Objective: To determine the test threshold for IM in the management of patients with sore throat., Design and Setting: Online surveys were sent to a convenience sample of US primary care clinicians regarding their decision making about whether or not to order a test for IM in a patient with sore throat., Method: 7 clinical vignettes were created, each with a different combinations of symptoms and signs. The probability of IM for each vignette was estimated by the investigator based on the number of symptoms present to generate a plausible range of disease probabilities. Clinicians were then asked to decide whether to test or not test for IM, and mixed-effect logistic regression was used to determine the test threshold for IM where half of physicians chose to test and half chose not to test., Results: A total of 117 clinicians provided responses for a total of 819 clinical vignettes. The overall test threshold for IM as estimated using the logistic regression was 9.5% (95% CI: 8.2% to 10.9%). The test threshold for clinicians practicing greater than 10 years was significantly higher than for those practicing less or equal to 10 years (10.5% vs 7.3%, P = .02 ). No significant differences between specialties and practice sites were found with respect to the test threshold., Conclusion: This study identified a test threshold for IM of approximately 10% based on realistic clinical vignettes. This threshold was stable regarding the clinician's specialty and practice sites and could be used in the development of a clinical prediction rule to determine the cutoff for low- versus high-risk groups., Competing Interests: Conflict of interest: none., (© Copyright by the American Board of Family Medicine.)

Objective: This study aimed to explore lymphocyte subset determinations as an aid to understanding the pathophysiology of infectious mononucleosis (IM), pneumonia due to mycoplasma infection (P-MI) and Henoch-Schönlein purpura in children., Methods: The peripheral blood lymphocyte subsets of 45 children with IM, 20 children with P-MI, and 31 children with Henoch-Schönlein purpura (HSP), who were treated in the pediatrics department of our hospital from April 2019 to February 2020, were determined by flow cytometry, and the number and percentage of lymphocyte subsets with CD3+, CD3 + CD4+, CD3 + CD8+, CD3 + CD4+/CD3 + CD8+, CD3-CD16 + CD56+, and CD3-CD19 + cells were observed, and the results were compared and analyzed., Results: (1) The percentages of CD3+, CD3 + CD8 + lymphocyte subsets in children in IM group were significantly higher than those in children with P-MI and HSP, and the percentages of CD3-CD19 + lymphocyte subsets in children in IM group were significantly lower than those in children with P-MI and HSP. The percentages of CD3 + CD4 + lymphocyte subsets in children in the three groups were the lowest in children with IM, and the highest in children with P-MI.The differences in the percentages of CD3+, CD3 + CD4+, CD + CD8+, and CD3-CD19 + lymphocyte subsets among the IM, P-MI, and HSP groups were statistically significant (P < 0.01). (2) The results of CD3 + CD4+/CD3 + CD8 + in the three groups were the lowest in children with IM and the highest in children with P-MI. There was a significant difference among the three groups (P < 0.01); The ages of the children with IM and P-MI were lower than that of the children with HSP (p < 0.01), while there was no difference in the ages of the children with IM and P-MI (p > 0.05). (3) The difference in the percentage of CD3-CD16 + CD56 + lymphocyte subsets among the three groups was not statistically significant (P > 0.05)., Conclusion: The determination of peripheral blood lymphocyte subsets is of significance for understanding the pathophysiology of IM, mycoplasma pneumonia, and HSP in children., (© 2022. The Author(s).)

Splenic rupture is the most serious complication of infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) infection, with a mortality rate of over 1 in 10. We reported a case of spontaneous atraumatic splenic rupture secondary to IM in a young man. The patient presented with abdominal pain caused by splenic rupture as the initial symptom. The diagnosis and treatment process went through a series of twists and turns, including the emergency department, general surgery department, and infection department. This case suggests that clinicians should consider the possibility of EBV infection in young patients with spleen rupture without obvious cause to avoid misdiagnosis and missed diagnosis., (© 2022 Wiley Periodicals LLC.)

It has generally been reported that patients with COVID-19 show a fever, cough, and/or respiratory failure as the most common clinical symptoms but some have unusual symptoms, such as anosmia, diarrhea, and throat pain. We herein report a 26-year-old woman with chief complaints of lymphadenopathy and a fever. First, she underwent a laboratory examination, which showed a high proportion of atypical lymphocytes (19%) and an increase in hepatic enzyme activities, and was then hospitalized with a diagnosis of infectious mononucleosis (IM). However, the blood examination did not show any increase in anti-Epstein-Barr virus VCM-IgM. Subsequently, she developed tonsillar hypertrophy with purulent plugs. An additional examination for infection of other pathogens revealed positivity only for SARS-CoV-2 in a loop-mediated isothermal amplification (LAMP) test. The patient was transferred to the COVID-19-specific isolation ward, and none of the ward staff, patients, or either of the two otolaryngologists who had directly examined this patient showed positive signs for SARS-CoV-2 in a LAMP test. Consequently, this case suggests that even if patients show clinical symptoms and signs of common diseases for otolaryngologists, such as IM, we should keep in mind the possibility of COVID-19 without arbitrarily assuming that IM is caused by Epstein-Barr virus., (Copyright © 2021. Published by Elsevier B.V.)

Competing Interests: Competing interests: None declared.

Epstein-Barr virus (EBV) is very common, with the infection rate in adults over 90% worldwide. Infectious mononucleosis (IM) is caused by primary infection with EBV. Most IM patients are generally considered to have a favorable prognosis, but a few patients will also develop complications. Children with severe symptoms will require hospitalization. However, the disease burden of children hospitalized with IM in China has been rarely described. In this study, we included the Face sheets of discharge medical records from 27 member children's hospitals of Futang Research Center of Pediatric Development from Jan 1st, 2016 to Dec 31st, 2020, and medical information such as gender, age, region, time of admission, length of stay and expenditure were extracted. There were 24,120 IM cases, which accounted for 0.42% (24,120/5,693,262) of all hospitalized cases during this period. The ratio of male to female was 1.48:1. Hospitalization for IM in the 4-6 ​years age group was the highest among inpatients of all age groups. Case numbers increased year by year between 2016 and 2020, and the monthly hospitalization was generally high from Jul to Sep but reduced from Jan to Feb per year. Bronchitis/pneumonia and hepatic dysfunction were two common complications in hospitalized IM patients. The median length of stay was 8 days, and the median cost of hospitalization was 970.59 US dollars. This study will help understand the epidemiological characteristics and disease burden of hospitalized children with IM in China., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022 The Authors. Publishing services by Elsevier B.V. All rights reserved.)