Acute Horner syndrome secondary to glandular fever due to Epstein Barr virus infection.

We present a clinical situation where a 47-year old female patient consulted with left partial ptosis and miosis that started, two weeks before, with an episode of glandular fever secondary to Epstein-Barr infection. Apraclonidine 0.5% and Phenylephrine 1% drop testing was performed with results consistent with suspected left Horner Syndrome (HS), with a probable postganglionic location. Magnetic Resonance Angiography (MRA) at the moment of the acute presentation did not show any image suggesting carotid arterial dissection but showed irregular narrowing of the left internal carotid artery on its paravertebral extracranial way, consistent to enlarged intra-carotid sheath lymphoid tissue. A week later, a Doppler ultrasound was performed, showing bilateral images compatible with internal carotid arterial dissection. When Postganglionar HS is suspected, the first aetiology to rule out is a carotid arterial dissection because of its potentially fatal outcome and for being a more described entity as postganglionic HS aetiology. However, it is also evidenced that a certain diagnose is not always possible. Furthermore, we describe the enlarged internal carotid artery sheath lymphoid tissue as a possible cause of sympathetic nerve disruption causing a Postganglionar HS, although not common.

Case Report: Splenic Infarction in Infectious Mononucleosis due to Epstein-Barr Virus Infection.

Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis (IM) and IM is a clinical syndrome typically characterized by fever, pharyngitis, and cervical lymph node enlargement. We describe the case of a 19-year-old man with IM complicated by splenic infarction. The patient visited our hospital because of upper abdominal pain without a fever and sore throat. Abdominal computed tomography revealed a low-density area in the spleen, which indicated splenic infarction. The next day, he developed a fever. After diminishing abdominal pain and fever, he developed pharyngitis accompanied by fever. Acute EBV infection was confirmed by serological tests. The patient was successfully managed with no specific therapy. Splenic infarction is a rare complication of IM and this case showed that splenic infarction can precede a fever and pharyngitis.

Effects of chloroquine or hydroxychloroquine treatment on non-SARS-CoV2 viral infections: A systematic review of clinical studies.

Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used as antiviral agents for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. We performed a systematic review to examine whether prior clinical studies that compared the effects of CQ and HCQ to a control for the treatment of non-SARS-CoV2 infection supported the use of these agents in the present SARS-CoV2 outbreak. PubMed, EMBASE, Scopus and Web of Science (PROSPERO CRD42020183429) were searched from inception through 2 April 2020 without language restrictions. Of 1766 retrieved reports, 18 studies met our inclusion criteria, including 17 prospective controlled studies and one retrospective study. CQ or HCQ were compared to control for the treatment of infectious mononucleosis (EBV, n = 4), warts (human papillomavirus, n = 2), chronic HIV infection (n = 6), acute chikungunya infection (n = 1), acute dengue virus infection (n = 2), chronic HCV (n = 2), and as preventive measures for influenza infection (n = 1). Survival was not evaluated in any study. For HIV, the virus that was most investigated, while two early studies suggested HCQ reduced viral levels, four subsequent ones did not, and in two of these CQ or HCQ increased viral levels and reduced CD4 counts. Overall, three studies concluded CQ or HCQ were effective; four concluded further research was needed to assess the treatments' effectiveness; and 11 concluded that treatment was ineffective or potentially harmful. Prior controlled clinical trials with CQ and HCQ for non-SARS-CoV2 viral infections do not support these agents' use for the SARS-CoV2 outbreak.

Harm as a Necessary Component of the Concept of Medical Disorder: Reply to Muckler and Taylor.

Wakefield's harmful dysfunction analysis asserts that the concept of medical disorder includes a naturalistic component of dysfunction (failure of biologically designed functioning) and a value (harm) component, both of which are required for disorder attributions. Muckler and Taylor, defending a purely naturalist, value-free understanding of disorder, argue that harm is not necessary for disorder. They provide three examples of dysfunctions that, they claim, are considered disorders but are entirely harmless: mild mononucleosis, cowpox that prevents smallpox, and minor perceptual deficits. They also reject the proposal that dysfunctions need only be typically harmful to qualify as disorders. We argue that the proposed counterexamples are, in fact, considered harmful; thus, they fail to disconfirm the harm requirement: incapacity for exertion is inherently harmful, whether or not exertion occurs, cowpox is directly harmful irrespective of indirect benefits, and colorblindness and anosmia are considered harmful by those who consider them disorders. We also defend the typicality qualifier as viably addressing some apparently harmless disorders and argue that a dysfunction's harmfulness is best understood in dispositional terms.

Lymphoma Mimicking Chronic Active Epstein-Barr Virus: A Case Report.

Epstein-Barr virus (EBV) is the main cause of infectious mononucleosis (IM), a self-limiting infection among immunocompetent patients. EBV is also implicated in the development of several malignancies. We describe a case of a previously healthy 34-year-old man who presented with non-tender, enlarging, right cervical lymphadenopathy for over a year that was associated with significant weight loss, fevers, and night sweats. Two fine needle core biopsies showed inconclusive then reactive tissue, respectively. A third excisional biopsy demonstrated a reactive lymph node with EBV-positive IM. There was no evidence of lymphoma by histologic examination or flow cytometry. A diagnosis of chronic active EBV (CAEBV) was rendered. Subsequent lymph node debulking six months later showed classic Hodgkin lymphoma (CHL) positive for EBV. The patient underwent chemotherapy with full treatment response. This is an unusual presentation of EBV infection that led to either a delayed onset or delayed diagnosis of CHL.

Spontaneous lymphoblastoid cell lines from patients with Epstein-Barr virus infection show highly variable proliferation characteristics that correlate with the expression levels of viral microRNAs.

The Epstein-Barr virus (EBV) induces B-cell proliferation with high efficiency through expression of latent proteins and microRNAs. This process takes place in vivo soon after infection, presumably to expand the virus reservoir, but can also induce pathologies, e.g. an infectious mononucleosis (IM) syndrome after primary infection or a B-cell lymphoproliferation in immunosuppressed individuals. In this paper, we investigated the growth characteristics of EBV-infected B-cells isolated from transplant recipients or patients with IM. We found that these cells grew and withstood apoptosis at highly variable rates, suggesting that the expansion rate of the infected B-cells widely varies between individuals, thereby influencing the size of the B-cell reservoir and the ability to form tumors in infected individuals. All viruses investigated were type 1 and genetically close to western strains. EBV-infected B-cells expressed the transforming EBV latent genes and microRNAs (miRNAs) at variable levels. We found that the B-cell growth rates positively correlated with the BHRF1 miRNA levels. Comparative studies showed that infected B-cells derived from transplant recipients with iEBVL on average expressed higher levels of EBV miR-BHRF1 miRNAs and grew more rapidly than B-cells from IM patients, suggesting infection by more transforming viruses. Altogether, these findings suggest that EBV infection has a highly variable impact on the B-cell compartment that probably reflects the genetic diversity of both the virus and the host. It also demonstrates the unexpected finding that B-cells from different individuals can grow at different speed under the influence of the same virus infection.

Spontaneously Ruptured Spleen Samples in Patients With Infectious Mononucleosis: Analysis of Histology and Lymphoid Subpopulations.

OBJECTIVES: Spontaneous rupture of the spleen is occasionally seen as the presenting event in infectious mononucleosis (IM). Diagnosis of these cases can be very challenging. METHODS: We describe the morphologic and immunohistochemical findings in a series of seven splenectomy specimens removed after spontaneous rupture in patients with IM. Most cases were submitted for a second opinion since the histology of the cases suggested malignant lymphoma. RESULTS: All the cases showed similar findings, with red pulp expansion occupied by activated T and B cells, including scattered large lymphocytes with both T- and B-cell markers, together with a polymorphic background rich in cytotoxic T cells. Clonality analysis revealed T-cell receptor clonal patterns in four of the six cases evaluated. CONCLUSIONS: IM should be considered a possible diagnosis in any case of splenic rupture whose histology suggests possible aggressive lymphoma.

Detection of Apoptotic Lymphocytes Through Sysmex XN-1000 As a Diagnostic Marker for Mononucleosis Syndrome.

BACKGROUND: The infectious mononucleosis (IM) includes clue elements, apoptotic and atypical lymphocytes. In IM, the evaluation of dot plot provided by Sysmex XN-1000 analyzer revealed a stretched lymphocytic cluster, white cell differential channel (WDF), on cytogram. METHODS: In this study, we analyzed 698 samples that include 39 IM, 76 chronic lymphoproliferative disorders, 25 nonclonal lymphocytosis, and 40 healthy donors. Five hundred eighteen samples with other diseases or interference were evaluated. The algorithm was validated on 40,000 files that were received from internal database of Sysmex-Dasit. RESULTS: The analysis of flow cytometry standard (FCS) files in WDF channel and presumed apoptotic lymphocytes counts on side scatter/forward scatter (SSC/FSC) and SSC/SFL (where SFL is side fluorescence) dot plot revealed excellent correlation among apoptotic cells on peripheral blood smear (R(2)  = 0.79 and 0.75). There was a variation of positional parameters in lymphocyte clusters WX, WY, and WZ. If WX-SSC > 500 and WY-SFL > 1,000 and WZ-FSC > 700, specificity equals to 99% and sensitivity equals to 100%. If nucleated red blood cell (NRBC) <0.03 × 10(3) /µl, specificity equals to 100%. In received files, positives were 1% adding the simultaneous presence of a percentage of events in the two gates relating to the apoptotic lymphocytes of 1.2% of WBC. CONCLUSION: On Sysmex XN-1000, dot-plot observation allowed immediate detection of IM. Meanwhile, an algorithm based on the parameters on these plots can be calculated with excellent performance.

Kinetics of Epstein-Barr Virus (EBV) Neutralizing and Virus-Specific Antibodies after Primary Infection with EBV.

Prospective studies of antibodies to multiple Epstein-Barr virus (EBV) proteins and EBV neutralizing antibodies in the same individuals before, during, and after primary EBV infection have not been reported. We studied antibody responses to EBV in college students who acquired primary EBV infection during prospective surveillance and correlated the kinetics of antibody response with the severity of disease. Neutralizing antibodies and enzyme-linked immunosorbent assay (ELISA) antibodies to gp350, the major target of neutralizing antibody, reached peak levels at medians of 179 and 333 days after the onset of symptoms of infectious mononucleosis, respectively. No clear correlation was found between the severity of the symptoms of infectious mononucleosis and the peak levels of antibody to individual viral proteins or to neutralizing antibody. In summary, we found that titers of neutralizing antibody and antibodies to multiple EBV proteins increase over many months after primary infection with EBV.

Infectious mononucleosis, other infections and prostate-specific antigen concentration as a marker of prostate involvement during infection.

Although Epstein-Barr virus has been detected in prostate tissue, no associations have been observed with prostate cancer in the few studies conducted to date. One possible reason for these null findings may be use of cumulative exposure measures that do not inform the timing of infection, i.e., childhood versus adolescence/early adulthood when infection is more likely to manifest as infectious mononucleosis (IM). We sought to determine the influence of young adult-onset IM on the prostate by measuring prostate-specific antigen (PSA) as a marker of prostate inflammation/damage among U.S. military members. We defined IM cases as men diagnosed with IM from 1998 to 2003 (n = 55) and controls as men without an IM diagnosis (n = 255). We selected two archived serum specimens for each participant, the first collected after diagnosis for cases and one randomly selected from 1998 to 2003 for controls (index), as well as the preceding specimen (preindex). PSA was measured in each specimen. To explore the specificity of our findings for prostate as opposed to systemic inflammation, we performed a post hoc comparison of other infectious disease cases without genitourinary involvement (n = 90) and controls (n = 220). We found that IM cases were more likely to have a large PSA rise than controls (≥ 20 ng/mL: 19.7% versus 8.8%, p = 0.027; ≥ 40% rise: 25.7% versus 9.4%, p = 0.0021), as were other infectious disease cases (25.7% versus 14.0%, p = 0.020; 27.7% versus 18.0%, p = 0.092). These findings suggest that, in addition to rising because of prostate infection, PSA may also rise because of systemic inflammation, which could have implications for PSA interpretation in older men.