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BMJ Clinical Evidence Jul 2014The definition of severe recurrent throat infections is arbitrary, but recent criteria have defined severe tonsillitis as: five or more episodes of true tonsillitis a... (Review)
Review
INTRODUCTION
The definition of severe recurrent throat infections is arbitrary, but recent criteria have defined severe tonsillitis as: five or more episodes of true tonsillitis a year; symptoms for at least 1 year; and episodes that are disabling and prevent normal functioning. Diagnosis of acute tonsillitis is clinical, and it can be difficult to distinguish viral from bacterial infections. Rapid antigen testing has a very low sensitivity in the diagnosis of bacterial tonsillitis, but more accurate tests take longer to deliver results. Bacteria are cultured from few people with tonsillitis. Other causes include infectious mononucleosis from Epstein-Barr virus infection, cytomegalovirus, toxoplasmosis, HIV, hepatitis A, and rubella.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of tonsillectomy in children and adults with acute recurrent or chronic throat infections? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 15 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: cold-steel tonsillectomy and diathermy tonsillectomy.
Topics: Electrocoagulation; Humans; Tonsillectomy; Tonsillitis
PubMed: 25051184
DOI: No ID Found -
European Journal of Pediatrics Oct 2020In previously healthy subjects, vulvar ulcers are mostly caused by sexually transmitted microorganisms. Lipschütz's acute vulvar ulceration, first reported in 1912, is...
In previously healthy subjects, vulvar ulcers are mostly caused by sexually transmitted microorganisms. Lipschütz's acute vulvar ulceration, first reported in 1912, is a non-sexually acquired condition characterized by sudden onset of a few genital ulcers. We systematically review presentation, underlying causes, and disease duration of Lipschütz's ulceration. A comprehensive source of Excerpta Medica, National Library of Medicine, and Web of Science databases was performed. Reports including cases of apparently previously healthy females affected by Lipschütz's ulceration were selected. A predefined database was used to extract data on demographics, history, clinical and microbiological findings, and treatment.The search disclosed 158 cases. Almost 90% of cases were ≤ 20 years of age and sexually inactive. Lesions were usually one to about three, painful, ≥ 10 mm large, well-delimited, with a fibrinous and necrotic center and a symmetric distribution. Voiding disorders and enlarged inguinal lymph nodes were observed in a large subset of cases. Canker sores were noted in 10% of patients. Lipschütz's vulvar ulceration occurred concomitantly with an infectious disease in 139 cases. Infectious mononucleosis syndrome (N = 40) was the most frequently detected well-defined infection, followed by mycoplasma species infections (N = 11). The disease resolved after ≤ 3 weeks.Conclusions: Lipschütz's ulceration mainly affects both sexually inactive and, less frequently, sexually active subjects ≤ 20 years of age, presents with ≤ 3 vulvar ulcers, resolves without recurrences within 3 weeks and is temporarily associated with an infection, most frequently a flu-like illness or an infectious mononucleosis syndrome. What is Known: • Lipschütz's acute vulvar ulceration is a non-sexually acquired condition, which is characterized by a sudden onset of a few necrotic and painful genital ulcers. • The condition tends to resolve spontaneously and is usually triggered by an infection. What is New: • The condition mainly affects subjects ≤ 20 years of age, tends to resolve within 3 weeks, and is usually temporarily associated with a flu-like illness or an infectious mononucleosis syndrome. • Systemic corticosteroids do not reduce disease duration.
Topics: Diagnosis, Differential; Female; Humans; Infant, Newborn; Recurrence; Stomatitis, Aphthous; Ulcer; Vulvar Diseases
PubMed: 32296983
DOI: 10.1007/s00431-020-03647-y -
Frontiers in Immunology 2022Epstein-Barr virus (EBV) is the causal agent of infectious mononucleosis and has been associated with various cancers and autoimmune diseases. Despite decades of...
BACKGROUND
Epstein-Barr virus (EBV) is the causal agent of infectious mononucleosis and has been associated with various cancers and autoimmune diseases. Despite decades of research efforts to combat this major global health burden, there is no approved prophylactic vaccine against EBV. To facilitate the rational design and assessment of an effective vaccine, we systematically reviewed pre-clinical and clinical prophylactic EBV vaccine studies to determine the antigens, delivery platforms, and animal models used in these studies.
METHODS
We searched Cochrane Library, ClinicalTrials.gov, Embase, PubMed, Scopus, Web of Science, WHO's Global Index Medicus, and Google Scholar from inception to June 20, 2020, for EBV prophylactic vaccine studies focused on humoral immunity.
RESULTS
The search yielded 5,614 unique studies. 36 pre-clinical and 4 clinical studies were included in the analysis after screening against the exclusion criteria. In pre-clinical studies, gp350 was the most commonly used immunogen (33 studies), vaccines were most commonly delivered as monomeric proteins (12 studies), and mice were the most used animal model to test immunogenicity (15 studies). According to an adaptation of the CAMARADES checklist, 4 pre-clinical studies were rated as very high, 5 as high, 13 as moderate quality, 11 as poor, and 3 as very poor. In clinical studies, gp350 was the sole vaccine antigen, delivered in a vaccinia platform (1 study) or as a monomeric protein (3 studies). The present study was registered in PROSPERO (CRD42020198440).
CONCLUSIONS
Four major obstacles have prevented the development of an effective prophylactic EBV vaccine: undefined correlates of immune protection, lack of knowledge regarding the ideal EBV antigen(s) for vaccination, lack of an appropriate animal model to test vaccine efficacy, and lack of knowledge regarding the ideal vaccine delivery platform. Our analysis supports a multivalent antigenic approach including two or more of the five main glycoproteins involved in viral entry (gp350, gB, gH/gL, gp42) and a multimeric approach to present these antigens. We anticipate that the application of two underused challenge models, rhesus macaques susceptible to rhesus lymphocryptovirus (an EBV homolog) and common marmosets, will permit the establishment of correlates of immune protection and attainment of more generalizable data.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=198440, identifier PROSPERO I.D. CRD4202019844.
Topics: Animals; Disease Models, Animal; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Infectious Mononucleosis; Macaca mulatta; Mice; Serologic Tests
PubMed: 35493498
DOI: 10.3389/fimmu.2022.867918 -
Journal of Medical Virology May 2016In this meta-analysis, we evaluated the diagnostic role of Epstein-Barr virus deoxyribonucleic acid detection and quantitation in the serum of pediatric and young adult... (Meta-Analysis)
Meta-Analysis Review
In this meta-analysis, we evaluated the diagnostic role of Epstein-Barr virus deoxyribonucleic acid detection and quantitation in the serum of pediatric and young adult patients with infectious mononucleosis. The primary outcome of this meta-analysis was the sensitivity and specificity of Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) detection and quantitation using polymerase chain reaction (PCR). A systematic review and meta-analysis was performed by searching for articles that were published through September 24, 2014 in the following databases: Medline, Cochrane, EMBASE, and Google Scholar. The following keywords were used for the search: "Epstein-Barr virus," "infectious mononucleosis," "children/young adults/infant/pediatric," and "polymerase chain reaction or PCR." Three were included in this analysis. We found that for detection by PCR, the pooled sensitivity for detecting EBV DNA was 77% (95%CI, 66-86%) and the pooled specificity for was 98% (95%CI, 93-100%). Our findings indicate that this PCR-based assay has high specificity and good sensitivity for detecting of EBV DNA, indicating it may useful for identifying patients with infectious mononucleosis. This assay may also be helpful to identify young athletic patients or highly physically active pediatric patients who are at risk for a splenic rupture due to acute infectious mononucleosis.
Topics: Adolescent; Adult; Child; Child, Preschool; DNA, Viral; Female; Herpesvirus 4, Human; Humans; Infant; Infectious Mononucleosis; Male; Molecular Diagnostic Techniques; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity; Viral Load; Young Adult
PubMed: 26455510
DOI: 10.1002/jmv.24402 -
Clinical Otolaryngology : Official... Nov 2022A large proportion of patients with infectious mononucleosis (IM) have abnormal liver function tests (LFT) at presentation. There is no guideline regarding the... (Review)
Review
INTRODUCTION
A large proportion of patients with infectious mononucleosis (IM) have abnormal liver function tests (LFT) at presentation. There is no guideline regarding the management and follow-up of these patients. Some patients also have abdominal ultrasound (US) due to deranged LFT, the need for this practice is unclear. The aim of this systematic review was to evaluate the evidence base on LFT assessment in IM, time to resolution of derangement, and the role of abdominal US.
METHODS
A systematic search of PubMed, EMBASE and the Cochrane library was done. Two authors independently screened records for eligibility using pre-defined criteria. We included both adult and paediatric populations. Quality assessment of included studies was done.
RESULTS
A total of 3924 patients were included from 32 studies, of which LFT values were reported on 2779 patients. A combination of typical clinical features, heterophile antibodies and Epstein-Barr virus-specific antibodies were used to ascertain diagnosis. The following proportion of patients had abnormal LFT: aspartate transaminase (57%); alanine transaminase (62%); alkaline phosphatase (65%); bilirubin (16%); gamma-glutamyltransferase (41%). Reported median (interquartile range) time to resolution of LFT was 8 (6-12) weeks (n = 438). Maximum time to resolution was >6 months. Clinical hepatomegaly and splenomegaly were found in 35% and 44% of patients, respectively. Enlarged liver and spleen on US were seen in 16 of 29 and 38 of 38 of patients, respectively. There were no reports of decompensated liver disease.
CONCLUSION
Current evidence questions the need for routine assessment of LFT in immunocompetent patients presenting with IM; serial LFT assessments following initial abnormalities are not required in immunocompetent patients with subclinical derangement of LFT; routine US abdomen in IM to evaluate for derangement of LFT is not required.
Topics: Adult; Alanine Transaminase; Alkaline Phosphatase; Antibodies, Heterophile; Aspartate Aminotransferases; Bilirubin; Child; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Infectious Mononucleosis; Liver Diseases; Liver Function Tests; gamma-Glutamyltransferase
PubMed: 35834363
DOI: 10.1111/coa.13965 -
Swiss Medical Weekly May 2023Epstein-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...
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.
Topics: United States; Male; Humans; Infectious Mononucleosis; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Splenic Infarction; Retrospective Studies; Rupture, Spontaneous; Splenic Rupture
PubMed: 37245117
DOI: 10.57187/smw.2023.40081 -
JAMA Apr 2016Early, accurate diagnosis of infectious mononucleosis can help clinicians target treatment, avoid antibiotics, and provide an accurate prognosis. (Review)
Review
IMPORTANCE
Early, accurate diagnosis of infectious mononucleosis can help clinicians target treatment, avoid antibiotics, and provide an accurate prognosis.
OBJECTIVE
To systematically review the literature regarding the value of the clinical examination and white blood cell count for the diagnosis of mononucleosis.
DATA SOURCES
The databases of PubMed (from 1966-2016) and EMBASE (from 1947-2015) were searched and a total of 670 articles and abstracts were reviewed for eligibility.
STUDY SELECTION
Eleven studies were included that reported data sufficient to calculate sensitivity, specificity, or both for clinical examination findings and white blood cell count parameters compared with a valid reference standard.
DATA EXTRACTION AND SYNTHESIS
Data were abstracted from each article by at least 2 reviewers, with discrepancies reconciled by consensus. Clinical findings evaluated in only 1 study are reported with sensitivity, specificity, likelihood ratio (LR), and 95% confidence interval, which were calculated from the available data. Findings evaluated in only 2 studies were summarized with their range, findings evaluated in 3 studies were summarized with a univariate random-effects summary, and findings evaluated in 4 or more studies were summarized with a bivariate random-effects meta-analysis.
MAIN OUTCOMES AND MEASURES
Sensitivity, specificity, and LRs for the diagnosis of mononucleosis.
RESULTS
Mononucleosis is most commonly present among patients aged 5 to 25 years (especially those aged 16-20 years, among whom approximately 1 in 13 patients presenting with sore throat has mononucleosis). The likelihood of mononucleosis is reduced with the absence of any lymphadenopathy (summary sensitivity, 0.91; positive LR range, 0.23-0.44), whereas the likelihood increases with the presence of posterior cervical adenopathy (summary specificity, 0.87; positive LR, 3.1 [95% CI, 1.6-5.9]), inguinal or axillary adenopathy (specificity range, 0.82-0.91; positive LR range, 3.0-3.1), palatine petechiae (specificity, 0.95; positive LR, 5.3 [95% CI, 2.1-13]), and splenomegaly (specificity range, 0.71-0.99; positive LR range, 1.9-6.6). Symptoms are of limited value for the diagnosis of mononucleosis; sore throat and fatigue are sensitive (range, 0.81-0.83) but nonspecific. The presence of atypical lymphocytosis significantly increases the likelihood of mononucleosis (summary LR, 11.4 [95% CI, 2.7-35] for atypical lymphocytes ≥10%, 26 [95% CI, 9.6-68] for those with 20%, and 50 [95% CI, 38-64] for those with 40%). The combination of a patient having greater than 50% lymphocytes and greater than 10% atypical lymphocytes also is useful (specificity, 0.99; positive LR, 54 [95% CI, 8.4-189]).
CONCLUSIONS AND RELEVANCE
In adolescent and adult patients presenting with sore throat, the presence of posterior cervical, inguinal or axillary adenopathy, palatine petechiae, splenomegaly, or atypical lymphocytosis is associated with an increased likelihood of mononucleosis.
Topics: Adolescent; Adult; Axilla; Fatigue; Humans; Infectious Mononucleosis; Leukocyte Count; Lymphatic Diseases; Lymphocyte Count; Neck; Pharyngitis; Physical Examination; Purpura; Sensitivity and Specificity; Splenomegaly; Symptom Assessment; Young Adult
PubMed: 27115266
DOI: 10.1001/jama.2016.2111 -
Injury Mar 2016Infectious mononucleosis (IM) is a common viral illness that predominantly causes sore throat, fever and cervical lymphadenopathy in adolescents and young adults.... (Review)
Review
INTRODUCTION
Infectious mononucleosis (IM) is a common viral illness that predominantly causes sore throat, fever and cervical lymphadenopathy in adolescents and young adults. Although usually a benign, self-limiting disease, it is associated with a small risk of splenic rupture, which can be life-threatening. It is common practice therefore to advise avoiding vigorous physical activity for at least 4-6 weeks, however this is not based on controlled trials or national guidelines. We reviewed published case reports of splenic rupture occurring in the context of IM in an attempt to ascertain common factors that may predict who is at risk.
METHOD
A search of MEDLINE and EMBASE databases was performed for case reports or series published between 1984 and 2014. In total, 52 articles or abstracts reported 85 cases. Data was extracted and compiled into a Microsoft Excel(®) spreadsheet.
RESULTS
The average patient age was 22 years, the majority (70%) being male. The average time between onset of IM symptoms and splenic rupture was 14 days, with a range up to 8 weeks. There was a preceding history of trauma reported in only 14%. Abdominal pain was the commonest presenting complaint of splenic rupture, being present in 88%. 32% were successfully managed non-operatively, whereas 67% underwent splenectomy. Overall mortality was 9%.
CONCLUSIONS AND RECOMMENDATIONS
From our data, it appears that men under 30 within 4 weeks of symptom onset are at highest risk of splenic rupture, therefore particular vigilance in this group is required. As cases have occurred up to 8 weeks after the onset of illness, we would recommend avoidance of sports, heavy lifting and vigorous activity for 8 weeks. Should the patient wish to return to high risk activities prior to this, an USS should be performed to ensure resolution of splenomegaly. The majority of cases reviewed had no preceding trauma, although previous studies have suggested this may be so minor as to go unnoticed by the patient. It is therefore prudent to warn patients about the symptoms of splenic rupture to ensure prompt presentation and minimise treatment delay rather than focusing purely on activity limitation.
Topics: Humans; Infectious Mononucleosis; Rupture, Spontaneous; Splenectomy; Splenic Rupture; Splenomegaly
PubMed: 26563483
DOI: 10.1016/j.injury.2015.10.071 -
Annals of Neurology Mar 2006To characterize the association between infectious mononucleosis (IM), a frequent clinical manifestation of primary Epstein-Barr virus infection after childhood, and the... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To characterize the association between infectious mononucleosis (IM), a frequent clinical manifestation of primary Epstein-Barr virus infection after childhood, and the risk for multiple sclerosis (MS).
METHODS
We conducted a systematic review and meta-analysis of case-control and cohort studies of IM and MS.
RESULTS
The combined relative risk of MS after IM from 14 studies was 2.3 (95% confidence interval, 1.7-3.0; p < 10(-8)). Potential sources of heterogeneity (ie, study design, MS definition, and latitude) barely influenced our results.
INTERPRETATION
We conclude that Epstein-Barr virus infection manifesting as IM in adolescents and young adults is a risk factor for MS.
Topics: Adolescent; Adult; Child; Confidence Intervals; Epstein-Barr Virus Infections; Female; Humans; Infectious Mononucleosis; Male; Multiple Sclerosis; Odds Ratio; Retrospective Studies; Risk; Risk Factors
PubMed: 16502434
DOI: 10.1002/ana.20820 -
Pathogens (Basel, Switzerland) Mar 2023Accumulating evidence suggests that toxoplasmosis in immunocompetent hosts can be severe and life-threatening. (Review)
Review
BACKGROUND
Accumulating evidence suggests that toxoplasmosis in immunocompetent hosts can be severe and life-threatening.
METHODS
We performed a systematic review of severe toxoplasmosis cases in immunocompetent patients to gain insight into the epidemiology, clinical characteristics, radiological findings, and outcomes of these cases. We classified severe toxoplasmosis as cases with the symptomatic involvement of target organs (the lungs, central nervous system (CNS), and heart), disseminated disease, prolonged disease (>3 months), or a fatal outcome. Our primary analysis focused on cases published from 1985-2022 to avoid confounding with cases in AIDS patients.
RESULTS
We identified 82 pertinent articles (1985-2022) with a total of 117 eligible cases; the top five countries for these cases were French Guiana (20%), France (15%), Colombia (9%), India (9%), and Brazil (7%). Overall, 44% (51/117) of cases had pulmonary involvement, 39% (46/117) CNS, 31% (36/117) cardiac, 24% (28/117) disseminated disease, 2% (2/117) had prolonged disease, and 8% (9/117) of patients died. More than one organ was involved in 26% (31/117) of cases. Eighty-four percent (98/117) of cases occurred in the context of a recent acute primary infection; for the remaining, the exact timing of infection was unclear. Genotyping data were very sparse. Among those reporting genotyping data, 96% (22/23) were caused by atypical non-type II strains; one case was caused by a type-II strain. Only half of the cases reported risk factors. The most common risk factors were eating raw/undercooked meat or eating game meat (47% (28/60)), drinking untreated water (37% (22/60)), or living in a toxoplasmosis high-prevalence area (38% (23/60)). For the 51 pulmonary cases, the main clinical presentation was pneumonia or pleural effusions in 94% (48/51) and respiratory failure in 47% (24/51). For the 46 CNS cases, the main clinical presentation was encephalitis in 54% (25/46), meningitis in 13% (6/46), focal neurologic findings in 24% (11/46), cranial nerve palsies in 17% (8/46), Guillain-Barre syndrome or Miller Fisher syndrome in 7% (3/46), and Brown-Sequard syndrome in 2% (1/46) of cases; more than one clinical manifestation could also be present. Among the 41 CNS cases reporting the CNS imaging findings, 68% (28/41) had focal supratentorial lesions and 7% (3/41) had focal infratentorial lesions. Brain abscess-like/mass-like lesions were seen in 51% (21/41) of cases. For the 36 cardiac cases, the main clinical presentation was myocarditis in 75% (27/36), pericarditis in 50% (18/36), heart failure and/or cardiogenic shock in 19% (7/36), and cardiac arrhythmias in 22% (8/36); more than one manifestation could also be present. Illness was critical in 49% (44/90) of cases intensive care unit care was needed in 54% (29/54) of cases among those reporting this information, and 9 patients died.
CONCLUSION
The diagnosis of severe toxoplasmosis in immunocompetent hosts can be challenging. Toxoplasmosis should be considered in the differential diagnosis of immunocompetent patients presenting with severe illness of unclear etiology with pulmonary, cardiac, CNS, or multiorgan involvement/failure, or prolonged febrile illness, even in the absence of common exposure risk factors or common manifestations of toxoplasmosis (e.g., fever, mononucleosis-like illness, lymphadenopathy, and chorioretinitis). Fatal outcomes can also rarely occur in immunocompetent patients. Prompt initiation of anti- treatment can be lifesaving.
PubMed: 37111429
DOI: 10.3390/pathogens12040543