Association between Antibiotic Exposure and the Risk of Rash in Children with Infectious Mononucleosis: a Multicenter, Retrospective Cohort Study.

Present evidence suggests that the administration of antibiotics, particularly aminopenicillins, may increase the risk of rash in children with infectious mononucleosis (IM). This retrospective, multicenter cohort study of children with IM was conducted to explore the association between antibiotic exposure in IM children and the risk of rash. A robust error generalized linear regression was performed to address the potential cluster effect, as well as confounding factors such as age and sex. A total of 767 children (aged from 0 to 18 years) with IM from 14 hospitals in Guizhou Province were included in the final analysis. The regression analysis implied that exposure to antibiotics was associated with a significantly increased incidence of overall rash in IM children (adjusted odds ratio [AOR], 1.47; 95% confidence interval [CI], ~1.04 to 2.08; P = 0.029). Of 92 overall rash cases, 43 were probably related to antibiotic exposure: two cases (4.08%) in the amoxicillin-treated group and 41 (8.15%) in the group treated with other antibiotics. Regression analysis indicated that the risk of rash induced by amoxicillin in IM children was similar to that induced by other penicillins (AOR, 1.12; 95% CI, ~0.13 to 9.67), cephalosporins (AOR, 2.45; 95% CI, ~0.43 to 14.02), or macrolides (AOR, 0.91; 95% CI, ~0.15 to 5.43). Antibiotic exposure may be associated with an increased risk of overall rash in IM children, but amoxicillin was not found to be associated with any increased risk of rash during IM compared to other antibiotics. We suggest that clinicians be vigilant against the occurrence of rash in IM children receiving antibiotic therapy, rather than indiscriminately avoiding prescribing amoxicillin.

Corticosteroids for infectious mononucleosis.

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.

Decrease in in vivo coagulant potential of emicizumab in a patient with hemophilia A and inhibitor complicated with infectious mononucleosis.

Emicizumab prophylaxis significantly reduces bleeding episodes in patients with hemophilia A (PwHA). There is little information on coagulant potentials in emicizumab-treated PwHA with infection, however. We encountered an emicizumab-treated PwHA with inhibitor, complicated with Epstein-Barr virus-associated infectious mononucleosis (IM) in phase 1/2 study (ACE001JP/ACE002JP). Although it was a typical clinical course of IM, activated partial thromboplastin time was mildly prolonged but rotational thromboelastometry revealed severely impaired coagulant potential. The blood concentration of emicizumab decreased moderately in the low concentration range, resulting in an increased risk of bleeding and possibly leading to severe ileocecal bleeds requiring coil embolization. The blood concentrations of factors IX/X little decreased and antiemicizumab antibodies did not develop, however. After the influence by IM resolved, his coagulant potentials gradually recovered with the recovery of emicizumab concentration, and parameters by global coagulation assays improved. An IM case for emicizumab-treated PwHA may need to monitor using global coagulation assays.

Infección por virus de epstein barr y debut de lupus eritematoso sistémico (LES) en un adolescente / Epstein barr virus infection and systemic lupus erythematosus (SLE) debut in an adolescent / Infecção pelo vírus Epstein Barr e início de lúpus eritematoso sistêmico (LES) em adolescente

Introducción: El lupus eritematoso sistémico (LES), prototipo de enfermedad autoinmune, cursa con empujes y remisiones. Dada la diversidad de presentaciones posibles, su diagnóstico y tratamiento son un reto para el clínico, y se requiere tener un alto índice de sospecha. Objetivo: presentar el caso clínico de un adolescente que debuta con LES a forma de anemia hemolítica, probablemente gatillado por infección por virus de Epstein Barr. Caso clínico: Varón de 14 años, sin antecedentes a destacar. Consulta por fiebre de 7 días de evolución de hasta 39º C, odinofagia, astenia y adinamia. Al examen físico se constata palidez cutáneo mucosa, ictericia, adenopatías cervicales y hepatoesplenomegalia. El laboratorio muestra anemia severa regenerativa con aumento de las bilirrubinas a expensas de la indirecta sin hepatitis. Prueba de Coombs positiva. Anticuerpos específicos para Epstein Barr positivos, con lo que se diagnostica anemia hemolítica secundaria a mononucleosis y se inicia tratamiento corticoideo. En la evolución agrega eritema malar y limitación en flexión de codos y rodillas. Se reciben anticuerpos antinucleares y anti ADN nativo positivos con hipocomplementemia severa. Con diagnóstico de LES se inicia hidroxicloroquina y azatioprina, manteniéndose la prednisona. Conclusiones: Muchos virus (hepatitis C, Parvovirus B19, Epstein Barr y Citomegalovirus) se han descrito como posibles inductores o simuladores de LES. Es necesario mantener un alto índice de sospecha para realizar un diagnóstico oportuno y tratamiento precoz.

Introduction: Systemic lupus erythematosus (SLE), prototype of autoimmune disease, progresses with flares and remissions. Given the diversity of possible presentations, its diagnosis and treatment are a challenge for the clinician, and a high index of suspicion is required. Objective: To present the clinical case of an adolescent who debuted with SLE in the form of hemolytic anemia, probably triggered by Epstein Barr virus infection. Clinical case: 14 - year - old male, with no history to highlight. Consultation for fever of 7 days of evolution of up to 39º C, odynophagia, asthenia and adynamia. Physical examination revealed mucous skin pallor, jaundice, cervical lymphadenopathy, and hepatosplenomegaly. The laboratory shows severe regenerative anemia with increased bilirubin at the expense of indirect without hepatitis. Positive Coombs test. Specific antibodies for Epstein Barr were positive, with which hemolytic anemia secondary to mononucleosis was diagnosed and corticosteroid treatment was started. In the evolution, it adds malar erythema and limitation in flexion of the elbows and knees. Positive antinuclear and anti-native DNA antibodies are received with severe hypocomplementemia. With a diagnosis of SLE, hydroxychloroquine and azathioprine were started, maintaining prednisone. Conclusions: Many viruses (hepatitis C, Parvovirus B19, Epstein Barr and Cytomegalovirus) have been described as possible inducers or mimics of SLE. It is necessary to maintain a high index of suspicion for timely diagnosis and early treatment.

Introdução: O lúpus eritematoso sistêmico (LES), protótipo de doença autoimune, evolui com impulsos e remissões. Dada a diversidade de apresentações possíveis, seu diagnóstico e tratamento são um desafio para o clínico, sendo necessário um alto índice de suspeição. Objetivo: apresentar o caso clínico de uma adolescente que iniciou com LES na forma de anemia hemolítica, provavelmente desencadeada por infecção pelo vírus Epstein Barr. Caso clínico: Homem de 14 anos, sem antecedentes a destacar. Consulta por febre de 7 dias de evolução de até 39º C, odinofagia, astenia e adinamia. O exame físico revelou palidez cutânea mucosa, icterícia, linfadenopatia cervical e hepatoesplenomegalia. O laboratório mostra anemia regenerativa grave com aumento da bilirrubina em detrimento da indireta sem hepatite. Teste de Coombs positivo. Anticorpos específicos para Epstein Barr foram positivos, com o qual foi diagnosticada anemia hemolítica secundária à mononucleose e iniciado tratamento com corticosteróides. Na evolução, acrescenta eritema malar e limitação na flexão dos cotovelos e joelhos. Anticorpos antinucleares e anti-DNA nativos positivos são recebidos com hipocomplementemia grave. Com diagnóstico de LES, iniciou-se hidroxicloroquina e azatioprina, mantendo-se prednisona. Conclusões: Muitos vírus (hepatite C, Parvovírus B19, Epstein Barr e Citomegalovírus) têm sido descritos como possíveis indutores ou mimetizadores do LES. É necessário manter um alto índice de suspeição para diagnóstico oportuno e tratamento precoce.

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.

Severe Complications From Infectious Mononucleosis After Prolonged Steroid Therapy.

ABSTRACT: Infectious mononucleosis (IM) is a disease common among adolescents in the United States. Frequently, symptoms include sore throat, malaise, fevers, lymphadenopathy, and abdominal pain. Severe complications have been reported such as splenic rupture, acute upper airway obstruction, hepatitis, acute renal failure, and hematological and neurological complications. The mainstay of treatment is supportive care. Steroids are recommended for impending airway obstruction and hematological complications. However, steroids are commonly used in uncomplicated cases of IM, with insufficient evidence on the efficacy of steroids for symptom control. Furthermore, there is a lack of research on the adverse effects and long-term complications of steroid use for IM. We present a case of an adolescent boy who presented to his primary care physician with symptoms consistent with uncomplicated IM that was treated with a prolonged course of steroids. Subsequently, he developed worsening symptoms, including fevers, headache, vomiting, and left-sided facial swelling. He presented to a pediatric emergency department in decompensated septic shock as a result of polymicrobial bacteremia. During his hospital course, he developed pulmonary septic emboli, a sinus thrombus, an empyema, and orbital cellulitis complicated by Pott puffy tumor. In this case report, we summarize the current literature on steroid treatment of uncomplicated IM and highlight how our case addresses the use and possible complications of prolonged steroid use in uncomplicated IM.

Neutropenia por linfocitos grandes granulares secundaria a adalimumab y reactivación de mononucleosis: reporte de un caso y revisión de la literatura / Neutropenia induced by large granular lymphocytes secondary to adalimumab and reactivated mononucleosis: case report and literature review

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Cold type autoimmune hemolytic anemia- a rare manifestation of infectious mononucleosis; serum ferritin as an important biomarker.

BACKGROUND: Infectious mononucleosis is one of the main manifestations of Epstein - Barr virus, which is characterized by fever, tonsillar-pharyngitis, lymphadenopathy and atypical lymphocytes. Although 60% of patients with IMN develop cold type antibodies, clinically significant hemolytic anemia with a high ferritin level is very rare and validity of serum ferritin as an important biomarker has not been used frequently. CASE PRESENTATION: 18-year-old girl presented with fever, malaise and sore throat with asymptomatic anemia, generalized lymphadenopathy, splenomegaly and mild hepatitis. Investigations revealed that she had cold type autoimmune hemolysis, significantly elevated serum ferritin, elevated serum lactate dehydrogenase level with serological evidence of recent Epstein Barr infection. She was managed conservatively and her hemoglobin and serum ferritin levels normalized without any intervention following two weeks of the acute infection. CONCLUSION: Cold type autoimmune hemolytic anemia is a rare manifestation of infectious mononucleosis and serum ferritin is used very rarely as an important biomarker. Management of cold type anemia is mainly supportive and elevated serum ferritin indicates severe viral disease.

[Clinical effect of pidotimod oral liquid as adjuvant therapy for infectious mononucleosis].

OBJECTIVE: To study the clinical effect of pidotimod oral liquid as adjuvant therapy for infectious mononucleosis and its effect on T lymphocyte subsets. METHODS: A total of 76 children with infectious mononucleosis, who were admitted to the hospital between July 2016 and June 2017, were enrolled and randomly divided into two groups: conventional treatment and pidotimod treatment (n=38 each). The children in the conventional treatment group were given antiviral therapy with ganciclovir for injection and symptomatic treatment. Those in the pidotimod treatment group were given pidotimod oral liquid in addition to the treatment in the conventional treatment group. The course of treatment was two weeks for both groups. The two groups were compared in terms of the recovery of clinical indices and the changes in peripheral blood T lymphocyte subsets. RESULTS: Compared with the conventional treatment group, the pidotimod treatment group had significantly shorter fever clearance time, time to the disappearance of isthmopyra, time to the relief of lymph node enlargement, time to the relief of hepatosplenomegaly, and length of hospital stay (P<0.05). After treatment, the pidotimod treatment group had significant reductions in the percentages of CD3+ and CD8+ T cells and had significantly lower percentages of CD3+ and CD8+ T cells than the conventional treatment group (P<0.001). The pidotimod treatment group had significant increases in the percentage of CD4+ T cells and CD4+/CD8+ ratio after treatment, which was significantly higher than those in the conventional treatment group (P<0.001). The conventional treatment group had no significant changes in T lymphocyte subsets after treatment (P>0.05). CONCLUSIONS: Pidotimod oral liquid has a good clinical effect as the adjuvant therapy for infectious mononucleosis and can improve cellular immune function, so it holds promise for clinical application.

Infectious exposure, antibiotic use, and multiple sclerosis: A population-based incident case-control study.

BACKGROUND: The existing reports regarding the potential role of infections as well as antibiotic use in multiple sclerosis (MS) etiology are inconclusive. OBJECTIVES: We aimed to investigate the association of viral infections as well as antibiotic use and the risk of developing MS. MATERIALS & METHODS: This was a population-based incident case-control study of 547 incident cases and 1057 general population controls obtained from 22 municipality areas of Tehran (7/8/2013-17/2/2015). Multiple logistic regression models were used to determine the adjusted associations. RESULTS: Overall antibiotic use for ≥14 days during 3 years before the index date, significantly decreased the odds of MS OR 0.69 (95%CI: 0.53-0.91, P = .008). The results were consistent for different types of antibiotics, including penicillin OR 0.50 (95%CI: 0.34-0.75, P = .001) and cephalosporins OR 0.25 (95%CI: 0.12-0.50, P < .001). History of IM was associated with a more than 5fold increased risk of MS OR = 5.7 (95%CI, 1.28-25.37). There was no statistically significant association between any other single or cumulative number of viral infections with subsequent risk of MS (P > .05). CONCLUSIONS: Considering the possibility of reverse causation, the results of this large case-control study suggest that use of antibiotics may be associated with a decreased risk of MS. However, viral disease other than infectious mononucleosis was not associated with MS risk.

Valganciclovir for the Suppression of Epstein-Barr Virus Replication.

Epstein-Barr virus (EBV) causes infectious mononucleosis and can lead to lymphoproliferative diseases. We evaluated the effects of valganciclovir on oral EBV shedding in a randomized, double-blind, placebo-controlled study. Twenty-six men received oral valganciclovir or daily placebo for 8 weeks, followed by a 2-week "washout period" and then 8 weeks of the alternative treatment. Valganciclovir reduced the proportion of days with EBV detected from 61.3% to 17.8% (relative risk, 0.28; 95% confidence interval [CI], .21-.41; P < .001), and quantity of virus detected by 0.77 logs (95% CI, .62-.91 logs; P < .001). Further investigations into the impact of valganciclovir on EBV-associated diseases are needed.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis during pregnancy.

An 11-week pregnant, 32-year-old Japanese woman who had recovered from infectious mononucleosis visited our center due to fever, anorexia, and bilateral hypochondrial pain. Blood tests revealed leukopenia, thrombocytopenia and elevated ferritin. She was diagnosed with hemophagocytic lymphohistiocytosis (HLH). A high viral load of the Epstein-Barr virus (EBV) was recognized, indicating EBV-HLH. She was treated with a single dose of dexamethasone to protect the fetus. However, the disease was uncontrollable, necessitating etoposide and cyclosporine administration. Remission was obtained with these medications, and she has remained in remission for the 10 months since completion of chemotherapy. Although the occurrence of EBV-HLH during pregnancy is rare, it is possible that a change in cellular immunity associated with the pregnancy may contribute to EBV-HLH development.

Infección por virus de Epstein-Barr y hepatitis aguda colestásica / Infection with Epstein-Barr virus and acute cholestatic hepatitis

El Virus de Epstein-Barr (VEB) es un herpes virus cuyo medio de transmisión es a través de secreciones de una persona portadora del virus, siendo el hombre el único huésped. La primo infección por lo general es asintomática o puede manifestarse como mononucleosis infecciosa con la triada clásica de fiebre, faringitis y adenopatías. Esta cursa con elevación leve y autolimitada de transaminasas, por lo que solo un 5% de los casos se ha asociado con hepatitis aguda colestásica. Presentamos a un paciente con una infección por virus de Epstein-Barr y hepatitis aguda colestásica con historia de aparición de una masa cervical lateral derecha. Al examen físico evidencia ictericia a nivel de escleras, mucosas y ambos miembros superiores. Niveles de bilirrubina en sangre elevados. Paciente con ultrasonido hepático y vías biliares normal, colangiopancreatografía retrograda endoscópica normal por lo que se procede a realizar pruebas serológicas para VEB siendo esta positiva. Se da tratamiento con ganciclovir, mejorando pruebas de función hepática y disminuyendo ictericia, teniendo así una evolución favorable del paciente...(AU)

Epstein-Barr Virus (EBV) is a herpes virus, whose means of transmission is through secretions of a person carrying the virus, the man being the only host. The cousin infection is usually asymptomatic or may manifest as infectious mononucleosis with the classical triad of fever, pharyngitis and lymphadenopathy. This is a mild and self-limiting elevation of transaminases, which means that only 5% of the cases have been associated with acute cholestasis hepatitis. We present a patient with an Epstein-Barr virus infection and acute cholestasis hepatitis with a history of the appearance of a right lateral cervical mass. Physical examination shows jaundice at the level of sclera, mucosa and both upper limbs. Elevated blood bilirubin levels. Patient with hepatic ultrasound and normal bile ducts, normal endoscopic retrograde cholangiopancreatography, so serological tests for EBV are performed and this is positive. Ganciclovir is given, improving liver function tests and decreasing jaundice, thus having a favorable evolution of the patient...(AU)

Agranulocytosis occurrence following recent acute infectious mononucleosis.

Infectious mononucleosis secondary to Epstein-Barr virus typically follows a relatively benign and self-limited course. A small subset of individuals may develop further progression of disease including hematologic, neurologic, and cardiac abnormalities. A mild transient neutropenia occurring during the first weeks of acute infection is a common finding however in rare cases a more profound neutropenia and agranulocytosis may occur up to 6weeks following the onset of initial symptoms. We describe the case of an 18-year-old woman who presented 26days following an acute infectious mononucleosis diagnosis with agranulocytosis and fever. No source of infection was identified and the patient had rapid improvement in her symptoms and resolution of her neutropenia. The presence of fever recurrence and other non-specific symptoms in individuals 2-6weeks following acute infectious mononucleosis symptom onset may warrant further assessment for this uncommon event.