Kawasaki disease with a concomitant primary Epstein - Barr virus infection.

BACKGROUND: Kwasaki disease (KD) is the leading cause of acquired heart disease in children in most developed countries. The cause of KD remains unknown. The presumed theory is that KD occurs due to one or more infectious agents who evoke an abnormal immunological response in susceptible individuals. Epstein - Barr virus (EBV) infection has been considered as a suspected causative agent because of the potential effect on the immune system. CASE PRESENTATION: A previously healthy 19 month old boy presented with a 6 day history of fever accompanied by a diffuse macular erythematous rash that appeared 1 day after. The physical examination on admission revealed bilateral non-suppurative conjunctivitis, dry fissured and injected lips without "strawberry" tongue, diffuse macular rash on the trunk, face and limbs, swelling of the hands and feet, and right cervical lymphadenopathy (2 cm in diameter). Following fulfillment of all the clinical criteria, the diagnosis of KD was made and treatment with IVIG 2 g/Kg was administered along with oral aspirin (80 mg/ kg/day). However, despite the treatment, he remained febrile for an additional 2 days with persistent clinical manifestations. Therefore, he received a second 2 g/kg IVIG course with a favorable response. On the 14th day of illness the patient became febrile again and was readmitted. Blood examinations revealed remarkable leukocytosis up to 35.7 X 109/L with 87.3% lymphocytes and the blood smear revealed atypical lymphocytes and monocytes. The liver enzymes were elevated. The serology for infectious mononucleosis from his first admission revealed: IgM CMV (+), IgG CMV (-); IgM VCA EBV (+) IgG VCA EBV (-), IgG EBNA (-). To confirm infectious mononucleosis following the administration of 2 doses of IVIG, serum EBV PCR was performed and was positive (1.6X 103 cp/ml). CONCLUSIONS: We describe here a case of KD with a concomitant primary EBV infection. To the best of our knowledge, this is the first case in western country that describes KD with acute EBV infection as confirmed by PCR. The case we described stands as a contribution in favor of the possible role of EBV in the development of KD.

Mononucleosis-related fatigue: supplementary management with Robuvit®.

BACKGROUND: Infectious mononucleosis (IM) is a common disease of adolescents and young adults, characterized by a specific triad of symptoms represented by fever, sore throat and lymphadenopathy. IM may also affect older adults, with different, more intense signs and symptoms such as fatigue, general malaise, and diffuse body pain. The aim of this four-week-registry study was to evaluate the effects of Robuvit® supplementation on the main consequences of mononucleosis, particularly fatigue, in otherwise healthy adults. METHODS: All patients enrolled in this registry study experienced an episode of IM characterized by fatigue, a general feeling of unwellness, diffuse body and muscular pain, leukocytosis, and high levels of oxidative stress, at least 2 to 4 weeks prior to inclusion. Fever had already resolved at inclusion. All included patients were positively tested for the Epstein-Barr virus (EBV). Subjects were divided in two groups: those receiving the standard management (SM, N.=26; vitamin B, C, and D, balanced healthy diet, regular sleeping schedule, physical activity, 2 mg copper), and those treated with SM plus Robuvit® (N.=24) supplementation (300 mg/day). RESULTS: Supplementation with Robuvit® was safe, overall tolerability was good, and no side effects were reported. All patients completed the four-week treatment. After 4 weeks of treatment, a significant reduction in the rate of symptoms was evident in the Robuvit® group compared to the control group (P<0.05). CONCLUSIONS: Supplementation with Robuvit® is safe, well tolerated, and effective in controlling oxidative stress levels and improving fatigue and other symptoms related to IM episodes during the convalescence period.

Exercise and the Athlete With Infectious Mononucleosis.

OBJECTIVE: To determine appropriate management of the active individual with infectious mononucleosis (IM), including issues of diagnosis, the determination of splenomegaly, and other measures of disease status, the relationship of the disease to chronic fatigue syndrome (CFS), and the risks of exercise at various points in the disease process. DATA SOURCES: An Ovid/MEDLINE search (January 1996-June 2015) was widely supplemented by "similar articles" found in Ovid/MEDLINE and PubMed, reference lists, and personal files. MAIN RESULTS: Clinical diagnoses of IM are unreliable. Traditional laboratory indicators (lymphocytosis, abnormal lymphocytes, and a heterophile-positive slide test) can be supplemented by more sensitive and more specific but also more costly Epstein-Barr antigen determinations. Clinical estimates of splenomegaly are fallible. Laboratory determinations, commonly by 2D ultrasonography, must take account of methodology, the formulae used in calculations and the individual's body size. The SD of normal values matches the typical increase of size in IM, but repeat measurements can help to monitor regression of the disease. The main risks to the athlete are spontaneous splenic rupture (seen in 0.1%-0.5% of patients and signaled by acute abdominal pain) and progression to chronic fatigue, best avoided by 3 to 4 weeks of restricted activity followed by graded reconditioning. A full recovery of athletic performance is usual with 2 to 3 months of conservative management. CONCLUSIONS: Infectious mononucleosis is a common issue for young athletes. But given accurate diagnosis and the avoidance of splenic rupture and progression to CFS through a few weeks of restricted activity, long-term risks to the health of athletes are few.

DR3 regulation of apoptosis of naive T-lymphocytes in children with acute infectious mononucleosis.

Acute infectious mononucleosis (AIM) is a widespread viral disease that mostly affects children. Development of AIM is accompanied by a change in the ratio of immune cells. This is provided by means of different biological processes including the regulation of apoptosis of naive T-cells. One of the potential regulators of apoptosis of T-lymphocytes is a death receptor 3 (DR3). We have studied the role of DR3 in the regulation of apoptosis of naive CD4+ (nTh) and CD8+ (nCTL) T-cells in healthy children and children with AIM. In healthy children as well as in children with AIM, the activation of DR3 is accompanied by inhibition of apoptosis of nTh. In healthy children, the stimulation of DR3 resulted in the increase in apoptosis of nCTL. On the contrary, in children with AIM, the level of apoptosis of nCTL decreased after DR3 activation, which is a positive contribution to the antiviral immune response. In children with AIM, nCTL are characterized by reduced level of apoptosis as compared with healthy children. These results indicate that DR3 can be involved in the reduction of sensitivity of nCTL to apoptosis in children with AIM.

[FEATURES OF CLINICAL COURSE OF INFECTIOUS MONONUCLEOSIS IN CHILDREN DEPENDENT ON ETIOLOGY].

The article highlights the clinical features of infectious mononucleosis in children (based on the analysis of the data for children of different ages treated in Odessa clinical hospital of infectious diseases in connection with infectious mononucleosis) based on etiological factors.

Common questions about infectious mononucleosis.

Epstein-Barr is a ubiquitous virus that infects 95% of the world population at some point in life. Although Epstein-Barr virus (EBV) infections are often asymptomatic, some patients present with the clinical syndrome of infectious mononucleosis (IM). The syndrome most commonly occurs between 15 and 24 years of age. It should be suspected in patients presenting with sore throat, fever, tonsillar enlargement, fatigue, lymphadenopathy, pharyngeal inflammation, and palatal petechiae. A heterophile antibody test is the best initial test for diagnosis of EBV infection, with 71% to 90% accuracy for diagnosing IM. However, the test has a 25% false-negative rate in the first week of illness. IM is unlikely if the lymphocyte count is less than 4,000 mm3. The presence of EBV-specific immunoglobulin M antibodies confirms infection, but the test is more costly and results take longer than the heterophile antibody test. Symptomatic relief is the mainstay of treatment. Glucocorticoids and antivirals do not reduce the length or severity of illness. Splenic rupture is an uncommon complication of IM. Because physical activity within the first three weeks of illness may increase the risk of splenic rupture, athletic participation is not recommended during this time. Children are at the highest risk of airway obstruction, which is the most common cause of hospitalization from IM. Patients with immunosuppression are more likely to have fulminant EBV infection.

[A case of Crohn's disease following an infection by Epstein-Barr virus].

Infection by the Epstein-Barr virus (EBV) has been linked to the development of autoimmune diseases and recent studies have investigated its specific influence on inflammatory bowel diseases. This is a case report of a 20 year old patient who was diagnosed with Crohn's disease following a prolonged manifestation of infectious mononucleosis. The current information regarding the association between EBV and the development of inflammatory bowel diseases is discussed.

Meningococcemia en el contexto de una mononucleosis infecciosa / Meningoccocal disease in a patient with infectious mononucleosis

En la evaluación de los pacientes con síndrome febril, la detección de petequias asociada a un deterioro clínico importante debe orientar el diagnóstico de enfermedad meningocócica invasora. Sin embargo, algunos pacientes presentan un cuadro clínico sutil o atípico que dificulta el diagnóstico; los signos de alarma clínicos y analíticos son útiles para identificar a los niños que se beneficiarán de un tratamiento empírico precoz que mejore su pronóstico. Presentamos el caso de un niño de 3 años de edad, diagnosticado en nuestro centro de una enfermedad meningocócica invasora, insospechada por su evolución atípica, que acude al servicio de urgencias por presentar fiebre de 4 días de evolución, petequias y púrpura palpable, aunque manteniendo un buen estado general en todo momento (AU)

In the evaluation of patients with a febrile syndrome, detection of petechiae associated to an ill appearance should make us suspect an invasive meningococcal disease. Nevertheless, some patients present in a more subtle manner or with an atypical course that will make difficult the diagnosis. Clinical and analytical alarm sings could be useful to identify these children who would benefit from an early empirical treatment that improves their prognosis. We report a case of unsuspected invasive meningococcal disease because of unusual presentation in a 3-years-old boy. He came to the emergency room complaining of 4 days fever, petechiae and palpable purpura. The patient's clinical condition was all time preserved (AU)

Clinical and laboratory characteristics of infectious mononucleosis by Epstein-Barr virus in Mexican children.

BACKGROUND: Infectious mononucleosis (IM) or Mononucleosis syndrome is caused by an acute infection of Epstein-Barr virus. In Latin American countries, there are little information pertaining to the clinical manifestations and complications of this disease. For this reason, the purpose of this work was to describe the clinical and laboratory characteristics of infection by Epstein-Barr virus in Mexican children with infectious mononucleosis. METHODS: A descriptive study was carried out by reviewing the clinical files of patients less than 18 years old with clinical and serological diagnosis of IM by Epstein-Barr virus from November, 1970 to July, 2011 in a third level pediatric hospital in Mexico City. RESULTS: One hundred and sixty three cases of IM were found. The most frequent clinical signs were lymphadenopathy (89.5%), fever (79.7%), general body pain (69.3%), pharyngitis (55.2%), hepatomegaly (47.2%). The laboratory findings were lymphocytosis (41.7%), atypic lymphocytes (24.5%), and increased transaminases (30.9%), there were no rupture of the spleen and no deaths among the 163 cases. CONCLUSIONS: Our results revealed that IM appeared in earlier ages compared with that reported in industrialized countries, where adolescents are the most affected group. Also, the order and frequency of the clinical manifestations were different in our country than in industrialized ones.

Edema palpebral como expresión oligosintomática de mononucleosis infecciosa / Eyelid edema as an oligosymptomatic expression of infectious mononucleosis

La mononucleosis infecciosa es una enfermedad frecuente en la edad pediátrica, cuya máxima incidencia se encuentra en la primera infancia y en la adolescencia o inicio de la edad adulta. El edema palpebral bilateral puede ser un hallazgo clínico sutil en el curso de dicha entidad, y aunque no forma parte de los síntomas característicos, puede estar presente al inicio del cuadro hasta en un tercio de los pacientes. Presentamos cuatro casos clínicos, en los cuales el edema palpebral bilateral es el síntoma guía que orienta el diagnóstico, reflexionando así sobre la necesidad de incluir la mononucleosis infecciosa dentro del diagnóstico diferencial planteado frente al edema palpebral (AU)

Infectious mononucleosis is a common disease in children, whose incidence is highest in early childhood and adolescence or early adulthood. Bilateral eyelid edema may be a subtle clinical finding in the course of that entity, and although not part of the characteristic symptoms may be present at the onset of up to one third of patients. We present four cases in which bilateral eyelid edema is a symptom guide for the diagnosis, thus reflecting the need to include infectious mononucleosis in the differential diagnosis raised against the palpebral edema (AU)

Viruses and multiple sclerosis.

Multiple sclerosis (MS) is a heterogeneous disease that develops as an interplay between the immune system and environmental stimuli in genetically susceptible individuals. There is increasing evidence that viruses may play a role in MS pathogenesis acting as these environmental triggers. However, it is not known if any single virus is causal, or rather several viruses can act as triggers in disease development. Here, we review the association of different viruses to MS with an emphasis on two herpesviruses, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6). These two agents have generated the most impact during recent years as possible co-factors in MS disease development. The strongest argument for association of EBV with MS comes from the link between symptomatic infectious mononucleosis and MS and from seroepidemiological studies. In contrast to EBV, HHV-6 has been found significantly more often in MS plaques than in MS normal appearing white matter or non-MS brains and HHV-6 re-activation has been reported during MS clinical relapses. In this review we also suggest new strategies, including the development of new infectious animal models of MS and antiviral MS clinical trials, to elucidate roles of different viruses in the pathogenesis of this disease. Furthermore, we introduce the idea of using unbiased sequence-independent pathogen discovery methodologies, such as next generation sequencing, to study MS brain tissue or body fluids for detection of known viral sequences or potential novel viral agents.

T-cell receptor gene rearrangement in Epstein-Barr virus infectious mononucleosis.

This report describes the case of a previously healthy young man who presented with fever, pharyngitis, cervical lymphadenopathy, lymphocytosis, and severe thrombocytopenia. Serological tests for Epstein-Barr virus were diagnostic of a primary Epstein-Barr virus infectious mononucleosis but severe thrombocytopenia aroused the suspicion of a lymphoproliferative disease. T-cell receptor gene analysis performed on peripheral and bone marrow blood revealed a T-cell receptor γ-chain rearrangement without the evidence of malignancy using standard histologic and immunophenotype studies. Signs and symptoms of the infectious disease, blood count, and T-cell receptor gene rearrangement resolved with observation without the evidence of emergence of a lymphoproliferative disease. In the contest of a suspected lymphoproliferative disease, molecular results should be integrated with all available data for an appropriate diagnosis.

Overwhelming primary Epstein-Barr virus infection requiring corticosteroid treatment.

A 20-year-old woman presented with a 2-week history of fever and malaise. Physical examination was unremarkable. Viral infection was suspected and Epstein-Barr virus serology confirmed acute infectious mononucleosis. During admission, she gradually developed pancytopenia and liver enzyme abnormalities. The patient clinically deteriorated with persisting fever, orthostatic hypotension and hepatosplenomegaly. Bone marrow examination showed haemophagocytic lymphohistiocytosis (HLH). Treatment with high-dose corticosteroids was started and patient recovered quickly. Ferritin decreased immediately, fever resolved within 3 days, viral clearance was reached within 3 weeks. Steroid therapy was gradually tapered off in three months. The Histiocyte Society recommends immunochemotherapy with steroids, etoposide and cyclosporine. Potential side effects of etoposide are severe bone marrow depression and leukaemia. Our patient survived on corticosteroids alone. Early recognition of HLH and prompt treatment are of utmost importance for survival. Treatment with steroids alone can be life-saving.

[Infectious mononucleosis: etiology, immunological variants, methods of correction].

Clinical options of infectious mononucleosis course depending on infecting agent etiology are presented for Epstein-Barr virus (EBV), cytomegalovirus (CMV), mono and mixed forms of the disease. Examined cytokine profiles demonstrate analogous changes of serum cytokines in the acute stage of the disease irrespective of etiological factors. Data show that it is important and useful clinically and immunologically to include immunomodulators--in particular, cycloferon--info a complex therapy of different types of mononucleosis.

[Upper respiratory tract infections and sports]. / Infections des voies respiratoires supérieures et sport: qui joue?

Upper respiratory tract infections are frequent in athletes. Mainly of viral origin, they are treated symptomatically. Infectious mononucleosis is associated with an estimated 2% per hundred risk of splenic rupture, which occurs between day four and twenty one of the illness. Therefore return to play guidelines recommend avoiding, exercice during the first twenty one days. Physical exercise seems to influence the immune system, depending on the intensity and length of it. But the relationship between physical exercise and risk of infections remains controversial: some articles showing an increase in risk, whereas others suggesting a certain degree of protection, in athletes. The actual generally accepted working theory is the J-curve proposed by Nieman. This model remains to be formally proven.

Infectious mononucleosis in Turkish children.

The aim of this study was to analyze the demographic, clinical and laboratory characteristics and prognoses of children diagnosed with infectious mononucleosis (IM). The demographic features, referral complaints, clinical and laboratory findings, follow-up, and prognoses of 44 patients diagnosed with IM between January 2000 and June 2006 at the Infectious Diseases Department of Hacettepe University Ihsan Dogramaci Children's Hospital were analyzed retrospectively. The children suspected of IM based on clinical findings and whose diagnoses were proven by serological tests were enrolled in the study. In addition, the patients were divided into four groups -namely, age 0-4, age 5-8, age 9-12 and age 13-16, and the differences among groups were investigated in terms of their clinical and laboratory findings. The patients were aged between 3 months and 16 years. The median age was 4, and 56.8% of patients were below age 5. The male/female ratio was 1.6. No statistically significant variation was observed in the seasonal distribution of patients (p = 0.131). The most common referral complaints were swollen cervical lymph nodes or swollen neck (68.1%), followed by fever (43.1%) and sore throat (25%). Lymphadenopathy (79.5%), tonsillopharyngitis (72.7%), splenomegaly (34%), and hepatomegaly (25%) were the most common physical examination findings. Leukocyte count was normal in 68.3% of the cases. Leukocytosis was detected in 29.5% of the patients, and leukopenia in 2.2%. Lymphocytosis was detected in 44.7% of patients. Downey cell was detected in the peripheral blood smear of 23.6% of patients, and thrombocytopenia in 11.3%. Elevated alanine aminotransferase and aspartate aminotransferase levels were detected in 61.9% and 90.4% of patients who were investigated for these parameters, respectively. The clinical, hematological and biochemical findings of patients did not vary significantly among age groups (p > 0.05). Only one complication (hemophagocytic syndrome) was observed in one patient.

Deficiency of the proapoptotic SAP function in X-linked lymphoproliferative disease aggravates Epstein-Barr virus (EBV) induced mononucleosis and promotes lymphoma development.

The lack of functional SAP protein, a consequence of mutation or deletion of the SH2D1A gene is the cause of X-linked lymphoproliferative disease (XLP). Others and we have shown that SAP can be involved in apoptosis. Activation induced apoptosis plays a pivotal role in the termination of the lymphocyte proliferation in infectious mononucleosis IM. This mechanism is inefficient in the XLP patients. Primary EBV infection of boys with XLP leads therefore to fulminant, often even fatal disease. In addition, the condition predisposes to considerably elevated incidence of lymphomas. Chromosomal translocation that juxtaposes one of the three immunoglobulin loci to the c-myc proto-oncogene is the hallmark of Burkitt lymphomas (BL), whether they carry the Epstein-Barr Virus (EBV) or not. Ig/myc translocations occur as rare accidents of normal B lymphocyte differentiation. The activated myc would drive the cells to proliferate, however unless protected, the cells become prone to apoptosis. Our results with BL derived cell lines suggest that the fate of the precursor cells is decided by the expression of the proapototic SAP and EBV infection. We found SAP expression in eight of ten EBV carrying, but none of nine EBV negative BL lines. Therefore it seems that the apoptosis prone Ig/myc translocation carrying EBV negative precursors of BL can grow into lymphomas only if they do not express the proapoptotic SAP while SAP expressor, but EBV positive cells can survive and proliferate. This is probably due to the antiapoptotic function of EBNA-1 and the proliferation induced by activated myc.

Exantema por virus Epstein-Barr y mycoplasma pneumoniae / Epstein-Barr virus and mycoplasma pneumoniae exanthema

Introducción. Una de las manifestaciones de la mononucleosis infecciosaes el exantema polimorfo debido al virus Epstein-Barr(VEB) y desencadenado en ocasiones por amoxicilina. No es habitualencontrarse ante una coinfección por VEB y Mycoplasmapneumoniae en la que la principal manifestación clínica sea elexantema.Observación clínica. Presentamos el caso de una niña de 6 añoscon un exantema máculo-papuloso generalizado que varió en suforma de presentación. A la exploración física destacaban, apartedel exantema, adenopatías laterocervicales bilaterales y occipitales,hepatomegalia de 2 cm y fiebre (temperatura máxima: 38,7ºC).Los datos clínicos de la exploración física y los resultados analíticos(hemograma, fórmula leucocitaria, test de Paul-Bunnell y serolo-Exantema per virus Epstein-Barr i MycoplasmapneumoniaeGerardo Vizmanos 1, Marisa Lázaro 1, Óscar Rosell 2, Montserrat Capellà 1, Juli González 2,Ferran Barranco 21 ABS Alt Urgell Sud. 2 Servei de Pediatria; Fundació Sant Hospital. La Seu d'Urgell (Lleida)gías) condujeron al diagnóstico de mononucleosis infecciosa ycoinfección por Mycoplasma pneumoniae.Comentarios. Según la revisión de la literatura, es el primer casodescrito en niños de coinfección por VEB y Mycoplasma pneumoniaesin complicaciones respiratorias (neumonía) o neurológicas(meningitis o mielitis transversa)(AU)

Introduction. One of the clinical manifestations of infectious mononucleosisis a polymorph exanthema due to Epstein-Barr virus,and occasionally to amoxicillin administration. It's unusual to findEpstein-Barr virus and Mycoplasma pneumoniae co-infectionwhere the only clinical manifestation is exanthema.Case report. A 6 years-old girl presented with macular and papularexanthema. Physical examination showed that she had exanthema,latero-cervical and occipital adenopathies, hepatomegaly (2cm) and fever (maximum temperature: 38.7ºC). Clinical and laboratorydata led to the diagnosis of infectious mononucleosis andMycoplasma pneumoniae co-infection.Comments. After reviewing medical literature, we think it's thefirst case described in children of Epstein-Barr virus and Mycoplasmapneumoniae co-infection without respiratory (pneumonia)or neurological (meningitis or transverse myelitis) complications(AU)