Nonsteroidal Anti-Inflammatory Drugs Quickly Resolve Symptoms Associated with EBV-Induced Infectious Mononucleosis in Patients with Atopic Predispositions.

BACKGROUND: Infectious mononucleosis is a clinical syndrome most commonly associated with primary Epstein-Barr virus (EBV) infection. In adults, the symptoms can often be severe and prolonged, sometimes causing serious complications. Analgesic or antipyretic drugs are normally used to relieve the symptoms. However, there is no causal treatment for the disease. CASE REPORT: Two cases of adult patients with atopic predispositions developed nocturnal fever, general fatigue, pharyngitis and lymphadenopathy after an exacerbation of atopic symptoms or those of allergic rhinitis. Due to the positive results for EBV viral-capsid antigen (VCA) IgM and negative results for EBV nuclear antigen (EBNA) IgG, diagnoses of infectious mononucleosis induced by EBV were made in both cases. Although oral antibiotics or acetaminophen alone did not improve the deteriorating symptoms, including fever, headache and general fatigue, nonsteroidal anti-inflammatory drugs (NSAIDs), such as tiaramide or loxoprofen, completely improved the symptoms quickly after the initiation. CONCLUSIONS: In these cases, given the atopic predispositions of the patients, an enhanced immunological response was likely to be mainly responsible for the pathogenesis of the symptoms. In such cases, NSAIDs, that are known to reduce the activity of EBV, may dramatically improve the deteriorating symptoms quickly after the initiation. In the present cases, the immunosuppressive property of these drugs was considered to suppress the activity of lymphocytes and thus provide the rapid and persistent remission of the disease.

Chronic and recurrent benign lymphadenopathy without constitutional symptoms associated with human herpesvirus-6B reactivation.

Chronic/recurrent behaviour may be encountered in some distinct atypical or malignant lymphoproliferations, while recurrences are not generally observed in reactive/benign lymphadenopathies. We retrospectively analysed a consecutive series of 486 human immunodeficiency virus-negative adults, who underwent lymphadenectomy. Neoplastic and benign/reactive histopathological pictures were documented in 299 (61·5%) and 187 (38·5%) cases, respectively. Of note, seven of the 111 (6·3%) patients with benign lymphadenopathy without well-defined aetiology, showed chronic/recurrent behaviour, without constitutional symptoms. Enlarged lymph nodes were round in shape and hypoechoic, mimicking lymphoma. Reactive follicular hyperplasia and paracortical expansion were observed. Human herpesvirus (HHV)-6B positive staining in follicular dendritic cells (FDCs) was documented in all seven patients. Serological, molecular and immunological examinations suggested HHV-6B reactivation. Among the remaining 104 cases with reactive lymphoid hyperplasia in the absence of well-known aetiology and without recurrences, positivity for HHV-6B on FDCs was found in three cases, whereas in seven further patients, a scanty positivity was documented in rare, scattered cells in inter-follicular regions. Immunohistochemistry for HHV-6A and HHV-6B was invariably negative on 134 lymph nodes, with either benign pictures with known aetiology or malignant lymphoproliferative disorders, tested as further controls. Future studies are warranted to investigate a potential association between HHV-6B reactivation and chronic/recurrent benign lymphadenopathy.

Perihepatic nodes detected by point-of-care ultrasound in acute hepatitis and acute-on-chronic liver disease.

AIM: To study the manifestations of perihepatic lymph nodes during the episode of acute hepatitis flare by point-of-care ultrasonography. METHODS: One hundred and seventy-six patients with an episode of acute hepatitis flare (ALT value > 5 × upper normal limit) were enrolled retrospectively. Diagnosis of etiology of the acute hepatitis flare was based on chart records and serological and virological assays. The patients were categorized into two groups (viral origin and non-viral origin) and further defined into ten subgroups according to the etiologies. An ultrasonograpy was performed within 2 h to 72 h (median, 8 h). The maximum size of each noticeable lymph node was measured. Correlation between clinical parameters and nodal manifestations was analyzed RESULTS: Enlarged lymph nodes (width ≥ 5mm) were noticeable in 110 (62.5%) patients, mostly in acute on chronic hepatitis B (54.5%). The viral group had a higher prevalence rate (89/110 = 80.9%) and larger nodal size (median, 7 mm) than those of the non-viral group (21/66 = 31.8%; median, 0 mm) (P < 0.001 for both). Meanwhile, there were significant differences in the nodal size between acute and chronic viral groups (P < 0.01), and between acute hepatitis A and non-hepatitis A viral groups (P < 0.001). In logistical regression analysis, the nodal width still showed strong significance in multivariate analysis (P < 0.0001) to stratify the two groups. The area under the curve of ROC was 0.805, with a sensitivity of 80.9%, a specificity of 68.2%, positive predictive value of 80.92%, negative predictive value of 68.18%, and an accuracy of 76.14%. CONCLUSION: Point-of-care ultrasonography to detect perihepatic nodal change is valuable for clarifying the etiologies in an episode of acute hepatitis flare.

Clinical characteristics and laboratory findings in Danish children hospitalized with primary Epstein-Barr virus infection.

BACKGROUND: Epstein-Barr virus (EBV) positive infectious mononucleosis (IM) is a common disease in adolescents. However, IM is often considered a rare disease in early childhood. We aimed to describe the classical presentation of adolescent EBV-associated IM compared to EBV infection at younger age. METHODS: All immunocompetent children hospitalized at Hvidovre University Hospital, Copenhagen between 2002 and 2013, who presented with clinical features that prompted a laboratory test for EBV, and who tested positive by presence of EBV-specific antibodies, heterophile antibodies or a positive EBV PCR were included (n = 95). RESULTS: Children aged 1-2 years were the age group most commonly hospitalized with acute EBV infection (27% of the cohort), followed by teenagers aged 14-15 years (23%). Fever, cervical lymphadenopathy, tonsillitis and fatigue were the most common physical findings overall. Dividing the children into three age groups (0-4 years, 5-10 years and 11-15 years) revealed that the oldest age groups significantly more often suffered from headache, tonsillitis, sore throat, abdominal pain and nausea. Young children typically presented with a runny nose, fever, fatigue and cervical adenitis. Compared with children under 5, children aged 5-15 years more often showed lymphocytosis (84% vs 62%), elevated alanine aminotransferase (77% vs 33%) and lactate dehydrogenase (79% vs 44%). CONCLUSION: EBV infection is common in young children, and children less than 3 years of age constitute the largest group of hospitalizations for acute EBV infection. EBV-associated IM should be suspected in febrile children of all ages with tonsillitis, lymphadenopathy, lymphocytosis and elevated liver enzymes.

[Skin disorder as an indication of viral infection]. / Huidafwijking als aanwijzing voor virusinfectie.

BACKGROUND: Gianotti-Crosti syndrome (GCS) is a dermatosis primarily affecting children between 2 and 6 years of age. It is characterized by multiple, itching, monomorphous, pink to red-brown papules or papulovesicles between 1 and 5 mm in size. GCS is associated with viral infections such as hepatitis B virus and Epstein-Barr virus (EBV). It is often accompanied by fever, hepatosplenomegaly and lymphadenopathy. The syndrome is self-limiting and disappears within 2 months. No treatment is therefore required. CASE DESCRIPTION: We report a case of a 16-year-old female who presented with itching papulovesicles on the extremities and on the buttocks. She was diagnosed with GCS because of the clinical findings, histopathological tests and positive EBV serology. CONCLUSION: GCS can also affect patients older than 6 years of age. Moreover, this syndrome may be a first sign of infection with Epstein-Barr virus, hepatitis B virus, HIV or other viral infections.

Pediatric inflammatory adenopathy.

The differential diagnosis in pediatric lymphadenopathy includes bacterial, viral, fungal, and idiopathic causes. A systematic approach to patient evaluation is necessary because the differential diagnosis, presentation, and work up must consider infectious, immunologic, neoplastic, and idiopathic disorders. A thorough history and examination are vital to determining the diagnosis and ruling out a malignant process.

Epstein-Barr virus-infected cells in IgG4-related lymphadenopathy with comparison with extranodal IgG4-related disease.

IgG4-related lymphadenopathy with increased numbers of Epstein-Barr virus (EBV)-infected cells has been reported but not fully described. We analyzed 31 cases of IgG4-related lymphadenopathy and 24 cases of extranodal IgG4-related diseases for their possible relationship with EBV. Other types of reactive lymph nodes (22) and angioimmunoblastic T-cell lymphoma (AITL) (10) were also studied for comparison. EBV-encoded RNA (EBER) in situ hybridization revealed EBER(+) cells in 18 of 31 cases (58%) of IgG4-related lymphadenopathy. Increased EBER(+) cells were found in only 4 of 22 (18.1%) non-IgG4-related reactive lymphoid hyperplasia in patients of a similar age (P=0.002) and in only 5 of 24 (21%) extranodal IgG4-related biopsies (P=0.006). Interestingly, all patients with EBER(+) progressively transformed germinal center-type IgG4-related lymphadenopathy had systemic lymphadenopathy and/or extranodal involvement. AITL also is associated with EBV, and IgG4-related lymphadenopathy sometimes mimics the morphology of AITL; however, the number of IgG4(+) cells in AITL was significantly less than that in IgG4-related lymphadenopathy (P<0.001). Increased numbers of regulatory T cells are seen in IgG4-related disease; however, there was not a significant difference between the EBER(+) and EBER(-) cases. In conclusion, the presence of increased numbers of EBV-infected cells in IgG4-related lymphadenopathy, compared with other reactive lymphadenopathy or extranodal IgG4-related disease, suggests that there may be a relationship at least between nodal IgG4-related disease and EBV. It is important to avoid overdiagnosing these cases as malignant lymphomas or EBV-related lymphoproliferative disorders.

Sonographic appearance of cervical lymphadenopathy due to infectious mononucleosis in children and young adults.

AIM: To depict the grey-scale and Doppler features of cervical lymphadenopathy due to infectious mononucleosis (IM) and to compare the findings with other benign conditions and lymphoma. MATERIALS AND METHODS: One hundred and four patients <30 years old with 138 enlarged lymph nodes (LNs) were enrolled for sonographic analysis. These LNs were grouped as: IM LNs (59 LNs in 30 patients), lymphoma (30 LNs in 30 patients), bacterial lymphadenitis (24 LNs in 20 patients), tuberculosis (TB; 14 LNs in 13 patients), and reactive hyperplasia (11 LNs in 11 patients). Sonographic assessments included shape, echotexture, hilum, border, matting, cystic necrosis, calcification, and vascular pattern. For each sonographic feature, Fisher's exact test was performed to determine whether the difference between IM LNs and any another aetiology were statistically significant. RESULTS: IM LNs tended to be round in shape (69%), heterogeneous in echotexture (61%), absent of echogenic hilum (66%), indistinct margins (80%), bilateral distribution (91%), and matting (83%) [even bilateral matting (66%)], and central hilar vascularity (89.8%). On analysis, bilateral matting had the highest specificity to IM LNs; however, its sensitivity was relatively low. In contrast to IM LNs, TB LNs were more likely to have unilateral matting, cystic necrosis, and calcification. Indistinct margins and decreased echogenicity of the hilum were more frequently seen in IM LNs than in bacterial LNs. Furthermore, central hilar vascularity was a common feature of IM LNs and other benignity, which can distinguish these from lymphoma and TB LNs. CONCLUSION: Although an individual sonographic feature had considerable overlaps between IM LNs and other aetiologies, the combination of several features may be helpful in the diagnosis of IM.

[Lymphadenopathy: demarcation to malignant lymphomas]. / Lymphadenopathie: Grenzziehung zu malignen Lymphomen.

Recognition of the differential diagnosis between lymphadenitis and malignant lymphoma requires good knowledge of the basic forms of the disease as well in depth knowledge of the structure of the individual compartments. There are defined forms of lymphadenitis where the differential diagnosis to certain lymphoma entities is known. Other reactive structural alterations show indistinct limits so that a decision is only possible after using additional techniques, such as immunohistochemistry and molecular analyses. Finally, there are marginal areas which can only be clarified by including clinical data.

An unusual case of anaemia and lymphadenopathy in a soldier on deployment.

We describe the case of a British soldier, originally from southeast Africa, who presented to the British military hospital in Helmand Province, southern Afghanistan, with a history of constitutional upset, profound anaemia and diffuse lymphadenopathy with hepatosplenomegaly. Following evacuation to the UK investigations revealed a rare (and a not so rare) diagnosis. This case raises a number of questions regarding the population at risk, the prevalence of endemic diseases in this population and laboratory capabilities in the deployed setting.

Evidence for reactivation of human herpesvirus 6 in generalized lymphadenopathy in a patient with drug-induced hypersensitivity syndrome.

The present case provides direct evidence of human herpesvirus 6 reactivation in resected lymph node tissue in a patient with drug-induced hypersensitivity syndrome. This case clearly demonstrates that appropriate pathological evaluation of lymphadenopathy for drug-induced hypersensitivity syndrome, which mimics malignant lymphoma in clinical, radiological, and pathological findings, is required.

The Baboon (Papio spp.) as a model of human Ebola virus infection.

Baboons are susceptible to natural Ebola virus (EBOV) infection and share 96% genetic homology with humans. Despite these characteristics, baboons have rarely been utilized as experimental models of human EBOV infection to evaluate the efficacy of prophylactics and therapeutics in the United States. This review will summarize what is known about the pathogenesis of EBOV infection in baboons compared to EBOV infection in humans and other Old World nonhuman primates. In addition, we will discuss how closely the baboon model recapitulates human EBOV infection. We will also review some of the housing requirements and behavioral attributes of baboons compared to other Old World nonhuman primates. Due to the lack of data available on the pathogenesis of Marburg virus (MARV) infection in baboons, discussion of the pathogenesis of MARV infection in baboons will be limited.

HIV-1 pathogenesis: the virus.

Transmission of HIV-1 results in the establishment of a new infection, typically starting from a single virus particle. That virion replicates to generate viremia and persistent infection in all of the lymphoid tissue in the body. HIV-1 preferentially infects T cells with high levels of CD4 and those subsets of T cells that express CCR5, particularly memory T cells. Most of the replicating virus is in the lymphoid tissue, yet most of samples studied are from blood. For the most part the tissue and blood viruses represent a well-mixed population. With the onset of immunodeficiency, the virus evolves to infect new cell types. The tropism switch involves switching from using CCR5 to CXCR4 and corresponds to an expansion of infected cells to include naïve CD4(+) T cells. Similarly, the virus evolves the ability to enter cells with low levels of CD4 on the surface and this potentiates the ability to infect macrophages, although the scope of sites where infection of macrophages occurs and the link to pathogenesis is only partly known and is clear only for infection of the central nervous system. A model linking viral evolution to these two pathways has been proposed. Finally, other disease states related to immunodeficiency may be the result of viral infection of additional tissues, although the evidence for a direct role for the virus is less strong. Advancing immunodeficiency creates an environment in which viral evolution results in viral variants that can target new cell types to generate yet another class of opportunistic infections (i.e., HIV-1 with altered tropism).

Profile of EBV associated infectious mononucleosis.

During a 5 year period, 33 children (22 males) were diagnosed to have infectious mononucleosis (M:F::2:1; age 9 mo-15 y). The common clinical features observed were fever (100%), lymphadenopathy (84%) hepatosplenomegaly (81%), tonsillar enlargement (45%), neck swelling (30%), upper respiratory symptoms (21%), epitrochlear node enlargement (20%), vomiting and diarrhea (1%). Ten children had complications; upper airway obstruction and hemophagocytic lymphohistocytosis occurred in four each and septic shock in two. EBV associated infectious mononucleosis in hospitalized children was found to affect mainly preschool children and had a favorable prognosis.

Three cases of aggressive natural killer cell leukemia with a lethal hemorrhagic complication.

Aggressive natural killer cell leukemia (ANKL) is a rare malignant disease of NK cells that has a median survival of less than 2 months and a strong association with the Epstein-Barr virus. Herein, we report three Japanese cases of the disease. A 21-year male patient, a 31-year female patient, and a 76-year female patient presented with high fever, lymphadenopathy, hepatosplenomegaly, and severe liver damage. All three cases had granular lymphocytes in both peripheral blood and bone marrow. The phenotype of these cells was CD2(+)CD3(-)CD56(+)HLA-DR(+). All cases had a high copy number of serum Epstein-Barr virus DNA in the peripheral blood and were diagnosed with ANKL. Case 1 and Case 2 were treated with chemotherapy, but suffered from gross intestinal bleeding or massive bleeding in the cerebellum, resulting in death. Although not treated with chemotherapy, Case 3 also suffered gross bleeding from an atypical duodenal ulcer and died from hemorrhagic shock 15 days after admission. There have been no previous reports of such acute lethal hemorrhagic complications with ANKL. The present cases suggest that patients with ANKL need a sufficient supply of coagulation factors, and that chemotherapy for this disease should be carefully designed with promising agents. [J Clin Exp Hematopathol 52(2) : 101-106, 2012].

What a differential a virus makes: a practical approach to thoracic imaging findings in the context of HIV infection--part 2, extrapulmonary findings, chronic lung disease, and immune reconstitution syndrome.

OBJECTIVE: The Centers for Disease Control and Prevention reported more than one million people with HIV infection in the United States in 2006, an increase of 11% over 3 years. Worldwide, nearly 34 million people are infected with HIV. Pulmonary disease accounts for 30-40% of acute hospitalizations of HIV-seropositive patients, underscoring the importance of understanding the range of cardiothoracic imaging findings associated with HIV infection. This article will cover extrapulmonary thoracic diseases, chronic lung diseases, and immune reconstitution inflammatory syndrome in HIV-infected patients. Our approach is focused on the radiologist's perspective by recognizing and categorizing key imaging findings to generate a differential diagnosis. The differential diagnosis can be further refined by incorporating clinical data, such as patient demographics, CD4 count, and presenting symptoms. In addition, with prolonged survival of HIV-infected patients in the era of highly active antiretroviral therapy, radiologists can also benefit from awareness of imaging features of a myriad of chronic cardiopulmonary diseases in this patient population. Finally, the change of imaging findings and clinical status in response to treatment provides important diagnostic information, such as in immune reconstitution syndrome. CONCLUSION: Developing a practical approach to key cardiothoracic imaging findings in HIV-infected patients will aid the radiologist in generating a clinically relevant differential diagnosis and interpretation, thereby improving patient care.