Herpesvirus-Associated Lymphadenitis Distorts Fibroblastic Reticular Cell Microarchitecture and Attenuates CD8 T Cell Responses to Neurotropic Infection in Mice Lacking the STING-IFNα/ß Defense Pathways.

Type I IFN (IFN-α/ß)-driven immune responses to acute viral infection are critical to counter replication and prevent dissemination. However, the mechanisms underlying host resistance to HSV type 1 (HSV-1) are incompletely understood. In this study, we show that mice with deficiencies in IFN-α/ß signaling or stimulator of IFN genes (STING) exhibit exacerbated neurovirulence and atypical lymphotropic dissemination of HSV-1 following ocular infection. Synergy between IFN-α/ß signaling and efficacy of early adaptive immune responses to HSV-1 were dissected using bone marrow chimeras and adoptive cell transfer approaches to profile clonal expansion, effector function, and recruitment of HSV-specific CD8(+) T cells. Lymphotropic viral dissemination was commensurate with abrogated CD8(+) T cell responses and pathological alterations of fibroblastic reticular cell networks in the draining lymph nodes. Our results show that resistance to HSV-1 in the trigeminal ganglia during acute infection is conferred in part by STING and IFN-α/ß signaling in both bone marrow-derived and -resident cells, which coalesce to support a robust HSV-1-specific CD8(+) T cell response.

Human herpesvirus 6 lymphadenitis in drug rash with eosinophilia and systemic symptoms syndrome: a lymphoma mimic.

AIMS: Lymphadenopathy, haematological abnormalities and constitutional symptoms are among the non-specific manifestations seen in drug rash with eosinophilia and systemic symptoms (DRESS), an uncommon but potentially fatal cutaneous adverse drug reaction. The ubiquitous human herpesvirus 6 (HHV-6) plays a unique role in the pathogenesis of DRESS, with emerging data suggesting that reactivation occurs in most cases and contributes to the clinical manifestations, including lymphadenopathy. Further, in the appropriate clinical context, demonstration of HHV-6 reactivation may lend support to a diagnosis of DRESS. The histopathology of DRESS-associated HHV-6 lymphadenitis is reported rarely, with morphologic and immunophenotypic characteristics concerning for T cell lymphoma. The aim is to characterize the histopathology of HHV-6 lymphadenitis in the context of DRESS and to highlight this as an important cause of lymphadenopathy that may be a clinical, morphologic and immunophenotypic mimic of lymphoma. METHODS AND RESULTS: We describe a case of lymphoma-mimicking lymphadenitis in which the histopathological demonstration of reactivation of HHV-6 infection lent support to the clinical diagnosis of DRESS. CONCLUSION: Lymph node biopsies concerning for T cell lymphoma should be evaluated for HHV-6 involvement in a clinical context suggestive of DRESS.

Neurogenic inflammation and colliquative lymphadenitis with persistent orthopox virus DNA detection in a human case of cowpox virus infection transmitted by a domestic cat.

Cowpox viruses are orthopoxviruses that may survive in the environment for years. Rodents are regarded as the primary hosts, but transmission to other species has been reported. This report describes a cowpox virus infection in a cat with subsequent transmission to its owner leading to protracted, atypical and severe clinical signs. A young cat presented with multiple crusts and plaques on the neck, muzzle and tail base. The owner developed an erythematous lesion with elevated margins, central necrosis and crust formation below the left breast, a neurogenic inflammation, enlarged regional lymph nodes, a colliquative lymphadenitis and concomitant flu-like symptoms. Cultures were taken at the first visit from the cat's lesional skin and the patient's skin, and polymerase chain reaction with sequencing of the haemagglutinin region of both were positive for cowpox virus. The patient was treated with various antibiotics and methylprednisolone and was in clinical remission after 7 months.

Spontaneous resolution of post-transplant localized cytomegalovirus lymphadenitis mimicking tumor recurrence.

Compromised T-cell immunity persists for up to 1 year after autologous stem cell transplantation (ASCT), and patients treated with ASCT are more likely to develop atypical lymphoid hyperplasia that mimics tumor recurrence. Here, we present a case of cervical lymphadenitis due to cytomegalovirus (CMV) reactivation in a patient who had undergone ASCT for Burkitt lymphoma, which mimicked tumor recurrence on computed tomography and positron emission tomography-computed tomography 6 months after ASCT. This lesion was confined to the regional lymph nodes and was not accompanied by signs of systemic involvement, such as fever, splenomegaly, an elevated C-reactive protein level, or viremia. The localized CMV lymphadenitis resolved spontaneously without treatment after 6 months (12 months after ASCT) and the elevated CMV immunoglobulin-M titer normalized 6 months after resolution. Our experience with this case suggests that cautious follow-up without anti-CMV treatment should be considered in cases of post-ASCT localized CMV lymphadenitis without systemic involvement in patients with complete engraftment.

Dermatopathic lymphadenitis associated with human papilloma virus infection and verruca vulgaris.

Here we present a pediatric case of human papilloma virus associated with dermatopathic lymphadenitis (DL). A 5-year-old boy presented to the pediatric oncology clinic with swelling of the neck and warts on his lower jaw. His blood chemistry and complete blood count were normal, as was chest x-ray. HIV, EBV, CMV, and parvovirus serologies were negative. The patient was investigated for malignancy and lymphoma but no association was found. Histopathologic examination of the lymph node and the lesion revealed DL and verruca vulgaris, respectively. DL represents a benign form of reactive lymph node hyperplasia and described in patients with HIV and EBV infections. It is a rare entity described in patients with human papilloma virus infection. To our knowledge, this is the first report of DL in a patient with human papilloma virus infection.

Marseillevirus adenitis in an 11-month-old child.

A Marseillevirus (giant virus of amoeba) has been found in the blood and stool samples of individuals who otherwise appear to be healthy. During an attempt to define a serological cutoff for Marseillevirus by enzyme-linked immunosorbent assay (ELISA) in children, we serendipitously detected high antibody responses to Marseillevirus in an 11-month-old boy suffering from adenitis. Marseillevirus DNA was then found in his blood using PCR and with a unique sequence. We identified Marseillevirus in a lymph node using fluorescence in situ hybridization (FISH) and immunohistochemistry, and the lymph node was removed surgically. The child was declared to be cured 1 year later. We conclude that adenitis during early childhood may be caused by Marseillevirus.

Dermatopathic lymphadenitis with generalized erythroderma in a patient with epstein-barr virus-associated hemophagocytic lymphohistiocytosis.

Here, we describe a patient with Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) who simultaneously presented with generalized erythroderma and dermatopathic lymphadenitis (DL). A 63-year-old Korean woman presented at our hospital with fever, hepatosplenomegaly, axillary lymphadenopathy, and generalized erythrodermic eruption. The bone marrow biopsy findings were consistent with the diagnosis of HLH, and EBV DNA was detected using the polymerase chain reaction. Based on serologic tests that indicated a primary EBV infection, the patient was diagnosed with EBV-associated HLH. Histopathologic analysis of enlarged lymph nodes was consistent with DL, and EBV-encoded small nuclear RNA-positive mononuclear cells were detected. We assume that activated histiocytes, lymphocytes, and proinflammatory cytokines in HLH may have important roles in the development of generalized erythroderma and DL. Disrupted epidermal/dermal junctions owing to erythroderma may also be involved in the development of DL.

Herpesvirus infection with severe lymphoid necrosis affecting a beaked whale stranded in the Canary Islands.

This report describes the pathologic findings in a single, adult female Cuvier's beaked whale Ziphius cavirostris stranded in the Canary Islands. The study indicated that this whale died with a severe, systemic, herpesviral infection and clearly exhibited lesions different from those of the fat and gas embolic syndrome described in beaked whale mass strandings associated with sonar exposure. This is the first report of a cetacean alphaherpesvirus infection of the lymphoid system in a beaked whale.

Orofacial outcomes in adolescents with perinatally infected HIV in antiretroviral therapy.

OBJECTIVE: To assess the frequency of orofacial outcomes in adolescents with perinatally infected HIV in treatment with antiretroviral therapy (ART). DESIGN: A Brazilian institution-based retrospective study analyzing medical charts and medication dispensing data. METHODS: Medical records of 137 adolescents were reviewed. HIV viral load, CD4 T-cell count (CD4), ART regimen, nonadherence events, and prolonged ART discontinuation were recorded. The frequency of each outcome was determined. Associations between the most frequent outcomes and both records of undetectable viral load and CD4 at least 500 cells/µl were carried out. Associations of lymphadenitis, Group 1 orofacial manifestations and Group 2 orofacial manifestations with records of Center for Disease Control and Prevention (CDC) category C illness were also performed. Odds ratio (OR), confidence intervals (CI) and P values were provided. RESULTS: Cervical and submandibular lymphadenitis (45.25%), dental caries (32.84%) and periodontal issues (11.67%) were the most frequent orofacial outcomes. A detectable viral load (OR = 2.61, 95% CI 1.16--5.88) and CD4 less than 500 cells/µl (OR = 2.34, 95% CI 1.13--4.82) were associated with a greater risk of lymphadenitis. Orofacial outcomes associated with HIV were found in adolescents with longer ART discontinuation and a greater number of ART discontinuation events (P < 0.05). No association was found between records of CDC category C illness and group 1 orofacial manifestations, group 2 manifestations or lymphadenitis (P > 0.05). CONCLUSION: Orofacial outcomes, in particular, cervical and submandibular lymphadenitis were common among the adolescents assessed. Long-term ART and long-term exposure to HIV virus may have altered the orofacial outcome profile in adolescents perinatally infected by HIV.

Human Herpes Virus 6 (HHV-6)-associated Lymphadenitis: Pitfalls in Diagnosis in Benign and Malignant Settings.

Human herpes virus 6 (HHV-6) is a member of the ß-herpesvirinae subfamily. Most people acquire HHV-6 primary infection early in life and reactivation may occur, most often in immunocompromised individuals, leading to various clinical manifestations. HHV-6 infected cells may be identified in lymph nodes in both reactive and neoplastic conditions. Cases were retrieved from the hematopathology consultation service archives at National Institutes of Health from 2003 to 2017 in which infection by HHV-6 had been documented by immunohistochemical stains to HHV-6 gp60/110 envelope glycoprotein. Five cases of reactive lymphadenitis and 3 cases of lymphoma; 2 angioimmunoblastic T-cell lymphoma and 1 classic Hodgkin lymphoma, positive for HHV-6 were identified. The reactive lymph nodes showed marked paracortical hyperplasia and admixed large atypical lymphoid cells exhibiting pleomorphic nuclei, vesicular chromatin, and prominent eosinophilic intranuclear inclusions. Vascular proliferation and necrosis were also present, raising suspicion of peripheral T-cell lymphoma. The 3 cases of lymphoma showed similar viral inclusions, in addition to the characteristic features diagnostic of the lymphoma. Staining for HHV-6 was positive with a membranous and Golgi pattern and was restricted to cells with evident inclusions on hematoxylin and eosin. HHV-6 infected cells were positive for CD3 and CD4. HHV-6 lymphadenitis can present with morphologic atypia creating a diagnostic pitfall for lymphoma. In such cases, careful attention to the characteristic viral inclusions can lead to immunohistochemical analysis highlighting the replicating virus. In cases of lymphoma, identification of the inclusions is key in detecting the associated infection as well as in avoiding misinterpretation of the lymphoma subtype.

A case of facial cellulitis and necrotizing lymphadenitis due to cowpox virus infection.

We describe a patient with facial cellulitis/erysipelas due to cowpox virus inoculation in the respiratory epithelium of the nose. A cytopathic agent was isolated in cell culture, and the diagnosis of cowpox was confirmed by electron microscopy and polymerase chain reaction. The most likely source of infection was exposure to the family cats. In addition to the severe edematous cellulitis of the face, the clinical course was dominated by several areas of subcutaneous, necrotizing lymphadenitis, from one of which a huge abscess formed that had to be incised. Hyperbaric oxygen treatment was provided to prevent development of dermal necrosis. The healing process in the numerous areas of lymphadenitis was markedly protracted, and 1 persisting node (which yielded positive results on polymerase chain reaction) had to be excised 2 years after onset of disease. This is the first reported case of inoculation of cowpox virus in the respiratory mucosa of the nose. It resulted in a clinical course totally different than that for inoculation in the skin. We also present a short review of findings on orthopoxvirus infection that focuses on the chain of transmission.

The role of giant viruses of amoebas in humans.

Since 2003, dozens of giant viruses that infect amoebas (GVA), including mimiviruses and marseilleviruses, have been discovered. These giants appear to be common in our biosphere. From the onset, their presence and possible pathogenic role in humans have been serendipitously observed or investigated using a broad range of technological approaches, including culture, electron microscopy, serology and various techniques based on molecular biology. The link between amoebal mimiviruses and pneumonia has been the most documented, with findings that fulfill several of the criteria considered as proof of viral disease causation. Regarding marseilleviruses, they have been mostly described in asymptomatic persons, and in a lymph node adenitis. The presence and impact of GVA in humans undoubtedly deserve further investigation in medicine.

The ubiquity of asymptomatic respiratory viral infections in the tonsils and adenoids of children and their impact on airway obstruction.

BACKGROUND: Airway obstruction due to enlargement of tonsils and adenoids is a common pediatric problem resulting in sleep disordered breathing. The cause for the relatively abnormal growth of tonsils and adenoids is poorly understood. METHODS: Non-acutely ill children undergoing tonsillectomy and adenoidectomy (T&A) for various reasons were enrolled prospectively in a study to determine the frequency of asymptomatic respiratory viral infections in each lymphoid tissue and to relate the number and types of virus to the degree of airway obstruction. Molecular techniques were used to detect 9 respiratory viruses while Brodsky scores and measurements of percentages airway obstruction were used to estimate the degree of airway compromise due to the tonsil and adenoid, respectively. RESULTS: Viruses were detected in 70.9% of tonsils and 94.7% of adenoids, p < 0.001. Adenovirus was the most common virus detected at 71.1%. Adenoids had an average of 2.4 viruses compared to 0.92 for tonsils, p < 0.001. Higher Brodsky scores were only associated with EBV in tonsils, p = 0.03, while greater percentages of airway obstruction in the adenoids were associated with adenovirus, EBV, corona virus, parainfluenza virus and rhinovirus, p ≤ 0.005. CONCLUSIONS: Asymptomatic viral infections are common and directly related to the degree of airway obstruction significantly more often in adenoids than tonsils.

A case report of CMV lymphadenitis in an adult kidney transplant recipient.

Cytomegalovirus (CMV) infection following kidney transplantation is associated with increased morbidity and mortality. In this case report we describe a case of a 23-year-old woman with an unusual presentation of diffuse CMV lymphadenitis following kidney transplantation that did not respond to gangiclovir therapy. This case highlights the atypical presentation of CMV disease in a kidney transplant recipient, the importance of CMV hypergammaglobulin in the treatment of CMV infection post kidney transplantation, and the difficulties in transitioning care from pediatric to adult transplant programs.

Infectious lymphadenitis in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma: a rare, but important, complication.

The differential diagnosis of rapidly progressive or symptomatic lymphadenopathy in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) includes infectious lymphadenitis. We studied 286 (9%) of 3040 patients with CLL seen between 2003 and 2012 at Mayo Clinic Rochester who had 356 diagnostic lymph node biopsies to evaluate rapidly progressive or symptomatic lymphadenopathy. Most (85.4%) biopsies showed progressive CLL, 8.9% a second lymphoid malignancy, 3.9% infectious lymphadenitis, 1.1% reactive adenitis and 0.6% non-hematological malignancies. Of the 12 patients (14 biopsies) with infectious lymphadenitis, five patients had never been treated for their CLL, and seven had a specific microbiological diagnosis (herpes simplex n=3, Cryptococcus neoformans n=1, Mycobacterium n=1, coagulase negative Staphylococcus n=2). We conclude that infectious lymphadenitis is a rare complication of CLL with clinical characteristics similar to progressive CLL and transformation to a more aggressive lymphoma. Early recognition and antimicrobial therapy treatment of infectious lymphadenitis can be highly effective in these patients.