Epstein-Barr virus-related cutaneous necrotizing vasculitis in a girl heterozygous for factor V Leiden.

Fibrin-ring granuloma (FRG), which can be found in bone marrow or the liver, is a subtype of epithelioid granuloma characterized by a central fat vacuole and annular peripheral fibrinoid materials. FRG has been proven to be associated with many etiologies such as several infectious organisms (Coxiella burnett; Epstein-Barr Virus, EBV; cytomegalovirus, CMV; and hepatitis A virus), allopurinol induced hepatitis, Hodgkin's lymphoma, and peripheral T-cell lymphoma. We retrospectively reviewed 24 patients diagnosed with FRG by bone marrow biopsy at a single institute between 1995 and 2004. We reviewed clinical symptoms and laboratory findings of the patients, classified them by etiology, and compared prognosis of each group. The most common cause of FRG was acute or chronic EBV infection. Chronic or acute EBV infection was associated with 41.4% of patients (10/24). Of the remaining patients, 33.3% (8/24) were leukemia or lymphoma patients after chemotherapy, 4.2% (1/24) was a patient with hepatic failure, and 20.8% (5/24) were diagnosed as fever of unknown origin. The most common symptom and clinical finding were fever and cytopenia. EBV-associated group comprised chronic active EBV infection, EBV-associated hemophagocytic histiocytosis, acute EBV infection, EBV-associated lymphoproliferative disease, and Langerhans' cell histiocytosis. The EBV-associated group showed a lower survival probability compared with the non-EBV group (P<0.05). Patients with bone marrow fibrin ring granuloma accompanied by fever require an active workup to find out the cause of infectious agents including EBV infection particularly due to their poor prognosis.

Pulmonary lymphoepithelial carcinoma is an EBV-associated malignancy; however, the pathogenesis of virus-associated cancers remains incompletely elucidated. In particular, the early pathological changes and fate decisions of pulmonary epithelial cells following acute EBV infection have yet to be fully elucidated. This study aimed to investigate cell death modes of lung epithelial cells upon acute EBV infection. An acute infection model was established by co-culturing EBV-positive Akata cells with lung cancer cells. Following infection, we evaluated morphological alterations and modes of cell death using immunofluorescence staining and confocal laser scanning microscopy. The co-culture system successfully established a 72-h acute EBV infection in lung cancer cells, with ~10.3% of epithelial cells exhibiting EBV-associated GFP fluorescence. Under these conditions, the majority of epithelial cells underwent cell death. More than half of the epithelial cells died by day 5 of co-culture, and mortality progressively increased. At 72 h post-infection, immunofluorescence analysis of pMLKL, cGSDMD, and cCASP3 revealed a significant upregulation of pMLKL protein expression (p < 0.001), whereas no significant differences were observed in cGSDMD (p > 0.05) or cCASP3 (p > 0.05) levels. ~15.1% of the remaining epithelial cells following B-cell removal exhibited "cell-in-cell" structures. The internalized B cells underwent various forms of death, including apoptosis, pyroptosis, and necroptosis. Acute EBV infection drives lung cancer epithelial cell death through pMLKL-mediated necroptosis, without significant involvement of apoptosis or pyroptosis. Internalized B cells within "cell-in-cell" structures exhibit multiple death modalities. These findings provided novel insights into cellular fate decisions in EBV-infected epithelium prior to latency.

Introducción. La púrpura Henoch-Schönlein (PHS) es la forma más común de vasculitis en la infancia; esta se da en pequeños vasos sanguíneos y no es frecuente que genere complicaciones graves como la vasculitis bullosa, tal como sucedió en el caso que se presenta a continuación.Presentación del caso. Paciente masculino de cinco años con un cuadro clínico consistente en artralgias y aparición de lesiones purpúricas en miembros inferiores. Luego de ser diagnosticado con PHS, presentó lesiones bullosas, por lo que fue hospitalizado y se inició manejo analgésico y tópico; durante su estadía en el hospital se vigiló su función renal y, ya que no presentó otras complicaciones, se dio de alta.Conclusión. Las publicaciones disponibles sobre PHS sugieren que su presentación cutánea bullosa en pediatría no es frecuente y que no siempre se relaciona con un compromiso renal y/o gastrointestinal como la variante clásica; sin embargo, siempre debe vigilarse la función de estos sistemas sin importar la gravedad dérmica de esta vasculitis.

Although Henoch-Schönlein purpura (HSP) is the most common form of renal vasculitis in childhood, progression to ESRD is rare, and there are few data on outcomes of renal transplantation in patients with HSP. This is a matched retrospective cohort study of renal allografts using the United Network of Organ Sharing database (1987 to 2005). Of the 189,211 primary renal allografts, there were 339 with a diagnosis of HSP. The primary end point was allograft survival. Compared with the remainder of the database, the HSP population was younger (25 years versus 46 years), and had a higher proportion of women (47% versus 40%), live donors (50% versus 35%), and Caucasians (77% versus 60%). Controlling for age, gender, donor source, ethnicity, and year of transplantation, death-censored graft survival for patients with HSP was 80.0% at 5 years and 58.8% at 10 years compared with 79.0% at 5 years and 55.4% at 10 years in the non-HSP population. Among patients with reported causes of graft loss, failure from recurrent disease occurred in 13.6% of patients with HSP, compared with 6.6% in the non-HSP population. When analyzing allograft survival in recipients with HSP compared with those with IgA nephropathy, there was no difference in 10-year allograft survival (58.4% and 59.3%, respectively). These data indicate that although there is an increased risk of graft failure attributable to recurrent disease in patients with HSP, a diagnosis of HSP has little effect on overall renal allograft survival.

Purpura is a manifestation of pathological bleeding which may occur as the result of various underlying diseases or mechanisms. In general, the bleeding is due either to a deficiency in the clotting mechanism or to an increase in vascular permeability. The purpura which may result from an allergic or anaphylactoid reaction is commonly classified as attributable to an abnormal capillary response (1, 2). The name “Henoch's purpura” has been given to the type associated with gastro-intestinal symptoms, presumably due to an allergic serosanguineous involvement of the intestinal wall. However, other sites, particularly the skin and joints, are frequently involved. Thus, the terms Schonlein-Henoch's syndrome and anaphylactoid purpura are assigned to the exanthem found associated at different times with gastro-intestinal symptoms, joint symptoms, edema of the face and extremities, and nephritis. Gairdner (3) reviewed 12 cases of “anaphylactoid purpura.” He found a “rash” in all, gastro-intestinal symptoms in all but one, and articular symptoms in 10 of the 12. Eight patients passed blood in the stools. The disease is predominantly, but not exclusively, one of childhood and more frequently involves males. Since the gastro-intestinal symptoms are variable and frequently precede the skin eruption, many of the cases are confused with such conditions as appendicitis, ileitis, and intussusception, with frequent resort to unnecessary surgery (4). Abnormalities in the radiographic appearance of the small intestine occurring in a case of Henoch's purpura were described in 1946 by Whitmore and Peterson (5). Kraemer (1947) also reported small intestinal changes in a case of Henoch's purpura (6). These cases displayed two common features. First, the radiographic changes were demonstrable before the appearance of purpura on the skin. Second, the small intestine reverted to a normal pattern after the subsidence of symptoms. The two cases of anaphylactoid or Henoch's purpura reported here also demonstrate “pre-exanthematous” abnormal and reversible changes in the small intestine. This report may serve to emphasize the diagnostic importance of small intestinal abnormalities in cases of acute abdominal pain of uncertain etiology. Case Reports Case I: R. C., Italian male, age 6, was admitted to Danbury Hospital on July 9, 1948, because of generalized abdominal pain, associated with nausea and vomiting, as well as a mild diarrhea. Gross blood had been noted in the stools on the day of admission. During the four preceding days the child had complained of anorexia and occasional abdominal pain of no definite localization. About nine months previously, he had experienced similar abdominal pain of short duration but without melena. Physical examination on admission was entirely negative. No skin eruptions were noted.

Influence of Sex on Mortality and Perioperative Outcomes in Patients Undergoing TAVR: Insights From the FRANCE 2 Registry

Kawasaki disease (KD) and Henoch–Schönlein purpura (HSP) are the most frequent vasculitis in childhood. For both, a multifactorial mechanism has been hypothesised, with an abnormal immune response in genetically predisposed children. Gut microbiota (GM) alterations might trigger the hyperimmune reaction. Our aim was to explore the GM in KD and compare it with the GM of HSP and febrile children. Children diagnosed with KD, HSP and non-KD febrile illness (F) were enrolled. GM was profiled by 16S rRNA gene sequencing and compared with the profiles of healthy children from previous studies. We enrolled 13 KD, 10 HSP and 12 F children. Their GM significantly differed from controls, with an overall reduction in the relative abundance of beneficial taxa belonging to the Ruminococcaceae and Lachnospiraceae families. Potential KD and HSP signatures were identified, including smaller amounts of Dialister in the former, and Clostridium and Akkermansia in the latter. Notably, the GM structures of KD, HSP and F patients stratified by abdominal involvement, with more severe dysbiosis in those suffering from intestinal symptoms. This is the first study analysing GM in a mostly Caucasian cohort of KD and HSP children. Our data could open up new opportunities for childhood vasculitis treatment.

Henoch-Schönlein purpura (HSP) is a common autoimmune vasculitis in childhood. The detailed pathogenesis of HSP is still unclear, whereas several types of predisposing factors have been proved to be the...

Pain in adolescent chronic fatigue following Epstein-Barr virus infection.

Henoch-Schönlein purpura (HSP) is a common, benign vasculitis in childhood which occasionally follows a protracted course and prolonged length of hospital stay. We aimed to determine clinical and laboratory characteristics that allow prediction of prolonged length of hospital stay (4 or more days) in HSP patients. We have retrospectively reviewed all HSP cases that were admitted to the Dana Duek Children's hospital between 2000 and 2013. Univariable analysis was performed to study the variables that were statistically related to length of hospital stay. These variables along with other clinically relevant variables were analyzed using stepwise backward multiple regression analysis. Variables that remained significant in the final analysis were correlated with length of stay, were each given specific weight (according to their contribution to the final R(2)) and were used to assemble an HSP presentation severity score. Out of 107 charts that were screened, 89 children were retrieved for analysis. In univariate analysis, variables that were associated with prolonged (>4 days) length of stay were: abdominal pain as initial sole presentation, C-reactive protein (CRP) 45 mg/dL (1 or 0 point) and patient's age > 6 years (0.5 or 0 points). A score of ≥3 in patients diagnosed with HSP predicted a prolonged length of stay with a positive predictive value of 93 %. The HSP presentation severity score index that we describe here may serve as a practical tool to assess severity of HSP which may eventually reflected as prolonged length of hospital stay. This score should be validated in the future in an ongoing prospective study.

Surgical management of nonrenal genitourinary manifestations in children with Henoch-Schönlein purpura

SAT-401 RENAL PRONOSIS IN ADULTS IgA VASCULITIS

Background:People of all ages can suffer from Henoch-Schönlein purpura (HSP), but it is the most common vasculitis in childhood. The most important involving gene is located on chromosome 6p21.3, a region coding for human leukocyte antigens (HLAs). Among HLA genes, because of the high rate of polymorphisms, HLA-DRB1 is estimated to have a strong association with HSP. In this study, we aimed to assess the association of HLA-DRB1 alleles with HSP in Iranian children.Materials and Methods:This study consisted of thirty Iranian children with HSP and 35 healthy controls. Genomic DNA was extracted, and HLA typing was performed by polymerase chain reaction with sequence-specific primers technique.Results:The results have shown that HLA-DRB1*01 and HLA-DRB1*11 (P = 0.002, odds ratio [OR] = 7.579, confidence interval [CI] = 1.934–29.697 and P = 0.039, OR = 3.333, CI = 1.030–10.788), respectively, are the most frequent alleles associated with HSP in Iranian children population. The frequency of other alleles was not significantly different in both groups. The results also show no correlation between HLA types and disease manifestations.Conclusion:According to these results, there is an association between HLA-DRB1*01 and HLA-DRB1*11 gene polymorphisms and susceptibility to HSP in our study group.

Murine models of lymphocytic choriomeningitis virus infection suggest that the memory CD8(+) T cell repertoire is reflective of the CD8(+) T cell repertoire generated during acute infection. Less is known regarding the evolution of CD8(+) T cell repertoires during human viral infections. We therefore examined epitope-specific CD8(+) T cell responses in a large cohort of individuals with acute through latent Epstein-Barr virus infection. Using 16 of 20 published EBV epitopes restricted by HLA-A2, HLA-A3 or HLA-B7, we showed that lytic cycle-specific CD8(+) T cell responses predominated during acute EBV infection. However, whereas HLA-A2(+)-restricted BMLF-1-specific CD8(+) T cell responses were maintained through latency, HLA-A2(+)- and HLA-B7(+)-restricted BZLF-1, as well as HLA-A3(+)-restricted BRLF-1 CD8(+) T cell responses, were generated but not readily maintained. Analyses of CD8(+) T cell responses to EBV latent cycle Ags showed delayed detection and lower frequencies of latent epitope-specific CD8(+) T cell responses during acute EBV infection, with maintenance of these responses 1 yr post-EBV infection. Early BMLF-1 and EBNA-3A epitope-specific CD8(+) T cell frequencies did not correlate with their frequencies at 1 yr postinfection. Interestingly, populations of EBV-specific CD8(+) T cells were stable during 20 mo in our long term EBV-seropositive populations, suggesting homeostasis between virus and the host immune system. This study demonstrates that CD8(+) T cell repertoires generated during persistent viral infections are not simply reflective of the initial pool of CD8(+) T cells and provides evidence that the generation of CD8(+) T cell responses to a persistent infection is a dynamic process.

1 year after acute Zika virus infection in men