Pdf epsteinbarr virus related hemophagocytic syndrome in a. Epsteinbarr virus, hemophagocytic lymphohistiocytosis. Treatment of epsteinbarr virusrelated hemophagocytic. Virus associated hemophagocytic syndrome is a very serious complication of a viral infection.
Epsteinbarr virus associated secondary hemophagocytic lymphohistiocytosis with an unusual presentation of abdominal compartment syndrome hepatoma research is an open access journal and focuses on all topics related to hepatoma. Secondary hlh, more commonly observed in adult patients, is seen in the context of underlying triggering conditions. The syndrome, which has also been referred to as histiocytic medullary. Prompt initiation of treatment for hlh is essential for the survival of affected patients. Hlh is a distinct clinical entity characterized by fever, pancytopenia, splenomegaly, and hemophagocytosis in bone marrow, liver, or lymph nodes. Hemophagocytic lymphohistiocytosis hlh is an aggressive and lifethreatening syndrome of excessive immune activation. Treatment outcomes and prognostic factors in adult patients with.
Natural killer nkt cells that, for hereditary or acquired reasons, are unable to lyse. Clinicopathological study of severe chronic active epstein. It is considered to be synonymous to the macrophage activation syndrome, and is a condition in which t cell and natural killer nk cells and macrophages are aberrantly activated, which results in hypercytokinemia that causes cellular damage and dysfunction of. Acquired hlh is more frequently found in adults and is commonly secondary to infections, malignancies, or autoimmune diseases. The rapid deterioration of vital organs functions and high mortality rate seen in merscov has been observed previously in epsteinbarr virus ebv, severe acute respiratory syndrome caused by a coronavirus sarscov and avian and bird flu. The syndrome is associated with collagen vascular diseases, malignancies and infections most frequently caused by viruses, prominently linked with epsteinbarr viral infection. A case report of severe liver injury and hemophagocytic syndrome caused by chronic eb virus infection related to a mutation in the lyst gene. Differential cellular targets of epsteinbarr virus ebv. Pdf epsteinbarr virus related hemophagocytic syndrome. Epsteinbarr virus related hemophagocytic syndrome in a tcell rich b cell lymphoma article pdf available in annals of oncology 102. Prior to commencement of treatment, determination of ebv genome copy numbers d, ebv serology antivcaigm, igg,eadrigg and antiebna e, flow cytometry f, and, if possible, ebv tropism in subsets g of pb are required. Hemophagocytic syndromes and infection volume 6, number 6. Hematologic emergency in the critical care setting. Pdf a fatal ebv related hemophagocytic lymphohistiocytosis.
As a part of a themed collection of articles on ebv infection and human primary. Haemophagocytic syndrome is caused by a dysregulation in natural killer tcell function, resulting in activation and proliferation of lymphocytes or histiocytes with uncontrolled haemophagocytosis and cytokine overproduction. Introduction hemophagocytic syndrome hps is a rare disorder of the immune system that is synonymous with macrophage activation syndrome 1. Epsteinbarr virus related hemophagocytic lymphohistiocytosis. He achieved complete remission with rituximab alone. Ebv spreads most commonly through bodily fluids, primarily saliva. Figure 3 treatment regimens for epsteinbarr virus related hemophagocytic lymphohistiocytosis. Ebv related hemophagocytic lymphohistiocytosis poses unusual challenges to pediatric hematologists. Precise mechanism of ebv induced hlh has recently been found. Clinical characteristics and prognostic factors of adult. Hemophagocytic syndrome hps is clinically defined as a combination of fever, liver dysfunction, coagulation abnormalities, pancytopenia, progressive macrophage proliferation throughout the reticuloendothelial system, and cytokine overproduction, and may be primary or secondary to infectious, autoimmune, and tumoral diseases. We are reporting a patient who was diagnosed with epsteinbarr virus ebv related hlh. Hemophagocytic lymphohistiocytosis hlh is a rapidly progressive, lifethreatening syndrome of excessive immune activation. Although ebvassociated hlh carries a high mortality rate, quick diagnosis and appropriate treatment can subside the disease.
Case report alternative therapy for epsteinbarr virus. Hemophagocytic lymphohistiocytosis hlh is a relatively rare but lifethreatening disease with confusing clinical manifestations, rapidly deteriorating health, high morbidity and mortality. Hemophagocytic syndrome is a term used to describe the proliferation of nonneoplastic i. Xlinked lymphoproliferative syndrome xlp is a rare inherited immunodeficiency by an extreme vulnerability to epsteinbarr virus ebv infection, frequently resulting in hemophagocytic lymphohistiocytosis hlh. Epsteinbarr virus associated secondary hemophagocytic. B cells, t cells, nk cells, and histiocyticdendritic cells, are infected with the epsteinbarr virus ebv.
A hispanic 28yearold man presented with sore throat and fatigue for one. Epsteinbarr virus ebv is a ubiquitous virus that infects nearly all people worldwide without serious sequela. As a part of a themed collection of articles on ebv infection and human primary immune deficiencies. Epsteinbarr virus associated hemophagocytic lymphohistiocytosis. Pulmonary involvement in patients with hemophagocytic. Diagnosing hlh is challenging because of the rare occurrence, variable presentation, and. There was no response to treatment with rituximab, etoposide and. Epsteinbarr virusassociated hemophagocytic lymphohistiocytosis in a small child.
Haemophagocytosis is part of a sepsislike syndrome caused. Hlh can occur as a familial or sporadic acquired disorder. Hemophagocytic lymphohistiocytosis hlh is a rapidly fatal condition characterized by excessive immune activation. Haemophagocytic syndrome or haemophagocytic lymphohistiocytosis is a rare disease that is often fatal despite treatment. It is described as primary hlh familial hlh and secondary hlh acquired following malignancy, rheumatologic disorders, primary immune deficiencies or. The condition is rare but has been recognized in dogs and cats. Hemophagocytic lymphohistiocytosis hlh is a lifethreatening disease due to a highly stimulated but ineffective immune response, with uncontrolled proliferation of activated lymphocytes and macrophages that may lead to multisystem failure. Hemophagocytic lymphohistiocytosis hlh is a rare lifethreatening syndrome of immune dysregulation typified by extreme immunologic response and tissue infiltration of cytokineactivated tissue macrophages histiocytes as well as cytotoxic tlymphocytes that can lead to multiorgan system failure. Hemophagocytic lymphohistiocytosis hlh is an unusual syndrome characterized by fever, splenomegaly, jaundice, and the pathologic finding of hemophagocytosis phagocytosis by macrophages of. Epsteinbarr virusinduced hemophagocytic lymphohistiocytosis.
However, for patients who have genetic diseases which predispose them to the development of hemophagocytic lymphohistiocytosis hlh, ebv infection is a lifethreatening problem. There is an aberrant activation of lymphocytes and macrophages that results in hypercytokinemia. To our knowledge, this is the rst case of an adult patient with ebv related hlh who went into remission with rituximab therapy alone, without using the conventional chemotherapy. Epsteinbarr virus ebv is a member of the herpesvirus family that can infect humans.
Imashuku s, hibi s, ohara t, iwai a, sako m, kato m, et al. We report a case of hemophagocytic lymphohistiocytosis in a patient who presented. Mar 27, 2019 epsteinbarr virus ebv is a member of the herpesvirus family that can infect humans. Hemophagocytic lymphohistiocytosis hlh is a rare and potential lifethreatening clinical syndrome that results from uncontrolled activation of the immune system. Epsteinbarr virus ebv is a highly prevalent herpes virus that can cause transient infectious mononucleosis, ebvrelated malignancies, and chronic active ebv caebv infection. Hps may be the consequence of a familial immune dysregulatory disorder or be associated with a number of different infections, autoimmune disorders or malignancies, like lymphomas or carcinomas. Xlp are now divided into type 1 xlp1 and type 2 xlp2, which are caused by mutations of sh2d1aslamassociated protein sap and xlinked inhibitor of apoptosis protein xiap. Virus associated hemophagocytic syndrome genetic and. Acute kidney injury with epstein barr virusassociated. Epsteinbarr virus and hemophagocytic lymphohistiocytosis. Ebv infection of natural killer nk and t cells is likely to be a rare event and is strongly associated with a spectrum of lymphoproliferations characterized by the pathognomic presence of monoclonal ebv in the t andor nk cells. Hemophagocytic lymphohistiocytosis hlh is a disorder related to activation of cytotoxic t cells, natural killer nk cells and macrophages. The treatment of hlh generally includes a variety of potent.
First of all, the reactive disorder may be difficult to distinguish from infectious mononucleosis, septicemia, certain hematologic malignancies. Although ebv is the most common cause of infectionassociated hlh, recognition that at least some of the deaths associated with avian. It means that ebv infected b cells stimulate cytotoxic t lymphocytes leading to hypercytokinemia and stimulation of histolytic cells. Epsteinbarr virus ebvassociated haemophagocytic syndrome. Epsteinbarr virus ebv has been recognized as the leading infectious cause and is associated.
Ebv can also be the trigger in both familial and secondary cases. Clinical features and treatment strategies of epsteinbarr. It is a lifethreatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated. First of all, the reactive disorder may be difficult to distinguish from infectious mononucleosis, septicemia, certain hematologic malignancies, and systemic autoimmune disorders. Epsteinbarr virus ebv, also known as human herpesvirus 4, is a member of the herpes virus family. The treatment and prognosis of patients with hlh and the macrophage activation syndrome mas, a form of hlh in patients with. Nov 19, 2017 imashuku s, hibi s, ohara t, iwai a, sako m, kato m, et al. Hemophagocytic lymphohistiocytosis associated with. Hlh can occur as a familial or sporadic disorder, and it can be triggered by a variety of.
Hlh is a rare complication of epsteinbarr virus ebv infection. Xlp are now divided into type 1 xlp1 and type 2 xlp2, which are caused by mutations of sh2d1aslamassociated protein sap and x. Juan kang 1,2, weiqun zeng1,2, yixuan yang 1,2, peng hu 1,2, dazhi zhang 1,2, zhi zhou 1,2, dachuan cai 1,2, yu lei1,2, hong ren1,2 1chongqing city center for the study of liver disease treatment, institute for viral hepatitis. Jul 01, 2010 epsteinbarr virus ebv is a ubiquitous and predominantly b lymphotrophic human. Epsteinbarr virus ebv is a ubiquitous and predominantly b lymphotrophic human.
It is considered to be synonymous to the macrophage activation syndrome, and is a condition in which t cell and natural killer nk cells and macrophages are aberrantly activated, which results in hypercytokinemia that causes cellular damage and dysfunction of various organs. Oct 20, 2012 the epsteinbarr virus ebv infects b cells. Ebv infections are very common youve probably already contracted the virus without even knowing it. Characterization of epsteinbarr virus ebvinfected cells. Lung involvement in hlh has received little attention. Hemophagocytic lymphohistiocytosis hlh is not one condition but descriptive of a lifethreatening, hyperinflammatory syndrome with multiorgan involvement with a variety of triggers, both genetic and environmental. Epsteinbarr virus ebv has been recognized as the leading infectious cause and is associated with a poor outcome. Durham, in pathologic basis of veterinary disease sixth edition, 2017. A standard established treatment for hlh is described in the hlh94 protocol and. Signs and symptoms of virus associated hemophagocytic syndrome, include high fever, liver problems, enlarged liver and spleen, coagulation factor abnormalities, decreased red or white blood cells and platelets pancytopenia, and a buildup of histiocytes, a type of immune. Most people get infected with ebv at some point in their lives.
To improve the recognition as well as understanding of this disorder, we analyzed clinical characteristics and prognostic factors from 85 adult patients diagnosed with hlh in. Diagnosing hlh is challenging because of the rare occurrence, variable. Hlh may be diagnosed in association with malignant, genetic, or autoimmune. Hemophagocytic lymphohistiocytosis hlh is a rare and lifethreatening syndrome characterized by uncontrolled immune activation. Epsteinbarr virus ebv is a welldescribed trigger and xlinked lymphoproliferative disease is almost exclusively associated with ebv. Effective control of epsteinbarr virusrelated hemophagocytic lymphohistiocytosis with immunochemotherapy. Alternative therapy for epsteinbarr virus related hemophagocytic lymphohistiocytosis article pdf available in case reports in oncological medicine 2015. Hemophagocytic syndromes and infection volume 6, number. We aim to describe a case of secondary hlh due to primary epsteinbarr virus ebv infection. Hemophagocytic syndrome an overview sciencedirect topics. A fatal ebv related hemophagocytic lymphohistiocytosis hlh in. Allogeneic bone marrow transplantation for active epstein.
The haemophagocytic syndrome hps represents a severe and aggressive hyperinflammatory disease with major diagnostic and therapeutic difficulties. Epsteinbarr virusassociated lymphoproliferative diseases. Epsteinbarr virus infectionassociated hemophagocytic. Hemophagocytic syndrome, liver injury, ebv, lyst gene, stxbp2 gene. Hemophagocytic lymphohistiocytosis 2nd lymphoproliferative. Hemophagocytic lymphohistiocytosis hlh is an unusual syndrome characterized by fever, splenomegaly, jaundice, and the pathologic finding of hemophagocytosis phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors in bone marrow and other tissues. Epstein barr virus associated hemophagocytic syndrome. The mr imaging appearance of a case of virusassociated hemophagocytic syndrome complicated by diffuse cns infiltration is presented. Epsteinbarr virus associated hemophagocytic lymphohistiocytosis in a. The rapid deterioration of vital organs functions and high mortality rate seen in merscov has been observed previously in epsteinbarr virus ebv, severe acute respiratory syndrome caused by a coronavirus sarscov and avian and bird flu related hemophagocytic lymphohistiocytosis hlh. Hemophagocytic syndrome is a welldefined clinical disease that was first described by scott and robbsmith in 1939. Epsteinbarr virusrelated hemophagocytic lymphohistiocytosis ebvhlh is defined as a hemophagocytic syndrome associated with systemic.
We report a case of epsteinbarr virus associated hemophagocytic syndrome in a 19 year old boy who responded to treatment with steroids and etoposide. Acquired hemophagocytic lymphohistiocytosis hlh is a lifethreatening event that usually occurs as a complication of immunodeficiency. Poor outcomes of chronic active epsteinbarr virus infection. Infections associated with haemophagocytic syndrome the. Diagnosis of epsteinbarr virusrelated hemophagocytic lymphohistiocytosis ebvhlh must fulfill both the evidence of ebv infection and the diagnostic criteria for hlh. On the other hand, ebv causes stimulation, generation and uncontrolled secretion of tand. The study participants included 182 ebvhlh patients 95 boys and 87 girls with a median age of 2. The patient was started on a treatment regimen of 8 weeks with etoposide. Allogeneic bone marrow transplantation for active epsteinbarr virusrelated lymphoproliferative disease and hemophagocytic lymphohistiocytosis in an. Ebvassociated hemophagocytic lymphohistiocytosis ebvhlh, chronic. Pdf alternative therapy for epsteinbarr virus related. Although uncommon, hemophagocytic syndrome is a serious complication of ebv infection and can be fatal in many cases. The majority of ebvhlh occurs in apparently immunocompetent subjects, but some are associated with chronic active ebv infection status, xlinked lymphoproliferative. Accepted on january 25, 2019 introduction hemophagocytic syndrome hps is a syndrome of excessive immune activation characterized by various clinical symptoms of extreme inflammation.
Hemophagocytic syndrome, epstein barr virus, acute kidney injury 1. Epsteinbarr virusrelated hemophagocytic lymphohistiocytosis. To date, several genes have been implicated in these disorders. Cns involvement of virusassociated hemophagocytic syndrome. Hemophagocytic lymphohistiocytosis, also known as haemophagocytic lymphohistiocytosis british spelling, and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. Hemophagocytic lymphohistiocytosis 2nd lymphoproliferative disease related to chronic ebv. Pdf on aug 6, 2018, magliano g and others published a fatal ebv related hemophagocytic lymphohistiocytosis hlh in a young patient find, read and cite all the research you need on researchgate. Jul 01, 2008 epsteinbarr virus ebv is a highly prevalent herpes virus that can cause transient infectious mononucleosis, ebvrelated malignancies, and chronic active ebv caebv infection. Virusassociated hemophagocytic syndrome is a rare condition, precipitated by viral infection and characterized by proliferation of benign histiocytes with phagocytosis. Epsteinbarr virusassociated hemophagocytic lymphohistiocytosis. Ebvrelated hemophagocytic lymphohistiocytosis poses unusual challenges to pediatric hematologists.
Is secondary hemophagocytic lymphohistiocytosis behind the. It most frequently affects infants from birth to 18 months of age, but the disease is also observed in children and adults of all ages. Caebv infection is a persistent ebv infection in combination with infectious mononucleosislike symptoms in individuals without apparent immunodeficiency. This activation results in uncontrolled hypercytokinemia. Debate around infectiondependent hemophagocytic syndrome. Recommendations for the management of hemophagocytic. In contrast, hemophagocytic syndrome in adults usually has. A case report of severe liver injury and hemophagocytic.