Hemophagocytic lymphohistiocytosis hlh is a disorder related to activation of cytotoxic t cells, natural killer nk cells and macrophages. Diagnosing hlh is challenging because of the rare occurrence, variable presentation, and. The majority of ebvhlh occurs in apparently immunocompetent subjects, but some are associated with chronic active ebv infection status, xlinked lymphoproliferative. Most people get infected with ebv at some point in their lives. Epsteinbarr virusassociated hemophagocytic lymphohistiocytosis. Epsteinbarr virusinduced hemophagocytic lymphohistiocytosis. 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. Hematologic emergency in the critical care setting. Hemophagocytic syndrome, epstein barr virus, acute kidney injury 1. Is secondary hemophagocytic lymphohistiocytosis behind the.
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. However, for patients who have genetic diseases which predispose them to the development of hemophagocytic lymphohistiocytosis hlh, ebv infection is a lifethreatening problem. Pdf a fatal ebv related hemophagocytic lymphohistiocytosis. Epsteinbarr virusassociated lymphoproliferative 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 related hemophagocytic lymphohistiocytosis hlh.
Hlh may be diagnosed in association with malignant, genetic, or autoimmune. Ebv spreads most commonly through bodily fluids, primarily saliva. Caebv infection is a persistent ebv infection in combination with infectious mononucleosislike symptoms in individuals without apparent immunodeficiency. Diagnosing hlh is challenging because of the rare occurrence, variable. 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. Hemophagocytic syndrome an overview sciencedirect topics.
A standard established treatment for hlh is described in the hlh94 protocol and. The syndrome is associated with collagen vascular diseases, malignancies and infections most frequently caused by viruses, prominently linked with epsteinbarr viral infection. The patient was started on a treatment regimen of 8 weeks with etoposide. 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. Epsteinbarr virus and hemophagocytic lymphohistiocytosis. Debate around infectiondependent hemophagocytic syndrome. Effective control of epsteinbarr virusrelated hemophagocytic lymphohistiocytosis with immunochemotherapy. 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 lymphohistiocytosis 2nd lymphoproliferative disease related to chronic ebv. Parameters associated with hemophagocytic lymphohistiocytosis. Epsteinbarr virus ebv is a welldescribed trigger and xlinked lymphoproliferative disease is almost exclusively associated with ebv. 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.
We aim to describe a case of secondary hlh due to primary epsteinbarr virus ebv infection. A hispanic 28yearold man presented with sore throat and fatigue for one. Differential cellular targets of epsteinbarr virus ebv. Oct 20, 2012 the epsteinbarr virus ebv infects b cells.
Nov 19, 2017 imashuku s, hibi s, ohara t, iwai a, sako m, kato m, et al. As a part of a themed collection of articles on ebv infection and human primary. Hemophagocytic lymphohistiocytosis associated with. Epsteinbarr virusrelated hemophagocytic lymphohistiocytosis. Epsteinbarr virus related hemophagocytic syndrome in a tcell rich b cell lymphoma article pdf available in annals of oncology 102.
Poor outcomes of chronic active epsteinbarr virus infection. Hemophagocytic lymphohistiocytosis hlh is an aggressive and lifethreatening syndrome of excessive immune activation. Ebv related hemophagocytic lymphohistiocytosis poses unusual challenges to pediatric hematologists. Xlp are now divided into type 1 xlp1 and type 2 xlp2, which are caused by mutations of sh2d1aslamassociated protein sap and x. Clinical characteristics and prognostic factors of adult. Lung involvement in hlh has received little attention. The haemophagocytic syndrome hps represents a severe and aggressive hyperinflammatory disease with major diagnostic and therapeutic difficulties. Epsteinbarr virus infectionassociated hemophagocytic. Recommendations for the management of hemophagocytic. Characterization of epsteinbarr virus ebvinfected cells. 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. The treatment and prognosis of patients with hlh and the macrophage activation syndrome mas, a form of hlh in patients with. Epsteinbarr virus, hemophagocytic lymphohistiocytosis. 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.
Epsteinbarr virus associated hemophagocytic lymphohistiocytosis in a. Natural killer nkt cells that, for hereditary or acquired reasons, are unable to lyse. Treatment of epsteinbarr virusrelated hemophagocytic. 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. Ebvassociated hemophagocytic lymphohistiocytosis ebvhlh, chronic. Epsteinbarr virus ebv, also known as human herpesvirus 4, is a member of the herpes virus family. First of all, the reactive disorder may be difficult to distinguish from infectious mononucleosis, septicemia, certain hematologic malignancies.
To date, several genes have been implicated in these disorders. Haemophagocytosis is part of a sepsislike syndrome caused. 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. A fatal ebv related hemophagocytic lymphohistiocytosis hlh in. Diagnosis of epsteinbarr virusrelated hemophagocytic lymphohistiocytosis ebvhlh must fulfill both the evidence of ebv infection and the diagnostic criteria for hlh. It is described as primary hlh familial hlh and secondary hlh acquired following malignancy, rheumatologic disorders, primary immune deficiencies or. 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. 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. On the other hand, ebv causes stimulation, generation and uncontrolled secretion of tand. Virus associated hemophagocytic syndrome is a very serious complication of a viral infection. This activation results in uncontrolled hypercytokinemia.
Allogeneic bone marrow transplantation for active epstein. 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. Virus associated hemophagocytic syndrome genetic and. 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. Epsteinbarr virus ebv is a ubiquitous and predominantly b lymphotrophic human. 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. B cells, t cells, nk cells, and histiocyticdendritic cells, are infected with the epsteinbarr virus ebv. Pdf epsteinbarr virus related hemophagocytic syndrome. 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. We report a case of epsteinbarr virus associated hemophagocytic syndrome in a 19 year old boy who responded to treatment with steroids and etoposide.
Allogeneic bone marrow transplantation for active epsteinbarr virusrelated lymphoproliferative disease and hemophagocytic lymphohistiocytosis in an. The treatment of hlh generally includes a variety of potent. Durham, in pathologic basis of veterinary disease sixth edition, 2017. We report a case of hemophagocytic lymphohistiocytosis in a patient who presented. Epsteinbarr virus ebv is a highly prevalent herpes virus that can cause transient infectious mononucleosis, ebvrelated malignancies, and chronic active ebv caebv infection. Hlh is a distinct clinical entity characterized by fever, pancytopenia, splenomegaly, and hemophagocytosis in bone marrow, liver, or lymph nodes. 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. Hemophagocytic lymphohistiocytosis hlh is a rapidly fatal condition characterized by excessive immune activation. The condition is rare but has been recognized in dogs and cats.
Epsteinbarr virusrelated hemophagocytic lymphohistiocytosis ebvhlh is defined as a hemophagocytic syndrome associated with systemic. The mr imaging appearance of a case of virusassociated hemophagocytic syndrome complicated by diffuse cns infiltration is presented. Hemophagocytic lymphohistiocytosis hlh is an unusual syndrome characterized by fever, splenomegaly, jaundice, and the pathologic finding of hemophagocytosis phagocytosis by macrophages of. There is an aberrant activation of lymphocytes and macrophages that results in hypercytokinemia.
Epstein barr virus associated hemophagocytic syndrome. Hemophagocytic lymphohistiocytosis hlh is a rapidly progressive, lifethreatening syndrome of excessive immune activation. 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. Although ebv is the most common cause of infectionassociated hlh, recognition that at least some of the deaths associated with avian. Epsteinbarr virus associated secondary hemophagocytic. Pulmonary involvement in patients with hemophagocytic. Case report alternative therapy for epsteinbarr virus. Hemophagocytic syndromes and infection volume 6, number 6. Prompt initiation of treatment for hlh is essential for the survival of affected patients. Acquired hlh is more frequently found in adults and is commonly secondary to infections, malignancies, or autoimmune diseases. Hemophagocytic lymphohistiocytosis hlh is a rare and lifethreatening syndrome characterized by uncontrolled immune activation. Imashuku s, hibi s, ohara t, iwai a, sako m, kato m, et al. Clinical features and treatment strategies of epsteinbarr. Pdf on aug 6, 2018, magliano g and others published a fatal ebv related hemophagocytic lymphohistiocytosis hlh in a young patient find, read and.
Although uncommon, hemophagocytic syndrome is a serious complication of ebv infection and can be fatal in many cases. The syndrome, which has also been referred to as histiocytic medullary. A case report of severe liver injury and hemophagocytic syndrome caused by chronic eb virus infection related to a mutation in the lyst gene. Hlh can occur as a familial or sporadic acquired disorder. He achieved complete remission with rituximab alone. Hemophagocytic lymphohistiocytosis 2nd lymphoproliferative. Hlh is a rare complication of epsteinbarr virus ebv infection. Treatment outcomes and prognostic factors in adult patients with. Ebv can also be the trigger in both familial and secondary cases. Epsteinbarr virus ebv is a member of the herpesvirus family that can infect humans. Jul 01, 2010 epsteinbarr virus ebv is a ubiquitous and predominantly b lymphotrophic human. Epsteinbarr virusassociated hemophagocytic lymphohistiocytosis in a small child.
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. As a part of a themed collection of articles on ebv infection and human primary immune deficiencies. Figure 3 treatment regimens for epsteinbarr virus related hemophagocytic lymphohistiocytosis. Epsteinbarr virus ebv is a ubiquitous virus that infects nearly all people worldwide without serious sequela. Epsteinbarr virus ebv has been recognized as the leading infectious cause and is associated.
Virusassociated hemophagocytic syndrome is a rare condition, precipitated by viral infection and characterized by proliferation of benign histiocytes with phagocytosis. Precise mechanism of ebv induced hlh has recently been found. Acute kidney injury with epstein barr virusassociated. 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. Hemophagocytic lymphohistiocytosis in pediatric patients. Cns involvement of virusassociated hemophagocytic syndrome.
A case report of severe liver injury and hemophagocytic. Mar 27, 2019 epsteinbarr virus ebv is a member of the herpesvirus family that can infect humans. 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. Clinicopathological study of severe chronic active epstein.
The study participants included 182 ebvhlh patients 95 boys and 87 girls with a median age of 2. Introduction hemophagocytic syndrome hps is a rare disorder of the immune system that is synonymous with macrophage activation syndrome 1. It is a lifethreatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated. Hemophagocytic syndrome is a welldefined clinical disease that was first described by scott and robbsmith in 1939. Infections associated with haemophagocytic syndrome the. Hemophagocytic syndrome, liver injury, ebv, lyst gene, stxbp2 gene. Although ebvassociated hlh carries a high mortality rate, quick diagnosis and appropriate treatment can subside the disease. Hemophagocytic syndromes and infection volume 6, number. Epsteinbarr virus related hemophagocytic lymphohistiocytosis. Pdf epsteinbarr virus related hemophagocytic syndrome in a. Hemophagocytic lymphohistiocytosis hlh is a rare and potential lifethreatening clinical syndrome that results from uncontrolled activation of the immune system.
In most cases, ebvpositive patients develop a severe form of infectious mononucleosis which typically manifests with fever, tonsillopharyngitis, lymphadenopathy and hepatosplenomegaly. We are reporting a patient who was diagnosed with epsteinbarr virus ebv related hlh. 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. Secondary hlh, more commonly observed in adult patients, is seen in the context of underlying triggering conditions. First of all, the reactive disorder may be difficult to distinguish from infectious mononucleosis, septicemia, certain hematologic malignancies, and systemic autoimmune disorders.
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. It means that ebv infected b cells stimulate cytotoxic t lymphocytes leading to hypercytokinemia and stimulation of histolytic cells. Ebv infections are very common youve probably already contracted the virus without even knowing it. Hemophagocytic lymphohistiocytosis hlh is a relatively rare but lifethreatening disease with confusing clinical manifestations, rapidly deteriorating health, high morbidity and mortality. Epsteinbarr virus ebvassociated haemophagocytic syndrome. Haemophagocytic syndrome or haemophagocytic lymphohistiocytosis is a rare disease that is often fatal despite treatment. There was no response to treatment with rituximab, etoposide and. Epsteinbarr virus ebv has been recognized as the leading infectious cause and is associated with a poor outcome. Hemophagocytic syndrome is a term used to describe the proliferation of nonneoplastic i. Hlh can occur as a familial or sporadic disorder, and it can be triggered by a variety of. Epsteinbarr virus associated hemophagocytic lymphohistiocytosis. Alternative therapy for epsteinbarr virus related hemophagocytic lymphohistiocytosis article pdf available in case reports in oncological medicine 2015. Acquired hemophagocytic lymphohistiocytosis hlh is a lifethreatening event that usually occurs as a complication of immunodeficiency.
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