Hemophagocytic syndrome is a clinical condition characterized by the infiltration. Infection associated hemophagocytic histiocytosis and its effect on hematological parameters marrow in general, cellularity and maturation of erythropoiesis, myelopoiesis and megakaryocytes. Hemophagocytic lymphohistiocytosis hlh is a rare and often. Cytomegalovirus infectionassociated hemophagocytic syndrome. Hemophagocytic lymphohistiocytosis resulting from a.
Infection associated with hemophagocytic lymphohisticytosis triggered by nosocomial infection. Hemophagocytic lymphohistiocytosis hlh is a rapidly progressive, lifethreatening syndrome of excessive immune activation. The spectrum of human illness caused by cytomegalovirus cmv is diverse and mostly dependent on the host. The disease is defined by the hlh2004 criteria, requiring five of eight findings, and is further differentiated into either primary or secondary causes.
The acquired forms of hemophagocytic syndrome include infectionassociated hemophagocytic syndrome, historically known as histiocytic medullary reticulosis or virusassociated hemophagocytic syndrome, which is a benign, potentially reversible but often fatal disorder that occurs primarily in immunocompromised patients. Here, we sought to characterize infectious triggers in a large, multicentre cohort of patients. A clinicopathological analysis of 26 patients with. Cytomegalovirus cmv infection is a virus that can be transmitted to a developing child before birth. Hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis hlh, is a rare and life. We report two cases of cytomegalovirus cmv viraemia resulting in severe pneumonitis and associated haemophagocytic syndrome manifesting in patients with inflammatory bowel disease, on stable doses of azathioprine in clinical remission. Disseminated cytomegalovirus associated hemophagocytic lymphohistiocytosis in an elderly patient to the editor. Four of 357 patients, including two of 318 patients with b cell precursor acute lymphoblastic leukemia bcpall and two of 39 of those with t cell acute. While the disease is often fatal, classic management of hlh revolves around early diagnosis and initiation of protocolized therapy. Hemophagocytic syndrome associated with cytomegalovirus infection in a severely immunocompromised aids patient. Histoplasmosis associated hemophagocytic lymphohistiocytosis hlh is a rare disorder with limited data regarding treatment and outcome. Subsequently, hlh has been reported in association with a variety of infections, and the term reactive hemophagocytic syndrome has been suggested to distinguish hlh associated with an identifiable infectious or noninfectious etiology from its hereditary forms. Histoplasmosisassociated hemophagocytic lymphohistiocytosis.
Debate around infectiondependent hemophagocytic syndrome. Successful treatment of cytomegalovirus associated. Hemophagocytic syndrome an overview sciencedirect topics. There is no standard therapy for vahs and the clinical course is variable. Clinical characteristics and genetic analysis of childhood. Primary hlh tends to be of genetic etiology, while secondary hlh results from other insults such as. Infections associated with haemophagocytic syndrome the. Pdf pregnancyrelated hemophagocytic lymphohistiocytosis. Infection associated hemophagocytic syndrome medicnote. For most healthy people who acquire cmv after birth, there are few symptoms and no longterm health consequences. Mortality rate associated with secondary hs ranges between 8% and 24% 1. Hemophagocytic lymphohistiocytosis hlh is a rare and often deadly syndrome characterized by severe inflammation and cytokine. Diversity and combinations of infectious agents in 38. The syndrome is characterized by fever, altered mental status, hepatosplenomegaly, cytopenia, liver dysfunction.
Successful treatment of infection associated hemophagocytic. Epstein barr virus ebv infection is the most common cause of infection associated with secondary. Peak cmv viral load was 371 000 copiesml with evidence of endorgan cmv in the lungs and colon. We present a case of haemophagocytic lymphohistiocytosis hlh in the context of disseminated cytomegalovirus cmv viraemia in a 50yearold man with wellcontrolled hiv infection and ulcerative colitis uc, for which he was receiving azathioprine. Nogueira 1, laira vidal, bruno terra 2, thiago pagot 1, jorge i. Hemophagocytic lymphohistiocytosis hlh is a disease that results from severe. Hemophagocytic lymphohistiocytosis hlh is an unusual syndrome characterized by fever, hepatosplenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, and pathologic findings of hemophagocytosis in the bone marrow and other tissues. Hemophagocytic lymphohistiocytosis hlh is a rare but lifethreatening hyperinflammatory. Prompt initiation of treatment for hlh is essential for the survival of affected patients. Hemophagocytic syndrome associated with cytomegalovirus. Hemophagocytic lymphohistiocytosis hlh is a rare yet potentially fatal clinicopathological entity because of uncontrolled immune system activation.
Hemophagocytic lymphohistiocytosis resulting from a cytokine. Hemophagocytic lymphohistiocytosis hlh is a rare and often deadly syndrome characterized by severe inflammation and cytokine dysregulation. We report the successful management of this syndrome with ganciclovir, corticosteroids and the new interleukin 1 inhibitor anakinra. Eculizumab in a child with atypical haemolytic uraemic. Treatment of hemophagocytic lymphohistiocytosis in adults. The syndrome is characterized by fever, altered mental status, hepatosplenomegaly, cytopenia, liver dysfunction, and. When a diagnosis of hemophagocytic syndrome is made identification of an ethiological cause may not be easy.
Leading viral triggering agents are epsteinbarr virus ebv, cytomegalovirus cmv, and adenovirus. Clinical characteristics and prognostic factors of adult. Hemophagocytic lymphohistiocytosis hlh is a clinical syndrome caused by a highly active but ineffective immune response, including impaired or absent function of natural killer nk cells and cytotoxic t cells, and the release of proinflammatory cytokines. 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. Hemophagocytic syndromes and infection volume 6, number. Hereditary and acquired hemophagocytic lymphohistiocytosis. Hemophagocytic lymphohistiocytosis hlh is a potentially fatal syndrome that results from inappropriate activation of the immune system. Pdf acute cytomegalovirus cmv infection associated. The acquired forms of hemophagocytic syndrome include infection associated hemophagocytic syndrome, historically known as histiocytic medullary reticulosis or virus associated hemophagocytic syndrome, which is a benign, potentially reversible but often fatal disorder that occurs primarily in immunocompromised patients. Hemophagocytic lymphohistiocytosis associated with. Successful modified therapy in a patient with probable.
Diversity and combinations of infectious agents in 38 adults. In most cases, treatment of the underlying condition promotes complete. Sorry, we are unable to provide the full text but you may find it at the following locations. We report a case of cgd with repeated salmonella septicemia complicated with hlh, and the cgd mutation identified has not been reported. We report our experience in managing a previously healthy pregnant patient who presented in the third trimester of pregnancy with hlh. However all of these features are not necessary for diagnosis. This case highlights the complexity of pregnancyrelated hlh and identifies some key areas in the management of this disease that should be addressed in order to improve survival in this potentially fatal disease. Hemophagocytic lymphohistiocytosis associated with visceral. Infectionassociated hemophagocytic syndrome is a lifethreatening condition characterized by prolonged fever, hepatosplenomegaly, and cytopeniamost commonly, thrombocytopenia and anemia. Hemophagocytic lymphohistiocytosis hlh is an aggressive and lifethreatening syndrome of excessive immune activation. Hemophagocytic lymphohistiocytosis hlh is a disorder characterized by uncontrolled mature histiocyte proliferation. A case of uc patient who suffered cytomegalovirus infection after performing fmt without donor screening was reported 37 and therefore we do not support performing fmt without.
Although we could not be able to document the virus or bacteria infection in our cases, depending. Successful treatment of cytomegalovirus associated hemophagocytic lymphohistiocytosis with the interleukin 1 inhibitor anakinra. It is characterized by proliferation and activation of benign histiocytes, causing dysfunction of. The smears were also examined for lymphocytes, abnormal cells, histiocytes, hemophagocytosis and parasites. The patient was diagnosed with virus associated hemophagocytic syndrome and was successfully treated with antiviral therapy consisting of intravenous ganciclovir, gamma globulin, and granulocytecolony stimulating factor.
Virus associated hemophagocytic syndrome vahs is a rare complication in early cytomegalovirus cmv infection. Disseminated cytomegalovirus associated hemophagocytic. Acute cytomegalovirus infection related to the immunosuppressive therapy, resulting in hemophagocytosis syndrome and neutropenic fever was diagnosed. Apr 05, 2019 hemophagocytic lymphohistiocytosis hlh is a rare but potentially fatal disease of normal but overactive histiocytes and lymphocytes that commonly appears in infancy, although it has been seen in all age groups. Hemophagocytic lymphohistiocytosis hlh is a syndrome characterized by high fever, maculopapular rash, neurological symptoms, abnormal liver functions and coagulopathy. Infection associated hs accounts for nearly 50% of all cases of hlh. 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 our hospital from april 2005.
Cytomegalovirus cmv infection is usually harmless and rarely causes illness. Pregnancyassociated hemophagocytic lymphohistiocytosis. Infection associated with hemophagocytic lymphohisticytosis. Hemophagocytic lymphohistiocytosis hlh is a relatively rare but lifethreatening disease with confusing clinical manifestations, rapidly deteriorating health, high morbidity and mortality. Infection associated hemophagocytic syndrome is a lifethreatening condition characterized by prolonged fever, hepatosplenomegaly, and cytopeniamost commonly, thrombocytopenia and anemia. Successful treatment of infectionassociated hemophagocytic syndrome with intravenous immunoglobulin lignancy in the bone marrow andor lymph nodes1. Soon after admission, the girl became anuric and required continuous venovenous haemodiafiltration. Fever, hepatosplenomegaly, pancytopenia, lymphadenopathy, and rash often comprise the initial presentation. Cytomegalovirusassociated hemophagocytic syndrome in a 59.
What nephrologists need to know about hemophagocytic syndrome. Epsteinbarr virus infectionassociated hemophagocytic. 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. Acute cytomegalovirus infectionassociated hemophagocytic. Many viral agents are known to trigger hlh but cytomegalovirus cmv associated hlh is rarely described. Infection associated hemophagocytic syndrome infectionassociated hemophagocytic syndrome iahs. Virusassociated hemophagocytic syndrome vahs is a rare complication in early cytomegalovirus cmv infection. The most consistent association is with viral infections but, as. 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. Patients with fever, hepatosplenomegaly and pancytopenia suggesting lymphoproliferative disorders are usually admitted to hemathology departments. Jun 01, 2006 read successful treatment of cytomegalovirus.
Introduction hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis hlh, is a rare and lifethreatening disease that is frequently underrecognized in adults and associated with very high mortality despite treatment 1. Reactive haemophagocytic syndrome hs is a rare condition that occurs in patients with infections, haematological malignancies or autoimmune diseases. Study design between january 2007 and december 2009, 26 consecutive patients meeting the diagnostic criteria for iahlh, based. Infectionassociated hemophagocytic lymphohistiocytosis, also known as. In adults, hlh is typically a complication of infections, autoimmune diseases, and malignancies. Hemophagocytic lymphohistiocytosis hlh is characterized by severe immune activation and deregulation resulting in extreme and often lifethreatening inflammation 1. Hemophagocytic lymphohistiocytosis hlh is a rare, frequently under. Debate around infectiondependent hemophagocytic syndrome in. Hypercalcemia and disseminated cytomegalovirus infection. Per guidelines from the histiocyte society hlh94, therapy traditionally involves remission treatment.
Hemophagocytic syndrome can be primary genetic or secondary to another condition, especially severe infections, rheumatologic disorders or malignancies. We aim to describe a case of secondary hlh due to primary epsteinbarr virus ebv infection. It is characterized by proliferation and activation of benign histiocytes, causing dysfunction of various organs. The treatment and prognosis of patients with hlh and the macrophage activation syndrome mas, a form of hlh in patients with. Mar 20, 2014 hemophagocytic lymphohistiocytosis hlh is a potentially fatal syndrome that results from inappropriate activation of the immune system.
A report on the disseminated histoplasma capsulatum infection associated with the acquired immunodeficiency syndrome in this patient was presented as an abstract by drs bauman and romeo at the air force regional meeting of the american college of physicians, colorado springs, colorado, 26 march 1984. Cytomegalovirusassociated hemophagocytic syndrome in a. Successful treatment of infection associated hemophagocytic syndrome with intravenous immunoglobulin lignancy in the bone marrow andor lymph nodes1. Hepatitis a virus infectionassociated hemophagocytic. The syndrome is characterized by fever, altered mental status, hepatosplenomegaly, cytopenia, liver dysfunction, and hyperferritinemia. Pdf acute cytomegalovirus cmv infection associated with. Infectionassociated haemophagocytic syndrome iahs is a subtype of. Hemophagocytic syndromes and infection volume 6, number 6. Patients are frequently diagnosed with hlh in intensive care units icus, where they are treated for a lifethreatening condition classified as sepsis. Hlh may be familial or associated with di fferent types of infect ions, autoimmune dis. Disseminated cmv associated with hlh is uncommon in adults, this case is a type of. Nov 30, 2015 hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis hlh, is a rare and life. It is caused by uncontrolled activation if cytotoxic t cells and antigen presenting cells 1. Hereditary and acquired hemophagocytic lymphohistiocytosis ling zhang, md, jun zhou, md, and lubomir sokol, md, phd background.
Hemophagocytic syndrome associated with cytomegalovirus infection in a severely. Infectious agents contribute to a major part of the etiology of adultonset. Secondary hemophagocytic lymphohistiocytosis has a high mortality rate among adults despite recent advances in treatment. Cmv infections in immunocompromised patients cause substantial morbidity and mortality, especially among transplant recipients and those infected with the human immunodeficiency virus hiv. Hemophagocytic lymphohistiocytosis hlh is a rare disorder characterized by histiocyte activation associated with a hyperinflammatory state and phagocytosis of hematopoietic elements. Hemophagocytic lymphohistiocytosis hlh is a rare and lifethreatening syndrome characterized by uncontrolled immune activation. The pathophysiology of infection associated hlh following infection with nonviral pathogens may also be related to production of high levels of activating cytokines by host lymphocytes and monocytes. Cureus acute cytomegalovirus cmv infection associated. Cytomegalovirus associated haemophagocytic lymphohistiocytosis. 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.
Objective to analyse the clinicopathological presentation, outcome and importance of bone marrow haemophagocytosis in patients with infectionassociated haemophagocytic lymphohistiocytosis iahlh in a tertiary care hospital in northern india. Cytomegalovirusassociated hemophagocytic lymphohistiocytosis in. May 19, 2004 viral studies serum antibody titer and antigenemia of cytomegalovirus revealed systemic cytomegalovirus infection. Lymphohistiocytosis hemophagocytic lymphohistiocytosis. The major signs and symptoms of hlh are fever, cytopenia, hepatosplenomegaly, liver dysfunction, elevated levels of ferritin, and serum transaminases. Chandima divithotawela, the prince charles hospital, rode road, chermside, queensland 4032, australia. A diagnosis of hemophagocytic lymphohistiocytosis hlh accompanied by cmv infection was rendered. Recovery was achieved by the administration of parenteral ganciclovir, broad spectrum antibiotic and complex intensive care. Infectionassociated hemophagocytic syndrome iash with cgd has been observed in eight children and two adults 59. We described the clinical features, treatment, and outcomes of five patients in our institution with histoplasmosisassociated hlh. Hemophagocytic lymphohistiocytosis hlh is a rare, hyperinflammatory syndrome characterized by clinical signs and symptoms of extreme inflammation. Recommendations for the management of hemophagocytic.
Hemophagocytic lymphohistiocytosis has a broad clinical phenotype overlapping with systemic inflammatory response syndrome sirs, sepsis, and multiorgan dysfunction syndrome. A rare case of cytomegalovirus infection induced hemophagacytic. Hemophagocytic lymphohistiocytosis hlh is a severe hyperinflammatory syndrome induced by aberrantly activated macrophages and cytotoxic t cells. Hemophagocytic syndrome caused by primary herpes simplex. We described the clinical features, treatment, and outcomes of five patients in our institution with histoplasmosis associated hlh. We present the case of a 21monthold girl with two rare and lifethreatening conditions, atypical haemolytic uraemic syndrome ahus and haemophagocytic lymphohistiocytosis hlh, triggered by a cytomegalovirus cmv infection. A 44yearold woman was admitted with a 4day history of fever,headache,delir. It results in histiocytic proliferation with significant hemophagocytic activity in the bone marrow and massive release of inflammatory cytokines. Although various microorganisms are thought to trigger hs, most of the literature data on this topic have been gathered in singlecentre case series. Hlh may be diagnosed in association with malignant, genetic, or autoimmune diseases but is also prominently. Autoimmuneassociated hemophagocytic syndromemacrophage.
Haemophagocytic syndrome has been associated with a variety of viral, bacterial, fungal, and parasitic infections. This present study sought to analyze acute lymphoblastic leukemia all patients with hemophagocytic lymphohistiocytosis hlh registered in kyushuyamaguchi childrens cancer study group studies conducted between 1996 and 2007. Case presentation in april 2019, a 3yearold boy was referred to our hos. Histoplasmosisassociated hemophagocytic lymphohistiocytosis hlh is a rare disorder with limited data regarding treatment and outcome. Histoplasmosis is an endemic fungal disease with diverse clinical presentations. Hemophagocytic lymphohistiocytosis hlh is an unusual syndrome characterized by fever, splenomegaly, jaundice, and the pathologic finding of hemophagocytosis phagocytosis by macrophages of. Jan 16, 20 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. The primary genetic form, caused by mutations affecting lymphocyte cytotoxicity and immune regulation, is most common in children, whereas the secondary acquired form is most frequent in adults. Viral infections associated with the syndrome include ebv, cytomegalovirus, human herpesvirus 8 hhv8, hiv, influenza virus, parvovirus, hepatitis virus, and enterovirus.
Disseminated cmv infection and hlh in a patient with well. Haemophagocytic syndrome or haemophagocytic lymphohistiocytosis is a rare disease that is often fatal despite treatment. We have, along with a team of investigators at this center, accumulated strong evidence that cfs is caused by persistent herpes virus infection epsteinbarr virus, cytomegalovirus. Pregnancyrelated hemophagocytic lymphohistiocytosis. Hemophagocytic syndrome hps, which was first described in 1939, is a heterogeneous disorder characterized by excessive activation and proliferation. Dec 11, 2015 reactive haemophagocytic syndrome hs is a rare condition that occurs in patients with infections, haematological malignancies or autoimmune diseases. There have been multiple previous reports of cytomegalovirus cmv associated hlh developing in patients with ulcerative colitis receiving azathioprine. Infection associated hemophagocytic histiocytosis and its.
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