Pdf hemophagocytic lymphohistiocytosis hlh covers a wide array of related lifethreatening conditions featuring ineffective immunity characterized. This syndrome can sometimes occur in normal people with medical problems that can cause a strong activation of the immune system, such as infection or cancer. A rare, cancerlike disorder in which both certain types of immune system cells histiocytes and lymphocytes start to proliferate and damage body tissues or organs. Hemophagocytic lymphohistiocytosis hlh is a severe systemic inflammatory syndrome that can be fatal. Medical definition of hemophagocytic lymphohistiocytosis. Filipovich, helmut gadner, shinsaku imashuku, diane komp, stephan ladisch, david webb, and gritta janka, for the histiocyte. Hemophagocytic syndrome an overview sciencedirect topics. Pediatric hemophagocytic lymphohistiocytosis hlh blood. Hemophagocytic lymphohistiocytosis hlh is a rare and devastating disorder of uncontrolled immune activation that has gained increasing.
Hemophagocytic lymphohistiocytosis hlh is a disorder of widespread accumulation of lymphocytes and mature macrophages, sometimes with hemophagocytosis, primarily involving the spleen, lymph nodes, bone marrow, liver, and cerebral spinal fluid. Hemophagocytic lymphohistiocytosis hlh is a syndrome characterized by extreme immune activation, resulting in pathologic inflammation. Hemophagocytic lymphohistiocytosis hlh is a rare but lifethreatening hyperinflammatory. The incidence of neonatal hlh is not confirmed and may range from 1 in 50,000 to 150,000. A case report of hemophagocytic lymphohistiocytosis hlh. Secondary hemophagocytic lymphohistiocytosis in adults. Hemophagocytic syndromes and infection centers for disease. Hemophagocytic lymphohistiocytosis hlh is a syndrome of severe immune activation with macrophage and tcell infiltration resulting in, multi organ damage. Familial hemophagocytic lymphohistiocytosis genetics. Neonatal hemophagocytic lymphohistiocytosis american. Hemophagocytic lymphohistiocytosis hlh, also known as macrophage activation syndrome when occurring in the setting of a rheumatologic disorder, is a nonmalignant but oftenfatal disorder of immune dysregulation affecting multiple organs.
Hemophagocytic lymphohistiocytosis hlh is a syndrome describing patients with severe systemic hyperinflammation. People with hlh usually develop symptoms within the first months or years of life. Hemophagocytic lymphohistiocytosis hlh is a potentially fatal hyperinflammatory condition. The cumulative experiences from hlh94 and other studies have led to the development of a new treatment protocol presented here, hlh2004, which includesupdated diagnosticand therapeutic guidelinesfrom the. Hemophagocytic lymphohistiocytosis hlh is a lifethreatening disease where an underlying immune defect or triggering event initiates excessive activation of immune cells macrophages and lymphocytes leading to multiorgan dysfunction and failure. Hereditary and acquired hemophagocytic lymphohistiocytosis. Symptoms may include fever, enlarged liver or spleen, cytopenia decreased number of blood cells, and neurological abnormalities. Treatment of hemophagocytic lymphohistiocytosis with hlh. Hemophagocytic lymphohistiocytosis hlh is a rapidly progressive, lifethreatening syndrome of excessive immune activation.
Hemophagocytic lymphohistiocytosis hlh is a rare lifethreatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and. Hlh2004 chemoimmunotherapy includesetoposide,dexamethasone,cyclos porine a upfront and, in selected patients, intrathecal therapy with methotrexate and corticosteroids. Hemophagocytic lymphohistiocytosis hlh is a rare disease that usually occurs in infants and young children. Cutaneous manifestations of hemophagocytic lymphohistiocytosis. Sebastian fn bode, kai lehmberg, andrea maulpavicic, thomas vraetz, gritta janka, udo zur stadt, stephan ehl. A a gradient of hemophagocytic lymphohistiocytosis hlh severity correlates with the defect in cytotoxic activity of lymphocytes that results from various genetic defects in humans and mice. Acquired hemophagocytic lymphohistiocytosis hlh is a lifethreatening event that usually occurs as a complication of immunodeficiency. Hereditary and acquired hemophagocytic lymphohistiocytosis ling zhang, md, jun zhou, md, and lubomir sokol, md, phd background. Information specific to adult hlh is limited, and current diagnostic.
Hlh is a rare but potentially lifethreatening disorder that results from natural killer and cytotoxic tcell dysregulation leading to cytokine overproduction and. The term secondary hlh is used when your doctor thinks the condition may have occurred for a variety of other noninherited reasons. A retrospective analysis of case records of 52 children diagnossed with hlh was performed. A case of pediatric anaplastic large cell lymphoma with. Hemophagocytic lymphohistiocytosis hlh is a disease with major diagnostic and therapeutic difficulties. This study aims to describe the incidence, clinical and biological features, and outcome. Familial forms result from genetic defects in natural killer cells and. Acute kidney injury akiin the setting of hemophagocytic lymphohistiocytosis hlh is poorly characterized. B evolving view of the risk factors inducing hlh development. Treatment of hemophagocytic lymphohistiocytosis with hlh 94 immunochemotherapy and bone marrow transplantation. Of the 52 children % n 7 had familial hlh and 87% n. Hscores greater than 169 are 93% sensitive and 86% specific for hlh.
Recommendations for the management of hemophagocytic. Hemophagocytic lymphohistiocytosis hlh is a lifethreatening syndrome characterized by a dysregulated hyperinflammatory response associated with aberrant activation of lym phocytes and. Note that bone marrow haemophagocytosis is not mandatory for a diagnosis of hlh. The diagnosis includes a spectrum of inherited or acquired. In adults, many different conditions, including infections and cancer, can cause 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. Familial and acquired hemophagocytic lymphohistiocytosis. Unlike other iraes, hlh triggered by immune checkpoint blockade is not well described. Hemophagocytic lymphohistiocytosis hlh covers a wide array of related lifethreatening conditions featuring ineffective immunity characterized by an uncontrolled hyperinflammatory response. Hlh comprises two different conditions that may be. Hscores can be calculated using an online hscore calculator. Isolated reports have described the development of hlh in patients with infection due to ehrlichia chaffeensis, transmitted through the. Pediatric hemophagocytic lymphohistiocytosis hlh read.
Hlh may be diagnosed in association with malignant, genetic, or autoimmune diseases but is also prominently. Hemophagocytic lymphohistiocytosis hlh is extremely rare in the neonatal period. It can be an inherited condition, or it can occur as a result of immunosuppression as in organ transplants or infection. Hemophagocytic syndromes and infection volume 6, number. To study the profile of children with hemophagocytic lymphohistiocytosis hlh in a tertiary care hospital for children. The initial clinical presentation commonly includes fever, hepatosplenomegaly, and pancytopenia. Haemophagocytic lymphohistiocytosis hlh is a poten. Hemophagocytic lymphohistiocytosis hlh, a rare but potentially fatal syndrome of immune hyperactivation, may be an underrecognized immunerelated adverse event irae. Hemophagocytic lymphohistiocytosis hlh is an acute, lifethreatening syndrome that occurs in children and young adults typified by reactive proliferation of histiocytes in the bone marrow, liver, spleen, and lymph nodes with characteristic hemophagocytosis in affected tissues and over. Hemophagocytic lymphohistiocytosis hlh covers a wide array of related diseases including hlh, autosomal recessive familial hlh fhl. To investigate the clinical features of adult patients with hemophagocytic lymphohistiocytosis hlh and to explore possible risk factors for death, we.
Chemoimmunotherapy for hemophagocytic lymphohistiocytosis. Hlh, or hemophagocytic syndrome, is a rare and almost universally fatal condition in adults. Characteristic features include unremitting fever, cytopenias, hepatosplenomegaly, and elevation of typical hlh biomarkers. 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. Background hemophagocytic lymphohistiocytosis is a rare, rapidly progressive, and potentially fatal disorder of activated histiocytes. It is seen in both children and adults and is recognized as primary driven by underlying genetic mutations that abolish critical.
Hemophagocytic lymphohistiocystosis johns hopkins medicine. Hemophagocytic lymphohistiocytosis hlh is a lifethreatening disease due to uncontrolled immune activation. Hemophagocytic lymphohistiocytosis mimicking septic shock. Hemophagocytic lymphohistiocytosis hlh is an unusual syndrome characterized by fever, splenomegaly, jaundice, and the pathologic finding of. Hemophagocytic lymphohistiocytosis gene sequencing panel. Acute kidney injury in adults with hemophagocytic lymphohistiocytosis florence aulagnon, md,1 nathanael lapidus, md, phd,2,3. Hemophagocytic lymphohistiocytosis with immunotherapy. Hemophagocytic lymphohistiocytosis hlh has become more widely recognized in adults, with all ages affected. Pulmonary involvement in patients with hemophagocytic. According to a large populationbased study published in sweden, it was estimated to occur in 1.
Hemophagocytic lymphohistiocytosis hlh is a lifethreatening syndrome characterized by a dysregulated hyperinflammatory response associated with aberrant activation of lymphocytes and. Familial forms of hlh fhl, which are increasingly found also in adolescents and adults, are due to genetic defects leading to impaired function of natural killer cells and cytotoxic t. Familial hemophagocytic lymphohistiocytosis is a disorder in which the immune system produces too many activated immune cells lymphocytes called t cells, natural killer cells, b cells, and macrophages histiocytes. The incidence varies based on ethnicity, particularly in populations in which consanguinity is common. Hemophagocytic lymphohistiocytosis hlh is a lifethreatening syndrome in which an uncontrolled and ineffective immune response, triggered in most cases by infectious agents, leads to severe hyperinflammation. Hemophagocytic lymphohistiocytosis radiology reference.
A high index of suspicion is essential for early diagnosis and treatment. Hemophagocytic lymphohistiocytosis hlh, also known as hemophagocytic syndrome hps, is a rare, lifethreatening, hematologic disorder. The true incidence remains uncertain, and the diagnosis is challenged both by the lack of recognition of hemophagocytic syndrome and by uncertain diagnostic criteria. Histiocyte society hlh2004 hemophagocytic lymphohistiocytosis. Prompt initiation of treatment for hlh is essential for the survival of affected patients. It is described as primary hlh familial hlh and secondary hlh acquired following malignancy, rheumatologic disorders, primary immune deficiencies or infection alone. Hemophagocytic lymphohistiocytosis hlh, is an uncommon, lifethreatening hyperinflammatory syndrome caused by severe hypercytokinemia with excessive activation of lymphocytes and macrophages due to a highly stimulated but ineffective immune process. This article describes lung involvement in hlh and assesses whether it affects the prognosis. Pdf hemophagocytic lymphohistiocytosis hlh is a disorder charecterised by immune dysregulation. The hlh2004 criteria remain as the common diagnostic. Recent advances in the diagnosis and treatment of hemophagocytic lymphohistiocytosis. Skin eruptions are described in up to 65% of patients. Hemophagocytic lymphohistiocytosis hlh is a severe hyperinflammatory syndrome induced by aberrantly activated macrophages and cytotoxic t cells.
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. Hemophagocytic lymphohistiocytosis hlh is an aggressive syndrome characterized by abnormal, excessive activation of the immune system. The hscore11 generates a probability for the presence of secondary hlh. Pmc images search for hemophagocytic lymphohistiocytosis hlh. Hemophagocytic lymphohistiocytosis is a lifethreatening disorder characterized by unbridled activation of cytotoxic t lymphocytes, natural killer nk cells, and macrophages resulting in hypercytokinemia and immunemediated injury of multiple organ systems. Hlh can be primary or secondary to an autoimmune process, immunodeficiency, malignancy, or infections. Hemophagocytic lymphohistiocytosis in children springerlink. Secondary hemophagocytic lymphohistiocytosis has a high mortality rate among adults despite recent advances in treatment. Hemophagocytic lymphohistiocytosis hlh is a potentially fatal hyperinflammatory condition caused by a highly stimulated, but ineffective immune response, characterized by a dysregulated activation and proliferation of macrophages leading to. Hemophagocytic lymphohistiocytosis hlh is a condition in which the body makes too many activated immune cells macrophages and lymphocytes. 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. Approach to hemophagocytic syndromes histiocytosis association. It may occur as a primary genetic condition due to mutations in.
Hemophagocytic lymphohistiocytosis gene sequencing panel description. Treatment of hemophagocytic lymphohistiocytosis with. Patients can develop hepatitis, coagulopathy, liver failure, central nervous system involvement, multiorgan failure, and other manifestations. Hemophagocytic lymphohistiocytosis in pediatric patients. We analyzed the underlying diseases, clinical characteristics, 1aboratory. It was first described in 1952 by farquhar and claireaux and named familial hemophagocytic reticulosis as a familial disease characterized by hepatosplenomegaly, anemia, granulocytopenia, thrombocytopenia with illness, and irritability during. Hemophagocytic lymphohistiocytosis hlh, also known as hemophagocytic syndrome, is a rare disease mainly in children that is characterized by persistent spiky fever and hemophagocytosis by activated macrophages.
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