Hlh could be familial due to genetic defects leading to impaired function of natural killer and cytotoxic tcells or acquired. Primary hemophagocytic lymphohistiocytosis is a rare, fatal childhood disorder that may be familial or sporadic. Thrombotic thrombocytopenic purpura and hemophagocytic. Fever, hepatosplenomegaly, pancytopenia, lymphadenopathy, and rash often comprise the initial presentation. Haemophagocytic syndromes haemophagocytic lymphohistiocytosis have a wide range of causes, symptoms, and outcomes, but all lead to a hyperinflammatory response and organ damagemainly reported in paediatric patients, but reports of adult presentation are increasing.
It usually presents in childhood and can be associated with gene mutations. Rhs has not been associated previously with thrombotic thrombocytopenic purpura ttp. Ramoscasals m, britozeron p, lopezguillermo a, khamashta ma. Hemophagocytic lymphohistiocytosis hlh has been recognized as an inflammatory endpoint for a variety of conditions including autoimmune diseases, malignancies and infections. Durham, in pathologic basis of veterinary disease sixth edition, 2017.
As hemophagocytic syndrome hps was suspected from hyperferritinemia, bone marrow aspiration was conducted. Hemophagocytic syndrome is a rare and potentially fatal disorder characterized by pathological immune activation associated with a primary familial disorder, genetic mutations, or occurring as a sporadic condition. Thrombotic thrombocytopenic purpura ttp and hemophagocytic. In adults, many different conditions, including infections and cancer, can cause hlh. Classification of hemophagocytic syndrome primary or genetic hemophagocytic syndrome familial hemophagocytic lymphohistiocytosis immune deficiency syndrome type 1 hplh1, 9q21. The clinical features are fever, hepatosplenomegaly, lymphoadenopathy and pancytopenia, secondary to a phenomenon of phagocytosis of hematological elements and their precursors in bone marrow and peripheral lymphoid organs 1,2,3. Hemophagocytic lymphohistiocytosis hlh is a fatal clinical syndrome characterized by. An update on renal involvement in hemophagocytic syndrome. It is frequently complicated by acute kidney injury aki that often develops as acute tubular necrosis atn. Hlh may be diagnosed in association with malignant, genetic, or autoimmune diseases but is also prominently. Hemophagocytic lymphohistiocystosis johns hopkins medicine.
The mr imaging appearance of a case of virusassociated hemophagocytic syndrome complicated by diffuse cns infiltration is presented. Hemophagocytic lymphohistiocytosis hlh, 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 hlh may be inherited or acquired due to nongenetic factors. This means that to be affected, a person must have a change mutation in both copies of the responsible gene in each cell. How to approach thrombocytopenia hematology american. Introduction hemophagocytic lymphohistiocytosis hlh is a clinical syndrome caused by a highly active but ineffective immune response, including impaired or absent function of natural killer. Myeloid disorders hereditary causes of hemophagocytic lymphohistiocytosis published date. Hemophagocytic lymphohistiocytosis with immunotherapy. Acute kidney injury induced by thrombotic microangiopathy in a. A rare case of thrombotic microangiopathy in a patient with hemophagocytic syndrome is reported.
Jul 21, 2015 hemophagocytosis phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors in bone marrow and other tissues hemophagocytic lymphohistiocytosis uncommon, lifethreatening hyperinflammatory syndrome caused by severe hypercytokinemia due to a highly stimulated but ineffective immune process by. Acute kidney injury induced by thrombotic microangiopathy. Unusual causes of haemophagocytic syndrome fatin al sayes, mrcpath, frcpc haemophagocytic syndrome is rare, often fatal clinical disorder in which release of inflammatory cytokines from macrophages results in marked haemophagocytosis. The condition is rare but has been recognized in dogs and cats. Hemophagocytic syndrome an overview sciencedirect topics. Histiocytic glomerulopathy associated with macrophage.
Review the clinical features and epidemiology of hlh, its association with infection, and evidence that this syndrome results from disordered cellular immunity. It is a lifethreatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages. Acquired forms of hlh are usually encountered as aresult of viral infections. We are presenting two unusual cases of adults with haemophagocytic syndrome. Analysis of the genetic and molecular pathophysiology of these syndromes have improved the understanding of the crosstalk.
Hemophagocytic lymphohistiocytosis hlh is characterized by fever, cytopenia, splenomegaly, and lymphohistiocytic proliferation with hemophagocytosis. Hemophagocytic syndromes histiocytosis association. The identification of hemophagocytic histiocytes in bone marrow or, less commonly, in spleen or lymph node tissue represents a key diagnostic feature of hlh. A complicated case with overlapping features of ttp, aiha, and. Islands of erythroid precursors are also prominent. Thrombocytopenia is defined as a platelet count below the 2.
As a service to our customers we are providing this early version of the manuscript. Hemophagocytic lymphohistiocytosis hlh also known as hemophagocytic syndrome is a clinical entity characterized by a sustained activation of the mononuclear phagocytic system that may result in an extreme hyperinflammatory response. 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, 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 hlh is an aggressive and lifethreatening syndrome of excessive immune activation. The latter can be secondary to infections, malignancies, or autoimmune diseases. A multicenter retrospective analysis of 162 patients, the american journal of medicine 2014, doi.
Recently, we experienced a patient who developed hyperinflammatory lymphohistiocytosis hlh hemophagocytic syndrome hps and thrombotic microangiopathy tma induced by community. Hemophagocytic lympho histiocytosis hlh is a disorder of uncontrolled, pathologic activation of the immune system leading to extreme hyperinflammation. Hemophagocytic lymphohistiocytosis hlh is a fatal clinical syndrome. Hemophagocytic syndrome is a term used to describe the proliferation of nonneoplastic i. Unlike other iraes, hlh triggered by immune checkpoint blockade is not well described. Pdf thrombotic thrombocytopenic purpura and hemophagocytic. However, tma is rarely detected in patients with hlh, despite the frequent development of renal complications. An 18yearold girl was admitted following prolonged fever, watery diarrhea, abdominal discomfort. A case report article pdf available in medicine 9744. Haemophagocytic lymphohistiocytosis hlh is a syndrome of severe. Hemophagocytic lymphohistiocytosis radiology reference. Hemophagocytic lymphohistiocytosis hlh is a rare disorder of the immune system primarily affecting young infants and children, although it can develop for the first time at any age. Hlh represents the extreme end of a severe uncontrolled hyperinflammatory reaction that can occur in many underlying conditions. Arber, in modern surgical pathology second edition, 2009.
Abstract hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis hlh, is a heterogenic syndrome, which leads to an acute, lifethreatening in. Hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis hlh, is a heterogenic syndrome, which leads to an acute, lifethreatening inflammatory reaction. Acute kidney injury induced by thrombotic microangiopathy in. Hemophagocytic syndromes and infection volume 6, number. Prompt treatment is critical, but the greatest barrier to a successful. 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. Depending on the etiology, hlh can be divided into genetic i. It typically affects infants and young children but can be seen at all ages 5. The hlh2004 criteria remain as the common diagnostic guide.
Pathology outlines hemophagocytic lymphohistiocytosis. Hemophagocytic lymphohistiocytosis linkedin slideshare. Reactive hemophagocytic syndrome associated with thrombotic. Hereditary and acquired hemophagocytic lymphohistiocytosis. Familial hemophagocytic lymphohistiocytosis may be associated with primary immunodeficiency syndromes such as chediakhigashi syndrome, griscelli syndrome type 2, hermanskypudlak syndrome type 2 and xlinked lymphoproliferative disorder types 1 and 2 hematology am soc hematol educ program 2011. Cns involvement of virusassociated hemophagocytic syndrome. It is a lifethreatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated. Secondary hemophagocytic lymphohistiocytosis in zoonoses.
Soluble hemoglobinhaptoglobin scavenger receptor cd163 as a lineagespecific marker in the reactive hemophagocytic syndrome. Both ttp and hlh result from deregulation of the immune system. Clinically, patients present signs of severe inflammation, with unremitting fever, cytopenias. Hlh occurs both in children and adults, and can be triggered by various inherited as well as acquired factors. Ppt hemophagocytic syndromes powerpoint presentation free. The latter, also termed the reactive hemophagocytic syndrome rhs, has been associated with a variety of infectious and noninfectious etiologies. It can be further classified as primary and secondary hlh. Hemophagocytic lymphohistiocytosis hlh is a lifethreatening hyperinflammatory syndrome and not an independent disease. Infection by both streptococcus pneumoniae and influenza virus can cause these complications. Hemophagocytosis phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors in bone marrow and other tissues hemophagocytic lymphohistiocytosis uncommon, lifethreatening hyperinflammatory syndrome caused by severe hypercytokinemia due to a highly stimulated but ineffective immune process by. Introduction hemophagocytic lymphohistiocytosis hlh is a clinical syndrome caused by a highly active but ineffective immune response, including impaired or absent function of. Results of the third us national health and nutrition examination survey nhanes iii support the traditional value of 150. There are no published reports of coexisting ttp and hlh in elderly patients. Thrombotic microangiopathy in hemophagocytic syndrome.
Hemophagocytic lymphohistiocytosis hlh is a potentially fatal hyperin. Familial hlh is inherited in an autosomal recessive manner. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as. Activation of monocytes in rhs is due to stimulation by high levels of activating cytokines. Hemophagocytic syndrome hps is mainly characterized by massive infiltration of bone marrow. 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. Hemophagocytic syndrome in children and adults springerlink. When t cells and macrophages do not talk the hemophagocytic syndromes. Development of hemophagocytic syndrome and thrombotic microangiopathy due to community. A case of systemic lupus erythematosus associated with. Familial hemophagocytic lymphohistiocytosis genetic and.
Ppt hemophagocytic syndromes powerpoint presentation. 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 lymphohistiocytosis hlh, also known as hemophagocytic syndrome, is an inherited or acquired histiocyte activation syndrome that is potentially fatal. Key clinical message development of hemophagocytic syndrome and thrombotic. Macrophage activation syndrome mas is a severe condition due to a hyperinflammatory response resulting from exaggerated activation and proliferation of nonmalignant macrophages. Familial and acquired hemophagocytic lymphohistiocytosis. Hemophagocytic syndromes and infection volume 6, number 6. For claims with a date of service on or after october 1, 2015, use an.
It is characterized by smallvessel plateletrich thrombi that cause thrombocytopenia, microangiopathic hemolytic anemia, and sometimes organ damage. Hemophagocytic syndrome has been described as a disorder of morphologically normal macrophages. Hemophagocytic lymphohistiocytosis hlh, a rare but potentially fatal syndrome of immune hyperactivation, may be an underrecognized immunerelated adverse event irae. This is a pdf file of an unedited manuscript that has been accepted for publication. Hemophagocytic lymphohistiocytosis hlh is an aggressive and. Hemophagocytosis may be related to primary or secondary syndromes and is discussed in more detail in chapter 42. Hemophagocytic lymphohistiocytosis hlh is a fatal clinical syndrome characterized by excessive immune activation and inflammation. According to a large, populationbased study published in sweden, it was estimated to occur in 1. Hemophagocytic lymphohistiocytosis hlh is an unusual syndrome characterized by fever, splenomegaly, jaundice, and the pathologic finding of hemophagocytosis phagocytosis by macrophages of. Hemophagocytic lymphohistiocytosis in pediatric patients. If you have hlh, your bodys defense system, called your immune system, does not. Mas falls under the umbrella group of diseases known as of hemophagocytic lymphohistiocytosis hlh or hemophagocytic syndrome hps. Thrombotic thrombocytopenic purpura ttp and hemophagocytic lymphohistiocytosis hlh are rare hematologic conditions and have high mortality. Sporadic, familial, and reactive hlh varieties exist.
Thrombotic thrombocytopenic purpura and hemophagocytic lymphohistiocytosis in an elderly man. Thrombotic thrombocytopenic purpura ttp and hemophagocytic lymphohistiocytosis hlh are rare hematologic conditions. Thrombotic thrombocytopenic purpura ttp was suspected from the emergence of fragmented red cells, hemolysis, thrombocytopenic purpura, headache, renal dysfunction and fever. Hemolytic uremic syndrome hus or thrombotic thrombocytopenic purpura ttp is a well characterized disorder associated with tma 5, 6. Virusassociated hemophagocytic syndrome is a rare condition, precipitated by viral infection and characterized by proliferation of benign histiocytes with phagocytosis. Nov 22, 2018 development of hemophagocytic syndrome and thrombotic microangiopathy due to community. Jun 24, 2002 the latter, also termed the reactive hemophagocytic syndrome rhs, has been associated with a variety of infectious and noninfectious etiologies. Lymphohistiocytosis hemophagocytic lymphohistiocytosis. Clinical features and diagnosis of hemophagocytic lymphohistiocytosis. Hemophagocytic lymphohistiocytosis hlh is a rare disease that usually occurs in infants and young children. Meanwhile, renal thrombotic microangiopathy tma is a rare pathologic finding that mostly occurs in hemolytic uremic syndrome or thrombotic. Both streptococcus pneumoniae and influenza virus are important pathogens of community.
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