Hlh has multifaceted clinical presentations with often nonspecific signs and symptoms that are often found in other clinical conditions. 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. Characteristic laboratory values include increased ferritin, triglycerides, transaminases, bilirubin, lactate dehydrogenase, soluble interleukin2 receptor. Hemophagocytic lymphohistiocytosis hlh is a frequently fatal and likely underdiagnosed disease involving a final common pathway of hypercytokinemia, which can result in endorgan damage and death. Hemophagocytic lymphohistiocytosis hlh is a rapidly progressive, lifethreatening syndrome of excessive immune activation. This means that to be affected, a person must have a change mutation in both copies of the responsible gene in each cell. Because of the severity of the resulting immune compromise, coagulation disorders and anemia, patients with hlh usually require critical care. Oct 27, 2016 hemophagocytic lymphohistiocytosis hlh is an aggressive and life threatening syndrome which results from excessive immune activation, that can rapidly deteri slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising.
Many patients have an underlying immune disorder, although in some patients the underlying disorder is not known. Jul 21, 2015 hemophagocytic lymphohistiocytosis definition, etiology, pathophysiology, primary and secondary hlh, clinical findings, investigations, diagnostic criteria, slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. The term secondary hlh is used when your doctor thinks the condition may have occurred for a variety of other noninherited reasons. It is a lifethreatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated. Imaging plays an important role in determining the extent of involvement of hemophagocytic lymphohistiocytosis. 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. The identification of hemophagocytic histiocytes in bone marrow or, less commonly, in spleen or lymph node tissue represents a key diagnostic feature of hlh. Primary, or familial, hlh is when the condition is inherited. 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. Michael jordan developed the perforindeficient animal model that is helping advance the study of better treatments for hlh. Alemtuzumab is a highly effective treatment of relapsingremitting multiple sclerosis rrms with a complex safety profile, including secondary autoimmunity in 40% of patients. In adults, many different conditions, including infections and cancer, can cause hlh.
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 a severe hyperinflammatory syndrome induced by aberrantly activated macrophages and cytotoxic t cells. Hemophagocytic lymphohistiocytosis hlh is an inherited disease of the immune system. Background hemophagocytic lymphohistiocytosis hlh is a lifethreatening emergency and any delay in diagnosis andor treatment is associated with high mortality.
The symptoms of the primary and secondary forms of hemophagocytic lymphohistiocytosis hlh include. Familial forms result from genetic defects in natural killer cells and. Incidence is reported as one case per million persons per year. Hemophagocytic lymphohistiocytosis hlh is a reactive syndrome characterized by phagocytosis of hematopoietic elements. Hemophagocytic lymphohistiocytosis hlh is an unusual syndrome characterized by fever, splenomegaly, jaundice, and the pathologic finding of hemophagocytosis phagocytosis by macrophages of. If you have problems viewing pdf files, download the latest version of adobe reader. Although bone marrow analysis did not reveal hemophagocytosis, she had some clinical and laboratory pointers to hemophagocytic lymphohistiocytosis hlh. Hemophagocytic lymphohistiocytosis hlh is a clinical syndrome characterized by uncontrolled hyper. Pdf hemophagocytic lymphohistiocytosis hlh is a lifethreatening hyperinflammatory syndrome and not an independent disease.
Sep 11, 2017 hemophagocytic lymphohistiocytosis hlh may be inherited or acquired due to nongenetic factors. We report a case of several autoimmune disorders eventually presenting as severe multi organ dysfunction syndrome caused by adult hemophagocytic lymphohistiocytosis hlh. Hemophagocytic lymphohistiocytosis hlh is a condition with different underlying causes. Haemophagocytic lymphohistiocytosis postalemtuzumab. Hemophagocytic lymphohistiocytosis definition, etiology, pathophysiology, primary and secondary hlh, clinical findings, investigations, diagnostic criteria, slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. Hemophagocytic lymphohistiocytosis hlh is a rare disease that usually occurs in infants and young children. Hemophagocytic lymphohistiocytosis hlh is rarely diagnosed in adults. How i treat hemophagocytic lymphohistiocytosis in the. Hemophagocytic lymphohistiocytosis hlh is a rare syndrome of pathologic immune activation in children that is increasingly being recognized in adults. If you have hlh, your bodys defense system, called your immune system, does not. Cd38, daratumumab, hemophagocytic lymphohistiocytosis, multiple myeloma, natural killer cells introduction hemophagocytic lymphohistiocytosis hlh is a reactive syndrome characterized by phagocytosis of hematopoietic elements.
Early recognition is essential to effective management. It is seen in both children and adults and is recognized as primary driven by underlying genetic mutations that. Hlh is an uncontrolled, selfpropelling hyperinflammation. Hemophagocytic lymphohistiocytosis may be inherited or caused by certain conditions or diseases, including infections, immunodeficiency inability of the body to fight infections, and cancer. Manifestations may include lymphadenopathy, hepatosplenomegaly, fever, and neurologic abnormalities. In the past, hlh was believed to be caused by abnormal histiocytes and thus was referred to as. Steps of granule exocytosis along with proteins required at each step with their. Hemophagocytic lymphohistiocytosis hlh is a devastating disorder of uncontrolled immune activation characterized by clinical and laboratory evidence of extreme inflammation. 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. 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. It is a lifethreatening condition that can be defined as either primary or secondary hlh. Hemophagocytic lymphohistiocystosis johns hopkins medicine.
These immune cells see the bodys internal organs as invaders. Thus, no clear consensus exists on clinical manifestations and differences between pediatric and adult cases of this condition. Medical definition of hemophagocytic lymphohistiocytosis. This syndrome can be caused by genetic mutations affecting cytotoxic function familial hlh or be secondary to infectious, rheumatologic, malignant, or metabolic. Abnormal blood tests such as a low red blood cells, b low platelets, and c low. The parents of an affected person usually each carry one mutated copy of the.
Prompt initiation of treatment for hlh is essential for the survival of affected patients. Hemophagocytic lymphohistiocytosis is a disorder characterized as an overproduction of white blood cells lymphocytes and histiocytes. Familial hemophagocytic lymphohistiocytosis fhl refers to genetic forms that are caused by an abnormal variant in a gene. The hemophagocytic syndrome, also called hemophagocytic lymphohistiocytosis hlh, is a collection of nonmalignant but frequently lifethreatening disorders, associated with an ever growing list of genetic and acquired causes 17,18 box 5. Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126 tollfree. 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, 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.
Familial hlh is inherited in an autosomal recessive manner. It can be initiated in a predisposed individual by various triggering factors. 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. 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. Your critical care patient may have hlh hemophagocytic. Results of followup laboratory test done 4 weeks after discharge showed improvement in his condition. Severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and histiocytes macrophages secreting high amounts of inflammatory cytokines threatens the life of the patient.
Hemophagocytic lymphohistiocytosis is a rare, lifethreatening syndrome characterized by abnormal, excessive activation of the immune system. Hemophagocytic lymphohistiocytosis hlh is a potential severe complication. Hemophagocytic lymphohistiocytosis hlh is a lifethreatening condition associated with hyperinflammation and organ dysfunction. It may occur as a primary genetic condition due to mutations in genes important in the cytolytic secretory pathway that cause perforin and granzymes to induce apoptosis in target cells. Hlh may be diagnosed in association with malignant, genetic, or autoimmune. 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.
Hemophagocytic lymphohistiocytosis hlh is a hyperinflammatory syndrome caused by defective lytic capability of cytotoxic t lymphocytes and nk cells, which results in proliferation of benign hemophagocytic histiocytes. Hemophagocytic lymphohistiocytosis hlh is a group of rare disorders of the immune system. Hereditary and acquired hemophagocytic lymphohistiocytosis ling zhang, md, jun zhou, md, and lubomir sokol, md, phd background. Hemophagocytic lymphohistiocytosis in pediatric patients. Aug 15, 2017 hemophagocytic lymphohistiocytosis hlh was first described in 1939 by scott and robbsmith. Hlh is a progressive syndrome of unchecked immune activation and tissue damage. Hemophagocytic lymphohistiocytosis hlh is a rare immune system disease. Hemophagocytic lymphohistiocytosis hlh, an uncontrolled overactivation of the immune system, is well characterized in pediatric patients, yet, much less is known about this lifethreatening condition in adult patients.
Familial hemophagocytic lymphohistiocytosis genetics home. To investigate the clinical features of adult patients with hemophagocytic lymphohistiocytosis hlh and to explore possible. Hemophagocytic lymphohistiocytosis in a patient with. Histiocyte society hlh2004 hemophagocytic lymphohistiocytosis study group treatment protocol of the second international hlh study 2004 start of the study. The treatment and prognosis of patients with hlh and the macrophage activation syndrome mas, a form of hlh in patients with.
Arber, in modern surgical pathology second edition, 2009. Hemophagocytic lymphohistiocytosis clinical analysis of 103 adult patients jing li, md, qian wang, md, wenjie zheng, md, jie ma, md, wei zhang, md, wenze wang, md, and xinping tian, md abstract. It can be an inherited condition, or it can occur as a result of immunosuppression as in organ transplants or infection. The familial, primary form presents in childhood through one of several possible autosomal recessive mutations, or through an inherited immunodeficiency syndrome. Hereditary and acquired hemophagocytic lymphohistiocytosis. It can be triggered by conditions that affect immune homeostasis as infections, malignancies, and rheumatologic disorders. A secondary form of hlh, triggered by serious infections, was subsequently described in. Hemophagocytic lymphohistiocytosis hlh, also known as hemophagocytic syndrome, is an inherited or acquired histiocyte activation syndrome that is potentially fatal.
Familial hemophagocytic lymphohistiocytosis genetic and. Hemophagocytic syndromes and infection volume 6, number 6. 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. Fever, hepatosplenomegaly, pancytopenia, lymphadenopathy, and rash often comprise the initial presentation. Hemophagocytic lymphohistiocytosis in critically ill.
Hemophagocytic lymphohistiocytosis hlh is a potentially fatal hyperin. He is now leading a multicenter clinical trial testing a new approach for treating hlh. For language access assistance, contact the ncats public information officer. We analyzed the underlying diseases, clinical characteristics, 1aboratory. Advances in pathophysiology, diagnosis, and treatment shanmuganathan chandrakasan, md, and alexandra h. After yesterdays post on alemtuzumabrelated posts, many people are asking about haemophagocytic lymphohistiocytosis hlh, which has been included as a complication of alemtuzumab treatment as is now in the smpc summary of product characteristics. 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. The results of bone marrow biopsy were compatible with a diagnosis of hemophagocytic lymphohistiocytosis hlh. Hemophagocytic lymphohistiocytosis hemophagocytic syndrome what every physician needs to know.
As hlh is often complicated by organ failure, patients will require admission to the intensive care unit for organ support therapy. Hlh can occur as a familial or sporadic disorder, and it can be triggered by a variety of. Recommendations for the management of hemophagocytic. 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. Cardinal symptoms of hlh are prolonged fever, hepatosplenomegaly and pancytopenia. The bodys immune system fights off infections and anything else it sees as foreign invaders to the body. Lymphohistiocytosis hemophagocytic lymphohistiocytosis. Hemophagocytic lymphohistiocytosis hlh hematology and. Hemophagocytic lymphohistiocytosis hlh may be inherited or acquired due to nongenetic factors. Hemophagocytic lymphohistiocytosis hlh was originally described as a genetic disorder of immune regulation, presenting in neonates with protracted fever, hepatosplenomegaly, and cytopenia. Hemophagocytic lymphohistiocytosis and other hemophagocytic disorders. Most reported cases of hlh associated with scrub typhus were single cases or case series with a small sample sizes. This overactivation of the immune system causes fever and damages the liver.
Familial hemophagocytic lymphohistiocytosis in two brothers. A rare disorder in which histiocytes and lymphocytes types of white blood cells build up in organs including the skin, spleen, and liver, and destroy other blood cells. Excessive amounts of immune system proteins called cytokines are also produced. Hemophagocytic lymphohistiocytosis hlh covers a wide array of related lifethreatening conditions featuring ineffective immunity characterized by an uncontrolled hyperinflammatory response. Filipovich, md h emophagocytic lymphohistiocytosis hlh is a potentially lifethreatening disorder characterized by immune dysregulation, overwhelming immune activation, and in. A rare case of hemophagocytic lymphohistiocytosis in an. Adult hemophagocytic lymphohistiocytosis causing multi.
Symptoms of hlh reflect immune activation and hypercytokinemia. Hemophagocytic lymphohistiocytosis hlh is a rare disease that can be fatal in pregnancy. There are several names used to describe this condition. Primary hemophagocytic lymphohistiocytosis is a rare, fatal childhood disorder that may be familial or sporadic.
Primary hlh is divided into familial hlh fhlh15, in which hlh is. Hemophagocytic lymphohistiocytosis hlh is a life threatening hyperinflammatory syndrome characterized by excessive activation of macrophages and t cells resulting from defective cytotoxicity. In hlh, there is a deregulation of tlymphocytes and excessive production of cytokines leading to. Secondary hemophagocytic lymphohistiocytosis has a high mortality rate among adults despite recent advances in treatment. It is seen in both children and adults and is recognized as primary driven by underlying genetic mutations that abolish critical. Figure 4 depicts the events occurring at the immunologic synapse and highlights molecules important in process of granule exocytosis. Hemophagocytosis may be related to primary or secondary syndromes and is discussed in more detail in chapter 42. We report two cases of severe hlh that highlight etoposide use in pregnancy. Sometimes a microbial often viral cause is found, but this is common as a trigger of hlhfhl. It is described as primary hlh familial hlh and secondary hlh acquired following malignancy, rheumatologic disorders, primary immune deficiencies or. Hemophagocytic lymphohistiocytosis symptoms, treatments. In 1994, the histiocyte society organized the first treatment protocol for hlh hlh 94, which dramatically increased this survival rate to 54 percent with a.
The following case demonstrates a rare instance in which undiagnosed systemic lupus erythematosus sle presented as hlh. Jun 12, 2014 hemophagocytic lymphohistiocytosis hlh covers a wide array of related diseases including hlh, autosomal recessive familial hlh fhl, familial erythrophagocytic lymphohistiocytosis, viralassociated hemophagocytic syndrome, and autoimmuneassociated macrophage activation syndrome mas. Excessive amounts of white blood cells build up and may damage organs. The patient was started on dexamethasone and etoposide. Clinical and laboratory tests might lead to fatal misinterpretation without awareness of its diagnostic evaluation, as hlh shares common features with sepsis and immune. Hemophagocytic lymphohistiocytosis linkedin slideshare.
Hemophagocytic lymphohistiocytosis in 2 patients with. As of april 2018, abnormalities in multiple genes have been identified as. Hemophagocytic lymphohistiocytosis hlh is a rare but lifethreatening hyperinflammatory. Acute liver failure caused by hemophagocytic lymphohistiocytosis in adults.
A 71yearold indian female presented with a 3month history of weight loss and fatigue. Hemophagocytic lymphohistiocytosis hlh is an aggressive and lifethreatening syndrome of excessive immune activation. Hemophagocytic lymphohistiocytosis associated with scrub. Undiagnosed systemic lupus erythematosus presenting as. Familial hemophagocytic lymphohistiocytosis is a disorder which presents with fever, pancytopenia, liver dysfunction and also an increase in nonmalignant histiocytes with prominent hemophagocytosis in various organs. Hlh is a condition in which the body makes too many activated macrophages and lymphocytes. In this disease, the immune cells grow out of control. Current updates on classification, diagnosis and treatment of.
840 1540 1339 72 211 1208 265 1334 1323 1156 1353 626 813 1645 1359 1457 180 1152 1508 492 661 216 140 1114 1617 298 878 1619 816 294 749 750 356 61 1076 824 1116 977 926 250 531 587 157 1134 544 1087 1384