OCULAR INVOLVEMENT IN HEMOPHAGOCYTIC SYNDROME: A NOVEL FUNDUSCOPIC MANIFESTATION AND REVIEW OF THE LITERATURE. Suhr Kristin S,Chiang Michael F,Flynn John T,Engelbert Michael Retinal cases & brief reports PURPOSE:Hemophagocytic syndrome (HS) is a rare disease with a spectrum of ocular findings. The authors report a unique funduscopic presentation of HS in a neonate and a discussion of diagnosis, typical features, management, and outcome. METHODS:Single case report with retrospective analysis of the published literature of patients with HS and ocular findings from 1950 to present using the key terms hemophagocytic, lymphohistiocytosis, ocular, and ophthalmic. Literature search from 1950 to the present was performed through PubMed/MEDLINE and the Cochrane database. Requirement for inclusion was that the article or abstract was written in English. RESULTS:A 4-week-old neonate with HS demonstrated bilateral discrete white dots within the retina, which resolved incompletely over the course of the next months but showed increased pigmentation. CONCLUSION:With so few documented ophthalmic cases of HS in existence, the ocular findings at this point can be seen as diverse and variable. However as more cases are reported, hopefully this will allow for increased recognition of the ophthalmic manifestations and sequelae and in turn lead to improved treatment of this disease. 10.1097/ICB.0000000000000255
    [Hemophagocytic syndrome: diagnostic problems]. Czogała Małgorzata,Czogała Wojciech,Balwierz Walentyna Przeglad lekarski Hemophagocytic syndrome (HS) is a rare but life-threatening disease caused by inappropriate activation of T-lymphocytes and histiocytes, hipercytokinemia and hemophagocytosis. The most common symptoms are fever, hepatosplenomegaly, unspecific neurological abnormalities, pancytopenia, coagulopathy, hiperferritinemia and lipid abnormalities. HS is classified into two forms: primary, inherited (Familial Hamophagocytic Lymphohistiocytosis--FHL) and secondary (associated with infection, malignancy, autoimmune disease). In spite of the fact that diagnostic guidelines are available it often remains unrecognised. Prognosis of HS depends on the form of disease and in case of secondary HS on the underlying disease. Development of the treatment protocols (HLH-94, HLH-2004) which combine immunochemiotherapy with hematopoietic stem cell transplantation has strongly improved prognosis in HS especially in the primary form. Three-year overall survival for children with HS is now over 50%. Early diagnosis and appropriate therapy is crucial for effectiveness of the treatment. Popularisation of the knowledge about the syndrome, diagnostic guidelines and treatment protocols can contribute to more frequent appropriate recognition of HS and to improvement of the treatment results.
    [Genetic defects and pathogenesis of hemophagocytic syndrome]. Ishii Eiichi [Rinsho ketsueki] The Japanese journal of clinical hematology
    Hemophagocytic syndrome as one of main manifestations in untreated systemic lupus erythematosus: two case reports and literature review. Qian Jie,Yang Cheng-De Clinical rheumatology Hemophagocytic syndrome (HPS) is an unusual but fatal disorder characterized by pancytopenia and activation of macrophages. We describe two cases of untreated systemic lupus erythematosus (SLE) with HPS that presented as one of the manifestations of SLE. The onset of HPS was after parturition for one patient, and after abortion for the other. Bone marrow examination revealed severe hemophagocytosis in both patients. One patient responded to pulsed methylprednisone alone, and the other responded to pulsed methylprednisone plus intravenous immunoglobulin (IVIG). We believe accurate diagnosis, intensive therapy, and sufficient supportive cares are essential in improving patients' prognosis. 10.1007/s10067-006-0245-y
    Hemophagocytic syndrome in a pregnant patient with systemic lupus erythematosus, complicated with preeclampsia and cerebral hemorrhage. Pérard Laurent,Costedoat-Chalumeau Nathalie,Limal Nicolas,Hot Arnaud,Cohen Judith,Vauthier-Brouzes Danièle,Nieszkowska Ania,Belmatoug Nadia,Piette Jean-Charles Annals of hematology 10.1007/s00277-007-0277-7
    Enterovirus-associated hemophagocytic syndrome in children with malignancy: report of three cases and review of the literature. Katsibardi Katerina,Moschovi Maria A,Theodoridou Maria,Spanakis Nicholas,Kalabalikis Panagiotis,Tsakris Athanassios,Tzortzatou-Stathopoulou Fotini European journal of pediatrics Enteroviruses can cause severe manifestations in children with malignancy. Infection-associated hemophagocytic syndrome (IAHS) due to enterovirus is a rare entity in children. Patients with malignancy and IAHS due to enterovirus were retrospectively evaluated at the University of Athens' Hematology-Oncology pediatric unit within a 6-year period (2000-2006). IAHS occurred in three cases among 56 patients with documented enteroviral infection. The diagnosis of IAHS was confirmed by bone marrow aspiration and biopsy. Nested reverse transcriptase-polymerase chain reaction (RT-PCR), sequencing of the amplified alleles, and immunohistochemistry were performed to document the presence of enterovirus. The type of enterovirus was specified by indirect immunofluorescence assay. At the early phase of the disease, patients presented mild, non-specific viral symptoms, persistent unexplained fever, and pancytopenia. At the late phase, patients had more severe manifestations, such as persistent high fever, diarrhea, weight loss, hepatosplenomegaly, and hepatic dysfunction. The therapeutic approach consisted of supportive care, administration of immunoglobulin (400 mg/kg or 2 g/kg), and pleconaril. All patients had fatal outcome; two patients succumbed to multiorgan failure (MOF), while one patient succumbed to ventricular fibrillation. IAHS usually has fulminant course and leads to severe and life-threatening complications, such as liver failure and MOF. IAHS should always be included in the differential diagnosis of viral syndrome or unexplained fever. The therapeutic approach for IAHS should be administered as early as possible, before the progression to irreversible tissue damage. Early therapeutic intervention involving high doses of immunoglobulin might be beneficial for the patient's outcome. 10.1007/s00431-007-0436-9
    [Hemophagocytic Syndrome: a clinical presentation of systemic lupus erythematosus]. Silva Danilo da Fonseca Reis,Anunciação Fernando Antônio Costa,Arcoverde Josué da Costa,Costa Loyana Pinheiro,Marques Igor Denizarde Bacelar,Pinheiro Gevina da Silva,Moreira Maria do Socorro Teixeira Almeida Acta reumatologica portuguesa Hemophagocytic Syndrome is a clinical condition characterized by the activation of either macrophages or histiocytes with a prominent hemophagocytosis feature in the bone marrow and other reticuloendothelial systems. It leads to the phagocytosis of erythrocytes, leukocytes, platelets, and their precursors. The presence of hemophagocytosis can be associated to infections, malignancies, autoimmune diseases, drugs and a variety of other medical conditions. We report a case of a previously healthy 23 year-old woman that developed hemophagocytosis at the same time that she fulfilled diagnostic criteria for systemic lupus erythematosus. Lupus-related hemophagocytic syndrome is a rare and potentially fatal entity. It offers significant differential diagnosis challenges and requires urgent therapeutic intervention. There are only few cases reported in the literature. In this article, we briefly reviewed what is currently known about this syndrome. However, much is still needed in order to better understand its causes, all the immunopathogenic mechanisms, as well as its clinical aspects.
    Abiotrophia defectiva endocarditis and associated hemophagocytic syndrome--a first case report and review of the literature. Kiernan Thomas J,O'Flaherty Niamh,Gilmore Ruth,Ho Emily,Hickey Mary,Tolan Michael,Mulcahy David,Moore David P International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases In this manuscript we describe the first association in the literature between Abiotrophia defectiva endocarditis and the hemophagocytic syndrome. There are multiple important clinical points of information that must be highlighted from this case. A. defectiva is an aggressive organism with a high level of resistance to antibiotic pharmacotherapy with a high predilection for embolic complications and valvular destruction despite treatment with sensitive antibiotics. A. defectiva endocarditis has not been previously associated with the hemophagocytic syndrome. However, this case highlights the serious hematological complications that can occur with this dangerous bacterial pathogen. 10.1016/j.ijid.2008.01.014
    [Hemophagocytic syndrome as primary manifestation in a patient with systemic lupus erythematosus after parturition]. Yoshida Shuzo,Takeuchi Tohru,Itami Yasuo,Hata Kenichiro,Watanabe Koko,Shoda Takeshi,Kotani Takuya,Makino Shigeki,Hanafusa Toshiaki Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology A 33-year-old woman presented with fever, malar rash, lymphadenopathy and pancytopenia 3 weeks after parturition. Serum C3 level was decreased and antinuclear antibody, anti-dsDNA antibody and anti-SS-A antibody were positive. Serum ferritin level was elevated (3454 ng/ml), and bone marrow aspirate revealed hemophagocytosis. She was diagnosed having systemic lupus erythematosus (SLE) associated with hemophagocytic syndrome (HPS). Oral prednisolone (55 mg/day) was initiated. Clinical manifestations and pancytopenia were improved and serum ferritin level was decreased. However, elevated anti-dsDNA antibody titer and reduced C3 level continued for a month after steroid therapy. The additional therapy of tacrolimus (3 mg/day) improved clinical and laboratory findings. This is a rare SLE case associated with HPS as primary manifestation after parturition. 10.2177/jsci.32.66
    Hemophagocytic syndrome after hematopoietic stem cell transplantation: a prospective observational study. Abdelkefi Abderrahman,Jamil Wassim Ben,Torjman Lamia,Ladeb Saloua,Ksouri Habib,Lakhal Amel,Hassen Assia Ben,Abdeladhim Abdeladhim Ben,Othman Tarek Ben International journal of hematology The aim of this prospective observational study was to evaluate the incidence of hemophagocytic syndrome (HPS) after hematopoietic stem cell transplantation (HSCT). Between July 2006 and December 2007, all patients who received a HSCT in our institution were included in this study. All the following criteria were needed for the diagnosis of HPS: sustained fever over 7 days; cytopenia (neutropenia and/or thrombocytopenia); presence of more than 3% mature macrophages in bone marrow; hyperferritinaemia (>1,000 ng/mL). During this study, 171 patients received a HSCT (68 allogeneic and 103 autologous). The median age was 32 years (3-62). We observed six cases of HPS (6/68; 8.8%) after allogeneic stem cell transplantation (ASCT): one case of EBV-related HPS, two cases of CMV-related HPS, and three cases with no evidence of bacterial, fungal or viral infections. We observed only one case of CMV-related HPS (1/103; 0.9%) after autologous stem cell transplantation. Four patients died despite aggressive supportive care. To our knowledge, this is the first prospective observational study conducted with the aim to evaluate the incidence of HPS after HSCT. This study provides a relatively high incidence of HPS after ASCT. When sustained fever with progressive cytopenia and hyperferritinaemia are observed, HPS should be suspected, and bone marrow aspirate considered. The rapid diagnosis of HPS and the early initiation of an appropriate treatment are essential for patient management. 10.1007/s12185-009-0261-1
    What nephrologists need to know about hemophagocytic syndrome. Karras Alexandre Nature reviews. Nephrology Hemophagocytic syndrome (HPs) is a rare but distinct condition caused by inappropriate and dysregulated activation of the immune system. HPs is characterized by febrile hepatosplenomegaly, pancytopenia, hypofibrinemia and liver dysfunction; these changes are associated with the infiltration of bone marrow and organs by nonmalignant macrophages that phagocytose blood cells. Primary HPs is linked to inherited immune dysregulation, whereas secondary HPs tends to be triggered by an infectious or neoplastic disease. Multiorgan failure can complicate this life-threatening condition and renal involvement has frequently been reported; however, precise descriptions of the renal manifestations of HPs are lacking. Acute kidney injury due to tubular necrosis is the most common renal presentation, but nephrotic syndrome can also occur. HPs can be observed in immunocompromised patients and nephrologists must be aware that this condition can occur in renal transplant recipients. Mortality in patients with HPs can be as high as 50%. Despite considerable advances in the treatment of familial HPs, no specific therapy has demonstrated a consistent capacity to control reactive HPs when combined with suppression of the triggering factor. This review summarizes the presentation, causes, pathophysiology and renal features of HPs for the benefit of the practicing nephrologist. 10.1038/nrneph.2009.73
    Primary mediastinal non-seminomatous germ cell tumor associated with hemophagocytic syndrome. Sada Eriko,Shiratsuchi Motoaki,Kiyasu Junnichi,Idutsu Kensaku,Ohtsuka Rie,Nagasawa Eriko,Karube Kennosuke,Takayanagi Ryoichi,Abe Yasunobu Journal of clinical and experimental hematopathology : JCEH A 20-year-old man with a primary non-seminomatous mediastinal germ cell tumor (yolk sac tumor and immature teratoma) developed hemophagocytic syndrome (HPS) three months after surgical resection. Around the same time, the patient was found to have bone metastases of the germ cell tumor. No other hereditary or acquired diseases related to HPS were found. The thrombocytopenia was refractory to corticosteroid therapy but improved after chemotherapy performed for germ cell tumor progression. Only three cases of germ cell tumor associated with reactive hemophagocytosis have been previously reported. Successful treatment of the present case by chemotherapy for HPS suggests a close relationship between this rare complication and germ cell tumor. 10.3960/jslrt.49.117
    Primary cutaneous anaplastic large-cell lymphoma presenting with hemophagocytic syndrome: a case report and review of the literature. Shimizu Yoko,Tanae Ken,Takahashi Naoki,Kohri Mika,Arai Eiichi,Bessho Masami,Niitsu Nozomi Leukemia research Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is a rare entity of lymphoma. We report a case of C-ALCL presenting with hemophagocytic syndrome and skin lesion with giant ulcer. Histopathological examination of the skin biopsy specimens showed non-epidermotropic infiltrates with cohesive sheets of large tumor cells. The tumor cells showed CD4-, CD8+, CD30+, CD56-, ALK-, TIA-1+, and granzyme B+. C-ALCL is generally a disorder that progresses slowly and has a good prognosis. Manifestation of a giant ulcer and hemophagocytic syndrome, such as in the present case, is rare. 10.1016/j.leukres.2009.07.001
    Secondary hemophagocytic syndrome in adults: a case series of 18 patients in a single institution and a review of literature. Shabbir Munira,Lucas John,Lazarchick John,Shirai Keisuke Hematological oncology Hemophagocytic lymphohistiocytosis (HLH) is rare in adults and is usually fatal without treatment. We present a consecutive series of 18 adults with HLH diagnosed at our institution between 2004 and 2009. All diagnoses were confirmed by pathology. The median age at diagnosis was 56 years (range: 18-73 years), with a male: female ratio of 2:1. Patients uniformly presented with fever. Fifty-five per cent of the patients presented with evidence of hepatomegaly or splenomegaly. All of the patients had at least a bi- or trilineage cytopenia. Elevated liver enzymes, hyperferritinemia, hypertriglyceridemia and hyperfibrinogenemia were seen in 50, 100, 40 and 50% of patients, respectively. The presumed causes were as follows; haematological malignancies (n = 4), post-autologous stem cell transplant (n = 2), infection (n = 2), rheumatologic illness (n = 2), sickle cell disease (n = 1), post-orthotopic liver transplant (n = 1) and idiopathic (n = 3). The median time from suspicion to diagnosis was 5 days (1-27 days). Corticosteroids and/or cyclosporine were the most frequently used treatment regimen. Other agents used were etoposide, IVIG, cyclophosphamide and chemotherapy. The mortality rate was 72%, with multi-system organ failure being the most common cause of death. Median survival time from diagnosis was 35 days. Six patients are alive to date. In a univariate analysis, the presence of fever was the only factor that was statistically significant for predicting a poor prognosis (early mortality) (p = 0.05). In conclusion, a high index of suspicion is the critical factor for early diagnosis. Early treatment with immunosuppressant is warranted, and a thorough diagnostic evaluation to identify the underlying cause should be undertaken. 10.1002/hon.960
    Hepatosplenic lymphoma presenting initially as hemophagocytic syndrome in a 21-year-old man with Crohn's disease: a case report and literature review. Côté-Daigneault Justin,Bernard Edmond-Jean Canadian journal of gastroenterology = Journal canadien de gastroenterologie 10.1155/2011/148927
    Hemophagocytic syndrome associated NK/T nasal type lymphoma presenting as hypereosinophilic syndrome: a case report and literature review. Romero Fernández Esperanza,Pardo José Ramón Paño,Doyle Andrew,Albendea Miguel Canales,de la Rúa Ana Rodríguez Leukemia research 10.1016/j.leukres.2010.12.020
    Lymphoma-associated hemophagocytic syndrome (LAHS) in advanced-stage mycosis fungoides/Sézary syndrome cutaneous T-cell lymphoma. Blom Astrid,Beylot-Barry Marie,D'Incan Michel,Laroche Liliane Journal of the American Academy of Dermatology BACKGROUND:Lymphoma-associated hemophagocytic syndrome (LAHS) is a rare clinicopathological entity. It has been described with primary cutaneous lymphomas, mostly of the subcutaneous panniculitis-like T-cell type, and only once with cutaneous T-cell lymphoma (CTCL). METHODS:We report the cases of 5 patients with epidermotropic CTCL who developed LAHS and died shortly thereafter. Unlike LAHS associated with systemic lymphomas, these CTCL-associated LAHS were late events, occurring several years after the initial lymphoma diagnosis. LIMITATIONS:The small number of patients reported renders definite conclusions difficult. Further reports would be needed to confirm our statements. CONCLUSION:LAHS is probably underdiagnosed in CTCL patients with acute inflammatory symptoms suggestive of infections but should be considered, especially when cytopenia and elevated triglyceride and ferritin levels are present. 10.1016/j.jaad.2010.05.029
    Infection-associated hemophagocytic syndrome among patients with dengue shock syndrome and invasive aspergillosis: a case series and review of the literature. Larbcharoensub Noppadol,Aroonroch Rangsima,Kanoksil Wasana,Leopairut Juvady,Nitiyanant Prawat,Khositseth Anant,Tangnararatchakit Kanchana,Chuansumrit Ampaiwan,Yoksan Sutee The Southeast Asian journal of tropical medicine and public health The authors report four autopsy cases of previously healthy children with dengue shock syndrome complicated with infection-associated hemophagocytosis and invasive aspergillosis. Hemophagocytosis is confirmed by histopathology of autopsied reticuloendothelial organs. All four children were identified to have invasive aspergillosis by histopathology and three cases were positive on fungal culture for Aspergillus spp. Regarding the cause of death among the four children without pre-existing underlying disease, three cases were directly ascribable to invasive aspergillosis and the remaining case was ascribed to dengue shock syndrome. The transmigration of preexisting fungi from the respiratory mucosa damaged by the dengue shock process is postulated as the pathogenesis of invasive aspergillosis. The main predisposing factor was found to be prolonged dengue shock syndrome. We reviewed the clinicopathologic features and therapeutic management of infection-associated hemophagocytic syndrome in patients with dengue shock syndrome and invasive aspergillosis.
    Hemophagocytic lymphohistiocytosis: a potentially underrecognized association with systemic inflammatory response syndrome, severe sepsis, and septic shock in adults. Raschke Robert A,Garcia-Orr Roxanne Chest BACKGROUND:Hemophagocytic lymphohistiocytosis (HLH) was originally described as a genetic disorder of immune regulation, presenting in neonates with protracted fever, hepatosplenomegaly, and cytopenia. A secondary form of HLH, triggered by serious infections, was subsequently described in adults. METHODS:We report three adult patients who presented with systemic inflammatory response syndrome and features consistent with severe sepsis and septic shock, who subsequently received a diagnosis of secondary HLH. We reviewed the relationship between infection-triggered HLH and septic shock from the perspective of the adult intensivist. RESULTS:The hyperinflammatory pathophysiologic characteristics of HLH and septic shock are closely intertwined. Clinical and laboratory features of HLH and septic shock overlap in some patients, making the syndromes difficult to distinguish. In our experience and review, progressive pancytopenia was the feature most likely to suggest secondary HLH in the adult patient with presumed (or definite) septic shock. Use of other HLH-2004 diagnostic criteria is hindered by the poor operating characteristics of these tests in critically ill adults. Bone marrow aspiration is the most useful diagnostic test, but may yield an initial false-negative result. CONCLUSION:The HLH-2004 treatment protocol is not of proven benefit in critically ill adults, but observational data suggest that aggressive immunosuppressive therapy should not be delayed. Further study of HLH in the critical care setting might provide important insights into the pathogenesis and clinical treatment of sepsis. 10.1378/chest.11-0619
    [Current and future directions of pathologic analysis in hemophagocytic syndrome]. Ishii Eiichi,Nagai Kozo Nihon rinsho. Japanese journal of clinical medicine Hemophagocytic syndrome is a rare disorder with dysfunction of cytotoxic T lymphocyte (CTL) or NK cell activity, leading to excessive production of inflammatory cytokines and various clinical symptoms. HLH can be classified as either primary or secondary form; primary HLH includes familial hemophagocytic lymphohistiocytosis (FHL) and several immune deficiencies. All affected genes are involved in the transport and membrane fusion, or exocytosis of perforin/granzyme in lytic granules. Making a rapid screening of FHL with flow cytometry followed by genetic analysis is mandatory for the appropriate treatment of this fatal disease. Whereas, pathogenesis of secondary HLH is still unknown; several genetic backgrounds to affect on the pathway of T-cell activity will be associated with secondary HLH. With perforin- or Munc-deficient mouse model that develop HLH-like symptoms after virus infection, CD8+ T cells and interferon-gamma have been proven to be necessary for the HLH development. These data will provide new targets for specific therapeutic intervention of HLH in the future.
    Hemophagocytic syndrome associated with visceral leishmaniasis in an immunocompetent adult-case report and review of the literature. Koubâa M,Mâaloul I,Marrakchi Ch,Mdhaffar M,Lahiani D,Hammami B,Makni F,Ayedi A,Jemâa M Ben Annals of hematology 10.1007/s00277-011-1367-0
    [A case of hemophagocytic lymphohistiocytosis syndrome caused by severe tuberculosis and literature review]. Li Jing,Yu Shan,Wang Mei,Chen Hong-bing,Wang Wei Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases OBJECTIVE:To investigate the clinical features of a case of hemophagocytic lymphohistiocytosis syndrome (abbreviated as hemophagocytic syndrome, HPS) caused by severe tuberculosis and therefore to improve early diagnosis of this condition. METHODS:The clinical features and process of diagnosis and treatment of a case with HPS caused by severe tuberculosis in July 2011 were analyzed, and the reported literatures of the disease were reviewed. RESULTS:The patient was a 16-year-old male. The primary manifestations were fever, cough, abdominal distention and edema. Laboratory analysis indicated pancytopenia (WBC 3.0×10(9)/L, Hb 98 g/L, PLT 34×10(9)/L), liver dysfunction (ALT 51.5 U/L, AST 211 U/L, TBIL 20 µmol/L, DBIL 17.6 µmol/L), coagulation abnormalities (extension of TT and APTT, FIB 0.56 g/L), high level of ferritin (662 µg/L), and hemophagocytosis in bone marrow. Sputum smear was positive for tubercule bacillus. After 2 months of antituberculous therapy with ethambutol, streptomycin and sodium aminosalicylate, along with administration of prednisolone, human immunoglobulin, and thymic peptide α(1), the patient's body temperature, function of coagulation and liver abnormalities all returned to normal, and repeated sputum smears became negative. CONCLUSIONS:Tuberculosis is a cause of reactive hemophagocytic syndrome. Patients with hemophagocytic symptom should be rigorously screened for tuberculosis, and antituberculous therapy should be initiated early to improve prognosis.
    Hemophagocytic syndrome in adult-onset Still's disease (AOSD): a must for biologics?--Case report and brief review of the literature. Bürgi Urs,Mendez Adriana,Hasler Paul,Hüllstrung Hans Dieter Rheumatology international A case of adult-onset Still's disease complicated by hemophagocytic lymphohistiocytosis is reported. Its management is being discussed on the background of the latest literature with special regard on the use of high-dose corticosteroids and immunosuppressive agents. 10.1007/s00296-010-1497-z
    Debate around infection-dependent hemophagocytic syndrome in paediatrics. Ansuini Valentina,Rigante Donato,Esposito Susanna BMC infectious diseases BACKGROUND: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 over-production, and may be primary or secondary to infectious, auto-immune, and tumoral diseases. The most consistent association is with viral infections but, as it is still debated whether any micro-organisms are involved in its pathogenesis, we critically appraised the literature concerning HPS and its relationship with infections. DISCUSSION:Infection-dependent HPS has been widely observed, but there are no data concerning its incidence in children. A better understanding of the pathophysiology of HPS may clarify the interactions between the immune system and the variously implicated potential infectious agents. Epstein-Barr virus (EBV) infection has been prominently associated with HPS, with clonal proliferation and the hyperactivation of EBV-infected T cells. However, a number of other viral, bacterial, fungal, and parasitic infections have been reported in association with HPS. In the case of low-risk HPS, corticosteroids and/or intravenous immunoglobulin or cyclosporine A may be sufficient to control the biological process, but etoposide is recommended as a means of reversing infection-dependent lymphohistiocytic dysregulation in high-risk cases. SUMMARY:HPS is a potential complication of various infections. A polymerase chain reaction search for infectious agents including EBV, cytomegalovirus and Leishmania is recommended in clinical settings characterised by non-remitting fever, organomegaly, cytopenia and hyperferritinemia. 10.1186/1471-2334-13-15
    A case of hemophagocytic syndrome in a patient with fulminant ulcerative colitis superinfected by cytomegalovirus. Mun Jun Il,Shin Sung Jae,Yu Byung Hyun,Koo Jee Hoon,Kim Dong Hoon,Lee Ki Myoung,Lee Kwang Jae The Korean journal of internal medicine Hemophagocytic syndrome (HPS) is an uncommon hematological disorder that manifests as fever, splenomegaly, and jaundice, with hemophagocytosis in the bone marrow and other tissues pathologically. Secondary HPS is associated with malignancy and infection, especially viral infection. The prevalence of cytomegalovirus (CMV) infection in ulcerative colitis (UC) patients is approximately 16%. Nevertheless, HPS in UC superinfected by CMV is very rare. A 52-year-old female visited the hospital complaining of abdominal pain and hematochezia for 6 days. She was diagnosed with UC 3 years earlier and had been treated with sulfasalazine, but had stopped her medication 4 months earlier. On admission, her spleen was enlarged. The peripheral blood count revealed pancytopenia and bone marrow aspiration smears showed hemophagocytosis. Viral studies revealed CMV infection. She was treated successfully with ganciclovir. We report this case with a review of the related literature. 10.3904/kjim.2013.28.3.352
    [Hemophagocytic syndrome. Current concepts]. Espinosa Bautista Karla Adriana,Garciadiego Fossas Pamela,León Rodríguez Eucario Gaceta medica de Mexico Hemophagocytic lymphohistiocytosis is a syndrome characterized by pathological immune activation that may occur as either a primary a familial disorder (associated with genetic mutations), or as a sporadic condition, associated to infections, malignancies or autoimmune diseases. The clinical picture is characterized by a disproportionate inflammation that causes fever, cytopenias, splenomegaly, bone marrow hemophagocytosis, hypertriglyceridemia and hypofibrinogenemia. Syndrome-related mortality is high, so it is important to maintain a high index of suspicion and start early treatment with immunochemotherapy and bone marrow transplantation in primary and refractory cases. In this article, we review the clinical manifestations, pathology, diagnosis and treatment of these patients.
    Q fever and Mediterranean spotted fever associated with hemophagocytic syndrome: case study and literature review. Lecronier M,Prendki V,Gerin M,Schneerson M,Renvoisé A,Larroche C,Ziol M,Fain O,Mekinian A International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases BACKGROUND:Hemophagocytosis during Q fever (QF) and Mediterranean spotted fever (MSF) is rare and only a few cases have been reported. We aimed to investigate the characteristics, outcome, and treatment of QF/MSF-associated hemophagocytosis. METHODS:We retrospectively reviewed all patients with a diagnosis of QF or MSF and suspected hemophagocytic syndrome (HS), according to Henter's criteria, between 2002 and 2011, and compared the latter to patients without HS or with lymphoma-associated HS. RESULTS:Seventeen patients with HS (median age 42 years, range 5-68 years; five females (29%)) with QF (n=8) and MSF (n=9) were included in this study. When comparing patients with QF- and MSF-associated HS with patients without HS (n=11), HS-associated signs (splenomegaly, ferritinemia, hypertriglyceridemia, and cytopenia) were significantly more frequent in patients with histological HS (p<0.05), along with a greater number of Henter's criteria. Despite the presence of HS-associated signs, treatment was similar in these two subgroups, including the time to recovery and the outcome. When compared to lymphoma-associated HS (n=10), the outcome in QF/MSF-associated HS was significantly different, with mortality in 70% of lymphoma patients versus none in QF- and MSF-associated HS (p<0.05). CONCLUSION:Hemophagocytosis is a rare occurrence during the course of QF and MSF. The presence of profound cytopenia is quite unusual in QF and MSF and should bring to mind the presence of associated HS. Nevertheless, hemophagocytic syndrome is associated with a good outcome in this condition. 10.1016/j.ijid.2012.12.026
    A case of recurrent autoimmune hemolytic anemia during remission associated with acute pure red cell aplasia and hemophagocytic syndrome due to human parvovirus B19 infection successfully treated by steroid pulse therapy with a review of the literature. Sekiguchi Yasunobu,Shimada Asami,Imai Hidenori,Wakabayashi Mutsumi,Sugimoto Keiji,Nakamura Noriko,Sawada Tomohiro,Komatsu Norio,Noguchi Masaaki International journal of clinical and experimental pathology The patient was a 47-year-old man diagnosed as having autoimmune hemolytic anemia (AIHA) in April 2011. He also had a congenital chromosomal abnormality, a balanced translocation. Treatment with prednisolone (PSL) 60 mg/day resulted in resolution of the AIHA, and the treatment was completed in November 2011. While the patient no longer had anemia, the direct and indirect Coombs tests remained positive. In May 2013, he developed recurrent AIHA associated with acute pure red cell aplasia (PRCA) and hemophagocytic syndrome (HPS) caused by human parvovirus B19 (HPV B19) infection. Tests for anti-erythropoietin and anti-erythropoietin receptor antibodies were positive. Steroid pulse therapy resulted in resolution of the AIHA, PRCA, as well as HPS. The serum test for anti-erythropoietin antibodies also became negative after the treatment. However, although the serum was positive for anti-HPV B19 IgG antibodies, the patient continued to have a low CD4 lymphocyte count (CD4, <300/μL) and persistent HPV B19 infection (HPV B19 DNA remained positive), suggesting the risk of recurrence and bone marrow failure.
    Clinical characteristics and treatment outcomes of autoimmune-associated hemophagocytic syndrome in adults. Kumakura Shunichi,Murakawa Yohko Arthritis & rheumatology (Hoboken, N.J.) OBJECTIVE:To better define the clinical characteristics and treatment outcomes of autoimmune-associated hemophagocytic syndrome (AAHS) in adults. METHODS:Adults with AAHS (defined as pathologic evidence of hemophagocytosis without any obvious cause other than an autoimmune disease) were identified through a review of the literature. RESULTS:Among 116 patients identified, underlying diseases included systemic lupus erythematosus (SLE) in 52.3%, adult-onset Still's disease (AOSD) in 26.7%, and dermatomyositis in 6.9%. Fever, lymphadenopathy, hepatomegaly, and splenomegaly were found in 86.8%, 41.0%, 41.8%, and 45.5% of patients, respectively. Cytopenia, liver dysfunction, and hyperferritinemia developed frequently, and coagulopathy was seen in 50.6% of patients. Normal or low C-reactive protein levels were characteristic of patients with underlying SLE. The most commonly used therapy was corticosteroids, which were initially administered in 95.7% of patients, with 57.7% responding. Patients with corticosteroid-refractory disease were usually treated with cyclosporine, intravenous cyclophosphamide (IV CYC), or intravenous immunoglobulin (IVIG), with IV CYC being highly effective. Treatment with biologic agents resulted in favorable effects in the majority of patients. The mortality rate was 12.9%. Male sex (odds ratio [OR] 6.47, 95% confidence interval [95% CI] 2.06-30.39, P < 0.01), dermatomyositis (OR 5.57, 95% CI 1.08-28.65, P < 0.05), and anemia (hemoglobin <8 gm/dl; OR 3.74, 95% CI 1.02-13.8, P < 0.05) were identified as factors associated with mortality. CONCLUSION:AAHS is potentially fatal. Corticosteroids are a mainstay of initial treatment. For corticosteroid-refractory disease, IV CYC may be beneficial as compared with cyclosporine or IVIG. Treatment that proceeds directly from corticosteroids to biologic agents is promising. 10.1002/art.38672
    Hyperinflammation, rather than hemophagocytosis, is the common link between macrophage activation syndrome and hemophagocytic lymphohistiocytosis. Weaver Lehn K,Behrens Edward M Current opinion in rheumatology PURPOSE OF REVIEW:Macrophage activation syndrome is the rheumatic disease-associated member of a group of hyperinflammatory syndromes characterized by uncontrolled cytokine storm. In this review, we highlight recent publications related to the pathoetiology of hyperinflammatory syndromes with an emphasis on how this new knowledge will guide our diagnosis, treatment, and future research efforts to better understand these deadly conditions. RECENT FINDINGS:The heterogeneity of clinical manifestations seen in patients with hyperinflammatory syndromes continues to grow as novel genetic and immunotherapeutic triggers of cytokine storm have been identified. Recent studies characterize unique cytokine and gene expression profiles from patients with different hyperinflammatory syndromes, whereas novel murine models begin to define networks of immune dysregulation thought to drive excessive inflammation in cytokine storm. SUMMARY:Emerging evidence suggests hypercytokinemia is the driving cause of immunopathology and morbidity/mortality in hyperinflammatory syndromes. Therefore, approaches to block cytokine function may be fruitful in treating hyperinflammatory syndromes with less toxicity than current therapies. However, not all hyperinflammatory syndromes result in the same pathogenic cytokine profile, implying that a personalized approach will be required for effective use of anticytokine therapies in the treatment of hyperinflammatory syndromes. 10.1097/BOR.0000000000000093
    Hemophagocytic syndrome in children and adults. Malinowska Iwona,Machaczka Maciej,Popko Katarzyna,Siwicka Alicja,Salamonowicz Małgorzata,Nasiłowska-Adamska Barbara Archivum immunologiae et therapiae experimentalis Hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis (HLH), is a heterogenic syndrome, which leads to an acute, life-threatening inflammatory reaction. HLH occurs both in children and adults, and can be triggered by various inherited as well as acquired factors. Depending on the etiology, HLH can be divided into genetic (i.e., primary) and acquired (i.e., secondary) forms. Among genetic HLH forms, one can distinguish between familial HLH and other genetically conditioned forms of HLH. Acquired HLH can be typically triggered by infections, autoimmune diseases, and malignancies. The most common symptoms of HLH are unremitting fever, splenomegaly, and peripheral blood cytopenia. Some severely ill patients present with central nervous system involvement. Laboratory tests reveal hyperferritinemia (often >10,000 μg/L), increased serum concentration of soluble receptor α for interleukin-2 (>2,400 U/L), hypertriglyceridemia, hypofibrinogenemia, coagulopathy, hyponatremia, hypoproteinemia, and elevated liver transaminases and bilirubin. Prognosis in HLH is very serious. Genetic HLH is always lethal if adequate therapy is not administered. Similarly, severe acquired cases often lead to death without appropriate treatment. Since HLH can be encountered by various specialists in the medical field, basic knowledge of this entity such as diagnostic criteria and treatment should be familiar to all physicians. 10.1007/s00005-014-0274-1
    [Analysis of 3 cases with Mycoplasma pneumoniae-associated hemophagocytic syndrome and review of literature]. Lu Zhiwei,Yang Jun,Wang Ying,He Yanxia,Bai Daming,Ma Hongling,Zheng Yuejie Zhonghua er ke za zhi = Chinese journal of pediatrics OBJECTIVE:To analyze the clinical characteristics of Mycoplasma pneumoniae-associated hemophagocytic syndrome (MP-HLH). METHOD:A retrospective investigation of the clinical manifestation, laboratory test, imagelogy, clinical course and outcome of 3 cases with MP-HLH seen between June 2013 and July 2013 in Shenzhen Children's Hospital, and review of relevant literature were conducted. RESULT:Of the 3 cases of MP-HLH, 2 were males, one was female, the ages were 1 year, 3 years and 6 years, respectively. They had no underlying disease previously. All the 3 cases had onset of fever, cough as main symptoms. Diagnosis of refractory Mycoplasma pneumoniae pneumonia was made, which was accompanied by decreased neutrophils [(0.08-0.68)×10(9)/L], hemoglobin [(79-103) g/L], platelet [(64-157)×10(9)/L], plasma fibrinogen [(1.3-1.5) g/L], lactate dehydrogenase [(1,170-1,285) U/L] and increased serum ferritin [(936.7-39 789.0) µg/L] in the third week of course. In two cases the T lymphocytes decreased, and the NK cell activity decreased significantly in one. Bone marrow cytology showed prompted bone marrow hyperplasia, and the phenomenon of phagocytosed blood cells. CT scan was performed for all the cases and consolidation with pleural effusion were shown. Two cases were admitted to PICU, and required endotracheal intubation and mechanical ventilation. Flexible bronchoscopy and bronchial lavage were performed and bronchial cast was found in two cases. All of them were treated with macrolide combined with other antibiotics, glucocorticoids and gamma globulin combination therapy, including one case given dexamethasone [10 mg/(m2·d)], cyclosporine[6 mg/(kg·d)], etoposide [150 mg/(m2·d)] chemotherapy. Two cases were cured, and 1 case died. The authors summarized the 18 cases reported in domestic and foreign literature. Foreign children were diagnosed and treated with steroids in 1-2 weeks, and 10 cases were cured, and 2 cases died. They died of massive hemorrhage and meningoencephalitis, and domestic children were diagnosed and treated within two to 4 weeks after onset, 5 cases were cured, one case died of severe pneumonia. CONCLUSION:MP-HLH is a rare disease in children, and had acute onset, rapid progression and high mortality. Early treatment with steroids was associated with a good prognosis, the key to successful treatment is early diagnosis and treatment, avoiding the immune cascade. Too late a diagnosis or development of serious complications may lead to death.
    Ebola Virus Disease has Features of Hemophagocytic Lymphohistiocytosis Syndrome. van der Ven Andre J A M,Netea Mihai G,van der Meer Jos W M,de Mast Quirijn Frontiers in medicine 10.3389/fmed.2015.00004
    A heart breaking case of rapidly developing severe hemophagocytic syndrome secondary to chronic active EBV infection; a case report and review of the literature. Tawfik Khoury,Liron Yosha,Ayman Abu Rmieleh,Schneider Ronen,Wolf D G,Ronen Levi Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology Epstein-Barr virus (EBV, HHV-4) is a gamma Herpesvirus with a 90% >seroprevalence in adults. Reactivations in non-immuno compromised individuals usually cause mild or no symptoms at all. Rarely, host immunity-virus balance is interrupted, resulting in a chronic active EBV infection. The following case illustrates the rapid development of severe hemophagocytic syndrome during chronic active EBV infection in a 73 year old woman who presented with lower extremity pain and edema, splenomegaly and abnormal liver enzymes. A diagnosis of chronic active EBV infection was made following an extensive investigation and the patient died secondary to rapidly progressive hemophagocytic syndrome. 10.1016/j.jcv.2015.03.017
    Dengue infection associated hemophagocytic syndrome: Therapeutic interventions and outcome. Wan Jamaludin Wan Fariza,Periyasamy Petrick,Wan Mat Wan Rahiza,Abdul Wahid S Fadilah Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology Infection associated hemophagocytic syndrome is increasingly recognized as a potentially fatal complication of dengue fever. It should be suspected with prolonged fever beyond seven days associated with hepatosplenomegaly, hyperferritinemia, worsening cytopenias and development of multiorgan dysfunction. Surge of similar pro-inflammatory cytokines observed in dengue associated hemophagocytic syndrome and multiorgan dysfunction may indicate they are part of related inflammatory spectrum. A proportion of patients recovered with supportive therapy, however most required interventions with corticosteroids, intravenous immunoglobulin or chemotherapy. We report three cases of dengue associated IAHS with good outcome following early recognition and treatment with dexamethasone and intravenous immunoglobulin. 10.1016/j.jcv.2015.06.004
    Hemophagocytic Syndrome in the Setting of AIDS and Disseminated Histoplasmosis: Case Report and a Review of Literature. Subedee Anup,Van Sickels Nicholas Journal of the International Association of Providers of AIDS Care Hemophagocytic lymphohistiocytosis (HLH) is traditionally regarded as a rapidly progressive and often fatal illness. In patients with AIDS, HLH usually occurs secondary to opportunistic infections. Although popular guidelines exist for the diagnosis and management of HLH in general, no formal study has evaluated their applicability among adult patients who develop HLH in the setting of AIDS and opportunistic infections. The study reports on a case of HLH in a patient with AIDS and disseminated histoplasmosis. Eighteen other previously reported cases of HLH in the setting of AIDS and histoplasmosis were reviewed. Majority of the cases occurred in patients with a CD4 count of less than 70 cells/mm(3). Overall mortality was 44%. Not getting antifungal treatment and having Histoplasma in blood were the 2 main risk factors for death. Among the patients who had a timely diagnosis of histoplasmosis and were initiated on antifungal therapy, the survival rates were significantly better, especially in the post-2000 ad period. 10.1177/2325957415570740
    [Acquired hemophagocytic syndrome treated with HLH 94-04 chemotherapy protocol: Report of four cases]. Beffermann C Nicole,Pilcante S Javier,Ocqueteau T Mauricio,Sarmiento M Mauricio Revista medica de Chile Hemophagocytic syndrome is a severe condition of excessive immune activation that has a high mortality in the absence of treatment. The syndrome is classified as primary if associated with congenital or hereditary problems, or secondary/acquired if associated with infectious, autoimmune or oncology diseases. We report four adult cases of the syndrome, one with viral, two with autoimmune and one with idiopathic causes who were successfully treated with HLH 94-04 chemotherapy protocol. Our experience shows that a high index of suspicion, early diagnosis and an opportune therapy are essential in the treatment of this disease. 10.4067/S0034-98872015000900010
    Hemophagocytic Syndrome and Critical Illness: New Insights into Diagnosis and Management. Tothova Zuzana,Berliner Nancy Journal of intensive care medicine Hemophagocytic lymphohistiocytosis (HLH) comprises a heterogeneous group of diseases that are characterized by a hyperinflammatory state due to uncontrolled T cell, macrophage, and histiocyte activation, accompanied by excessive cytokine production. This rare condition is almost uniformly fatal unless promptly recognized and treated. Much progress has been made in the last two decades in our understanding of the mechanisms underlying familial, and to a lesser extent, acquired cases of HLH. Recurrent mutations in more than 10 different genes have now been identified, involving biological pathways converging on intracellular vesicle trafficking and cytolytic granule exocytosis. Mechanisms underlying the majority of patients with acquired HLH, however, remain elusive, hampering both diagnostic evaluation and therapeutic management of these patients. Given that the majority of intensive care unit (ICU) patients with sepsis or multiorgan failure share many features of HLH, it is especially critical for pediatric and adult intensivists to be able to recognize patients with bona fide HLH and initiate treatment without delay. In this article, we review our current understanding of the pathophysiology, clinical testing, diagnosis, and treatment of patients with HLH, especially as it pertains to the care of critically ill patients in pediatric and medical ICUs. 10.1177/0885066613517076
    An update on renal involvement in hemophagocytic syndrome (macrophage activation syndrome). Esmaili Haydarali,Mostafidi Elmira,Mehramuz Bahareh,Ardalan Mohammadreza,Mohajel-Shoja Mohammadali Journal of nephropathology CONTEXT:Hemophagocytic syndrome (HPS) is mainly characterized by massive infiltration of bone marrow by activated macrophages and often presents with pancytopenia. Thrombotic microangiopathy (TMA) is also present with thrombocytopenia and renal involvement. Both conditions could coexist with each other and complicate the condition. EVIDENCE ACQUISITION:Directory of Open Access Journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science with keywords relevant to; Hemophagocytic syndrome, macrophage activation syndrome, interferon-gamma and thrombotic microangiopathy, have been searched. RESULTS:Viral infection, rheumatologic disease and malignancies are the main underlying causes for secondary HPS. calcineurin inhibitors and viral infections are also the main underlying causes of TMA in transplant recipients. In this review, we discussed a 39-year-old male who presented with pancytopenia and renal allograft dysfunction. With the diagnosis of HPS induced TMA his renal condition and pancytopenia improved after receiving intravenous immunoglobulin (IVIG) and plasmapheresis therapy. CONCLUSIONS:HPS is an increasingly recognized disorder in the realm of different medical specialties. Renal involvement complicates the clinical picture of the disease, and this condition even is more complex in renal transplant recipients. We should consider the possibility of HPS in any renal transplant recipient with pancytopenia and allograft dysfunction. The combination of HPS with TMA future increases the complexity of the situation. 10.15171/jnp.2016.02
    A case of anti-aminoacyl tRNA synthetase antibody syndrome complicated by hemophagocytic syndrome. Azuma Kota,Tamura Masao,Kurajoh Masafumi,Hosono Yuji,Nakajima Ran,Tsuboi Kazuyuki,Abe Takeo,Ogita Chie,Yokoyama Yuichi,Furukawa Tetsuya,Yoshikawa Takahiro,Saito Atsushi,Nishioka Aki,Sekiguchi Masahiro,Azuma Naoto,Kitano Masayasu,Tsunoda Shinichiro,Omura Koichiro,Koyama Hidenori,Matsui Kiyoshi,Mimori Tsuneyo,Sano Hajime Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology A 48-year-old woman had suffered from a fever and general fatigue, and visited the other hospital for fever elevation in November 2013, at which time interstitial lung disease was revealed. In January 2014, she experienced an eruption in the hand and developed peripheral blood flow damage. Under a diagnosis of adult Still's disease, the patient was administered 0.5 mg of betamethasone as well as cyclosporin at 75 mg/day. In November 2014, general fatigue, fever, and headache were noted, while MRI revealed an enlarged hypophysis and laboratory findings were positive for the anti-pituitary cell antibody, thus a diagnosis of autoimmune hypophysitis was made. Although disease activity was low, she requested hospitalization and was admitted by the Division of Endocrinology and Metabolism at our hospital in May 2015, though only observed. Fever developed again, along with interstitial lung disease, Raynaud's phenomenon, and pain in the crural area again, and we considered the possibility of another disease. After stopping administration of betamethasone and cyclosporin, we made a diagnosis of anti-aminoacyl tRNA synthetase antibody syndrome, and administered methylprednisolone at 500 mg for 3 days as well as prednisolone at 35 mg/day following steroid pulse therapy. Although her condition soon improved, fever, muscle pain, and pancytopenia returned after 3 days. Bone marrow findings revealed the existence of hemophagocytosis, for which we again gave methylprednisolone at 500 mg for 3 days and cyclosporin at 125 mg/day. Thereafter, the patient recovered and was discharged from the hospital. 10.2177/jsci.39.538
    [X-linked lymphoproliferative syndrome type 1 complicated with secondary hemophagocytic lymphohistiocytosis and ileal perforation: case report and literature review]. Xiao L,Guan X M,Meng Y,Zhao X D,Xian Y,An Y F,Yu J Zhonghua er ke za zhi = Chinese journal of pediatrics OBJECTIVE:To analyze and summarize the clinical characteristics, laboratory tests and treatment of X-linked lymphoproliferative syndrome type 1 (XLP-1). METHOD:A retrospective study was done in 2012 on an XLP-1 patient to collect the data on clinical manifestation, laboratory examination, gene and protein expression, complications and prognosis. Literatures were reviewed in Pubmed with the key word"X-linked lymphoproliferative syndrome". RESULT:The patient with persistent high fever, jaundice, abdominal distension, hepatosplenomegaly and lymphadenectasis, rash and suspicious positive family history; the patient eventually died of hemophagocytic lymphohistiocytosis (HLH), with intestinal perforation, intestinal infection and bleeding after being infected with EB virus. This patient with SH2D1A gene exon 1 large fragment of the coding region of the nucleotide deletion and insertion mutations causing missense mutations (p.Leu25Lys) and nonsense mutations (stop codon TAG was inserted after missense mutation so that the protein encoded by the early termination of the 25 amino acids), which led to SAP protein missing. The expression of SAP in his mother was also partly missing. Retrieval of reports on XLP-1 was conducted through literature search (included totally 157 cases) at home and abroad, positive family history accounted for 60.6%(40/66); lymphoma incidence accounted for 49.7%(72/145); low gamma globulin occurred in 24.8%(39/157) of cases; secondary HLH ratio accounted for 43.3%(68/157); XLP-1 in patients with hemorrhagic enteritis and gastritis was low, accounted for only 2.6%(3/116). CONCLUSION:XLP-1 patients occasionally develop necrotic enteritis complicated with ileal perforation.XLP-1 with large fragment deletion of SH2D1A gene might be associated with serious gastrointestinal manifestations. 10.3760/cma.j.issn.0578-1310.2016.04.013
    Fulminant Epstein-Barr virus-associated hemophagocytic syndrome in a renal transplant patient and review of the literature. Romiopoulos I,Pyrpasopoulou A,Onoufriadis I,Massa E,Mouloudi E,Kydona C,Giasnetsova T,Gerogianni N,Myserlis G,Solonaki F,Nikodimopoulou M,Mandala E,Antachopoulos C,Roilides E Transplant infectious disease : an official journal of the Transplantation Society We describe a rare fulminant case of Epstein-Barr virus-associated hemophagocytic syndrome (HPS) in a 37-year-old female renal transplant patient, indistinguishable from severe sepsis clinically and in the laboratory. HPS involves rapidly escalating immune system activation, resulting in a cytokine cascade, which can, especially in immunocompromised patients, lead to multi-organ failure, and even death. Thirty-two Herpesviridae-associated HPS cases in renal transplant patients have been reported and are reviewed. Overall mortality is 47% (15/32 cases). 10.1111/tid.12586
    Hemophagocytic lymphohistiocytosis in a patient with Sjögren's syndrome: case report and review. García-Montoya L,Sáenz-Tenorio C N,Janta I,Menárguez J,López-Longo F J,Monteagudo I,Naredo E Rheumatology international Hemophagocytic lymphohistiocytosis (HLH) is a very rare syndrome with a mortality up to 95% of cases if not treated. It is characterised by an excessive activation of the immune system that leads to a disproportionate and destructive inflammatory response. The high mortality rates are in part due to a delay in the diagnosis, and therefore clinicians must maintain a high index of suspicion. When the treatment is started early, the survival rate reaches around 55% of cases. HLH usually presents with persistent fever, pancytopenia, and organomegaly and is associated with very high levels of serum ferritin. In this manuscript, we present the case of a patient with primary Sjögren's syndrome who developed HLH after an acute infection by Cytomegalovirus. We will describe and discuss the pathogenesis, differential diagnosis and a pragmatic approach to the treatment for this critically important and, when diagnosed early, potentially curable syndrome. 10.1007/s00296-016-3601-5
    Clinical features and prognostic factors of adult secondary hemophagocytic syndrome: Analysis of 47 cases. Guo Yiqun,Bai Yu,Gu Li Medicine This study aimed to investigate the relationship between clinical features and prognosis of adult secondary hemophagocytic syndrome (HPS).A retrospective analysis was conducted on the pathogenesis, clinical manifestations, laboratory examinations, treatment options, and prognosis of 47 patients with adult secondary HPS diagnosed from January 2013 to December 2015.The average age at disease onset was (46.26 ± 18.98) years with a male:female ratio of 1:1.14. Thirteen patients died, with the highest mortality rate in patients with HPS underlying blood system malignancy (33.33%, 2/6). The mortality rate in patients with HPS underlying autoimmune disorders was the lowest (18.75%, 3/16). The Kaplan-Meier analysis indicated that signs of hemorrhage, pulmonary and nervous system involvement, serous effusion, and decrease in the blood platelet count were associated with death. The Cox regression analysis revealed that signs of hemorrhage, pulmonary involvement, serous effusion, and nervous system involvement were independent risk factors of patient death.Adult secondary HPS has multiple etiologies and diversified clinical features. The risk of death increases in patients with signs of hemorrhage, serous effusion, pulmonary involvement, and nervous system involvement. 10.1097/MD.0000000000006935
    Hemophagocytic syndrome: primary forms and predisposing conditions. Sepulveda Fernando E,de Saint Basile Geneviève Current opinion in immunology Hemophagocytic lymphohistiocytosis (HLH, also referred to a hemophagocytic syndrome) is a life-threatening condition in which uncontrolled activation of lymphocytes and macrophages, and thus the secretion of large amounts of inflammatory cytokines, leads to a severe hyperinflammatory state. Over the last few decades, researchers have characterized primary forms of HLH caused by genetic defects that impair lymphocytes' cytotoxic machinery. Other genetic causes of HLH not related to impaired cytotoxicity have also recently been identified. Furthermore, the so-called 'acquired' forms of HLH are encountered in the context of severe infections, autoimmune and autoinflammatory diseases, malignancy, and metabolic disorders, and may also be associated with primary immunodeficiencies. This implies that a variety of disease mechanisms can lead to HLH. Today's research seeks to gain a better understanding of the various pathogenetic and environmental factors that converge to induce HLH. 10.1016/j.coi.2017.08.004
    [Eperythrozoonosis complicated with hemophagocytic syndrome: report of four cases and review of literature]. Li J G,Zhang D,Zhou Z X,Li S N,Kang M,Lai J M Zhonghua er ke za zhi = Chinese journal of pediatrics To analyze the clinical characteristics of eperythrozoonosis complicated with hemophagocytic syndrome (HPS) in 4 children. Four patients diagnosed with eperythrozoonosis complicated with HPS in the Children's Hospital Affiliated Capital Institute of Pediatrics during the period from June 2014 to July 2016 were enrolled. The clinical manifestations, laboratory examination data and therapeutic strategies were analyzed. A literature search (search terms included 'eperythrozoonosis' and 'hemophagocytic syndrome') was conducted using CNKI, Wanfang database, Chinese biomedical literature database and PubMed to include recently published studies (searched from the database establishment to January 2017). Four patients were included in the study. One was boy and the other three were girls. The age range of the 4 patients was between 9 months and 17 years (9 months, 2 years and 17 years, 11 months respectively). All the patients presented with recurrent high fever. During the course of fever, 3 patients presented with rash, and 2 patients presented with joint pain and swelling, which mimicked systemic juvenile idiopathic arthritis. Only 1 patient had the contact history of infectious disease. All patients had normal or decreased white blood cell count ((0.80-13.12)×10/L), suffered from varied degrees of anemia and showed the increased C reactive protein (13.0-84.7 mg/L) anderythrocyte sedimentation rate (13-72 mm/1 h). Examination of peripheral blood smears confirmed eperythrozoonosis. After fever continued about 1 month, all the 4 patients rapidly progressed. Among the 4 patients, 1 patient died for giving up further therapy, and the other 3 patients completely recovered after treatment, including azithromycin for the treatment of eperythrozoonosis, and high-dose intravenous methylprednisolone pulse therapy and human immunoglobulin for the treatment of HPS. For the disease not satisfactory, the hemophagocytic lymphohistiocytosis-2004 (HLH-2004) protocol is given. After the hospitalization of 1 to 2 months, the conditions improved and the children were discharged from hospital. Three patients were followed up for 8 months to 2 years, and their conditions were stable. In the PubMed database, no report was found. Nine cases of children with eperythrozoonosis were found in CNKI, Wanfang database and Chinese biomedical literature database, and 1 case was complicated with HPS. These findings, taken together our report, provided the data of 5 children with eperythrozoonosis complicated with HPS (4 cases were younger than 2 years old). A patient had contact history of infectious disease. Five patientss showed fever of unknown origin. All the patients had severe eperythrozoonosis, and 2 cases at younger age died. Children with eperythrozoonosis often present with the protracted fever of unknown origin, and clinical manifestations mimic those of juvenile idiopathic arthritis (systemic type). The patients with eperythrozoonosis of mild-to-moderate disease severity may have a good prognosis. Children with severe eperythrozoonosis, especially those HPS cases with early onset before 2 years old, may have high risk of mortality. Once the patient's condition aggravates in the course of fever, HPS should be highly suspected. For the patients with eperythrozoonosis complicated with HPS, early diagnosis and the combination of anti-infection with the treatment of HPS are crucial for a good prognosis. For the treatment of HPS, HLH-2004 protocol is recommended. 10.3760/cma.j.issn.0578-1310.2018.04.013
    An effective diagnostic index for lymphoma-associated hemophagocytic syndrome. Xie M,Li L,Zhu L,Zhou D,Yang X,Sun J,Zhu J,Zhu M,Zheng Y,Xie W,Ye X QJM : monthly journal of the Association of Physicians BACKGROUND:Lymphoma-associated hemophagocytic syndrome (LAHS) is a highly fatal immune disorder. Poor prognosis is partly attributed to under diagnosis or delayed diagnosis. AIM:Early identification of LAHS patients based on the laboratory findings could improve the outcomes. DESIGN:Retrospective observational cross-sectional study. METHODS:From January 2011 to June 2016, 282 adult patients with hemophagocytosis in bone marrow were enrolled, and 114 hemophagocytic lymphohistiocytosis (HLH) patients with definite underlying cause were finally included for analysis. The HLH patients were further divided into LAHS (76 out of 114) and non-malignancy-associated HLH (38 out of 114) groups. RESULTS:Compared to non-malignancy-associated HLH, LAHS patients had significantly elevated lactate dehydrogenase (LDH) levels, increased thickness of spleen, higher proportion of patients with lymphadenopathy and significantly decreased peripheral blood cell count. In multivariate logistic regression model analysis, thickness of spleen ≥5 cm (OR = 17.9, 95%CI 1.35-236.6; P = 0.028), IL-6 level ≥55.1 pg/ml (OR = 12.01, 95%CI 1.03-138.9; P = 0.047) and IL-10 level ≥425.9 pg/ml (OR = 51.18, 95%CI 2.53-1035.1; P = 0.010) were independent predictors of LAHS diagnosis. Based on the regression parameters, we established a diagnostic index with weighted risk scores of 1 assigned to thickness of spleen and IL-6 level respectively, and a score of 3 assigned to IL-10 level. A diagnostic index ≥ 2 points had the best AUC value (0.889) with 84.2% of sensitivity and 93.7% of specificity for predicting LAHS. CONCLUSIONS:LAHS can be considered when HLH patients have a diagnostic index ≥2 points, so actively looking for evidence of lymphoma and effective chemotherapy may be necessary. 10.1093/qjmed/hcy103
    Reactive hemophagocytic syndrome in the setting of acute human immunodeficiency virus 1 infection: case report and review of the literature. Tulloch Luis G,Younes Ramee,Jeng Arthur International journal of STD & AIDS We report a case of reactive hemophagocytic syndrome (RHS) in the setting of acute human immunodeficiency virus type 1 infection (AHI). In addition, we review 11 previously reported cases of RHS precipitated by AHI and discuss strategies in the diagnosis and management of these overlapping clinical entities. 10.1177/0956462418788689
    Disseminated toxoplasmosis associated with hemophagocytic syndrome after kidney transplantation: A case report and review. Gay Juliette,Gendron Nicolas,Verney Charles,Joste Valentin,Dardé Marie-Laure,Loheac Charlotte,Vrtovsnik François,Argy Nicolas,Houze Sandrine Transplant infectious disease : an official journal of the Transplantation Society Disseminated toxoplasmosis is infrequent after kidney transplant transmission but life-threatening because of a lack of diagnostic suspicion as well as specific chemoprophylaxis recommendations. Solid organ transplantation has resulted in few cases of disseminated toxoplasmosis presenting with associated hemophagocytic syndrome. Herein, we report, within the context of a donor/receiver mismatch, a case of a toxoplasmosis associated with hemophagocytic syndrome in a kidney transplant recipient. Molecular and serological investigations confirmed Toxoplasma gondii transmission through the kidney graft. 10.1111/tid.13154