scholarly journals Advances in Hemophagocytic Lymphohistiocytosis: Pathogenesis, Early Diagnosis/Differential Diagnosis, and Treatment

2011 ◽  
Vol 11 ◽  
pp. 697-708 ◽  
Author(s):  
Yong-Min Tang ◽  
Xiao-Jun Xu
Keyword(s):  
Immune Response ◽  
Differential Diagnosis ◽  
Early Diagnosis ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Clinical Symptoms ◽  
Molecular Genetic ◽  
Hematopoietic Stem ◽  
Curative Therapy ◽  
New Finding ◽  
Life Threatening

Hemophagocytic lymphohistiocytosis (HLH) is a histiocytic disorder characterized by a highly stimulated, but ineffective, immune response to antigens, which results in life-threatening cytokine storm and inflammatory reaction. Considerable progress has been made during the past 2 decades. Detection of molecular genetic abnormalities in genes involved in immune response pathways, such as PRF1, STX11, UNC13D, STXBP2, RAB27A, LYST, AP3B1, SH2D1A, and BIRC4, is confirmatory for the diagnosis. Clinical diagnosis is largely made according to HLH-2004 criteria. However, a new finding of the Th1/Th2 cytokine pattern (significant increase of IFN-γ and IL-10 with slightly increased or normal level of IL-6) is a useful biomarker for the early diagnosis, differential diagnosis, and the monitoring of the disease. Intensive immunosuppressive therapy is generally accepted as treatment for the relief of clinical symptoms/signs, while allogeneic hematopoietic stem cell transplantation is currently the only potentially curative therapy option for severe familial forms of HLH.

scholarly journals Nivolumab treatment of relapsed/refractory Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis in adults

Blood ◽  
2020 ◽  
Vol 135 (11) ◽  
pp. 826-833 ◽  
Author(s):  
Pengpeng Liu ◽  
Xiangyu Pan ◽  
Chong Chen ◽  
Ting Niu ◽  
Xiao Shuai ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Epstein Barr Virus ◽  
Sequencing Analysis ◽  
Hematopoietic Stem ◽  
Barr Virus ◽  
Life Threatening ◽  
Programmed Death Protein 1 ◽  
Epstein Barr

Abstract Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening hyperinflammatory syndrome triggered by EBV infection. It often becomes relapsed or refractory (r/r), given that etoposide-based regimens cannot effectively clear the virus. r/r EBV-HLH is invariably lethal in adults without allogeneic hematopoietic stem cell transplantation. Here, we performed a retrospective analysis of 7 r/r EBV-HLH patients who were treated with nivolumab on a compassionate-use basis at West China Hospital. All 7 patients tolerated the treatment and 6 responded to it. Five of them achieved and remained in clinical complete remission with a median follow-up of 16 months (range, 11.4-18.9 months). Importantly, both plasma and cellular EBV-DNAs were completely eradicated in 4 patients. Single-cell RNA-sequencing analysis showed that HLH syndrome was associated with hyperactive monocytes/macrophages and ineffective CD8 T cells with a defective activation program. Nivolumab treatment expanded programmed death protein-1–positive T cells and restored the expression of HLH-associated degranulation and costimulatory genes in CD8 T cells. Our data suggest that nivolumab, as a monotherapy, provides a potential cure for r/r EBV-HLH, most likely by restoring a defective anti-EBV response.

scholarly journals Human Adenovirus 7-Associated Hemophagocytic Lymphohistiocytosis-like Illness: Clinical and Virological Characteristics in a Cluster of Five Pediatric Cases

2020 ◽  
Author(s):  
William R Otto ◽  
Edward M Behrens ◽  
David T Teachey ◽  
Daryl M Lamson ◽  
David M Barrett ◽  
...  
Keyword(s):  
Genetic Predisposition ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Definitive Treatment ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Threatening Condition ◽  
Epidemiology Data ◽  
Life Threatening

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregulation. Children often suffer from primary genetic forms of HLH, which can be triggered by infection. Others suffer from secondary HLH as a complication of infection, malignancy, or rheumatologic disease. Identifying the exact cause of HLH is crucial, as definitive treatment for primary disease is hematopoietic stem cell transplant. Adenoviruses have been associated with HLH but molecular epidemiology data are lacking. Methods We describe the clinical and virologic characteristics of 5 children admitted with adenovirus infection during 2018–2019 who developed HLH or HLH-like illness. Detailed virologic studies, including virus isolation and comprehensive molecular typing were performed. Results All patients recovered; clinical management varied but included immunomodulating and antiviral therapies. A genetic predisposition for HLH was not identified in any patient. Adenovirus isolates were recovered from 4/5 cases; all were identified as genomic variant 7d. Adenovirus type 7 DNA was detected in the fifth case. Phylogenetic analysis of genome sequences identified 2 clusters—1 related to strains implicated in 2016–2017 outbreaks in Pennsylvania and New Jersey, the other related to a 2009 Chinese strain. Conclusions It can be challenging to determine whether HLH is the result of an infectious pathogen alone or genetic predisposition triggered by an infection. We describe 5 children from the same center presenting with an HLH-like illness after onset of adenovirus type 7 infection. None of the patients were found to have a genetic predisposition to HLH. These findings suggest that adenovirus 7 infection alone can result in HLH.

Early Diagnosis and Treatment of the Patients with Acquired Hemophagocytic Lymphohistiocytosis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3552-3552
Author(s):  
Zhao Wang ◽  
Yini Wang ◽  
Cuicui Feng ◽  
Liping Tian
Keyword(s):  
Early Diagnosis ◽  
Diagnostic Criteria ◽  
Peripheral Blood ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Nk Cell ◽  
Clinical Symptoms ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Final Diagnosis ◽  
Nk Cell Activity

Abstract Acquired hemophagocytic lymphohistiocytosis (HLH) is a life threatening condition characterized by uncontroling hyperinflammation on the basis of various infection, tumor and inherited immune deficiency. Awareness of the clinical symptoms and of the diagnostic criteria of HLH is crucial in order not to overlook HLH and to start life-saving therapy in time. In this study, we reviewed 57 suspected HLH patients from March 2006 to June 2008. 25 healthy subjects were enrolled in the study as control. NK cell activity in peripheral blood was tested by a released LDH assay. Meanwhile, solution interleukin-2 receptor (sCD25) was examined with ELISA double antibody sandwich assay. The level of glycosylated ferritin was also detected and the ratio of glycosylated ferritin to ferritin was determined. 41 out of 57 patients were definitely diagnosed according to HLH-2004 diagnostic criteria in this study and 16 patients were excluded. We found that the level of NK cell activity and the ratio of glycosylated ferritin in the all 41 final diagnozed HLH patients were significantly lower than those in the 16 excluded patients and 25 healthy control subjects (p<0.01). Meanwhile, the level of sCD25 in peripheral blood was much higher in all the 41 HLH patients than that in the excluded and healthy people (p<0.05). We compared the coincidence of each diagnostic index in the 41 HLH patients before and after final diagnosis. It was found that 100% patients had abnormal expression on NK cell activity, sCD25 and glycosylated ferritin in the early disease. The three diagnostic indexes were more sensitive and specific than other indexes, such as fever, hepatosplenomegaly, cytopenia, hyper-triglyceridemia, hypo-fibrinogenemia. 41 diagnosed patients received the regimen containing methylprednisolone and immunoglobulin, with or without fludarabine, 26 out of 41 were markedly improved after treatment, 10 out of 41 were exacerbated, and other 5 patients gave up treatment. It is concluded that detection of NK cell activity, sCD25 and glycosylated ferritin may play a very important role in the early diagnosis of HLH. Our data also suggest that fludarabine combined with methylprednisolone and immunoglobulin (FDIg) may provide a new viewpoint for HLH therapy.

scholarly journals Optimization of Early Diagnostics of Prostate Cancer

2020 ◽  
Vol 6 (5) ◽  
pp. 97-104
Author(s):  
N. Stepanov ◽  
Z. Duvayarov ◽  
I, Bystrova ◽  
T. Chepaikina ◽  
V. Kostrova
Keyword(s):  
Prostate Cancer ◽  
Differential Diagnosis ◽  
Early Diagnosis ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Diagnostic Errors ◽  
Decay Products ◽  
Examination Methods ◽  
Special Examination ◽  
Diagnostic Capabilities

The prevalence and incidence of prostate cancer is gradually increasing both in our country and in countries near and far abroad. The difficulties in the differential diagnosis of prostate cancer are convincingly evidenced by the fact that the level of diagnostic errors reaches 40%. It should be noted that in assessing the differential diagnostic capabilities of the indicators of the clinical and special examination methods for patients with lower urinary tract symptoms, disagreements were found in 46–77% of the analyzed clinical signs, the changes of which mainly reflect the negative nature of the effect of tumor decay products on the patient’s body. The aim of the study was to improve the early diagnosis of prostate cancer by using the mathematical method of differential diagnosis of prostate pathology, as well as the rationale for the proposed method for early diagnosis of prostate cancer in patients with clinical symptoms. Using our proposed method for early diagnosis of prostate cancer makes the diagnosis not only reliable and accurate, but also independent of the level of qualification of the urologist and his personal experience, allows you to unify, optimize and personify the differential diagnosis of prostatic hypertrophy and prostate cancer.

scholarly journals Case Report: Secondary Hemophagocytic Lymphohistiocytosis With Disseminated Infection in Chronic Granulomatous Disease—A Serious Cause of Mortality

2020 ◽  
Vol 11 ◽  
Author(s):  
Jacqueline D. Squire ◽  
Stephanie N. Vazquez ◽  
Angela Chan ◽  
Michele E. Smith ◽  
Deepak Chellapandian ◽  
...  
Keyword(s):  
Immune Deficiency ◽  
Chronic Granulomatous Disease ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Fungal Infections ◽  
Primary Immune Deficiency ◽  
Granulomatous Disease ◽  
Simultaneous Treatment ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Life Threatening

Chronic granulomatous disease (CGD) is a primary immune deficiency due to defects in phagocyte respiratory burst leading to severe and life-threatening infections. Patients with CGD also suffer from disorders of inflammation and immune dysregulation including colitis and granulomatous lung disease, among others. Additionally, patients with CGD may be at increased risk of systemic inflammatory disorders such as hemophagocytic lymphohistiocytosis (HLH). The presentation of HLH often overlaps with symptoms of systemic inflammatory response syndrome (SIRS) or sepsis and therefore can be difficult to identify, especially in patients with a primary immune deficiency in which incidence of infection is increased. Thorough evaluation and empiric treatment for bacterial and fungal infections is necessary as HLH in CGD is almost always secondary to infection. Simultaneous treatment of infection with anti-microbials and inflammation with immunosuppression may be needed to blunt the hyperinflammatory response in secondary HLH. Herein, we present a series of X-linked CGD patients who developed HLH secondary to or with concurrent disseminated CGD-related infection. In two patients, CGD was a known diagnosis prior to development of HLH and in the other two CGD was diagnosed as part of the evaluation for HLH. Concurrent infection and HLH were fatal in three; one case was successfully treated, ultimately receiving hematopoietic stem cell transplantation. The current literature on presentation, diagnosis, and treatment of HLH in CGD is reviewed.

scholarly journals Hemophagocytic Lymphohistiocytosis: A Life Threatening Cytopenic Condition

2021 ◽  
Vol 15 (2) ◽  
pp. 98-102
Author(s):  
Suranjit Kumar Saha ◽  
MM Shahin Ul Islam ◽  
Nasir Uddin Ahmed ◽  
Prativa Saha
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Clinical Manifestations ◽  
Specific Treatment ◽  
Gene Mutations ◽  
Multiple Organ ◽  
Treatment Modalities ◽  
Hematopoietic Stem ◽  
Organ Systems ◽  
Life Threatening ◽  
Poor Outcomes

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder that occurs in many underlying conditions in all age. This is characterized by unbridled activation of cytotoxic T lymphocytes, natural killer (NK) cells and macrophages resulting in raised cytokine level. Those cytokines and immune mediated injury occur in multiple organ systems. It may be primary and secondary. Primary HLH is familial, childhood presentation and associated with gene mutations. Secondary HLH is acquired, adulthood presentation that occurs in infections, malignancies inflammatory and autoimmune diseases etc. Clinical manifestations include fever, splenomegaly, lymphadenopathy, neurologic dysfunction, coagulopathy, features of sepsis etc. Laboratory investigation includes cytopenias, hypertriglyceridemia, hyperferritinemia, abnormal liver function, hemophagocytosis, and diminished NKcell activity. Treatment modalities include immunosuppressive, immunomodulatory agents, cytostatic drugs, T-cell antibodies, anticytokine agents and hematopoietic stem cell transplantation (HSCT). Besides those, aggressive supportive care combined with specific treatment of the precipitating factor can produce better outcome. With treatment more than 50% of children who undergo transplant survive, but adults have quite poor outcomes even with aggressive management. Faridpur Med. Coll. J. 2020;15(2): 98-102

scholarly journals A Case of Hemophagocytic Syndrome due to Tuberculosis: Uncommon Manifestation of a Common Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Arijit Singha ◽  
Adreesh Mukherjee ◽  
Riddhi Dasgupta ◽  
Tapas Das
Keyword(s):  
Immune Response ◽  
Early Detection ◽  
Early Diagnosis ◽  
Clinical Condition ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Hemophagocytic Syndrome ◽  
Immune Dysregulation ◽  
Diagnosis And Treatment ◽  
Common Disease ◽  
Immunocompromised Patients

Hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis (HLH), is the manifestation of immune dysregulation. It is associated with ineffective but exaggerated immune response and infiltration of active lymphocytes and histiocytes in various organs. This devastating clinical condition has myriad of clinical and biochemical manifestations such as fever, splenomegaly, pancytopenia, hypertrygliceridemia, and hyperferritinemia. It can be either primary or secondary. Primary HLH usually presents in childhood. Secondary HLH occurs due to infection mostly viruses but other aetiologies are also important as early detection and treatment may improve survival. Hemophagocytosis due to tuberculosis is uncommon. Only handful of cases have been reported mostly in immunocompromised patients. We report a case of hemophagocytic syndrome associated with disseminated tuberculosis in an immunocompetent women highlighting early diagnosis and treatment is a demanding need in this devastating disease.

Familial and Acquired Hemophagocytic Lymphohistiocytosis

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 82-88 ◽  
Author(s):  
Gritta Janka ◽  
Udo zur Stadt
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Clinical Symptoms ◽  
Cytotoxic T Cells ◽  
Interleukin 2 ◽  
Life Saving ◽  
Threatening Condition ◽  
Immune Deficiencies ◽  
Life Threatening ◽  
Infected Cells ◽  
Cardinal Symptoms

AbstractHemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by uncontrolled hyperinflammation on the basis of various inherited or acquired immune deficiencies. Cardinal symptoms are prolonged fever, hepatosplenomegaly and cytopenias. Central nervous system (CNS) symptoms are common. Biochemical markers include elevated triglyceride and ferritin, high levels of the α chain of the soluble interleukin-2 receptor and low fibrinogen. Impaired function of natural killer (NK) cells and cytotoxic T-cells (CTL) is a characteristic of all forms of HLH.Genetic HLH occurs in familial forms (FHLH), in which HLH is the primary and only manifestation, and in association with the immune deficiencies Chédiak-Higashi syndrome (CHS), Griscelli syndrome (GS) and X-linked lymphoproliferative syndrome (XLP), in which secondary HLH occurs sporadically. Most patients with acquired HLH have no known underlying immune deficiency. Both acquired and genetic forms are triggered by infections, mostly viruses, or other stimuli. HLH also occurs as a complication of rheumatic diseases (macrophage activation syndrome) and of malignancies. The recent discovery of several genetic defects causing FHLH as well as the identification of the genes responsible for CHS, GS and XLP have underscored the role of granule (perforin/granzymes)-mediated cytotoxicity in both the killing of infected cells and the termination of the immune response. The immediate aim of therapy is suppression of the increased inflammatory response by immunosuppressive/immunomodulatory agents and cytotoxic drugs. Genetic cases can only be cured with stem cell transplantation. Awareness of the clinical symptoms and of diagnostic criteria for HLH is crucial to starting life-saving therapy in time.

SPONTANEOUS HETEROTOPIC PREGNANCY WITH UNSTABLE VITALS: A CASE REPORT

2021 ◽  
pp. 35-36
Author(s):  
Anshika Agarwal
Keyword(s):  
Early Diagnosis ◽  
Vaginal Bleeding ◽  
Clinical Symptoms ◽  
Transvaginal Ultrasound ◽  
Heterotopic Pregnancy ◽  
Intrauterine Pregnancy ◽  
Spontaneous Conception ◽  
Beta Hcg ◽  
Maternal Morbidity And Mortality ◽  
Life Threatening

A spontaneous heterotopic pregnancy is a rare obstetric entity which can be life threatening if early diagnosis is missed. There is co-existing intra uterine and extra uterine pregnancy, most often tubal and rarely cervical or ovarian. It is extremely rare in spontaneous conception but incidence is increasing with the use of ART’s. Early diagnosis is difcult probably because of the lacking clinical symptoms. It usually presents as a ruptured ectopic pregnancy. Timely diagnosis and intervention is of utmost importance to prevent maternal morbidity and mortality. Abdominal pain, swelling, peritoneal irritation, enlarged uterus, vaginal bleeding, pallor, tachycardia, features of shock may be a few presenting features. With the advances in technology, transvaginal ultrasound proves to be a great diagnostic tool in early diagnosis of heterotopic pregnancy. Serum beta-hcg levels is of importance. Intervention can be medical or surgical depending on the hemodynamic condition of the patient and the viability of the intrauterine pregnancy. Heterotopic pregnancy is an unusual diagnosis and so is often ignored in the presence of an intrauterine pregnancy. But as it can prove to be life threatening so its diagnosis as a differential should always be kept in mind. Early diagnosis and prompt and effective treatment can save a life or two!

Federal clinical guidelines. Primary immunodeficiency: severe combined immunodeficiency

2020 ◽  
Vol 17 (3) ◽  
pp. 97-114
Author(s):  
Yulia A. Rodina ◽  
Elena V. Deripapa ◽  
Alexandra L. Laberko ◽  
Dmitry E. Pershin ◽  
Ekaterina V. Kalinina ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Early Diagnosis ◽  
Primary Immunodeficiency ◽  
Severe Combined Immunodeficiency ◽  
Complex Treatment ◽  
Combined Immunodeficiency ◽  
Hematopoietic Stem ◽  
Family Counselling ◽  
Life Threatening

Severe combined immunodeficiency (SCID) is the most life-threatening form of primary immunodeficiency, fatal within the first years of life if hematopoietic stem cell transplantation (HSCT) is not performed. Early diagnosis is crucial for prevention of multiple life-threatening complications, which in turn allows for successful HSCT. Current publication contains clinical recommendations for diagnosis of SCID and its complications, complex treatment, including HSCT, prenatal diagnostics and genetic family counselling.

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