Search

A woman in the 70s with a decreased appetite and weight loss (4 kg) in the last 3 months was referred to our hospital. An enhanced CT scan of the abdomen showed a hepatocellular carcinoma (HCC) of 83 mm in diameter of the liver with metastasis to the para-aortic lymph nodes, the left adrenal gland, and the right lower lung lobe (cStage IVb). She was started on atezolizumab + bevacizumab (Atezo-Bev) therapy. A week after the treatment, she began to have a decreased appetite, fever in the 39 °C range, subcutaneous bleeding, and a slight headache when walking. So she was urgently admitted to our hospital. We diagnosed her as having a hemophagocytic syndrome and administered 1 g steroid pulse therapy for 3 days followed by 1 mg/kg of prednisone. Her condition began to improve. This is the first case report of a hemophagocytic syndrome in a patient with HCC treated with Atezo-Bev. [ABSTRACT FROM AUTHOR]

Rationale: Lepromatous leprosy can have many atypical presentations, obscuring early diagnosis. We present a case of lepromatous leprosy, presenting with atypical features, which made a diagnostic dilemma. Patient concerns: A 48-year-old man presented with bilateral lower limb oedema and scaly “ichthyosis like” skin rash in both hands and feet, hepatosplenomegaly and pancytopenia, over a course of three months, without any classical features of leprosy. A skin biopsy revealed an unexpected diagnosis of borderline lepromatous leprosy. Diagnosis: Lepromatous leprosy. Interventions: Multi-drug regimen treatment with rifampicin, dapsone and clofazimine for lepromatous leprosy. Outcomes: The patient made a good clinical recovery. Lessons: In endemic settings, clinicians should be aware of similar atypical manifestations of leprosy to face the global challenge of eradicating this chronic deforming disease.

Introduction: Adult hemophagocytic lymphohistiocytosis (HLH) is a rare disease with a dismal prognosis. Early diagnosis and prompt management are necessary for improved outcomes. Methods: This multicenter retrospective study investigated the etiologies, survival, and prognostic factors of HLH, including the utility of HLH-2004 criteria and HScore in real-life clinical practice. Results: A total of 147 HLH patients were identified by using a combination of hemophagocytosis identification in bone marrow and the HLH-related international classification disease-10. A total of 116 (78.9%) patients fulfilled the HLH diagnosis by HScore, while 91 (61.9%) patients fulfilled 5 of 8 HLH-2004 criteria. In Thailand, the clinical application of HLH-2004 criteria needed to be reduced from 8 to 6 due to a lack of sCD25 and natural killer cell activity tests. Using the adapted HLH-2004 with a cutoff value of 4 resulted in 132 (89.9%) cases meeting the diagnostic criteria. Among these 132 confirmed HLH patients by using adapted HLH-2004, HLH was triggered by infection (29.5%), autoimmune disease (12.9%), malignancy (40.9%), and unknown cause (16.7%). Median overall survival of HLH patients was extremely short (67 days). Ferritin >6,000 μg/L, HLH from infection, malignancy, and unknown etiology were demonstrated as independent prognostic factors for inferior survival (hazard ratio [HR] 2.47; 95% confidence interval [CI] 1.39–4.37, HR 4.69; 95% CI 1.38–15.92, HR 6.09; 95% CI 1.84–20.14, and HR 6.02; 95% CI 1.64–22.05, respectively). Conclusion: Ferritin is a helpful biomarker for HLH diagnosis and prognostic prediction. Autoimmune disease-triggered HLH has favorable outcomes. Future prospective study is required to verify the use of the adapted HLH-2004 criteria. [ABSTRACT FROM AUTHOR]

Rationale: Lepromatous leprosy can have many atypical presentations, obscuring early diagnosis. We present a case of lepromatous leprosy, presenting with atypical features, which made a diagnostic dilemma. Patient concerns: A 48-year-old man presented with bilateral lower limb oedema and scaly "ichthyosis like" skin rash in both hands and feet, hepatosplenomegaly and pancytopenia, over a course of three months, without any classical features of leprosy. A skin biopsy revealed an unexpected diagnosis of borderline lepromatous leprosy. Diagnosis: Lepromatous leprosy. Interventions: Multi-drug regimen treatment with rifampicin, dapsone and clofazimine for lepromatous leprosy. Outcomes: The patient made a good clinical recovery. Lessons: In endemic settings, clinicians should be aware of similar atypical manifestations of leprosy to face the global challenge of eradicating this chronic deforming disease. [ABSTRACT FROM AUTHOR]

A 55-year-old man presented with dizziness and left lower limb weakness, leading to the discovery of a cerebral mass in his left frontal lobe. The mass was diagnosed as histiocytic sarcoma (HS), an exceedingly rare and aggressive hematopoietic tumor that primarily affects various parts of the body. The diagnosis was confirmed through histological examination, immunohistochemistry, and exclusion of other potential tumor lineages. The study highlights the importance of accurate diagnosis and potential therapeutic targets for HS. [Extracted from the article]

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of severe, dysregulated inflammation driven by the inability of T cells to clear an antigenic target. When associated with malignancy (mHLH), the HLH syndrome is typically associated with extremely poor survival. Here, we review the diagnosis of secondary HLH (sHLH) syndromes in adults, with emphasis on the appropriate workup and treatment of mHLH. At present, the management of HLH in adults, including most forms of mHLH, is based on the use of corticosteroids and etoposide following the HLH-94 regimen. In some cases, this therapeutic approach may be cohesively incorporated into malignancy-directed therapy, while in other cases, the decision about whether to treat HLH prior to initiating other therapies may be more complicated. Recent studies exploring the efficacy of other agents in HLH, in particular ruxolitinib, offer hope for better outcomes in the management of mHLH. Considerations for the management of lymphoma-associated mHLH, as well as other forms of mHLH and immunotherapy treatment-related HLH, are discussed.

Background: Histoplasmosis is caused by Histoplasma capsulatum which can lead to a broad spectrum of disease. Culture remains the gold standard till date; however, this is a slow-growing fungus that may take a considerable time before a conclusion can be made. This case highlights the importance of careful bone marrow evaluation to identify the fungal bodies, especially in the presence of increased hemophagocytic activity. Case Presentation: We present a 36-year-old man with newly diagnosed retroviral disease, presented with fever, pancytopenia, and hepatosplenomegaly. Bone marrow aspirate smear showed increased hemophagocytic activity with the presence of intracellular organisms. Trephine biopsy showed similar features with the presence of fungal bodies detected via Periodic acid-Schiff stain. Conclusion: In conclusion, bone marrow examination plays a crucial role in the diagnosis of some fungal infections, especially in centers where culture or serological tests are not readily available. [ABSTRACT FROM AUTHOR]

Background: Ferritin is an established biomarker in the diagnosis of secondary hemophagocytic lymphohistiocytosis (HLH), which is diagnosed by the HLH‐2004 criteria. Among these criteria, detection of hemophagocytosis through invasive procedures may delay early life saving treatment. Our aim was to investigate the value of hemophagocytosis in diagnosing HLH in critically ill patients. Methods: In this secondary analysis of a retrospective observational study, we included all patients aged ≥18 years and admitted to any adult ICU at Charité—Universitätsmedizin Berlin between January 2006 and August 2018, who had hyperferritinemia (≥500 μg/L) and underwent bone marrow biopsy during their ICU course. Results: Two hundred fifty‐two patients were included, of whom 31 (12.3%) showed hemophagocytosis. In multivariable logistic regression analysis, maximum ferritin was independently associated with hemophagocytosis. By removing hemophagocytosis from HLH‐2004 criteria and HScore, prediction accuracy for HLH diagnosis was only marginally decreased compared to the original scores. Conclusions: Our results strengthen the diagnostic value of ferritin and underline the importance of considering HLH diagnosis in patients with high ferritin but only four fulfilled HLH‐2004 criteria, when hemophagocytosis was not assessed or not detectable. Proof of hemophagocytosis is not required for a reliable HLH diagnosis. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Chediak Higashi syndrome (CHS), a rare form of autosomal recessive disorder has been reported globally in less than 500 cases over the past two decades. It clinically manifests as repeated episodes of infection, haemorrhagic sequelae, partial albinism, photosensitivity and late neurological signs (neuropathy, cognitive impairment etc). The pathognomonic morphological finding is the presence of abnormally large intra-cytoplasmic granules, particularly in leucocytes. Almost 85% of CHS cases advance into an accelerated phase, characterized by cytopenias and hemophagocytosis, leading to multi -organ failure. Case presentation: The child in the present case had consanguinity and a positive family history of recurrent infections. She had repeated episodes of bacterial infections. She also had a history of photosensitivity. CBC reported cytopenias. Peripheral smear showed neutrophi ls with characteristic large sized abnormal intra-cytoplasmic granules. Bone marrow biopsy was performed which also showed similar granules in leucocytes along with hemophagocytosis. Other clinical and biochemical markers also pointed towards hemophagocyti c lymphohistiocytosis (HLH), thus patient was diagnosed as CHS in an accelerated phase. She received eight doses of chemotherapy but eventually expired. Conclusion: The definitive treatment is hematopoietic stem cell transplantation which improves the hematological and immune aspects of CHS but not the neurological. Steps should be taken for early diagnosis and to prevent advancement into the accelerated phase. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) is the most severe type of leishmaniasis which is caused by infection of Leishmania donovani complex. In the BALB/c mouse model of VL, multinucleated giant cells (MGCs) with heavy parasite infection consist of the largest population of hemophagocytes in the spleen of L. donovani-infected mice, indicating that MGCs provide the parasites a circumstance beneficial for their survival. Although ATP6V0D2 is a demonstrated factor inducing the formation of hemophagocytic MGCs during L. donovani infection, functions of this protein in shaping the infection outcome in macrophages remain unclear. Here we evaluated the influence of upregulated ATP6V0D2 on intracellular survival of the parasites. L. donovani infectioninduced hemophagocytosis of normal erythrocytes by macrophages was suppressed by RNAi-based knockdown of Atp6v0d2. The knockdown of Atp6v0d2 did not improve the survival of amastigotes within macrophages when the cells were cultured in the absence of erythrocytes. On the other hand, reduced intracellular survival of amastigotes in macrophages by the knockdown was observed when macrophages were supplemented with antibody-opsonized erythrocytes before infection. There, increase in cytosolic labile iron pool was observed in the L. donovani-infected knocked-down macrophages. It suggests that ATP6V0D2 plays roles not only in upregulation of hemophagocytosis but also in iron trafficking within L. donovani-infected macrophages. Superior access to iron in macrophages may be how the upregulated expression of the molecule brings benefit to Leishmania for their intracellular survival in the presence of erythrocytes. [ABSTRACT FROM AUTHOR]

Hemophagocytic syndrome is a key point in the pathogenesis of severe forms of multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C). The factors associated with hemophagocytosis in patients with MIS-C were assessed in the present study of 94 boys and 64 girls ranging in age from 4 months to 17 years, each of whose HScore was calculated. In accordance with a previous analysis, patients with HScore ≤ 91 (n = 79) and HScore > 91 (n = 79) were compared. Patients with HScore > 91 had a higher frequency of symptoms such as cervical lymphadenopathy, dry cracked lips, bright mucous, erythema/swelling of hands and feet, peeling of fingers, edematous syndrome, hepatomegaly, splenomegaly, and hypotension/shock. They also had a higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and D-dimer levels, and a tendency to anemia, thrombocytopenia, and hypofibrinogenemia. They more often needed acetylsalicylic acid and biological treatment and were admitted to ICU in 70.9% of cases. Conclusion: The following signs of severe MIS-C were associated with HScore > 91: myocardial involvement, pericarditis, hypotension/shock, and ICU admission. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition that has been increasingly recognized in adults and is characterized by a hyperinflammatory state due to immune dysregulation. Its nonspecific presentation, the lack of clinician familiarity given its rarity, and shared clinical features with sepsis and other syndromes can lead to a delay in diagnosis and a poor prognosis. Significant liver function abnormalities as the initial manifestation of HLH are uncommon and can range from mild elevation of aminotransferases to fulminant hepatic failure with high mortality rates. The authors encountered a case of adult HLH mimicking acute viral hepatitis in which a markedly elevated ferritin level led to a prompt diagnosis, early initiation of treatment, and a successful outcome. Clinicians, including gastroenterologists and hepatologists, are often called upon to evaluate patients with abnormal liver tests and may lack experience in the early diagnosis and management of liver dysfunction in the context of HLH. Thus, we expand our reporting to a narrative review of literature which explores the pathogenesis of HLH, challenges associated with its diagnosis, previous reports of liver disease associated with the syndrome, recommended treatments for the familial and adult variations including the role of liver transplantation, and the outcomes of these treatments. [ABSTRACT FROM AUTHOR]

Background: Hemophagocytic syndrome or hemophagocytic lymphohistiocytosis (HL) is an immune hyperactivation of multifactorial etiology, characterized by excessive activation of lymphocytes and macrophages, as well as numerous pro-inflammatory cytokines. It has a non-specific and highly variable clinical presentation, with splenomegaly being one of the clinical manifestations. Due to its nature, it can manifest during childhood or adult life, which is why it is a disease of diagnostic and therapeutic complexity. Clinical case: 38-year-old male patient without comorbidities, who presented with abdominal pain, choluria, fever > 38 °C and diaphoresis of more than 10 days of evolution. A bone marrow aspirate was performed as part of the diagnostic approach with data compatible with hemophagocytosis and cytopenias. The immunosuppressive management did not show the expected response, which is why an open splenectomy was performed as the last therapeutic option with adequate hematological control. A documentary review of the disease was carried out, and of the therapeutic options, emphasizing surgical management in case of refractoriness to medical treatment. Conclusions: Splenectomy increases the overall survival rate and the time free of HL progression, even though there are still no studies to determine with certainty the ideal time to perform a splenectomy in patients with pancytopenia without splenomegaly who suffer from hemophagocytic syndrome. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition due to extensive and uncontrolled immune activation. There is sparse literature on HLH in kidney transplant recipients. We report a case of a 27-year -old male kidney transplant recipient who presented with dengue fever and acute allograft dysfunction. Following improvement in allograft function with supportive treatment, he was found to have worsening pancytopenia with unusually high serum ferritin levels. Bone marrow aspiration performed for pancytopenia revealed hemophagocytosis. A diagnosis of HLH secondary to dengue viral infection was made based on the modified HLH diagnostic criteria (2009). He received supportive treatment and steroids and was discharged in a stable condition with normal kidney allograft functions. To our knowledge, this is the first case report of HLH secondary to dengue viral infection in a kidney allograft recipient managed successfully with timely diagnosis and appropriate treatment. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) is the most severe type of leishmaniasis which is caused by infection of Leishmania donovani complex. In the BALB/c mouse model of VL, multinucleated giant cells (MGCs) with heavy parasite infection consist of the largest population of hemophagocytes in the spleen of L. donovani-infected mice, indicating that MGCs provide the parasites a circumstance beneficial for their survival. Although ATP6V0D2 is a demonstrated factor inducing the formation of hemophagocytic MGCs during L. donovani infection, functions of this protein in shaping the infection outcome in macrophages remain unclear. Here we evaluated the influence of upregulated ATP6V0D2 on intracellular survival of the parasites. L. donovani infection-induced hemophagocytosis of normal erythrocytes by macrophages was suppressed by RNAi-based knockdown of Atp6v0d2. The knockdown of Atp6v0d2 did not improve the survival of amastigotes within macrophages when the cells were cultured in the absence of erythrocytes. On the other hand, reduced intracellular survival of amastigotes in macrophages by the knockdown was observed when macrophages were supplemented with antibody-opsonized erythrocytes before infection. There, increase in cytosolic labile iron pool was observed in the L. donovani-infected knocked-down macrophages. It suggests that ATP6V0D2 plays roles not only in upregulation of hemophagocytosis but also in iron trafficking within L. donovani-infected macrophages. Superior access to iron in macrophages may be how the upregulated expression of the molecule brings benefit to Leishmania for their intracellular survival in the presence of erythrocytes.

Le syndrome d'activation macrophagique (SAM) est l'une des complications graves de la maladie de Still tant chez l'enfant que chez l'adulte. Dans l'état actuel des connaissances, sa pathogénie implique l'activation d'acteurs de l'immunité à la fois innée et acquise, notamment les monocytes, les cellules NK et certaines populations lymphocytaires CD8 positives. L'interleukine 18 (IL-18) et l'interféron γ (IFN-γ) semblent jouer un rôle central. La détection d'un SAM doit être une préoccupation constante au cours de la maladie de Still. Les signes d'alerte sont l'apparition d'une cytopénie d'une ou plusieurs lignées sanguines, l'augmentation progressive des enzymes hépatiques, des LDH, des triglycérides et de la ferritine sérique, la chute du fibrinogène et l'activation des voies de coagulation. Le diagnostic de SAM peut être facilité par l'utilisation de scores spécifiques du SAM (H ou M scores) ou des critères de classification. Le traitement du SAM varie selon sa sévérité et peut comprendre les glucocorticoïdes par voie intraveineuse à forte dose, les immunoglobulines polyvalentes par voie intraveineuse, les inhibiteurs de la voie de l'IL-1 tel que l'anakinra, la ciclosporine, voire des inhibiteurs de la voie de l'IFN-γ. L'utilisation de l'étoposide (VP-16) est réservée aux formes les plus graves. Macrophage activation syndrome (MAS) is one of the serious complications of Still's disease in both children and adults. According to current knowledge, its pathogenesis involves the activation of both innate and acquired immune players, notably monocytes, NK cells and specific CD8-positive lymphocyte populations. Interleukin 18 (IL-18) and interferon γ (IFN-γ) appear to play a central role. The detection of MAS should be a constant concern in Still's disease. Warning signs include the occurrence of cytopenia of one or more cell lines, a progressive increase in liver enzymes, LDH, triglycerides and serum ferritin, a fall in fibrinogen and activation of coagulation pathways. Diagnosis of MAS can be facilitated by the use of specific MAS scores (H or M scores) or classification criteria. MAS treatment varies according to its severity, and may include high-dose intravenous glucocorticoids, intravenous polyvalent immunoglobulins, inhibitors of the IL-1 pathway such as anakinra, ciclosporin, or even inhibitors of the IFN-γ pathway. Etoposide (VP-16) is reserved for the most severe forms. [ABSTRACT FROM AUTHOR]

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a disease of multi-organ dysfunction due to excessive immune activation causing widespread inflammation and tissue destruction. It is a severe condition associated with high morbidity and mortality. Early identification is crucial for prompt treatment. The objective of this case series is to underscore the intricacy of managing HLH in individuals with renal dysfunction. Methods: This is a retrospective study of patients diagnosed with HLH in a nephrology department over a period of 30 years. We retrospectively reviewed the medical files by applying the Revised HLH-2004 criteria. Results: Among the 14 female patients included, the mean age was 45.2 years (range 23-78). Nine patients presented with sudden onset of fever and chills. Physical examination revealed purpura in 3 cases, hepatomegaly and splenomegaly in 6 and 5 cases respectively, and peripheral lymphadenopathy in 1 case. Hemorrhagic complications were observed in 5 cases, hypertriglyceridemia in 9 cases, and hyperferritinemia in all cases. Hypothyroidism was observed in all cases, and impaired renal function was detected in 11 of them, with 5 experiencing it as a result of lupus nephritis, and 1 case attributed to pre-eclampsia. Hemophagocytosis was confirmed through sternal puncture in 11 cases. Treatment involved etiological therapy with corticosteroids and immunosuppressants and/or anti-infectives. Intravenous immunoglobulins were administered in 6 cases, while 2 cases required coagulation factor transfusions. Unfortunately, 9 patients did not survive. Conclusion: The study highlights the need for increased awareness and prompt recognition of HLH, particularly in patients with associated renal complications. [ABSTRACT FROM AUTHOR]

Abstract Background Fulminant hemolytic streptococcal infection is a condition of sudden onset and rapidly progressing septic shock caused by Streptococcus pyogenes. It causes beta (complete) hemolysis. Although type A Streptococcus occurs more frequently, all streptococci that cause beta-hemolysis are eligible as causes. This report describes a rare autopsy case of fulminant group A streptococcal infection in a neonate. Case presentation A 16-day-old girl, 3300 g, born by spontaneous delivery at 41 weeks 1 day, experienced a 1-day history of low-grade fever, malaise, and a few hours of cyanosis and anuria, prompting her parents to bring her to the hospital. Her eldest brother, who lived with her, had been infected with Streptococcus approximately one month earlier, and had been treated with ten days of antibiotics. The infant died three hours after presentation. Autopsy findings indicated her to be 52 cm in length, weighing 3585 g, with medium build and normal nutrition. Her lungs were slightly oligemic with decreased volumes. The liver and kidneys were mildly enlarged. The spleen was markedly enlarged. The adrenal glands showed diffuse cortical hemorrhage (Fig. 1). There was some thymic atrophy (thymus weight 7.4 g,

Background: Fulminant hemolytic streptococcal infection is a condition of sudden onset and rapidly progressing septic shock caused by Streptococcus pyogenes. It causes beta (complete) hemolysis. Although type A Streptococcus occurs more frequently, all streptococci that cause beta-hemolysis are eligible as causes. This report describes a rare autopsy case of fulminant group A streptococcal infection in a neonate. Case presentation: A 16-day-old girl, 3300 g, born by spontaneous delivery at 41 weeks 1 day, experienced a 1-day history of low-grade fever, malaise, and a few hours of cyanosis and anuria, prompting her parents to bring her to the hospital. Her eldest brother, who lived with her, had been infected with Streptococcus approximately one month earlier, and had been treated with ten days of antibiotics. The infant died three hours after presentation. Autopsy findings indicated her to be 52 cm in length, weighing 3585 g, with medium build and normal nutrition. Her lungs were slightly oligemic with decreased volumes. The liver and kidneys were mildly enlarged. The spleen was markedly enlarged. The adrenal glands showed diffuse cortical hemorrhage (Fig. 1). There was some thymic atrophy (thymus weight 7.4 g, < 1 SD below the mean). Histopathological findings included chronic and neutrophilic infiltration of the tonsils and multiple septic emboli containing cocci in the lungs. Perivascular inflammatory cell infiltrates were observed in the lungs, myocardium, kidneys, adrenal glands, brain, meninges, and liver, with micro-necrotic changes in the kidneys and liver. Fibrin thrombi were observed in multiple renal glomeruli. Hemophagocytosis by macrophages was observed in the spleen, liver, lymph nodes, bone marrow, and adrenal glands. Immunostaining showed positive results for group A Streptococcus antibody in the tonsils, with bacterial masses. Blood cultures were positive for group A Streptococcus pyogenes. Conclusions: Because of the lower respiratory tract infection and suspected sibling transmission, in addition to the adrenal hemorrhages, a diagnosis of fulminant sepsis with group A Streptococcus pyogenes with associated Waterhouse–Friderichsen syndrome was made. [ABSTRACT FROM AUTHOR]

A 10‐year‐old spayed female domestic short‐haired cat presented with depression, anorexia, and tachypnea. A complete blood count revealed moderate regenerative anemia, severe leukopenia, and mild thrombocytopenia. Antibodies against feline immunodeficiency virus (FIV) were also detected. Abdominal radiography and ultrasonography revealed severe splenomegaly. Cytologic evaluation of the spleen revealed macrophagic infiltration with hemophagocytosis. Bone marrow aspiration revealed erythroid hyperplasia with no other abnormalities. A presumptive diagnosis of hemophagocytic syndrome secondary to immune‐mediated hemolytic anemia was made based on a positive direct Coombs test result. Blood transfusion, prednisolone, and immunosuppressive treatments were performed; however, the blood abnormalities did not improve. The cat was then administered prednisolone and chlorambucil, followed by splenectomy. Leukopenia immediately recovered, and packed cell volume increased slightly. However, the blood abnormalities recurred, and the cat died. To the best of our knowledge, this is the first report of hemophagocytic syndrome secondary to immune‐mediated disease in an FIV‐positive cat. [ABSTRACT FROM AUTHOR]

Background and Aims: While dengue infection is common in India, there is scarce information on dengue hepatitis. The aim of this study was to analyze the incidence, spectrum and outcome of dengue hepatitis. Methods: We retrospectively analyzed consecutive patients, who had hepatitis among those with dengue infection admitted to two tertiary care hospitals in western India from January 2016 to March 2021. Diagnosis of dengue infection was made by serology. Dengue hepatitis was diagnosed and the severity of dengue was categorized by standard criteria. Results: Of 1664 patients admitted with dengue fever during the study period, 199 patients had hepatitis (i.e. incidence of dengue hepatitis was 11.9%). Of the 199 dengue hepatitis patients (age: 29 [13 – 80] years, median [range], 67% males), 100 patients (50%) had severe dengue, 73 (36%) had severe dengue hepatitis, 32 (16%) had dengue shock syndrome and eight (4%) had acute liver failure. Forty-five patients (23%) had acute lung injury and 32 (16%) had acute kidney injury. The dengue hepatitis patients were treated with standard medical care, including vital organ support, as needed—166 (83%) patients survived, while 33 patients (17%) died (cause of death: multi-organ failure: 24 patients, septic shock: nine patients). The presence of shock independently predicted mortality (odds ratio 6.4, 95% confidence interval: 1.2 – 34). Among patients with dengue hepatitis, mortality rate was higher in those with severe dengue (23%), dengue shock syndrome (47%), severe dengue hepatitis (24%) and acute liver failure (38%). Conclusion: In this large series of hospitalized patients with dengue infection, the incidence of dengue hepatitis was 11.9%. Among 199 dengue hepatitis, 17% died; multi-organ failure was the commonest cause for death and death rate was higher in patients with more severe disease. The presence of shock at presentation independently predicted mortality. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a complex, often under-recognized hyperinflammatory immune dysregulation syndrome arising in a diverse range of clinical scenarios and conditions. The accurate and timely diagnosis of HLH is crucial for patient survival, and usually requires a high level of clinical suspicion. The histologic corollary to clinical HLH – hemophagocytosis – is neither necessary or sufficient for the diagnosis of HLH, as it may be seen in a variety of reactive conditions, or may be absent in true HLH. Nevertheless, the finding of hemophagocytosis in specific clinical situations should prompt the consideration of HLH and further testing to exclude the condition. While traditionally described in bone marrow, identification of hemophagocytosis in other tissues, including lymphoid, splenic, liver, or neural tissue, can be an important asset to the overall recognition of HLH. In this review, we discuss the underlying pathophysiology and etiologies of, morphologic aspects hemophagocytosis and its associated histologic findings in different tissues and give a brief overview of diagnostic criteria and clinical evaluation. [ABSTRACT FROM AUTHOR]

Introduction: Secondary hemophagocytic syndrome (HPS) and systemic inflammatory response syndrome (SIRS) share similar clinical findings as a result of hyperinflammation. Due to high mortality rates in HPS; it is critical to diagnose promptly. Thus, this study aimed to evaluate the diagnostic and prognostic significance of inflammatory markers in these two increased inflammatory states. Methods: We conducted a prospective observational study including patients hospitalized in the intensive care unit of the Internal Medicine Department of Ege University Hospital. Results: Thirty‐three patients with HPS and 46 patients with SIRS were evaluated. Serum ferritin and sIL‐2r levels were significantly higher in the HPS group than in the SIRS group, as expected. Receiver operating curve (ROC) analysis showed that the optimal cutoff for ferritin to distinguish HPS from SIRS was 1703 μg/L (sensitivity: 75%, specificity: 94.1%, area under the curve (AUC): 0.871, p < 0.001), and that for sIL‐2r was 5888 U/ml (sensitivity: 45.5%, specificity: 89.1%, AUC: 0.698, and p = 0.001). Temporal changes (Δ) in ferritin were determined as a mortality predictor. When evaluated in terms of prognostic significance in ROC analysis, a decrease in ferritin of less than 38% was the cutoff value (sensitivity: 92.3%, specificity: 76.9%, AUC: 0.888, and p < 0.001), in mortality. Contrarily, neither baseline nor temporal change in sIL‐2r did not achieve prognostic significance as a mortality predictor. Conclusion: In this single‐center study, serum ferritin level was found to be a particularly more valuable diagnostic and prognostic marker than sIL‐2r in patients with HPS. [ABSTRACT FROM AUTHOR]

Asciminib, a "Specifically Targeting the ABL Myristoyl Pocket" inhibitor, is a new drug in the treatment of tyrosine kinase inhibitor (TKI) resistant chronic myeloid leukemia (CML). Hemocytopenias associated with asciminib are common adverse events documented by clinical trials. We report a case of precipitous onset pancytopenia with the initiation of asciminib treatment in a patient with TKI resistant CML. This case had a confounding array of laboratory findings that evidenced a drug induced hemophagocytic component. We hope that our case stimulates further reporting of similar cases to enhance the understanding of the pathophysiology underlying asciminib induced hemocytopenias. [ABSTRACT FROM AUTHOR]

Background: Dengue fever is a mosquito-borne infectious disease endemic in over 100 countries around the world. Among the complications that dengue can cause the Hemophagocytic Lymphohistiocytosis is one of great concern for its severity and complex diagnosis. Case report: Hereby we document a case of this disease expressed on a previously healthy 6-year-old female patient whose dengue infection was so severe that needed intensive care management with vasoactive drugs and diuretics. After a short period of wellness began newly with fever, pancytopenia, hepatitis, and inflammatory response symptoms. Discussion: A Dengue associated Hemophagocytic Lymphohistiocytosis syndrome was suspected and treated with intravenous corticosteroids on a 3-day scheme at no signs of malignancy with excellent response. The health care professionals must know about this not novel entity in order to reach an efficient diagnosis and treatment mostly, but not only, those in tropical and sub-tropical regions of the word were dengue virus is endemic.

Hemophagocytic syndrome is a key point in the pathogenesis of severe forms of multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C). The factors associated with hemophagocytosis in patients with MIS-C were assessed in the present study of 94 boys and 64 girls ranging in age from 4 months to 17 years, each of whose HScore was calculated. In accordance with a previous analysis, patients with HScore ≤ 91 (n = 79) and HScore > 91 (n = 79) were compared. Patients with HScore > 91 had a higher frequency of symptoms such as cervical lymphadenopathy, dry cracked lips, bright mucous, erythema/swelling of hands and feet, peeling of fingers, edematous syndrome, hepatomegaly, splenomegaly, and hypotension/shock. They also had a higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and D-dimer levels, and a tendency to anemia, thrombocytopenia, and hypofibrinogenemia. They more often needed acetylsalicylic acid and biological treatment and were admitted to ICU in 70.9% of cases. Conclusion: The following signs of severe MIS-C were associated with HScore > 91: myocardial involvement, pericarditis, hypotension/shock, and ICU admission.

Leishmaniasis is a cause of infection associated with hemophagocytic lymphohistiocytosis (HLH). The measurement of the CD8+ CD38high/HLA-DR+ T cells in children presenting with acute onset of shock and multisystem organ failure represents an important parameter to distinguish HLH from sepsis or healthy control. Conclusion: We report a case series of 4 Italian children suffering from HLH secondary to visceral Leishmaniasis in which the lymphocyte subset assay suggests a potential role of CD38high/HLA-DR+ CD8+ T cells as HLH diagnostic biomarkers. What is Known: • Visceral Leishmaniasis is a well-known cause of infection associated with hemophagocytic lymphohistiocytosis (HLH). • The measurement of the CD8+CD38high/HLA-DR+T cells in children presenting with acute onset of shock and multisystem organ failure represents an important diagnostically useful parameter to readily distinguish HLH from sepsis or healthy controls. What is New: • We report a case series of 4 Italian children suffering from HLH secondary to visceral Leishmaniasis in which the lymphocyte subset assay suggests a potential role of CD38high/HLA-DR+CD8+T cells as HLH diagnostic biomarker. • The flow cytometry assay, performed at the disease onset before starting treatment, revealed a mean percentage value of CD38 cells of 36.95% among CD8+T cells. [ABSTRACT FROM AUTHOR]

Hemophagocytic Lymphohistiocytosis syndrome is fatal hyper‐inflammatory condition due to over‐activation of the immune system, being of primary and secondary types. This case report emphasizes the difficulty and challenge in and of the HLH diagnosis, and therapy should be employed promptly given the high mortality associated with HLH. Hemophagocytic Lymphohistiocytosis is a rare and often fatal inflammatory disease that requires high suspicion in any patient with fever, unexplained cytopenia, splenomegaly and increased inflammatory markers. If diagnosed, treatment should be administered promptly without delay. [ABSTRACT FROM AUTHOR]

Abstract Hemophagocytic Lymphohistiocytosis syndrome is fatal hyper‐inflammatory condition due to over‐activation of the immune system, being of primary and secondary types. This case report emphasizes the difficulty and challenge in and of the HLH diagnosis, and therapy should be employed promptly given the high mortality associated with HLH.

An 83-year-old woman with asymptomatic pulmonary sarcoidosis presented to our hospital with fever and malaise for three months. Abdominal CT showed splenomegaly, and bone marrow examination revealed non-caseating granulomas. Pancytopenia was diagnosed due to bone marrow and splenic lesions of sarcoidosis. Steroid pulses were administered, but the patient died without response to treatment. Pathological autopsy results showed non-caseating granulomas and hemophagocytosis in the spleen and bone marrow. This suggested hemophagocytic syndrome, which was not suspected before death, in addition to sarcoidosis. In patients with splenomegaly and pancytopenia with history of pulmonary sarcoidosis, hemophagocytic syndrome should be considered in differential diagnosis.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper activation of the immune system. Rare cases associated with HELLP syndrome and other similar conditions in pregnancy have been reported. Despite the improved survival rates with etoposide and dexamethasone-based regimens, HLH remains a challenging disease. Experience in pregnant patients is exceedingly rare.

Hemophagocytic Lymphohistiocytosis (HLH) is a rare life‐threatening condition characterized by widespread activation of the immune system leading to tissue damage all over the body. It is divided into primary HLH due to inborn error in lymphocytes, T cells, and macrophages and secondary HLH which is mostly due to infections, systemic connective tissue diseases, and lymphoid malignancies. Here, we report a 34‐year‐old man with a history of high‐grade fever, chills, and rigor, eschar, splenomegaly with the laboratory findings of thrombocytopenia, hypochromic RBCs with anisocytosis and basophilic stippling, elevated transaminases, and a positive Weil Felix test along with positive PCR results for Orientia tsutsugamushi and the presence of IgG and IgM antibodies. A detailed workup was done to rule out other etiology for fever. Diagnosis of HLH secondary to Rickettsia infection was made with a thorough history, clinical evaluation, and a variety of investigations. The patient was treated with Doxycycline, Ciprofloxacin, Etoposide, and Dexamethasone but unfortunately, the patient died during treatment due to multiorgan failure. Patients with scrub typhus typically respond well to therapy; therefore, early detection and antibiotic treatment can help avoid serious complications. Scrub typhus with the hemophagocytic syndrome can result in DIC and multiorgan failure. Despite its rarity, scrub typhus may be lethal; as a result, practitioners must be aware of the necessity of detecting and treating suspected cases as soon as possible. We learned that a systematic diagnostic approach, use of diagnostic criteria, and prompt treatment are very crucial in this disease. [ABSTRACT FROM AUTHOR]

Hemocytes in the hemolymph of insects perform innate immunity, but systematic studies to compare immunotoxicity of pesticides on hemocytes are still few. In this study, an insect hemocyte system was used to assess the impact of pesticides with different modes of action, which included loss of cell viability, inhibition of hemophagocytosis, and reduction of nitric oxide synthase (NOS) activity. Results showed that piericidin A was the most cytotoxic to hemocytes, chlorfluazuron and hexaflumuron were the next. Also, piericidin A, chlorfenapyr, and fipronil had strong inhibitory effects on hemophagocytosis, and the effects of piericidin A and chlorfenapyr were persistent, while that of fipronil was short-lived. Moreover, fenoxycarb and hexaflumuron selectively inhibited granulocyte phagocytosis, tebufenozide only showed inhibition on plasmatocyte phagocytosis, but both inhibitory effects were transient. Furthermore, fenoxycarb and hexaflumuron showed a short-term strong inhibitory effect on the activity of NOS, chlorfenapyr and piericidin A showed a weak induction of NOS activity, while other pesticides exhibited a strong induction. Taken together, piericidin A was the most toxic and imidacloprid was the least toxic to hemocytes, and the alterations in hemocyte functions compromised immunity. [ABSTRACT FROM AUTHOR]

Hemophagocytic disorders are severe and life-threatening conditions that can be genetic in origin [i.e., primary hemophagocytic lymphohistiocytosis (HLH)] or result from infections (i.e., secondary hemophagocytic lymphohistiocytosis), rheumatologic disease [i.e., macrophage activation syndrome (MAS)], and less frequently immunodeficiency or metabolic disease. Although rare, drug-induced hemophagocytosis needs to be considered in the work-up as it requires specific management strategies. Most drug-induced hemophagocytic disorders are related to Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). We present the case of a 7-year-old girl who initially presented with fever, maculopapular rash, and unilateral lymphadenopathy, who went on to develop hemophagocytosis secondary to DRESS caused by prolonged combination treatment with amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole. This case illustrates the importance of considering adverse drug reactions in the evaluations of patients with a hemophagocytic process. [ABSTRACT FROM AUTHOR]

Acne fulminans is a severe form of acne with a sudden onset, rapid ulceration of the lesions, and some systemic symptoms, with or without systemic symptoms. These papulopustular lesions, whose pathogenesis is not fully understood, may exacerbate with systemic isotretinoin or may be a component of some autoinflammatory syndromes. It is recommended to control these sudden pustular attacks with systemic steroids or anti‐inflammatory drugs. Here, in 12 patients with acne fulminans who developed exacerbation during systemic isotretinoin treatment and whose cytological examination revealed hemophagocytosis, colchicine treatment was started in addition to low‐dose isotretinoin treatment, and a very good response was obtained to this treatment approach that did not contain systemic corticosteroids. [ABSTRACT FROM AUTHOR]

Objective: An association exists between immune checkpoint inhibitors and hemophagocytic lymphohistiocytosis (HLH). Therefore, the main objective of this study was to collect data on this rare but potentially life-threatening immune-related adverse reaction to identify the medications that cause it, the clinical characteristics, and effective treatments., Methods: Literature in English and Chinese on immune checkpoint inhibitors causing HLH published from August 2014 to March 2024 was analyzed. Immune checkpoint inhibitors, immunotherapy, anti-PD-1, PD-L1 inhibitors, HLH, hemophagocytic lymphohistiocytosis, hemophagocytic syndrome keywords were used to find the literature on China Knowledge Network, Wanfang, PubMed and Emabase Databases., Results and Discussion: Twenty-four studies were included, with a total of 27 patients (18 males and 9 females) with a mean age of 58 years (range 26-86). The mean time to the onset of symptoms was 10.3 weeks (7 days-14 months). The main clinical characteristics were fever, cytopenia, splenomegaly, methemoglobinemia, hypofibrinogenemia, and bone marrow biopsy showed phagocytosis. Twenty-two patients improved after the treatment with steroids, cytokine blocking therapy and symptomatic treatment, four patients died, and one patient was not described., Conclusion: HLH should be not underestimated as a potentially serious adverse effect of immune checkpoint inhibitors since appropriate treatments may save the life of patients.

Objective: Macrophage activation syndrome (MAS) is characterized by multi-lineage cytopenias, hypercytokinemia, and tissue hemophagocytosis. Transcription factor Nrf2 is a master regulator of redox homeostasis. In this work we aim to investigate the role of Nrf2 in murine hyperinflammation and the mechanisms by which Nrf2 activation by red blood cell products regulates pro-inflammatory cytokine production., Methods: We induce murine MAS in wildtype and Nrf2 knockout (Nrf2 -/-) mice by repeat administration of TLR9-agonist CpG. Clinical and biochemical markers of disease were measured including complete blood counts, liver and spleen pathology, serum free heme, ferritin, and cytokine profiles. In vitro bone marrow derived macrophages and dendritic cells were used to investigate regulation of CpG-induced cytokine expression by oxidized red blood cells and hemin., Results: Patients with hyperinflammatory disease have higher levels of Nrf2 gene expression. Mice with CpG-induced hyperinflammation have elevated systemic lipid peroxidation which is exacerbated in Nrf2 -/- mice. Compared to wildtype controls, Nrf2 -/- mice develop significantly worse organomegaly, organ pathology, and reticulocytosis. Nrf2 -/- mice have exacerbated hypercytokinemia in cytokines central MAS physiology: IL-12, IFNg, and IL-10. In vitro we found that oxidized red blood cell lysates and hemin are able to suppress IL-12 transcription and protein production from bone marrow derived dendritic cells in a Nrf2-dependent manner., Conclusion: Together our findings show that transcription factor Nrf2 is highly expressed in patients with hyperinflammatory disease and demonstrate a protective role for Nrf2 in a murine model of MAS in part due to Nrf2-mediated suppression of proinflammatory cytokine production., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Abstract Background Secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare and fatal disease characterized by uncontrolled immune cell activation that can lead to a cytokine storm. Unfortunately, this condition can occur even during pregnancy, threatening both maternal and fetal lives. Case presentation A 23-year-old nulliparous woman at 26 weeks of gestation presented with continuous fever, coughing, and sore throat. Upon arrival at our hospital, her temperature was >38°C and laboratory findings indicated cytopenia (neutrophil count, 779/μL; hemoglobin level, 10.2 g/dL; platelet count, 29,000/μL), elevated ferritin level (1,308 ng/mL), and elevated soluble interleukin-2 receptor level (11,200 U/mL). Computed tomography showed marked splenomegaly. Bone marrow examination revealed hemophagocytosis, and blood examination showed a plasma Epstein–Barr virus (EBV) DNA level of 8.9 × 105 copies/μg. The monoclonal proliferation of EBV-infected T cells was confirmed by Southern blotting, and the patient was diagnosed with chronic active EBV-associated sHLH and T-cell lymphoproliferative disease. Immediately after admission, the patient’s condition suddenly deteriorated. She developed shock and disseminated intravascular coagulation, requiring endotracheal intubation along with methylprednisolone pulse and etoposide therapy. Although the patient recovered, she delivered a stillborn baby. After delivery, she was treated with reduced-dose dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC) and steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapies. Five months after diagnosis, she received human leukocyte antigen-haploidentical allogeneic bone marrow transplantation from her sister. She remains in remission for 5 months from the time of transplantation to the present. Conclusions sHLH, which may cause maternal and fetal death, should be carefully considered in critically ill pregnant women, particularly those presenting with continuous fever and cytopenia.

Abstract Hemophagocytic Lymphohistiocytosis (HLH) is a rare life‐threatening condition characterized by widespread activation of the immune system leading to tissue damage all over the body. It is divided into primary HLH due to inborn error in lymphocytes, T cells, and macrophages and secondary HLH which is mostly due to infections, systemic connective tissue diseases, and lymphoid malignancies. Here, we report a 34‐year‐old man with a history of high‐grade fever, chills, and rigor, eschar, splenomegaly with the laboratory findings of thrombocytopenia, hypochromic RBCs with anisocytosis and basophilic stippling, elevated transaminases, and a positive Weil Felix test along with positive PCR results for Orientia tsutsugamushi and the presence of IgG and IgM antibodies. A detailed workup was done to rule out other etiology for fever. Diagnosis of HLH secondary to Rickettsia infection was made with a thorough history, clinical evaluation, and a variety of investigations. The patient was treated with Doxycycline, Ciprofloxacin, Etoposide, and Dexamethasone but unfortunately, the patient died during treatment due to multiorgan failure. Patients with scrub typhus typically respond well to therapy; therefore, early detection and antibiotic treatment can help avoid serious complications. Scrub typhus with the hemophagocytic syndrome can result in DIC and multiorgan failure. Despite its rarity, scrub typhus may be lethal; as a result, practitioners must be aware of the necessity of detecting and treating suspected cases as soon as possible. We learned that a systematic diagnostic approach, use of diagnostic criteria, and prompt treatment are very crucial in this disease.

Hemophagocytic disorders are severe and life-threatening conditions that can be genetic in origin [i.e., primary hemophagocytic lymphohistiocytosis (HLH)] or result from infections (i.e., secondary hemophagocytic lymphohistiocytosis), rheumatologic disease [i.e., macrophage activation syndrome (MAS)], and less frequently immunodeficiency or metabolic disease. Although rare, drug-induced hemophagocytosis needs to be considered in the work-up as it requires specific management strategies. Most drug-induced hemophagocytic disorders are related to Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). We present the case of a 7-year-old girl who initially presented with fever, maculopapular rash, and unilateral lymphadenopathy, who went on to develop hemophagocytosis secondary to DRESS caused by prolonged combination treatment with amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole. This case illustrates the importance of considering adverse drug reactions in the evaluations of patients with a hemophagocytic process.

Leishmaniasis is caused by infection with protozoan parasites of the genus Leishmania. In both clinical and experimental visceral leishmaniasis, macrophage multinucleation is observed in parasitized tissues. However, the feature and the mechanism of macrophage multinucleation remained unclear. Here, we report that infection of Leishmania donovani, a causative agent of visceral leishmaniasis, induces multinucleation of bone marrow-derived macrophages (BMDMs) in vitro. When these infection-induced multinucleated macrophages were compared with cytokine-induced multinucleated giant cells, the former had higher phagocytic activity on red blood cells but no apparent changes on phagocytosis of latex beads. BMDMs infected with L. donovani had increased expression of ATP6V0D2, one of the components of V-ATPase, which was also upregulated in the spleen of infected mice. Infection-induced ATP6V0D2 localized in a cytoplasmic compartment, which did not overlap with the mitochondria, endoplasmic reticulum, or lysosomes. When ATP6V0D2 expression was recombinantly induced in BMDMs, the formation of multinucleated macrophages was induced as seen in the infected macrophages. Taken together, L. donovani infection induces multinucleation of macrophages via ATP6V0D2 upregulation leading to a unique metamorphosis of the macrophages toward hemophagocytes. [ABSTRACT FROM AUTHOR]

The information about toxic effects of thiamethoxam on non-target aquatic organisms is still incomplete. The semi-static toxicity test method was used to investigate the acute toxic effects of thiamethoxam on Eriocheir sinensis. The results showed that the median lethal concentration (LC50) of thiamethoxam to E. sinensis at 96 h was 510 μg/L, and the safety concentration (SC) was 51 μg/L. After 96 h exposure to thiamethoxam, the survival rates of crabs at concentrations of 0, 151.11, 226.67, 340, and 510 μg/L were 100%, 76.19%, 64.29%, 61.91%, and 46.43%, respectively. A significant (P < 0.05) decrease of the number of hemocytes was observed in thiamethoxam groups. With the increase of thiamethoxam concentration, the phagocytic activity of hemocytes, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and the activities of protease, amylase, and lipase of crabs increased firstly and then decreased, and the above indexes reached the maximum in 151.11 μg/L thiamethoxam group. Collectively, a high concentration of thiamethoxam (510 μg/L) had a great effect on the gene expression of immune metabolism-related factors in hepatopancreas and gill of crabs. These findings indicated that thiamethoxam exposure had the ability to impair immune and metabolic systems and resulted in the reduction of survival rate of crabs. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by prolonged fever, cytopenia, hepatosplenomegaly, and hemophagocytosis. This occurs as a result of activated macrophages and impaired function of natural killer cells and/or cytotoxic T lymphocytes. The NF-κB pathway plays a crucial role in hyperinflammation. Matrin3 (MATR3) is a nuclear RNA/DNA-binding protein that plays multiple roles in the regulation of gene expression. We enroll 62 patients diagnosed with secondary HLH and hemophagocytosis. Peripheral blood (PB) from 25 patients and 30 healthy volunteers and good quality bone marrow (BM) samples from 47 patients are collected and used for analysis. Clinical parameters, including age, sex, etiology, ferritin, fibrinogen, triglyceride, and viral infection status, had no association with survival prediction. Patients with downregulation of NF-κB and MATR3mRNA expression in the BM had a higher mortality rate. MATR3mRNA expression in PB was lower in patients compared to that in healthy volunteers. We use shRNA-MATR3-KD-THP1 cells to determine the efficacy of phagocytosis. We note that shRNA-MATR3-KD-THP1 cells had a higher phagocytic effect on necrotic Jurkat E6 cells and carboxylate modified polystyrene latex beads. Herein, we provide evidence of a new marker for clinical translation that can serve as a potential treatment target for secondary HLH. [ABSTRACT FROM AUTHOR]