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Abstract Cytokine storm syndromes such as hemophagocytic lymphohistiocytosis (HLH), Adult-onset Still’s disease (AOSD), and COVID-19 cytokine storm (CCS) are characterized by markedly elevated inflammatory cytokines. However clinical measurement of serum cytokines is not widely available. This study examined the clinical utility of C-reactive protein (CRP) and ferritin, two inexpensive and widely available inflammatory markers, for distinguishing HLH from AOSD and CCS. This single centre retrospective study included 44 secondary HLH patients, 14 AOSD patients, and 13 CCS patients. Baseline CRP and ferritin measured within 72 h of diagnosis and before administration of corticosteroids or other anti-inflammatory therapies were analyzed. The median CRP in HLH patients was lower than AOSD (71 mg/L vs. 172 mg/L, p 136 improves the specificity of HScore alone for HLH from 85.2 to 96.3%. Adding CRP 15,254 µg/L increases specificity for HLH from 88.9 to 100%. This study demonstrates that median CRP is lower in HLH than in AOSD and CCS, and median ferritin is lower in CCS than in HLH or AOSD. This study demonstrates the clinical utility of these widely available inflammatory markers for distinguishing between different cytokine storm syndromes.

Chronic granulomatous disease (CGD) is an inborn error of immunity. NADPH oxidase is an enzyme complex that produces various reactive oxygen species, such as superoxide anions and hydrogen peroxide. Mycobacterial infections in CGD are commonly observed in countries with a high prevalence of these microorganisms, such as those receiving the BCG vaccination at birth or having a high prevalence of tuberculosis. Non-tuberculous mycobacteria (NTM) infections are rare in CGD. The patient also presented with hemophagocytic lymphohistiocytosis, which resolved with gammaglobulin and cyclosporine. Herein, we describe the first case of M. chimaera infection in a female patient with autosomal recessive CGD caused by a pathogenic variant in CYBA.

Sukriye Miray Kilincer Bozgul,1 Ilkce Akgun Kurtulmus,2 Figen Yargucu Zihni,3 Nur Akad Soyer,4 Burcu Yagmur,5 Ajda Gunes,4 Gorkem Koymen,6 Devrim Bozkurt1 1Ege University, Faculty of Medicine, Department of Internal Medicine, Division of Intensive Care, Izmir, Turkey; 2Torbalı State Hospital, Izmir, Turkey; 3Ege University, Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Izmir, Turkey; 4Ege University, Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Izmir, Turkey; 5Ege University, Faculty of Medicine, Department of Cardiology, Izmir, Turkey; 6Izmir City Hospital, Department of Internal Medicine, Division of Medical Oncology, Izmir, TurkeyCorrespondence: Figen Yargucu Zihni, Ege University, Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Izmir, Turkey, Email figenyargucu@gmail.comBackground: Hemophagocytic syndrome (HPS) is a rare but life-threatening condition often complicated by heart failure (HF). This study aimed to identify predictors of acute heart failure in HPS patients using classification and regression tree (CART) analysis.Methods: A retrospective analysis was performed on 146 HPS patients without a diagnosis of HF. Variables such as age, cardiothoracic ratio (CTR), etiology, N-terminal pro-brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP), ferritin, triglyceride, and lactate dehydrogenase (LDH) levels at diagnosis were included. CART analysis was employed to develop models predicting heart failure status. The model’s performance was evaluated using sensitivity, specificity, and overall accuracy.Results: This study identified several key predictors of acute heart failure in HPS patients. CTR emerged as the most significant predictor, with patients exhibiting a higher ratio being at a greater risk of developing heart failure. NT-proBNP levels and CRP levels were also significant predictors, indicating cardiac stress and systemic inflammation. Age and etiology played crucial roles, with older patients and those with rheumatological causes showing a higher susceptibility to heart failure. The CART models demonstrated good accuracy, with CTR being the most important predictor.Conclusion: This study highlights critical factors, such as CTR, NT-proBNP, CRP levels, age, and etiology in predicting acute heart failure in HPS patients. Early identification of these predictors can facilitate timely interventions, potentially improving outcomes and reducing mortality rates. These findings provide valuable insights for clinical practice and pave the way for further research on acute heart failure management in HPS.Plain Language Summary: HPS is a serious condition that can lead to heart failure, a life-threatening complication. This study aimed to identify factors that predict heart failure in HPS patients to help doctors diagnose and treat it early. By analyzing data from 146 patients, we found that a higher cardiothoracic ratio, elevated NT-proBNP levels, and increased CRP levels were strong predictors of heart failure. These findings mean that doctors can monitor these factors in HPS patients to catch heart failure early and start treatment sooner, potentially saving lives. The study also found that women with HPS might be more likely to develop heart failure, suggesting they need closer monitoring. Overall, this research provides valuable information that can improve patient care and outcomes in HPS.Keywords: hemophagocytic syndrome, acute heart failure, CART analysis, predictive factors, inflammation

Cytokine storm syndromes such as hemophagocytic lymphohistiocytosis (HLH), Adult-onset Still's disease (AOSD), and COVID-19 cytokine storm (CCS) are characterized by markedly elevated inflammatory cytokines. However clinical measurement of serum cytokines is not widely available. This study examined the clinical utility of C-reactive protein (CRP) and ferritin, two inexpensive and widely available inflammatory markers, for distinguishing HLH from AOSD and CCS. This single centre retrospective study included 44 secondary HLH patients, 14 AOSD patients, and 13 CCS patients. Baseline CRP and ferritin measured within 72 h of diagnosis and before administration of corticosteroids or other anti-inflammatory therapies were analyzed. The median CRP in HLH patients was lower than AOSD (71 mg/L vs. 172 mg/L, p < 0.001) and CCS (71 mg/L vs. 121 mg/L, p = 0.0095) patients. Serum ferritin levels were lower in CCS compared to HLH (1,386 µg/L vs. 29,019 µg/L, p < 0.001) and AOSD (11,359 µg/L vs. 29,019 µg/L, p = 0.035). A CRP < 130 mg/L when combined with an HScore > 136 improves the specificity of HScore alone for HLH from 85.2 to 96.3%. Adding CRP < 130 mg/L to ferritin > 15,254 µg/L increases specificity for HLH from 88.9 to 100%. This study demonstrates that median CRP is lower in HLH than in AOSD and CCS, and median ferritin is lower in CCS than in HLH or AOSD. This study demonstrates the clinical utility of these widely available inflammatory markers for distinguishing between different cytokine storm syndromes. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma variant of Richter syndrome (HL-type RS) is a very rare disease, in which chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) is transformed into novel Hodgkin lymphoma. The most important prognostic factor of HL-type RS is the clonal relationship between HL-type RS and the preexisting CLL/SLL. Detailed confirmation of clonally unrelated HL-type RS cases have not been reported. To the best of our knowledge, this is the first case of HL-type RS confirmed as clone independent by a detailed comparison of immunoglobulin gene rearrangement clones and gene mutations. A 76-year-old man, diagnosed with SLL 1 year before transformation was treated with Zanubrutinib 3 months before transformation. When diagnosed with HL-type RS, he presented with symptoms of hemophagocytic syndrome. Positive therapeutic effects were achieved using a modified rituximab-doxorubicin, bleomycin, vinblastine, dacarbazine regimen in combination with Zanubrutinib. We also discuss a thorough review of the relevant literature we performed to help us better understand this rare disease. [ABSTRACT FROM AUTHOR]

Major Histocompatibility Complex Class II Deficiency is a rare primary immunodeficiency disease with autosomal recessive inheritance. It is characterized by the absence of Major Histocompatibility Complex Class II molecules on the surface of immune cells. In this article, we will present a four-month-old baby girl who presented with recurrent fever and progressive exacerbation of respiratory symptoms since a month ago. Relevant examinations suggested pancytopenia, a decrease in CD4 and CD3 ratio, and CD4/CD8 inversion, hypogammaglobulinemia, and diagnosis of hemophagocytic syndrome during treatment which all led to the consideration of the presence of immunodeficiency diseases, and the diagnosis of Major Histocompatibility Complex Class II Deficiency was made by peripheral blood whole-exon sequencing (WES). This case is remarkable in that it reveals features of hemophagocytic syndrome in a Major Histocompatibility Complex Class II Deficiency infant, most probably caused by cytomegalovirus, which rarely reported before, and the Major Histocompatibility Complex Class II Deficiency caused by a novel mutation site in the RFXANK gene which never reported, and it also describes the diagnostic and therapeutic course in detail. In addition, we have summarized the information related to Major Histocompatibility Complex Class II Deficiency triggered by mutations in the RFXANK gene to assist clinicians in early recognition and diagnosis. [ABSTRACT FROM AUTHOR]

Hemophagocytic syndrome (HPS) is a rapidly progressive and highly fatal disease, and is even more complex when it occurs during pregnancy. Currently, the HLH-94 protocol is commonly used for treatment for HPS, with ruxolitinib being mostly used for salvage therapy. Here, we report a pregnant woman who presented with fever, thrombocytopenia, splenomegaly, and subsequently developed into severe pneumonia and multiple organ dysfunction(MODS). The patient was diagnosed as HPS based on clinical manifestations, laboratory indexes, and hemophagocytosis observed in bone marrow aspirate smear. After receiving ruxolitinib as induction therapy combined with HLH-94 protocol, the patient significantly improved and eventually cured. [ABSTRACT FROM AUTHOR]

Objective To investigate preliminarily the causes of elevated ferritin in patients with hemophagocytic syndrome by analyzing the iron metabolism indexes, liver function and cytokine levels. Methods 41patients with the hemophagocytic syndrome and another 41 non-hemophagocytic syndrome patients with the elevated ferritin levels (as the control group) admitted to the First People’s Hospital of Yunnan Province from September2021 to May 2024 were recruited for iron metabolism, cytokine and liver function tests, and the differences between these indexes and their relationship with the ferritin were analyzed. Results Patients with the hemophagocytic syndrome had the significantly higher levels of ferritin and lower levels of soluble transferrin receptor compared to the control group. Cytokines IL-4, IL-8, IL-10, IL-1 β, IL-2, IFN-γ, TNF-α, TNF-β, IL-17A, and IL-17F were significantly higher than those in the control group, while transaminase, bilirubin, and lactate dehydrogenase were significantly higher than those in the control group. There was no significant correlation between ferritin and iron metabolism indicators, but it was negatively correlated with cytokine IL-4, positively correlated with IL-8 and IL-10, and positively correlated with LDH, ALT, and AST. Conclusion The ferritin of patients with hemophagocytic syndrome is significantly increased, but the iron metabolism process is not significantly different from that of the control group, and there are obvious inflammatory reactions and liver damage at the onset of the disease. The increase of ferritin is not correlated with iron metabolism indexes, but is related to the inflammation and liver damage. [ABSTRACT FROM AUTHOR]

Background: Hemophagocytic syndrome (HPS) is a rare but life-threatening condition often complicated by heart failure (HF). This study aimed to identify predictors of acute heart failure in HPS patients using classification and regression tree (CART) analysis. Methods: A retrospective analysis was performed on 146 HPS patients without a diagnosis of HF. Variables such as age, cardiothoracic ratio (CTR), etiology, N-terminal pro-brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP), ferritin, triglyceride, and lactate dehydrogenase (LDH) levels at diagnosis were included. CART analysis was employed to develop models predicting heart failure status. The model's performance was evaluated using sensitivity, specificity, and overall accuracy. Results: This study identified several key predictors of acute heart failure in HPS patients. CTR emerged as the most significant predictor, with patients exhibiting a higher ratio being at a greater risk of developing heart failure. NT-proBNP levels and CRP levels were also significant predictors, indicating cardiac stress and systemic inflammation. Age and etiology played crucial roles, with older patients and those with rheumatological causes showing a higher susceptibility to heart failure. The CART models demonstrated good accuracy, with CTR being the most important predictor. Conclusion: This study highlights critical factors, such as CTR, NT-proBNP, CRP levels, age, and etiology in predicting acute heart failure in HPS patients. Early identification of these predictors can facilitate timely interventions, potentially improving outcomes and reducing mortality rates. These findings provide valuable insights for clinical practice and pave the way for further research on acute heart failure management in HPS. Plain Language Summary: HPS is a serious condition that can lead to heart failure, a life-threatening complication. This study aimed to identify factors that predict heart failure in HPS patients to help doctors diagnose and treat it early. By analyzing data from 146 patients, we found that a higher cardiothoracic ratio, elevated NT-proBNP levels, and increased CRP levels were strong predictors of heart failure. These findings mean that doctors can monitor these factors in HPS patients to catch heart failure early and start treatment sooner, potentially saving lives. The study also found that women with HPS might be more likely to develop heart failure, suggesting they need closer monitoring. Overall, this research provides valuable information that can improve patient care and outcomes in HPS. [ABSTRACT FROM AUTHOR]

A case of pregnancy complicated with hemophagocytic syndrome (HPS) with fever combined with anemia as the first symptom was admitted to our hospital. The patient was 26 years old, 31+5 weeks pregnant, 3 pregnancies and 2 births.The patient experienced unexplained fever, anemia, and thrombocytopenia. After admission, extensive tests confirmed a diagnosis of secondary HPS, and she was treated with dexamethasone and intravenous immunoglobulin. Following consultations with the departments of hematology, obstetrics, and neonatology, it was determined that fetal lung maturation was complete. The patient underwent a lower segment cesarean section. Both the patient and the newborn were in good general condition postoperatively. The patient was then transferred to the hematology department for further treatment of HPS and underwent one course of treatment with dexamethasone and etoposide. A follow-up examination of her bone marrow, coagulation profile, and complete blood count showed good recovery, and she was discharged. The patient remained well at a two-week post-discharge outpatient follow-up. [ABSTRACT FROM AUTHOR]

To explore the clinical features, treatment, and prognosis of patients with lymphoma-associated hemophagocytic syndrome (LAHS) in a real-world clinical setting. We retrospectively examined LAHS patients diagnosed at our center between January 2016 and August 2023, focusing primarily on their clinical features, therapeutic approaches, overall response rate (ORR), and overall survival (OS). A combination of univariate and multivariate analyses was conducted to identify potential prognostic factors. A total of 86 patients diagnosed with LAHS were included to evaluate clinical characteristics and prognostic factors. Patients with T/NK cell lymphoma had a higher probability of developing hemophagocytic syndrome (HPS) during the clinical process than those with B cell lymphoma. The median survival time was 55 days for all patients, and 47 and 81 days for the T/NK cell LAHS and B cell LAHS cohorts, respectively (P = 0.025). Among the patients evaluated, the ORR was 42.2%. Patients starting with anti-lymphoma treatment had a better, albeit not significant, ORR than those beginning with anti-HPS treatment. In the univariate analysis, T/NK cell LAHS (P = 0.027), HPS onset at relapse (P = 0.036), higher baseline plasma EBV-DNA levels (> 4,000 copies/mL, P = 0.034), and treatments including cytokine adsorption and ruxolitinib (P < 0.001 and P = 0.017, respectively) were potentially associated with worse OS, while corticosteroid therapy benefited OS. In the multivariate analysis, T/NK cell LAHS (adjusted hazard ratio (aHR) = 2.007), cytokine adsorption therapy (aHR = 4.547), and corticosteroid therapy (aHR = 0.118) were independently associated with mortality. T/NK cell lymphoma was the main cause of LAHS and carried a worse prognosis. Whether anti-lymphoma or anti-HPS treatment should start first still requires prospective studies with larger sample sizes. The key point in controlling HPS is to block the cytokine storm promptly. Corticosteroid therapy is both effective and accessible and should be used early and in sufficient quantities. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma. Methods The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model. Results Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome (HR=8.50, 95% CI: 1.679-8.328, P=0.001), serum albumin (HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy (HR= 0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients. [ABSTRACT FROM AUTHOR]

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]

Hodgkin lymphoma variant of Richter syndrome (HL-type RS) is a very rare disease, in which chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) is transformed into novel Hodgkin lymphoma. The most important prognostic factor of HL-type RS is the clonal relationship between HL-type RS and the preexisting CLL/SLL. Detailed confirmation of clonally unrelated HL-type RS cases have not been reported. To the best of our knowledge, this is the first case of HL-type RS confirmed as clone independent by a detailed comparison of immunoglobulin gene rearrangement clones and gene mutations. A 76-year-old man, diagnosed with SLL 1 year before transformation was treated with Zanubrutinib 3 months before transformation. When diagnosed with HL-type RS, he presented with symptoms of hemophagocytic syndrome. Positive therapeutic effects were achieved using a modified rituximab-doxorubicin, bleomycin, vinblastine, dacarbazine regimen in combination with Zanubrutinib. We also discuss a thorough review of the relevant literature we performed to help us better understand this rare disease.

Hemophagocytic syndrome (HPS) is a rapidly progressive and highly fatal disease, and is even more complex when it occurs during pregnancy. Currently, the HLH-94 protocol is commonly used for treatment for HPS, with ruxolitinib being mostly used for salvage therapy. Here, we report a pregnant woman who presented with fever, thrombocytopenia, splenomegaly, and subsequently developed into severe pneumonia and multiple organ dysfunction(MODS). The patient was diagnosed as HPS based on clinical manifestations, laboratory indexes, and hemophagocytosis observed in bone marrow aspirate smear. After receiving ruxolitinib as induction therapy combined with HLH-94 protocol, the patient significantly improved and eventually cured.

Yan Chen,&ast; Xiaohuan Huang,&ast; Hongfei Chen, Junru Tong, Lingling Huang, Junyou Su, Li Deng Department of Obstetrics, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Deng; Junyou Su, Email dengli@gxmu.edu.cn; sujunyou@sr.gxmu.edu.cnBackground: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome characterized by excessive activation of NK cells and cytotoxic T lymphocytes, subsequently leading to macrophage activation and increased cytokine production. Misdiagnosis due to nonspecific clinical presentations and inadequate understanding of the disease can significantly jeopardize the safety of both the mother and the infant. We report a case of pregnancy combined with HLH and conduct a literature review to provide insights into the diagnosis and treatment of pregnancy-related HLH.Case Presentation: We discussed a case of a pregnant woman with persistent postpartum fever, serum ferritin, and elevated liver function, who failed to respond to repeated anti-infective therapy and was diagnosed with HLH after multidisciplinary diagnostic treatment. We gave dexamethasone treatment, and the patient’s temperature and blood cells quickly returned to normal. Finally, exome sequencing revealed heterozygous variation in UNC13D gene, so we considered this case as pregnancy combined with primary HLH (pHLH).Conclusion: We report the case of HLH diagnosed during pregnancy and show that early diagnosis and timely intervention can prevent rapid disease progression, reduce maternal mortality rates, and improve survival rates. Additionally, molecular genetic testing can confirm pathogenic gene mutations, providing essential genetic counseling for patients with pHLH who plan to conceive a healthy child.Keywords: hemophagocytic lymphohistiocytosis, hemophagocytic syndrome, pregnancy, case report

The spectrum of HHV-8-associated disorders includes Kaposi's sarcoma, primary effusion lymphoma, multicentric Castleman's disease, and the recently described KSHV inflammatory cytokine syndrome (KICS), a life-threatening disorder complicating HIV infection. There have been no reports in the literature concerning non-immunosuppressed individuals affected with KICS. We report here a KICS-like illness occurring in two elderly Greek men without HIV infection or other recognizable cause of immunosuppression. [ABSTRACT FROM AUTHOR]

Hemophagocytic syndrome/macrophage activation syndrome (HPS/MAS) is a serious clinical condition that frequently leads to multiple organ failure, including acute kidney injury (AKI). Although the pathogenesis of AKI is not yet fully understood, it is believed to result from uncontrolled activation of the immune system involving macrophages and cytotoxic lymphocytes. Renal histology in HPS/MAS often presents with characteristic foamy glomerular lesions (glomerular lipidosis) with massive macrophage infiltration, known as histiocytic glomerulopathy. In this review, we introduce the recently proposed concept of renal-limited HPS/MAS as a novel etiology of histiocytic glomerular lipidosis. Patients with renal-limited HPS/MAS often develop AKI but do not fulfill the diagnostic criteria for HPS/MAS because their systemic manifestations are less severe. Therefore, the diagnosis largely depends on characteristic histological findings, that is, diffuse and global glomerular accumulation of foamy macrophages and cytotoxic lymphocytes accompanied by the interaction of these cells as well as the exclusion of various differential diseases. Although there are no established therapeutic regimens, these patients receive various types of therapies, including high-dose glucocorticoids, immunosuppressants, or anti-interleukin-1 drug, and generally achieve favorable outcomes. We summarized the concept, diagnostic challenges, and recent topics of this disease entity and discussed treatment options based on our own experiences. [ABSTRACT FROM AUTHOR]

Background: Hemophagocytic Lymphohistiocytosis (HLH) is a rare and lifethreatening condition characterized by a severe impairment of the immune homeostasis. While Familial-HLH (FHL) is a known cause, the involvement of other Inborn Errors of Immunity (IEI) in pediatric-HLH remains understudied. Objective: This systematic review aimed to assess the clinical features, triggers, laboratory data, treatment, and outcomes of pediatric HLH patients with IEI other than FHL (IEInotFHL), emphasizing the importance of accurate identification and management. Methods: A systematic search for studies meeting inclusion criteria was conducted in PubMed, EMBASE, MEDLINE, and Cochrane Central. Quality assessment was performed through JBI criteria. Results: A comprehensive search yielded 108 records meeting inclusion criteria, involving 178 patients. We identified 46 different IEI according to IUIS 2022 Classification. Combined immunodeficiencies, immune dysregulation disorders, and phagocyte defects were the IEI most frequently associated with HLH. In 75% of cases, HLH preceded the IEI diagnosis, often with an unrecognized history of severe infections. Triggers reflected the specific infection susceptibilities within IEI groups. Liver and central nervous system involvement were less common than in FHL cases. Treatment approaches and outcomes varied, with limited long-term follow-up data, limiting the assessment of therapeutic efficacy across IEI groups. Conclusion: A comprehensive evaluation encompassing immunological, infectious, and genetic aspects is essential in pediatric-HLH. Relying solely on FHL or EBV susceptibility disorders tests is insufficient, as diverse other IEI can contribute to HLH. Early recognition of HLH as a potential warning sign can guide timely diagnostic investigations and facilitate tailored therapeutic interventions for improved outcomes. [ABSTRACT FROM AUTHOR]

Bacillus Calmette-Guérin (BCG) therapy is an adjuvant treatment for urothelial carcinomas of the upper urinary tract (UTUC). BCG therapy can result in various side effects. We present a case of a 67-year-old female with a history of UTUC who developed disseminated tuberculosis following BCG instillation into the upper urinary tract after conservative management. This complex clinical scenario required a multidisciplinary approach, including antibiotic therapy, immunoglobulin infusion, and tailored tuberculosis treatment. The case underscores the importance of vigilance, early detection, and tailored interventions in managing disseminated tuberculosis arising from BCG therapy and rare complications like hemophagocytic syndrome.

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome (HPS), is a benign histiocytosis with hyperreactive proliferation of the mononuclear phagocyte system caused by immune function abnormalities, which often occurs under the background of genetic mutations, inflammation, infection or tumors. Because the research on malignancy-associated HLH (M-HLH) is focused on hematological malignancies, reports on HLH secondary to solid tumors are rare. In this case, we report a 14-year-old girl who developed HLH during treatment for intracranial multifocal germinoma, and the disease was controlled after hormone combined with etoposide(VP-16) and other related treatments. To our knowledge, there have been no documented cases of HLH caused by intracranial multifocal germinoma. [ABSTRACT FROM AUTHOR]

Abstract Background Macrophage activation syndrome (MAS) is a severe and life-threatening syndrome associated with autoimmune diseases. The coexistence of MAS and juvenile dermatomyositis (JDM) is not well reported. This report describes a case of JDM with MAS and summarizes the clinical characteristics and prognosis of MAS in patients with JDM. Case presentation The patient was a 15-year-old female with JDM, presenting with heliotrope rash, muscle weakness, increased muscle enzyme, anti-nuclear matrix protein 2 (NXP2) antibody, and muscle biopsy consistent with JDM. The patient developed fever, cytopenia, and hyperferritinemia three months after the first manifestations. Hemophagocytosis was found in the bone marrow. The final diagnosis was JDM combined with MAS. Despite intensive treatment, the patient died of MAS. By reviewing the literature, we found 17 similar cases. Together with the present case, 18 patients were identified, the median age of disease onset was 13.5 years, and male to female ratio was 1.25: 1. Nine out of 16 (56.3%) patients were complicated with interstitial lung disease (ILD). The median time interval between JDM onset and MAS diagnosis was 9 weeks. At the onset of MAS, all (100%) patients had elevated levels of ferritin and serum liver enzymes. Among 18 patients, 14 (77.8%) had fever, 14/17 (82.4%) had cytopenia, 11/11 (100%) had hepatosplenomegaly, and 13/14 (92.9%) had hemophagocytosis. Five (27.8%) patients showed central nervous system (CNS) involvement. The mortality of MAS rate of in patients with JDM was 16.7%, despite various treatment methods. Conclusion . The coexistence of JDM and MAS is underestimated with increased mortality. Hepatosplenomegaly and increased serum levels of ferritin in patients with JDM should raise clinical suspicion for MAS.

BackgroundHemophagocytic Lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by a severe impairment of the immune homeostasis. While Familial-HLH (FHL) is a known cause, the involvement of other Inborn Errors of Immunity (IEI) in pediatric-HLH remains understudied.ObjectiveThis systematic review aimed to assess the clinical features, triggers, laboratory data, treatment, and outcomes of pediatric HLH patients with IEI other than FHL (IEInotFHL), emphasizing the importance of accurate identification and management.MethodsA systematic search for studies meeting inclusion criteria was conducted in PubMed, EMBASE, MEDLINE, and Cochrane Central. Quality assessment was performed through JBI criteria.ResultsA comprehensive search yielded 108 records meeting inclusion criteria, involving 178 patients. We identified 46 different IEI according to IUIS 2022 Classification. Combined immunodeficiencies, immune dysregulation disorders, and phagocyte defects were the IEI most frequently associated with HLH. In 75% of cases, HLH preceded the IEI diagnosis, often with an unrecognized history of severe infections. Triggers reflected the specific infection susceptibilities within IEI groups. Liver and central nervous system involvement were less common than in FHL cases. Treatment approaches and outcomes varied, with limited long-term follow-up data, limiting the assessment of therapeutic efficacy across IEI groups.ConclusionA comprehensive evaluation encompassing immunological, infectious, and genetic aspects is essential in pediatric-HLH. Relying solely on FHL or EBV susceptibility disorders tests is insufficient, as diverse other IEI can contribute to HLH. Early recognition of HLH as a potential warning sign can guide timely diagnostic investigations and facilitate tailored therapeutic interventions for improved outcomes.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371425, PROSPERO, CRD42022371425.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by a hyperinflammatory syndrome and impairment of multiple organ systems. Talaromycosis marneffei (TSM) is an opportunistic infection mostly found in immunosuppressed populations, such as those with acquired immunodeficiency syndrome (AIDS), and is prevalent in southern China. However, HLH secondary to TSM is extremely rare and has only been reported in isolated cases. A 30-year-old patient with recurrent high fever and progressive cytopenia was diagnosed with HLH secondary to disseminated TSM with AIDS and Alpha-thalassemia. The patient remained in sustained remission without recurrence after effective treatment with antifungals and glucocorticoids.

Background: Reactivation of EBV after novel coronavirus infection is common, and co-infection with EBV in patients with novel coronavirus pneumonia may lead to more severe clinical manifestations, prolong the duration of the underlying disease, or precipitate the progression of post novel coronavirus syndrome. EBV-induced hemophagocytic syndrome is a rare and life-threatening condition, and there are no reports of EBV reactivation leading to hemophagocytic syndrome after novel coronavirus infection. Case presentation: Here, we report a case of a 73-year-old man with EBV reactivation after novel coronavirus infection, who was diagnosed with hemophagocytic syndrome after bone marrow aspiration and died after being treated with acyclovir, dexamethasone. Conclusions: the aim of this report is to increase clinical awareness of this type of disease for early recognition and treatment.

Cytokine release syndrome (CRS) is a pathological condition characterized by an excessive immune response triggered by the administration of antibody drugs such as immune checkpoint inhibitors. This immune overactivation leads to hypercytokinemia, marked by the excessive release of cytokines. Con sequently, T lymphocytes and macrophages become excessively activated, resulting in the phagocytosis of autologous blood cells, a phenomenon known as hemophagocytic syndrome (HPS). In some cases, this condition can have severe consequences. In this report, we present a case of HPS caused by CRS as an immune-related adverse event (irAE) of pembrolizumab administration in a 64-year-old male patient. The patient had undergone laparoscopic radical nephrectomy for right renal cell carcinoma cT2aN0M1. He received pembrolizumab and axitinib as the primary treatment, followed by pazopanib as secondary treatment for the increasing number of lung metastases. Ten days after starting the second-line treatment, the patient developed fever and chills, necessitating urgent hospitalization. Upon admission, the patient exhibited a fever in the 39 ℃ range, low white blood cell and platelet counts, as well as elevated levels of FDP, D-dimer, serum ferritin, and soluble IL-2 receptor, leading to the diagnosis of hemophagocytic syndrome. On the third day of hospitalization, the patient's systolic blood pressure dropped to 68 mmHg, and he was transferred to the intensive care unit (ICU) in a state of shock. In addition to receiving high-dose steroids, the patient underwent endotoxin adsorption and hemodilution therapy, which gradually resulted in improvement. Twenty-eight months after being discharged from the hospital, the patient remains alive with no exacerbation of pulmonary metastases. [ABSTRACT FROM AUTHOR]

The study's aim was to enhance awareness of acquired hemophagocytic syndrome (HPS) in adults by analyzing clinical features, and investigating the relationship between factors such as the Systemic Inflammation Index (SII) and the prognosis of HPS. Clinical characteristics, survival data, and prognostic factors of 75 HPS patients admitted to our hospital between January 2012 and October 2022 were analyzed. In the high SII group, red blood cells, white blood cells, platelets, neutrophils, fibrinogen, and CD4 + cell activity were higher, and survival time was longer compared to the low SII group. Conversely, total bilirubin and direct bilirubin were higher in the low SII group (P ≤ 0.05). After applying the log-Rank or Breslow tests, HPS patients in the high SII group and those following the HLH-2004 protocol experienced a notably longer survival time. (χ2 = 4.291, P < 0.05; χ2 = 5.210, P < 0.05). Patients with poor prognosis showed higher age of onset, elevated levels of total, direct, and indirect bilirubin, and a greater rate of EBV infection, but reduced levels of red blood cells, platelets, hemoglobin, albumin, globulin, and HLH-2004 protocol usage rate(P < 0.05). Multivariate analysis and ROC curve results indicate that special attention is needed for patients with platelets < 42.5 × 109/L, albumin < 27.7 g/L, fibrinogen < 1.085 g/L, those not following the HLH-2004 protocol, and those who are EBV (+). Early diagnosis and following the HLH-2004 protocol are essential for patients with HPS clinical manifestations to improve prognosis. Additional research is necessary to examine the link between SII and HPS patients' prognosis. [ABSTRACT FROM AUTHOR]

The clinical features and short-term prognosis of patients admitted to the intensive care unit for herpes hepatitis are lacking. Of 33 patients admitted between 2006 and 2022, 22 were immunocompromised, 4 were pregnant women, and 23 died. Sixteen patients developed a hemophagocytic syndrome. Acyclovir was initiated a median (interquartile range) of 1 (0–3) day after admission. [ABSTRACT FROM AUTHOR]

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Key Clinical Message: In this report we highlight a case of HPS secondary to B‐cell lymphoma, aiming to facilitate the early recognition and treatment of HPS in its classic presentation by clinicians. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (hemophagocytic syndrome, HLH) is a life-threatening hyperinflammatory condition associated with a high mortality rate; it is characterized by hyperstimulation of histiocytes and cytotoxic T-cells, which leads to cytokine storm and multisystemic injury. Aim. To present our own clinical case of the HLH development at the key aspects of pathogenic mechanisms, differential diagnosis, and therapeutic management of this syndrome. Materials and methods. This article provides information on the HLH development in a 69-year-old man with the onset of this syndrome prior to a diagnosis of the underlying disease – splenic marginal zone lymphoma. The article summarizes the current literature data on clinical manifestations, diagnosis, and treatment of HLH. Results. This article describes a case of secondary HLH from our clinical practice. The most common causes of HLH are malignant neoplasm, infectious factors and rheumatic diseases (when associated with the latest, HLH is called “macrophage activation syndrome”). The main clinical symptoms are prolonged high fever and hepatosplenomegaly, typical laboratory changes such as cytopenia, hyperferritinemia, hypertriglyceridemia, elevated liver enzymes and low fibrinogen levels. Conclusions. Despite typical clinical features, HLH is a condition that often remains unrecognized and it is characterized by a poor prognosis. Prompt prescription of adequate treatment can improve patients’ prognoses and increase the survival rate.

Abstract Background Patients with Hodgkin lymphoma exhibit various clinical presentations. Needle biopsy of the lymph nodes is a minimally invasive procedure and a useful diagnostic method for malignant lymphomas. However, at times it is difficult to differentiate malignant lymphomas from reactive lymph node changes using a small amount of biopsy material. Case presentation A 77-year-old Japanese man was referred to the emergency department of our hospital owing to high fever and disturbance of consciousness. We diagnosed sepsis due to an acute biliary tract infection because he presented with Charcot’s triad—fever, jaundice, and right-sided abdominal pain. However, he did not respond well to antimicrobial therapy and his high fever persisted. Considering the swelling of the right cervical, mediastinal, and intraperitoneal lymph nodes and splenomegaly detected on computed tomography, a differential diagnosis of malignant lymphoma was needed. Hence, we performed a needle biopsy of the right cervical lymph node; however, the amount of sample obtained was insufficient in establishing a definitive diagnosis of malignant lymphoma. Furthermore, during hospitalization, the patient developed thrombocytopenia, anasarca, and renal insufficiency. These symptoms seemed to be the typical signs of the thrombocytopenia, anasarca, fever, reticulin fibrosis or renal insufficiency, and organomegaly syndrome. Next, an external incisional mass biopsy of the right cervical lymph node was performed, which helped identify Hodgkin and Reed–Sternberg cells. Collectively, we established a definitive diagnosis of Hodgkin lymphoma with lymphoma-associated hemophagocytic syndrome. Conclusions This case highlights the importance of performing an external incisional mass biopsy of the lymph nodes for the early diagnosis and treatment, if malignant lymphoma is strongly suspected.

Abstract Background Pregnancy-related intracranial hemorrhage (ICH) is a rare but potentially life-threatening event with complex and varied cause, such as HELLP syndrome and hemophagocytic syndrome. Case presentation A 33-year-old patient underwent a cesarean section with a preliminary diagnosis of "severe preeclampsia and class3 HELLP syndrome ". The patient had poor response to language before surgery, and the catheter drainage fluid was hematuria. Later, the surgeon reported severe bleeding in the operation. Following thromboelastography (TEG) result and postoperative laboratory tests confirmed class1 HELLP syndrome and ICH occurred on the second day after the surgery, and hemophagocytic syndrome was diagnosed during subsequent treatments. Conclusion For patients with HELLP syndrome, we should pay attention to their coagulation condition. The coagulation tests and platelet counts should be repeated if their clinical presentation changed. Those with neurological alarm signs should receive CT or MRI scan. If a pregnant woman had prolonged hemocytopenia and thrombocytopenia, not only the HELLP but also the hemophagocytic syndrome should be considered.

Abstract Background Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT), is a rare, aggressive subtype of non-Hodgkin lymphoma, and it usually presents as a destructive sinus mass that may attend epistaxis. However, ENKTCL-NT with the manifestation of peripheral neuropathy is pretty unusual. Case presentation A 17-year-old Chinese patient presented with peripheral neuropathy and positive auto-antibodies. However, she failed methylprednisolone pulse therapy and developed hemophagocytic syndrome. The diagnosis of CD30-positive primary cutaneous ENKTCL-NT was confirmed by pathological biopsy. Her disease was brought under control after five cycles of chemotherapy. Conclusions The report findings are helpful in the differential diagnosis of peripheral neuropathy and autoimmune disease. We should be alert for the development of ENKTCL-NT when the rash and peripheral neuropathy are the first symptoms and are accompanied by Epstein-Barr virus (EBV) infection.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical laboratory condition with high mortality rates, resulting from ineffective overactivation of the immune system. Data in the Brazilian literature is scarce, contributing to the challenge in standardizing conducts and performing an early diagnosis of HLH. Objective: To describe the clinical, laboratory, and evolutionary findings on HLH patients treated at a pediatric hospital. Methods: This is an observational, cross-sectional and retrospective study on children diagnosed with HLH, hospitalized between 2009 and 2019. The diagnostic criteria were those described in the Histiocyte Society protocol. The authors evaluated HLH patient laboratory tests, myelograms and bone marrow biopsies, clinical characteristics and therapy. Results: Twenty-three patients were included, 52.2% of whom were males. The age at diagnosis ranged from one to one hundred and eighty months. Four cases were classified as Primary HLH and nineteen, as Secondary HLH. The main triggers were infections and rheumatological diseases. All children had bicytopenia, and 95.4% had hyperferritinemia. Nineteen patients had liver dysfunction, sixteen had neurological disorders and fourteen had kidney injury. Pulmonary involvement was seen in 61.9%, acting as a worse prognosis for death (p = 0.01). Nine patients underwent the immuno-chemotherapy protocol proposed in the HLH 2004. The time to confirm the diagnosis varied from five to eighty days. The lethality found was 56.3%. Conclusions: The present study is the most extensive retrospective exclusively pediatric study published in Brazil to date. Despite the limitations, it was possible to demonstrate the importance of discussing HLH as a pediatric emergency.

Background: Macrophage activation syndrome (MAS) is a severe and life-threatening syndrome associated with autoimmune diseases. The coexistence of MAS and juvenile dermatomyositis (JDM) is not well reported. This report describes a case of JDM with MAS and summarizes the clinical characteristics and prognosis of MAS in patients with JDM. Case presentation: The patient was a 15-year-old female with JDM, presenting with heliotrope rash, muscle weakness, increased muscle enzyme, anti-nuclear matrix protein 2 (NXP2) antibody, and muscle biopsy consistent with JDM. The patient developed fever, cytopenia, and hyperferritinemia three months after the first manifestations. Hemophagocytosis was found in the bone marrow. The final diagnosis was JDM combined with MAS. Despite intensive treatment, the patient died of MAS. By reviewing the literature, we found 17 similar cases. Together with the present case, 18 patients were identified, the median age of disease onset was 13.5 years, and male to female ratio was 1.25: 1. Nine out of 16 (56.3%) patients were complicated with interstitial lung disease (ILD). The median time interval between JDM onset and MAS diagnosis was 9 weeks. At the onset of MAS, all (100%) patients had elevated levels of ferritin and serum liver enzymes. Among 18 patients, 14 (77.8%) had fever, 14/17 (82.4%) had cytopenia, 11/11 (100%) had hepatosplenomegaly, and 13/14 (92.9%) had hemophagocytosis. Five (27.8%) patients showed central nervous system (CNS) involvement. The mortality of MAS rate of in patients with JDM was 16.7%, despite various treatment methods. Conclusion:. The coexistence of JDM and MAS is underestimated with increased mortality. Hepatosplenomegaly and increased serum levels of ferritin in patients with JDM should raise clinical suspicion for MAS. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a condition of immune dysregulation and hyperinflammation, leading to organ failure and death. Malignancy, autoimmune conditions, and infections, including Mycobacterium tuberculosis (TB), are all considered triggers of HLH. The aim of this study was to review all reported cases of TB-associated HLH in English literature, and to summarize the epidemiology, diagnostics, treatment, and mortality in patients with concomitant HLH and TB. A systematic review of described cases with TB-associated HLH, via a structured literature search in the medical database PubMed, is presented. Additional articles were included through cross-referencing with existing review articles. Articles were reviewed based on a predetermined set of criteria. A total of 116 patients with TB-associated HLH were identified with a male:female ratio of about 3:2. The age at presentation ranged from 12 days to 83 years. Malignancy, autoimmunity, and renal failure were the most common comorbid conditions. Most patients received both tuberculostatic and specific immunomodulating treatment, which was associated with a 66% (48/73) survival rate compared to 56% (15/27) in those receiving only tuberculostatic treatment, and 0% (0/13) in those receiving only immunomodulating treatment. The survival rate was 55% overall. The overlapping presentation between disseminated TB and HLH poses challenging diagnostics and may delay diagnosis and treatment, leading to increased mortality. TB should be considered as a potential trigger of HLH; clinicians' knowledge and awareness of this may result in the appropriate investigations needed to ensure diagnosis and proper treatment. [ABSTRACT FROM AUTHOR]

This study aims to assess the efficacy of second allogeneic hemopoietic stem cell transplantation (allo-HSCT) for treating hemophagocytic syndrome with first engraftment failure. Among a total of 35 patients who underwent allo-HSCT between June 2015 and July 2021 for HLH, 10 patients who underwent a second HSCT following graft rejection were retrospectively analyzed. Various factors, such as the treatment course and outcome, the remission status, donor selection, and the conditioning regimen of patients before second allo-HSCT, were scrutinized for transplant-related complications and transplant-related mortality, as well as transplant outcomes. All the subjects have achieved complete donor engraftment, in which the neutrophils and platelets engraftment occurred in a median time of 12 d (range 10–19 d) and 24 d (range 11–97 d), respectively. Among the selected subjects, 20% of patients are diseased due to transplant-related thrombotic microangiopathy. Further, 90% of patients are diagnosed with aGVHD, in which 3 of them with grade I aGVHD, one patient with grade II aGVHD, two patients with grade III GVHD, and three patients with localized chronic GVHD. Moreover, 70% of patients showed signs of combined viral infections. Despite the complex symptoms, the overall survival rate is around 80%, with transplant-related mortality and the incidence of post-transplant GVHD of 20% and 60%, respectively. Together, our findings indicated that the second allo-HSCT showed great potential in treating hemophagocytic syndrome with engraftment failure. [ABSTRACT FROM AUTHOR]

Lymphoma-associated hemophagocytic syndrome (LAHS) is a rare and life-threatening clinical syndrome with rapidly deteriorating health and high mortality. We retrospectively analyzed clinical features and prognostic factors from 117 patients diagnosed with LAHS. The cumulative incidence rate of LAHS was 4.0% (117/2906). Patients were classified into B-cell LAHS (B-LAHS, n = 22) and T/natural killer (NK)-cell LAHS (T/NK-LAHS, n = 95) groups. Patients with T/NK-LAHS were younger and had lower neutrophil counts and fibrinogen values, higher LDH and transaminase levels, and were more likely to develop hemophagocytic syndrome (HPS) during the clinical course than those with B-LAHS. The median survival time for the entire cohort was 57 days, and for the T/NK-LAHS and B-LAHS groups, it was 52 and 154 days, respectively, after the diagnosis of LAHS. Patients with B-LAHS had superior 1-year OS (p = 0.003, 36.4% versus 14.5%) compared with those with T/NK-LAHS. Prognostic factor analysis revealed that elevated LDH levels (LDH > 1000 IU/L) (p = 0.004), T/NK-cell lineage (p

Abstract Background Etoposide remains the cornerstone of symptomatic management of critically ill patients with secondary hemophagocytic syndrome (sHS). Risk of healthcare-associated infections (HAIs) in this setting with etoposide has never been assessed. We sought to evaluate the association between etoposide administration, HAIs occurrence and survival in critically ill adult patients with sHS. In this retrospective single-center study conducted in a university hospital ICU between January 2007 and March 2020, all consecutive patients with sHS were included. HAIs were defined as any microbiologically documented infection throughout ICU stay. Competing risk survival analysis was performed to determine factors associated with HAIs. Propensity score-based overlap weighting was performed to adjust for factors associated with etoposide use. Results 168 patients with a median age of 49 [38, 59] were included. Forty-three (25.6%) patients presented with at least 1 microbiologically documented HAI throughout ICU stay. After adjustment, cumulative incidence of HAI was higher in patients receiving etoposide (p = 0.007), while survival was unaffected by etoposide status (p = 0.824). By multivariable analysis, etoposide treatment was associated with a higher incidence of HAIs (sHR 3.75 [1.05, 6.67]), whereas no association with survival (sHR 0.53 [0.20, 1.98]) was found. Other factors associated with increased mortality after adjustment included age, immunodepression, male sex, SOFA score > 13, and occurrence of HAI. Conclusions In patients with sHS, etoposide treatment is independently associated with increased occurrence of HAIs, whereas no association with survival was found. Intensivists should be aware of increased infectious risk, to promptly detect and treat infections in this specific setting. Studies to assess benefits from prophylactic anti-infectious agents in this setting are warranted and the lack of benefit of etoposide on survival needs to be interpreted cautiously.

Hemophagocytic lymphohistiocytosis (HLH) is a rare histiocytic disorder characterized by reactive hyperplasia of the mononuclear phagocytic system, which is primarily caused by dysfunction of cytotoxic killer cells and natural killer cells, leading to antigen clearance barriers and the overactivation of the mononuclear phagocytic system due to continuous antigen stimulation. HLH encompasses a group of clinical syndromes marked by the overproduction of inflammatory cytokines. A 68-year-old Chinese man presented with persistent fever, chills, nausea, and vomiting; the patient had no history of any underlying conditions. Laboratory investigations revealed decreased levels of red blood cells, white blood cells, and platelets, along with reduced natural killer cell activity, increased CD25, hyperferritinemia, and the detection of Rickettsia DNA in his blood, meeting the diagnostic criteria of the Histiocyte Society HLH-2004 guidelines. The patient was treated with antibiotics, improving anemia, glucocorticoid therapy, and continuous renal replacement therapy (CRRT), temporarily improving his condition. However, the patient died after 2 years from chronic renal failure caused by septic shock.

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.