Hemophagocytic Lymphohistiocytosis Research Articles

Does your unwell patient have haemophagocytic lymphohistiocytosis?

Haemophagocytic lymphohistiocytosis is a severe systemic hyperinflammatory syndrome characterised by dysregulation of immune cells and excessive production of cytokines, also known as a cytokine storm. It has distinctive clinical features with fever, hyperferritinaemia and falling blood counts. In adults, this usually occurs secondary to an underlying driver or trigger including infection, malignancy or rheumatic diseases. Prompt treatment with immunomodulatory therapy, including corticosteroids and the recombinant IL-1 receptor antagonist anakinra, is recommended to switch off the cytokine storm. Etoposide-based regimens are sometimes needed, and newer therapies such as emapalumab and JAK inhibitors are increasingly being used. The incidence of haemophagocytic lymphohistiocytosis has increased significantly over the last 20 years which may partly reflect increased awareness of the condition. Although relatively rare, haemophagocytic lymphohistiocytosis can be encountered by a broad range of hospital physicians, so knowing how to diagnose and treat this condition is essential. This article reviews the pathogenesis, clinical features, causes, diagnosis and treatment of haemophagocytic lymphohistiocytosis to improve physician recognition and management of this condition to improve future patient outcomes.

HLH Syndrome in a Community Hospital: The Challenge of an Early Diagnosis.

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory cytokine storm. It can be secondary to infections, malignancies, autoimmune diseases, or the manifestation of genetic disorders, including primary immune deficiency. HLH requires a high index of suspicion and is challenging for community hospitals. Medical records of children with HLH admitted to the Meir Medical Center in Israel between 2014 and 2017 were reviewed. Nine children met ≥5/8 HLH-2004 criteria. The median age was 1.1 year, and 78% of the patients were aged <2 years. All patients had prolonged fever, cytopenia, and elevated soluble interleukin-2 receptor, and 89% had elevated ferritin levels. Of three children who underwent gene panel evaluation, one had heterozygote genetic variants of UNC13D and STXBP2 of unclear significance, whereas the other two had no variants. Infection was identified in 8 of 9 patients: adenovirus, HHV6, EBV, and Streptococcus Group A. Only 2 patients received HLH-2004 therapy (dexamethasone, etoposide, cyclosporin-A) and the others received dexamethasone and/or intravenous gamma globulins (IVIG), with rapid resolution of fever (median 2 days). One patient (11%) died of Pseudomonas septicemia and multiorgan failure. At a median follow-up of 7 years (range 2.6-8.1 years), all others (8/9) are long-term survivors with no recurrent HLH, but 2 patients developed adenovirus-related bronchiolitis obliterans. Children presenting with prolonged fever and abnormal blood counts should be evaluated with ferritin, triglycerides, and fibrinogen levels which indicate possible HLH. Early intervention with corticosteroids and/or IVIG may prevent deterioration, spare them from chemotherapy and provide time for more elaborate testing to identify true HLH. Unfortunately, mortality remains a significant risk for these children.

Novel Presentation of Major Histocompatibility Complex Class II Deficiency with Hemophagocytic Lymphohistiocytosis

PurposeMajor histocompatibility complex (MHC) class II deficiency is one of the combined immune deficiency disorders caused by defects in the MHC class II regulatory genes leading to abnormal T cells development and function. Therefore, patients mainly present with increased susceptibility to infections, diarrhea, and failure to thrive. In this report, we present one MHC class II deficient patient with a novel presentation with Hemophagocytic Lymphohistiocytosis (HLH).MethodsImmunophenotyping of lymphocyte subpopulations and HLA-DR expression was assess by flow cytometry. Gene mutational analysis was performed by whole exome and Sanger sequencing.ResultsWe reported a 7-year-old girl, who was diagnosed at age of 2 years with MHC class II deficiency by genetic testing and flow cytometry. Two years later, she developed disseminated BCGitis which was treated with proper antimicrobial agents. At the age of 7 years, she presented with clinical features fulfilling 6 diagnostic criteria of HLH including evidence of hemophagocytic activity in bone marrow aspiration. Accordingly, the diagnosis of HLH was established and the patient was started on IV Dexamethasone, Anakinra and IVIG. Eventually, patient started to improve and was discharged in good condition. Few months later, the patient was readmitted with severe pneumonia and sepsis leading to death.ConclusionPatients with MHC class II deficiency might present with disseminated BCGitis especially if the patient has severe T cell lymphopenia. Additionally, this immune defect might be added to the list of inborn errors of immunity that can be complicated with HLH.

Human herpesvirus-6 infection in a critically ill and immunocompetent patient: a case report

BackgroundHuman herpesvirus-6 is a rare infection in an immunocompetent adult. In existing literature, there is a dearth of knowledge that mainly exists as case reports and case series.Case PresentationIn this case report, we described a 29-year-old female of Myanmarese descent patient from Myanmar who presented with altered mental status and non-specific respiratory and gastrointestinal symptoms. She was initially treated for pneumonia and discharged well. However, she re-presented to the hospital and was subsequently treated for severe central nervous system infection. Cerebrospinal fluid studies detected human herpesvirus-6 polymerase chain reaction with associated high serum human herpesvirus-6 concentration. This infection also triggered hemophagocytic lymphohistiocytosis. Treatment was initiated against both human herpesvirus-6 infection and hemophagocytic lymphohistiocytosis, and she responded to antiviral treatment and steroids, respectively.ConclusionThis case study highlights the need for prompt diagnosis and treatment of this severe disease and the dangerous complications. Additionally, the authors share insights on the diagnostic challenges faced in the treatment of this patient.

Clinical features and risk factors of hepatic sinusoidal obstruction syndrome in children after hematopoietic stem cell transplantation: A single-center experience

Hepatic sinusoidal obstruction syndrome (SOS) is an illness with serious life effects that develops after hematopoietic stem cell transplantation (HSCT). We investigated the risk factors and clinical features of hepatic SOS in children following HSCT in 210 children who underwent allogeneic or autologous HSCT between 2009 and 2021 were analyzed in the context of SOS. The syndrome developed in 22 (10.4%) patients:frequently in neuroblastoma [24% (5/21)], hemophagocytic lymphohistiocytosis [57% (4/7)], and thalassemia major [22% (7/31)]. The median time from HSCT to diagnosis was 16 (6−38) days. Severe disease occurred in 8 (36%) patients, and mild/moderate in 14 (64%) and 4 patients died (18%). In univariate analyses, patient’s age ≤ 2 years [odds ratio (OR)= 3.043, P = 0.028], pretransplant AST and ALT levels > 100 U/L (OR=3.576, P = 0.045), and chemotherapy/radiotherapy to abdomen before transplantation (OR = 3.162, P = 0.044) were determined as risk factors. In multivariate analysis, pre-transplant AST and ALT levels > 100 U/L (OR = 16.04, P = 0.010) and ferritin levels over 1000 mg/dl (OR=5.15, P = 0.047) were significant. The only independent risk factor on mortality was the age ≤ 2 years (P = 0.001). Although our study confirmed several risk factors for SOS, we failed to achieve some well-known risk factors. Precautions should be taken considering the factors affecting liver function before transplantation and the risk of SOS in infants receiving chemotherapy and radiotherapy before transplantation, such as neuroblastoma in which comparable results in respect to the chemotherapy only. The risk factors should be fully elucidated in multicenter studies to improve preventive and therapeutic strategies.

Aggressive Extranodal NK/T-cell Lymphoma with Hemophagocytic Syndrome

Aggressive Extranodal NK/T-cell Lymphoma with Hemophagocytic Syndrome

Novel plasma microRNA expression features in diagnostic use for Epstein-Barr virus-associated febrile diseases

BackgroundEpstein-Barr virus (EBV) is widely infected in humans and causes various diseases. Among them, microRNAs of EBV play a key role in the progression of EBV-associated febrile diseases. There're few specific indicators for rapid differential diagnosis of various febrile diseases associated with EBV, and the lack of more reliable screening methods with high diagnostic utility has led to spaces for improvement in the accurate diagnosis and efficient treatment of relevant patients, making EBV infection a complicated clinical problem. With recent advances in plasma microRNA testing, the apparent presence of EBV microRNAs in plasma can help screen for EBV infection. The gene networks targeted by these microRNAs can also indicate potential biomarkers of EBV-associated febrile diseases. This study aimed to identify some novel miRNAs as potential biomarkers for early diagnosis of respectively EBV-associated febrile diseases. Materials and methodsA total of 110 participants were recruited for this task. First, we performed high-throughput sequencing and preliminary PCR validation of differentially expressed miRNAs in 15 participants with EBV-associated fever (divided into 5 groups, common EBV carriers, infectious mononucleosis (IM) and chronic active EBV infection (CAEBV), EBV-associated Hemophagocytic Lymphohistiocytosis (EBV-HLH), and 3 healthy individuals). After a comprehensive analysis, 10 miRNAs with abnormal expression were screened, and then qRT-PCR was performed in the rest of 95 participants to detect the validation of miRNAs expression in plasma samples. Thereafter, we further investigated their potential for clinical application in EBV-related febrile diseases by using a combination of Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and Protein-protein interaction network analysis. ResultsThrough identification and detailed analysis of the obtained data, we found significant differences in the expression of Hsa-miR-320d, EBV-miR-BART22, and EBV-miR-BART2-3p in blood samples from patients with different EBV-related febrile diseases. We found that the expression levels of Hsa-miR-320d, EBV-miR-BART22, and EBV-miR-BART2-3p in plasma are indicative of determining different disease types of EBV-related febrile diseases, while EBV-miR-BART22 and EBV-miR-BART2-3p may be potential therapeutic targets. ConclusionThe expression levels of Hsa-miR-320d, EBV-miR-BART22, and EBV-miR-BART2-3p suggest that they may be used as transcriptional features for early differential diagnosis of EBV-related febrile diseases, and EBV-miR-BART22 and EBV-miR-BART2-3p may be potential therapeutic targets.

Outcome of primary hemophagocytic lymphohistiocytosis: a report on 143 patients from the Italian Registry.

Primary hemophagocytic lymphohistiocytosis (pHLH) is a severe, life-threatening hyperinflammatory syndrome caused by defects in genes of the granule-dependent cytotoxic pathway. Here we investigated the clinical presentation and outcome in a large cohort of 143 patients with pHLH diagnosed in the last 15 years and enrolled in the Italian registry. The median age at diagnosis was 12 months (interquartile range, 2-81), and 92 patients (64%) fulfilled the HLH-2004 criteria. Of 111 patients who received first-line combined therapy (HLH-94, HLH-2004, Euro-HIT protocols), 65 (59%) achieved complete response and 21 (19%) partial response. Thereafter, 33 patients (30%) reactivated, and 92 (64%) received hematopoietic stem cell transplantation, 78 of whom (85%) survived and were alive at a median follow-up from diagnosis of 67 months. Thirty-six patients (25%) died before hematopoietic stem cell transplantation and 14 (10%) after. Overall, 93 patients (65%) were alive after a median follow-up of 30 months. Unadjusted predictors of non-response were age <6 months and high ferritin and bilirubin levels, while predictors of pre-transplant and overall mortality were high ferritin and bilirubin levels. At multivariable analysis, high levels of ferritin predicted non-response, while high levels of bilirubin predicted pre-transplant and overall mortality. Despite recent advances in therapeutic management, pHLH remains a life-threatening condition with significant early mortality. Liver dysfunction is the main predictor of poor prognosis.

Hemophagocytic Lymphohistiocytosis (HLH) in Patients with Tick-Borne Illness: A Scoping Review of 98 Cases.

Hemophagocytic lymphohistiocytosis (HLH) secondary to tick-borne infections is a rare but potentially life-threatening syndrome. We performed a scoping review according to PRISMA guidelines to systematically analyze the existing literature on the topic. A total of 98 patients were included, with a mean age of 43.7 years, of which 64% were men. Most cases, 31%, were reported from the USA. Immunosuppression was present in 21.4%, with the most common cause being previous solid organ transplantation. Constitutional symptoms were the most common, observed in 83.7% of the patients, while fever was reported in 70.4% of cases. Sepsis was present in 27.6%. The most common laboratory abnormalities in this cohort were thrombocytopenia in 81.6% of patients, while anemia, leukopenia, and leukocytosis were observed in 75.5%, 55.1%, and 10.2%, respectively. Liver enzyme elevation was noted in 63.3% of cases. The H-score was analyzed in 64 patients, with the mean value being 209, and bone marrow analysis was performed in 61.2% of patients. Ehrlichia spp. was the main isolated agent associated with HLH in 45.9%, followed by Rickettsia spp. in 14.3% and Anaplasma phagocytophilum in 12.2%. Notably, no patient with Powassan virus infection or Lyme borreliosis developed HLH. The most common complications were acute kidney injury (AKI) in 35.7% of patients, shock with multiple organ dysfunction in 22.5%, encephalopathy/seizure in 20.4%, respiratory failure in 16.3%, and cardiac complications in 7.1% of patients. Treatment included antibiotic therapy alone in 43.9%, while 5.1% of patients were treated with immunosuppressants alone. Treatment with both antibiotics and immunosuppressants was used in 51% of patients. Appropriate empiric antibiotics were used in 62.2%. In 43.9% of cases of HLH due to tick-borne disease, patients received only antimicrobial therapy, and 88.4% of those recovered completely without the need for immunosuppressive therapy. The mortality rate in our review was 16.3%, and patients who received inappropriate or delayed empiric therapy had a worse outcome. Hence, we suggest empiric antibiotic treatment in patients who are suspected of having HLH due to tick-borne disease or in whom diagnostic uncertainty persists due to diagnostic delay in order to minimize mortality.

Association of a decreased platelet count with poor survival in patients with adult secondary hemophagocytic lymphohistiocytosis.

We aimed to examine the association between baseline platelet count (PLT) and the prognosis of adult secondary hemophagocytic lymphohistiocytosis (sHLH). Data from 292 patients with pretreatment platelet counts were retrospectively analysed from January 2016 to December 2020. We categorized platelet count into quartiles. Multivariable Cox proportional hazards models and restricted cubic splines (RCS) were used to evaluate the relationship between platelet count and mortality. During a median follow-up of 53 (interquartile ranges, 17-223) days, a total of 208 deaths occurred. After adjusting for multiple variables, a non-linear and inverse relationship was observed between platelet count and mortality in sHLH patient (P for nonlinearity=0.002). For non- lymphoma-associated haemophagocytic lymphohistiocytosis (non-LHLH), a similar curve was also observed (P for nonlinearity =0.028). Decreased PLT (PLT Q4) was associated with an increased risk of mortality (adjusted hazard ratio: 1.97; 95% confidence interval: 1.28-3.04; Ptrend =0.005). Similar results were observed in the LHLH subgroup (adjusted hazard ratio: 1.84; 95% confidence interval: 1.05-3.24; Ptrend =0.024) but not in the non-LHLH subgroup (Ptrend =0.266). Baseline platelet count demonstrated a nonlinear and inverse association with an increased risk of mortality among adult sHLH patients. This method is used to identify sHLH patients with inferior overall survival due to its low cost and universal availability.

Emergencies in Dengue Fever

Dengue is often seen as an acute infection with fever and thrombocytopenia where complications such as shock and hemorrhage need to be averted while the patient recovers with supportive care. However, dengue can also be a differential diagnosis in the emergency care setting. Acute encephalopathy, acute renal failure, hepatitis, liver failure, acute pancreatitis, noncardiogenic pulmonary edema, acute respiratory distress syndrome, compartment syndrome, intracranial bleeds, hemophagocytic lymphohistiocytosis are few of the emergencies that may be seen in the course of dengue fever. These complications need prompt recognition and management to ensure better outcomes.

Value of hemophagocytosis in the diagnosis of hemophagocytic lymphohistiocytosis in critically ill patients.

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. 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. 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. 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.

HLH as an additional warning sign of inborn errors of immunity beyond familial-HLH in children: a systematic review.

Hemophagocytic 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. 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. A systematic search for studies meeting inclusion criteria was conducted in PubMed, EMBASE, MEDLINE, and Cochrane Central. Quality assessment was performed through JBI criteria. 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. 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. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371425, PROSPERO, CRD42022371425.

Characterization of T-/natural killer cell lymphoproliferative neoplasms associated with systemic, chronic, active Epstein-Barr virus in adults: A report of 5 cases in a Western population.

Because of its low frequency in adult populations and clinical and laboratory overlap with hemophagocytic lymphohistiocytosis and other T-cell lymphomas, T-cell/natural killer (NK) cell systemic, chronic, active Epstein-Barr virus (EBV) (T/NK sCAEBV) infection remains underdiagnosed, preventing critical, prompt therapeutic interventions. We report a 5-case series that included 2 adult patients with T/NK sCAEBV and 3 additional adult patients with T/NK lymphomas with concomitant systemic EBV infection to review these entities' overlapping diagnostic and clinical features. Approximately 95% of the world population has been infected with EBV during their lifetime, and infection is usually asymptomatic, with symptomatic cases eventually resolving spontaneously. A small subset of immunocompetent patients develops CAEBV, a life-threatening complication resulting from EBV-infected T-cell or NK cell neoplastic lymphocytes. The sites of end-organ damage in T/NK sCAEBV demonstrate pathologic findings such as reactive lymphoid proliferations, making the diagnosis difficult to establish, with the only curative option being an allogeneic hematopoietic stem cell transplant. This diagnosis is most prevalent in Asia, with few cases reported in Western countries. Adult age is an independent risk factor for poor outcomes, and most cases are diagnosed in pediatric populations.

Low Percentage of Perforin-Expressing NK Cells during Severe SARS-CoV-2 Infection: Consumption Rather than Primary Deficiency.

Genetic defects in the ability to deliver effective perforin have been reported in patients with hemophagocytic lymphohistiocytosis. We tested the hypothesis that a primary perforin deficiency might also be causal in severe SARS-CoV-2 infection. We recruited 54 volunteers confirmed as being SARS-CoV-2-infected by RT-PCR and admitted to intensive care units or non-intensive care units and age- and sex-matched healthy controls. Compared with healthy controls, the percentage of perforin-expressing CD3-CD56+ NK cells quantified by flow cytometry was low in COVID-19 patients (69.9 ± 17.7 versus 78.6 ± 14.6%, p = 0.026). There was no correlation between the proportions of perforin-positive NK cells and T8 lymphocytes. Moreover, the frequency of NK cells producing perforin was neither linked to disease severity nor predictive of death. Although IL-6 is known to downregulate perforin production in NK cells, we did not find any link between perforin expression and IL-6 plasma level. However, we unveiled a negative correlation between the degranulation marker CD107a and perforin expression in NK cells (r = -0.488, p = 10-4). PRF1 gene expression and the frequency of NK cells harboring perforin were normal in patients 1 y after acute SARS-CoV-2 infection. A primary perforin defect does not seem to be a driver of COVID-19 because NK perforin expression is 1) linked neither to T8 perforin expression nor to disease severity, 2) inversely correlated with NK degranulation, and 3) normalized at distance from acute infection. Thus, the cause of low frequency of perforin-positive NK cells appears, rather, to be consumption.

Current and emerging pharmacotherapies for cytokine release syndrome, neurotoxicity, and hemophagocytic lymphohistiocytosis-like syndrome due to CAR T cell therapy.

Chimeric antigen receptor (CAR) T cells have revolutionized treatment of multiple hematologic malignancies. Engineered cellular therapies now offer similar hope to transform management of solid tumors and autoimmune disease. However, toxicities can be serious and often require hospitalization. We review the two chief toxicities of CAR T therapy, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and the rarer immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. We discuss treatment paradigms and promising future pharmacologic strategies. Literature and therapies reviewed were identified by PubMed search, cited references therein, and review of registered trials. Management of CRS and ICANS has improved, aided by consensus definitions and guidelines that facilitate recognition and timely intervention. Further data will define optimal timing of tocilizumab and corticosteroids, current foundations of management. Pathophysiologic understanding has inspired off-label use of IL-1 receptor antagonism, IFNγ and IL-6 neutralizing antibodies, and janus kinase inhibitors, with data emerging from ongoing clinical trials. Further strategies to reduce toxicities include novel pharmacologic targets and safety features engineered into CAR T cells themselves. As these potentially curative therapies are used earlier in oncologic therapy and even in non-oncologic indications, effective accessible strategies to manage toxicities are critical.

Germline defects of familial hemophagocytic lymphohistiocytosis-related genes presenting as adult-onset peripheral T-cell lymphoma.

Germline mutations in genes involved in perforin-granzyme-mediated cytotoxicity such as PRF1, UNC13D, STX11, and STXBP2 were known to cause familial hemophagocytic lymphohistiocytosis (FHL). In this study, we reported a unique group of 3 patients with germline mutations of UNC13D and STX11 genes and presented as adult-onset peripheral T-cell lymphoma (PTCL) with cytotoxic T-cell phenotype and atypical lymphoma presentations. CD107a degranulation assay and NK-cell activity analysis demonstrated impaired cytotoxic function of the NK/T-cells of the patients with FHL-related mutations. Gene expression profile study revealed that up-regulated genes of the cytotoxic T-cells were enriched in autoimmune-related pathways. It was possible that impaired cytotoxic lymphocyte-mediated immune surveillance and autoantigen stimulation may both participate in PTCL oncogenesis. Germline defects of FLH-related genes may represent a novel predisposing factor for PTCLs.

Multisystem inflammatory syndrome in children post-COVID-19: A case report

Multisystem inflammatory syndrome in children (MIS-C) is a complication associated with COVID-19. It is generally characterized by signs of inflammation, including fever and rashes. This is due to neutrophil hyperactivation and leads to a widespread release of inflammatory mediators, which can cause organ damage or even death in severe cases. These symptoms may mimic those of Kawasaki disease, toxic shock syndrome, hemophagocytic lymphohistiocytosis, etc. In this article, we describe one such case of MIS-C of a 21-month-old girl who presented with a high-grade fever of 38.1°C, which was not responsive to antibiotics. She went on to develop rashes on the next day, requiring more workup with detailed history and investigations. We will also discuss the similarities and differences of the mimicking diseases.

Familial Hemophagocytic Lymphohistiocytosis Due to PRF1 Mutation Triggered by Enterovirus.

Familial Hemophagocytic Lymphohistiocytosis Due to PRF1 Mutation Triggered by Enterovirus.

Comparison of different treatment regimens and analysis of prognostic factors in secondary hemophagocytic lymphohistiocytosis in adults: A single-center retrospective study.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease caused by immune hyperactivation. The overall survival (OS) of adults with secondary HLH remains suboptimal and new treatment strategies are needed. This study aimed to compare the efficacy of different regimens in the treatment of secondary HLH in adults and analyze the prognostic factors affecting patient survival. The clinical data of 245 adults with secondary HLH admitted to our hospital from January 2016 to October 2021 were analyzed retrospectively. The patients were divided into 3 groups according to different treatment regimens: corticosteroids therapy + chemotherapy + supportive treatment group (JHZ group), chemotherapy + supportive treatment group (HZ group) and corticosteroids therapy + supportive treatment group (JZ group). The clinical efficacy was compared among the 3 groups after treatment, and progression-free survival (PFS) and overall survival (OS) were calculated. Additionally, risk factors associated with prognosis were also analyzed with Cox regression analysis. The objective response rate (ORR) in the JHZ group was higher than that in the HZ group and JZ group, but there was no significant difference between the 3 groups. Also, the patients in the JHZ group had the longest OS and median PFS. Further Cox regression analysis suggested that hyperbilirubinemia was an independent risk factor for OS in secondary HLH patients. A combination of corticosteroids therapy, chemotherapy and supportive therapy is superior to the other 2 regimens in the clinical benefit in the treatment of secondary HLH in adults, and thus may be a preferred and feasible treatment regimen. Moreover, hyperbilirubinemia was a risk factor for prognosis that has crucial guiding significance for clinical treatment of patients with secondary HLH.