Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study.

IntroductionSerum ferritin is an acute phase protein, and serum ferritin levels have been noted to rise in response to pro-inflammatory cytokines. Hyperferritinemia is also common in secondary hemophagocytic lymphohistiocytosis (HLH); ferritin level has been shown to independently predict mortality in critically ill patients with HLH. This study sought to explore whether higher serum ferritin levels upon ICU admission could predict increased mortality and prolonged ICU stay in patients with tropical fever.ObjectivesThe objectives of this study were to determine the association between serum ferritin levels measured within 72 hours of ICU admission and mortality and and to assess the incidence of secondary HLH in patients with tropical infections.Materials and methodsThis was a prospective observational study conducted in the ICU of a tertiary teaching hospital between 1st January 2023 and 30th November 2023. Adult patients with acute febrile illness (fever >38.3°C) due to a tropical infection (defined as fever for more than 48 hours with no focus, and positive serological evidence or blood culture viz IgM for leptospira, NS1/IgM for dengue, Weil Felix/IgM for scrub typhus, IgM for brucella, anti-HAV IgM and HEV IgM for hepatitis A and E, peripheral smear for malaria, and blood culture for enteric fever or melioidosis) were made part of the study. Serum ferritin levels were measured within 72 hours of admission, irrespective of clinical findings. A diagnosis of HLH was made if if at least 5 of 8 diagnostic criteria based on HLH-2004 protocol were met. Mortality data were collected for all enrolled patients. Sample size was calculated after doing a pilot study using data of tropical fever patients admitted over 6 months duration. It showed a sample size requirement less than 10. Hence decision was made to take consecutive sampling over 1 year period. Statistical analysis was performed utilizing IBM SPSS Statistics version 25. The association between study variables and mortality was assessed using the Chi-square test. To compare the significance of mean differences in study variables concerning the outcome, the unpaired t-test was employed for parametric variables, and the Mann-Whitney U test was used for nonparametric variables. Receiver operator characteristic (ROC) curve analysis was utilized for assessing the predictive value of serum ferritin.Results28 patients were studied. The mean ferritin level of patients who survived (n=19) was 7548.65 ng/mL (median=2213, IQR 696.4-11211.4), while that of patients who succumbed to disease (n=9) was 22395.63 ng/mL (median=18185, IQR 4309.9–40000). This difference was statistically significant (p=0.017). 7 patients had secondary HLH. 18 patients received steroid therapy. Respiratory failure requiring intubation and mechanical ventilation was found to increase mortality (p=0.049), while shock (p=0.098), and secondary HLH (p=0.646) did not have a statistically significant association with mortality. Serum ferritin value higher that 6629.8 ng/mL was associated with poor outcome (AUC: 0.784, 95% CI: 0.595-0.972,).DiscussionSerum ferritin values can be predictive of clinical outcomes in patients with tropical fever. Incidence of secondary HLH has relatively increased in patients with tropical fever. However in the current study a statistically significant correlation between HLH and icu mortality could not be detected.

Ruxolitinib combined with dexamethasone in adult patients with newly diagnosed Hemophagocytic lymphohistiocytosis: A single-center pilot trial.

Hemophagocytic lymphohistiocytosis (HLH) is not one condition but descriptive of a life-threatening, hyper-inflammatory syndrome with multiorgan involvement with a variety of triggers, both genetic and environmental. It is described as primary HLH (familial HLH) and secondary HLH (acquired following malignancy, rheumatologic disorders, primary immune deficiencies or infection alone). Infections commonly precipitate HLH in those with primary HLH, in combination with an underlying disease (malignancy, rheumatologic or primary immune deficiency) or may be the sole trigger.1 Many people with “secondary” HLH may also have potentially pathogenic polymorphisms in an HLH- associated gene.2 Rapid diagnosis of HLH and initiation of appropriate treatment is essential to reduce mortality from this condition. PATHOGENESIS Across the spectrum of HLH, impaired natural killer (NK) and cytotoxic T lymphocytes (CTL) function has been a consistent finding. These cytotoxic deficiencies lead to loss of feedback inhibition on activated macrophages resulting in a “cytokine storm,” causing multiorgan tissue damage. The excessive activated macrophages engulf host blood cells (hemophagocytosis), which may be seen in biopsies from the bone marrow, lymph nodes, liver and spleen.1,3 Around 25% of all HLH presentations are thought to be autosomal recessive primary HLH and these commonly present in early life, although may develop at any age. Genes identified as causing monogenic HLH include: PRF1, UNC13D, STX11, STXBP2. Other genetic causes of HLH include primary immunodeficiency syndromes including Griscelli syndrome (RAB27A), Chediak-Higashi syndrome (LYST), Hermansky-Pudlak 2 (Ap3B1) and X-linked lymphoproliferative disease 1 and 2 (SH2D1A, XIAP).2 Viral infections are a common precipitant in primary HLH, malignancy and in those without known underlying disease. Epstein-Barr virus (EBV) is a well-described trigger and X-linked lymphoproliferative disease is almost exclusively associated with EBV.4,5 Other common viruses found in association with HLH include cytomegalovirus (CMV), parvovirus, herpes simplex virus (HSV) (particularly neonates), varicella-zoster virus (VZV), measles, human herpes virus (HHV)-6, HHV-8, H1N1 influenza virus, parechovirus, parvovirus, Dengue virus and HIV. Bacteria causing HLH are far less common, but Gram-negative bacterial infections, Brucellosis and Mycobacterium tuberculosis associated HLH have been described. HLH has also been described in fungal infections such as Histoplasma capsulatum and in parasitic infections such as Leishmania and malaria.6 Malignancy is a common cause of HLH, especially lymphoid malignancies with acute B-lymphoblastic leukemia being the commonest. Cytokines produced by malignant cells activate CTLs, NK cells and macrophages. HLH also can occur during hematopoietic stem cell transplantation, especially in the early phase.6 Rheumatologic conditions, especially systemic-onset juvenile idiopathic arthritis and less commonly polyarticular juvenile idiopathic arthritis, systemic lupus erythematous and Kawasaki disease can present with HLH at diagnosis, during treatment or any time in response to infection; therapeutic drugs themselves may trigger HLH. In the context of a rheumatologic condition, HLH is referred to as macrophage activating syndrome.6 Any of the primary immune deficiency disorders will increase the risk of HLH as a result of the immune dysregulation. In combined immune deficiencies, viral infections are commonly associated with HLH, especially EBV and CMV, and in chronic granulomatous disease patients, common infectious precipitants were Burkholderia cepacia, Leishmania and fungi. The development of HLH in patients with absence of T and NK cells indicates excess macrophage activation may occur independently of lymphocytes.7 CLINICAL PRESENTATION AND INVESTIGATION OF HLH Regardless of the underlying cause, HLH is a clinical diagnosis with supporting laboratory criteria. Typically, patients are febrile, acutely unwell with multiorgan involvement; therefore, the initial differential diagnosis includes liver disease, encephalitis, malignancy, autoimmune, rheumatologic diseases and general sepsis. A family history of immunodeficiency, consanguinity or autoimmunity may be relevant. Key clinical features identified in the HLH-94 study were hepatosplenomegaly (95%), fever (93%), lymphadenopathy (33%), neurologic symptoms (33%) and rash (31%).8 Other features include bleeding (epistaxis, hematemesis, rectal bleeding, petechiae and purpura), liver dysfunction and respiratory insufficiency. Specific features (such as albinism) may point towards syndromes predisposing to HLH (eg, Chediak-Higashi syndrome, Griscelli syndrome type 2 and Hermansky-Pudlak syndrome type 2). In the neonate, HLH may present with isolated central nervous system disease or fulminant liver failure.6 Figure 1 outlines suggested investigations and management. Early laboratory parameters in a septic child which indicate the development of HLH are a climbing ferritin >500 μg/L (ferritin >10 000 μg/L in children was found to be 90% sensitive and 96% specific for HLH9 however, diagnosis and treatment should not be delayed until ferritin reaches this threshold); evolving cytopenias which are transfusion dependent, (anemia and thrombocytopenia present in over 80% patients on presentation9); and multiple organ involvement (renal, liver, neurologic). High triglycerides and low fibrinogen further support the diagnosis of HLH. A rising C-reactive protein occurs, while erythrocyte sedimentation rate may fall due to reduced fibrinogen from liver consumption.6 Low immunoglobulins or lymphocyte subsets point towards an underlying immunodeficiency although commonly deranged by severe illness.FIGURE 1.: Investigation and management of HLH. CRP indicates C-reactive protein; ESR, erythrocyte sedimentation rate; HLA, human leukocyte antigen; IV, intravenous; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; PCR, polymerase chain reaction. Full blood count (FBC), Chest radiograph (CXR), haematopoietic stem cell transplant (HSCT).Bone marrow biopsy, where possible, is useful to provide evidence of hemophagocytosis and to look for any underlying malignancy. It should also be sent for microscopy, culture and viral and Leishmania polymerase chain reactions (in endemic areas). Hemophagocytosis is not always visualized in the bone marrow during HLH; it may also be present in lymph nodes, liver and spleen and is not specific for HLH. If lymphadenopathy is present, node biopsy should be taken as lymphoma is frequently the underlying condition. Cerebrospinal fluid shows a pleocytosis in 50% of cases and a high protein. DIAGNOSIS The HLH-2004 protocol uses the presence of 5/8 criteria to diagnose HLH: (1) fever, (2) splenomegaly, (3) bicytopenia, (4) hypertriglyceridemia and or hypofibrinogenemia, (5) hemophagocytosis, (6) low/absent NK cell activity, (7) hyperferritinemia (>500) and (8) high soluble interleukin-2 receptor levels.10 However, probable HLH should be considered and treated well before the presence of 5/8 criteria, as several of the tests are only done in reference laboratories and if treatment is delayed for these results, it may be too late to reverse the process. Other common features aiding diagnosis include liver enzyme derangement and neurologic abnormalities. All cases of HLH should be investigated for primary immunodeficiency syndromes, and underlying genetic causes as clinical presentation cannot distinguish between primary and secondary HLH. Soluble interleukin-2 receptor alpha is a useful marker of disease activity but is not available in most centers. Protein expression studies and genetic panels are helpful in diagnosing primary HLH conditions which will need HSCT for definitive cure. MANAGEMENT Patients with HLH commonly require pediatric intensive care support to maximize chances of survival. Replacement blood products are necessary to maintain hemoglobin, platelet levels and normal coagulation. Induction of amenorrhea is advised in menstruating girls. Whilst supportive therapy is given, the priorities for initial management are identifying and treating the trigger, exclusion of malignancy (as this diagnosis is difficult once immunosuppression has been given) and early immune modulation.11 These patients may deteriorate quickly and should be treated in centers with facilities for bone marrow transplantation and intensive care. Prompt aggressive therapy may be necessary even when infection is present. It may be possible to tailor therapy according to the severity of the condition and the rapidity of response. In some cases, where early intervention produces a rapid response then induction chemotherapy may be avoided or weaned with close monitoring. However, if the condition does not respond to initial management, then early recourse to more aggressive treatment will be necessary; in primary, persistent or recurring HLH, chemotherapy should be continued to HSCT.12 Opportunistic infection during therapy may confound the picture and careful surveillance is necessary particularly where symptoms recur after an apparent initial response. Key markers of response to treatment are resolution of fever, reducing ferritin (although it can be slow to decline and levels fluctuate with blood transfusions), reducing transfusion requirements, improved coagulation parameters and resolving organ dysfunction. Neurologic involvement should be monitored with serial cerebrospinal fluid analysis with each intrathecal therapy and neuroimaging. Weekly monitoring of soluble interleukin-2 receptor alpha or soluble CD163 may be helpful to guide reduction or increase in therapy. Markers of infection should be monitored for response to treatment.12 When induction therapy is being planned, HLA tissue typing should be sent to allow for rescue HSCT without delay if this becomes necessary. The HLH-1994 protocol8 recommends combination chemotherapy [etoposide, ciclosporin A, corticosteroids and intrathecal methotrexate if (central nervous system) involvement] followed by HSCT for persistent, recurring or primary HLH. The HLH-2004 protocol modified this with early cyclosporin, but survival was not significantly improved.10 An alternate regimen using steroids and anti-thymocyte globulin (ATG) was similarly effective.13 Survival is dramatically improved with these protocols compared with survival without treatment with an overall survival at 3 years of 55% (51% in the familial cases) and 3-year probability of survival 3 years after HSCT of 62%.8 Trials comparing a combination of the two main regimes (the Hybrid Immunotherapy trial and the European cooperative pilot study for testing Hydbrid ImmunoTherapy for Hemophagocytic LymphoHistiocytosis (Euro-HIT-HLH) trial) have finished recruiting, and results are awaited. Other studies of alternate or combination approaches have also been initiated with agents such as alemtuzumab, ruxolitinib and anti-interferon gamma monoclonal antibody. Alemtuzumab (monoclonal antibody to CD52 protein expressed on surface of mature T cells and NK cells) may be a useful salvage agent for refractory HLH enabling survival to HSCT.12 CONCLUSIONS HLH is a life-threatening hyperinflammatory condition that needs to be considered early in any patient with fever, multiorgan failure and cytopenias. Infection plays a key role as a trigger but also causes concern for clinicians when delivering the necessary immunosuppression to terminate the cytokine storm. Immunomodulatory treatment should be started if high clinical suspicion, and not wait for specific immunology and genetic testing. Early recourse to chemotherapy and planning for HSCT if HLH is recurrent or refractory to initial treatment. Survival has improved with this treatment, however, mortality remains very high.

Low Utility of the H-Score and HLH-2004 Criteria to Identify Patients with Secondary Hemophagocytic Lymphohistiocytosis after CAR-T Cell Therapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Background: Burden of disease in India (2005) had estimated that there had been an increase in number of stroke cases in India during the last one and a half decade by 17.05%, thus showing worrying upward trends of disease Objective: To investigate the profile, risk factors, and clinical outcomes in patients with acute stroke. Methods: The study design was prospective observational study was conducted including 65 patients aged more than 18 years admitted in medical wards from November 2017 to April 2018. Detailed clinical profile and investigations were done. Results: Total 70 patients were included in this study. There were more male percent (36.17%) than females (63.83%). The age distribution between the Male and Female and association between the age and gender is found not significant at 5% level of Significance. All patients underwent computed tomography or magnetic resonance imaging; 81% had cerebrovascular imaging.. Conclusion: In conclusion, recovery from acute stroke which found to be highly significant at 5% level of significance.

Modern management of children with haemophagocytic lymphohistiocytosis.

To assess the etiologies and outcomes of patients with secondary hemophagocytic lymphohistiocytosis in the PICU. Prospective observational cohort study. A single PICU at a pediatric tertiary hospital in Hanoi, Vietnam. Pediatric patients meeting the criteria for secondary hemophagocytic lymphohistiocytosis. None. Between June 2017 and May 2018, 25 consecutive patients with a mean (SD) age of 23.3 months (21.6 mo) were included. Collected variables included etiologies of hemophagocytic lymphohistiocytosis and clinical and laboratory findings at admission. The Pediatric Index of Mortality 2 score at admission was calculated. Outcomes were death and multiple organ dysfunction. The severity of multiple organ dysfunction was assessed by the Pediatric Logistic Organ Dysfunction 2 score. The mean (SD) Pediatric Index of Mortality 2 predicted mortality rate was 5.6% (7.6%). Cytomegalovirus and Epstein-Barr virus coinfections (60%) were the most common suspected etiology of hemophagocytic lymphohistiocytosis. Other etiologies included Epstein-Barr virus sole infections (20%), cytomegalovirus sole infections (16%), and one unknown cause (4%). Multiple organ dysfunction (excluding hematologic failure) was found in 22 patients (88%) with death occurring in 14 patients (56%). The mean (SD) Pediatric Logistic Organ Dysfunction 2 predicted mortality rate among patients with multiple organ dysfunction was 11.9% (11.2%). Despite having lower Pediatric Index of Mortality 2 predicted mortality rates at admission, Epstein-Barr virus-cytomegalovirus coinfection cases with multiple organ dysfunction had slightly greater Pediatric Logistic Organ Dysfunction 2 predicted mortality rates than Epstein-Barr virus sole infection cases with multiple organ dysfunction: 12.2% (10.5%) versus 11.3% (11.0%). However, these rates were lower than cytomegalovirus sole infection cases with multiple organ dysfunction (14.4% [16.3%]). Area under the curve values for Pediatric Index of Mortality 2 and Pediatric Logistic Organ Dysfunction 2 were 0.74 (95% CI, 0.52-0.95) and 0.78 (95% CI, 0.52-1.00), respectively, suggesting that both scales were fair to good at predicting mortality. Viral infections, particularly Epstein-Barr virus-cytomegalovirus coinfections, were a common cause of secondary hemophagocytic lymphohistiocytosis. The implication of these coinfections on the clinical course of hemophagocytic lymphohistiocytosis needs to be delineated.

Introduction: Data regarding the pattern and outcome of infective endocarditis from developing countries are sparse and there have been few studies in our part of the world understanding the clinical profile and outcome of patients with infective endocarditis. Methods: It was a hospital based descriptive retrospective cross-sectional with the objective on clinical profile and outcome of infective endocarditis patients admitted in tertiary care center in eastem part of Nepal. The study included cases admitted in department of internal medicine ward, BPKIHS with diagnosis of infective endocarditis from year 2008 to 2015. Results: A total of 20 patients were diagnosed as case of infective endocarditis during the period from 2008 to 2015 in department of internal medicine. The median age of study group was 31 years (range 14-56). Male to female ratio was 9:1. Among various risk factors, history of Intravenous drug use was the main risk factor present in 50% of patients, followed by definite rheumatic heart disease in 40% of study population. Fever, Chills and sweats were main symptom present in all patients anemia in 90 %, heart murmur in 80%, anorexia in 45%, myalgia in 35%, splenomegaly in 15%, neurological manifestation, clubbing, Roth's s and embolic phenomenon in 5% of patients. The most common valve involved was tricuspid valve, present in 50% patient, followed by mitral valve in 35% patient and aortic valve in 15% of patients. Anemia was most common laboratory abnormalities present in 90% of the patients followed by leukocytosis in 80% of patients, microscopic hematuria and disarranged renal function test was present in 40% of the patients. Blood culture positivity was seen in 30% of cases and the pathogen isolated was Staphylococcus aureus. Prior antibiotic treatment was received by 40% of patients. Acute Renal failure was the main complication appeared which was present in 25% of patients followed by Neurological manifestations in 5% and peripheral embolic phenomenon was present 5% of patients. Conclusion: The spectrum of our infective endocarditis patients differ from those seen in the west in terms of epidemiology, predisposing factors, microbiology, complications, and outcome. Fever, pallor and heart murmur were most common symptoms and acute renal failure was the most common complication. Majority of our patients improve despite having lack of surgical backup. Culture-negative endocarditis continues to have a high prevalence in developing countries like Nepal, largely due to prior antibiotic use before clinical presentation.

Background: Heat stroke is a growing public health concern exacerbated by rising temperatures and prolonged heat waves. This study examines the clinical profile, prognostic markers, and outcomes of heat stroke patients presenting to a tertiary care center in India and compares findings with previous global studies. Objective: The objective of this study was to analyze the clinical profile, prognostic markers, and outcomes of heat stroke patients presenting to a tertiary care center in India and to compare findings with previous global studies. Materials and Methods: A retrospective study was conducted between March and July 2024 at a tertiary care center in Eastern India. Data on demographics, clinical parameters, laboratory values, and outcomes were collected and analyzed using appropriate statistical methods. Results: During the study period, 43 patients were admitted with heat stroke, the mean age (in years) was 57, and 67% were male. The overall mortality rate was 21%. Significant predictors of mortality included hypotension (systolic blood pressure <100 mmHg, P = 0.040), tachypnea (respiratory rate >20/min, P = 0.001), Glasgow Coma Scale score <9 (P < 0.001), elevated creatinine, and multi-organ dysfunction syndrome involving the renal system and central nervous system (P < 0.01). Younger, active individuals were disproportionately affected due to occupational exposure to high ambient temperatures. Conclusion: Our findings highlight key clinical and biochemical predictors of poor outcomes in heat stroke. Indian patients, being younger and functionally active, may face increased exposure to high ambient temperatures.

Cytokine Patterns for Secondary HLH: Experiences from a Single Center

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease. In clinical practice, we have observed that some HLH patients who have features of systemic autoinflammatory diseases (SAIDs) exhibit unique clinical manifestations and outcomes different from other HLH patients.We analyzed data from 25 HLH patients who were considered to have SAIDs; data were collected from patients of our center between January 1, 2015 and September 1, 2018.The median age of the patients was 1.75 years. In the early phase, all patients had a fever and 92% of patients had a rash; 96% of patients had high white blood cell count (WBC), C-reaction protein, and erythrocyte sedimentation rate. With progression, the above laboratory results decreased gradually. During the HLH period, we compared SAIDs-related HLH and Epstein-Barr virus (EBV)-related HLH and found that rash was more common (92%, P < .001) and splenomegaly was less common (64%, P = .023) in SAIDs-related HLH. Further, WBC, ferritin, and Interleukin-6 levels in SAIDs-related HLH patients were higher than those in EBV-related HLH patients. In contrast, hemoglobin, triglyceride, sCD25, Interleukin-10, and interferon-γ levels in SAIDs-related HLH patients were lower compared with those in EBV-related HLH patients. SAIDs-related HLH patients received a modified HLH-2004 protocol at our center. Most patients had a good prognosis.We provide a summary of the unique clinical and laboratory features, treatment protocols, and outcomes of SAIDs patients with HLH at onset. The findings indicate that these patients had a better response to corticosteroids and cyclosporin compared with EBV-related HLH patients.

Context: To study the demographics and clinical profile of patients with acute pulmonary embolism (PE) and impact of management as per risk stratification on outcome of patients with acute PE. Materials and Methods: Prospective observational study of demographics, clinical profile, risk stratification, management, and outcome of patients presenting with acute PE from August 2016 to July 2017. Results: One hundred and fifty patients who were detected to have acute pulmonary thromboembolism with a mean age of 45.08 years, with 70% being males, were included in the study. There were 6 (4%) patients in high-risk group, 69 (46%) patients in intermediate-high subgroup, 39 (26%) patients in intermediate-low subgroup and 36 (24%) patients in low-risk group as per the ESC 2019 guidelines using sPESI score, shock/hypotension, right ventricle (RV) dysfunction and cardiac marker elevation. 72 patients (52%) had antecedent deep vein thrombosis (DVT) of which 60 patients has proximal, whereas 12 patients had distal DVT. One hundred and forty-seven patients (98%) had moderate-to-severe TR, 117 patients (78%) had evidence of right atrium/RV dysfunction and 27 patients (18%) had evidence of thrombus in the heart. Computed tomography pulmonary angiogram showed middle pulmonary artery thrombus/dilatation in 63 patients (42%), saddle thrombus in 18 patients (12%), partial thrombus in the left pulmonary artery (LPA) and right pulmonary artery (RPA) in 84 (56%) and 75 (50%) patients, respectively. Majority (86%) of patients with tenecteplase; 9 (10.3%) patients with streptokinase and 3 (3.4%) was thrmobolysed with alteplase. Conclusion: PE can present with unexplained dyspnea and atypical chest pain, among other signs and symptoms. Early diagnosis, risk stratification, and guideline-directed prompt management can lead to favorable outcome.

Ruxolitinib in adult patients with secondary hemophagocytic lymphohistiocytosis.

Studies on microorganisms in a large cohort of patients with congenital heart disease (CHD) and infective endocarditis (IE) are rare. Using a nationwide survey, the relationship between causative microorganisms and clinical profiles in patients with CHD and IE was investigated. Data from 188 patients with CHD (pediatric patients (n=113), mean age, 6.2+/-4.9 years; adult patients (n=75), mean age 28.4+/-13.4 years) and IE from 60 institutions were analyzed. Causative microorganisms were Streptococcus species (94:50.0%), Staphylococcus species (68:36.2%), Haemophilus species (9:4.8%), Candida (5:2.7%), Pseudomonas species (4:2.1%) and other unclassified microorganisms (8:4.3%). Staphylococcal IE was observed significantly higher in perioperative IE (11/16), in cyanotic patients (32/73) and patients younger than 1 year old (11/16). Streptococcal IE was observed significantly higher in acyanotic patients (64/109) and patients aged 16 years or older (48/75). Total mortality was 20/188 (10.6%) and was high for candidial (2/5; 40%) and pseudomonal IE (2/4; 50%). Mortality was highly associated with younger age, especially infants (5/16), and methicillin-resistant staphylococcal IE (6/15). The causative microorganisms are significantly related to the clinical profile and outcome in patients with IE and CHD. These results form the basis for selecting appropriate antibiotics for prevention and management.

To clarify the prevalence, risk factors, outcome, and outcome-related factors of hemophagocytic lymphohistiocytosis (HLH) in patients with dermatomyositis (DM), polymyositis (PM), or clinically amyopathic dermatomyositis (CADM). Data of patients with DM, PM, or CADM who were admitted to the First Affiliated Hospital of Zhejiang University from February 2011 to February 2019 were retrospectively collected. Patients diagnosed with HLH constituted the case group. A 1:4 case-control study was performed to identify risk factors for HLH in patients with DM, PM, or CADM through comparison, univariate, and multivariate logistic regression analysis. Intragroup comparison was made among patients with HLH to identify factors influencing unfavorable short-term outcome. HLH was a rare (4.2%) but fatal (77.8%) complication in patients with DM, PM, or CADM. The retrospective case-control study revealed that higher on-admission disease activity (p = 0.008), acute exacerbation of interstitial lung disease (AE-ILD, p = 0.002), and infection (p = 0.002) were risk factors for complication of HLH in patients with DM, PM, or CADM. The following intragroup comparison showed that higher on-admission disease activity (p = 0.035) and diagnosis of CADM (p = 0.039) might influence the short-term outcome of patients with HLH. However, no risk factor was identified after false discovery rate correction. In this study, secondary HLH was a fatal complication, with higher on-admission disease activity, AE-ILD, and infection working as risk factors. The underlying role of infection and autoimmune abnormality in HLH in connective tissue disease was subsequently noted. Clinical factors influencing the short-term outcome of patients with secondary HLH require further study.