INTRODUCTION

Macrophage Activation Syndrome (MAS) is a rare but life threatening pro-inflammatory complication of multiple autoimmune diseases leading to cytokine storm. We report a case of MAS as a presenting manifestation of Systemic Lupus Erythematosus.

A 32-year-old female, newly diagnosed with Systemic Lupus Erythematosus (SLE), presents with a 3-month history of fever and joint pains, which began a few days after receiving her first dose of a viral vector COVID-19 vaccine. She later developed facial edema, and her fever became persistent and unremitting. Upon presentation, she was initially hypotensive, tachycardic, with distended neck veins, with periorbital edema and muffled heart sounds. Initial work-up revealed pericardial effusion, anemia, thrombocytopenia, elevated creatinine, hypoalbuminemia, hematuria, and pyuria. She was intubated, started on inotrope, and underwent pericardiocentesis. Patient was classified as SLE based on Systemic Lupus International Collaborating Clinics Classification (SLICC) Criteria despite negative antinuclear antibody (ANA). Nevertheless, she was started on IV steroids and hydroxychloroquine. She was eventually extubated after significant clinical improvement. Further work-up for MAS was however done due to persistent febrile episodes. Hyperferritinemia, hypertriglyceridemia, hypercholesterolemia, pancytopenia, transaminitis, and splenomegaly on imaging were noted. She was then started on methylprednisolone pulse therapy. After treatment, marked clinical improvement, as well as resolution of transaminitis and pancytopenia were noted.

A high index of suspicion for MAS should exist in a patient with pyrexia of unknown origin with concomitant autoimmune disease. In this disease that can lead to progressive organ failure, early diagnosis and management is crucial. This case report culminates the need for diagnostic and therapeutic guidelines that will help in the early diagnosis and immediate treatment of this debilitating condition.

OBJECTIVE: To explore and summarize the clinical characteristics and treatment of aggressive NK-cell leukemia (ANKL), and provide new insights for clinical diagnosis and treatment of this disease. METHODS: The clinical data of 7 patients with ANKL admitted to the First Affiliated Hospital of Wannan Medical College from March 2014 to July 2021 were retrospectively analyzed, and their clinical characteristics, laboratory and imaging results, treatment and outcomes were analyzed. RESULTS: Among the 7 patients, 5 were males and 2 were females, with a median age of 47 (33-69) years old. The morphology of bone marrow cells in 7 patients showed similar large granular lymphocytes. Immunophenotyping revealed abnormal NK cells in 5 cases. By the end of follow-up, 6 cases died and 1 case survived, with a median survival time of 76.9 (4-347) days. CONCLUSION ANKL is a rare disease with short course and poor prognosis. If combined with hemophagocytic syndrome (HPS), the prognosis is even worse. There is no unified treatment method at present, and the use of PD-1 inhibitors may prolong the survival in some patients.
Male ; Female ; Humans ; Middle Aged ; Aged ; Retrospective Studies ; Leukemia, Large Granular Lymphocytic ; Leukemia, Prolymphocytic, T-Cell ; Prognosis ; Lymphohistiocytosis, Hemophagocytic

OBJECTIVE: To explore the high-risk clinical factors of early death in patients with secondary hemophagocytic lymphohistiocytosis (sHLH), and further identify the clinical factors related to the rapid progression of sHLH in the short term. METHODS: The clinical manifestations, laboratory examination and prognosis of sHLH patients were retrospectively analyzed. Continuous variables were grouped by median, univariate and multivariate Cox regression analysis and Kaplan-Meier survival curve were used to explore the risk factors affecting early death of sHLH. Then, a nomogram model was established with independent risk factors, Bootstrap resampling method was used for verification, and consistency index (C-index) and calibration curve were used to detect the prediction accuracy. RESULTS: A total of 126 sHLH patients were enrolled, with a median age of 48.5(16-88) years, including 74 males and 52 females. Fifty-five patients (43.6%) died within 30 days, including 39 males and 16 females. Univariate regression analysis showed that lymphocyte count <0.45×10⁹/L, platelet count (PLT) <39.5×10⁹/L, prothrombin time (PT)≥13.3 s, activated partial thromboplastin time (APTT)≥39.7 s, albumin (ALB) <25.9 g/L, lactate dehydrogenase (LDH)≥811 U/L, creatinine (Cr) ≥67 μmol/L and procalcitonin (PCT)≥0.61 ng/ml were risk factors for death within 30 days in sHLH patients. Multivariate regression analysis showed that lymphocyte count <0.45×10⁹/L, APTT≥39.7 s and ALB <25.9 g/L were independent risk factors for death within 30 days in sHLH patients. A nomogram model was established based on the above three risk factors, its C-index was 0.683, and the calibration chart showed good agreement between the observed and predicted values of sHLH. CONCLUSIONS Lymphopenia, prolonged APTT, and hypoalbuminemia are risk factors for early death of sHLH patients. Early identification and positive intervention are expected to reduce early mortality in sHLH patients. The nomogram model based on the above risk factors provides a method for clinicians to evaluate sHLH.
Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Lymphohistiocytosis, Hemophagocytic/complications* ; Retrospective Studies ; Prognosis ; Risk Factors ; Partial Thromboplastin Time ; Albumins

Cytomegalovirus (CMV) infection is currently prevalent in populations throughout the world, and 56%‍-94% of the global population is seropositive for CMV. CMV infection mainly affects immunocompromised hosts. In these cases, it can cause significant symptoms, tissue-invasive disease, and many sequelae including death (Dioverti and Razonable, 2016). The vast majority of healthy adults with CMV infection experience an asymptomatic course; when symptomatic, it manifests as a mononucleosis-like syndrome in approximately 10% of patients (Sridhar et al., 2018). The gastrointestinal tract and central nervous system appear to be the most frequent sites of severe CMV infection in immunocompetent individuals (Rafailidis et al., 2008). However, CMV infection is relatively rarely recorded in immunocompetent hosts.
Adult ; Humans ; Lymphohistiocytosis, Hemophagocytic/complications* ; Cytomegalovirus Infections/diagnosis* ; Gastrointestinal Tract ; Disease Progression

Humans ; Child ; Lymphohistiocytosis, Hemophagocytic ; Antibodies, Monoclonal/therapeutic use*

Humans ; Lymphohistiocytosis, Hemophagocytic ; Herpesvirus 4, Human ; Interleukin-2 ; Epstein-Barr Virus Infections/complications* ; T-Lymphocytes

OBJECTIVE: To explore the genetic basis for a patient with Familial hemophagocytic lymphohistiocytosis (FHL). METHODS: A 35-day-old male infant who was admitted to the Oriental Hospital Affiliated to Xiamen University on August 3, 2021 due to fever for over 7 hours was selected as the study subject. Whole exome sequencing (WES) was carried out for the proband and his parents, and candidate variants were selected based on the clinical phenotypes of the proband and confirmed by Sanger sequencing. RESULTS: WES and Sanger sequencing results revealed that the proband had harbored compound heterozygous c.67_71delinsGCCC and c.65delC variants of the PRF1 gene, which were respectively inherited from his mother and father. The c.67_71delinsGCCC variant was unreported previously. Based on the guidelines of American College of Medical Genetics and Genomics and clinical manifestations, it was classified as pathogenic (PVS1+PM2_Supporting+PM3+PP4). c.65delC was a known pathogenic variant (PVS1+PM2_Supporting+PM3_Strong+PP4). CONCLUSION The compound heterozygous variants of c.67_71delinsGCCC and c.65delC of the PRF1 gene probably underlay the disease in the proband. The identification of the novel variant has expanded the mutational spectrum of the PRF1 gene.
Male ; Female ; Humans ; Lymphohistiocytosis, Hemophagocytic/genetics* ; Genomics ; Mothers ; Mutation ; Phenotype

OBJECTIVE: To analyze the gene polymorphisms of patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province. METHODS: A total of 125 patients with lymphoma-associated hemophagocytic syndrome in Longyan, Fujian province, admitted to Longyan First Hospital from May 2017 to November 2020 were selected. Peripheral venous blood was collected from all the patients, and the genotypes of perforin 1 (PRF1) and interleukin-10 (IL-10) gene loci were detected by PCR-fluorescence probe method, and the correlation between PRF1 and IL-10 gene polymorphisms and lymphoma-associated hemophagocytic syndrome was analyzed. RESULTS: The mutation frequencies of PRF1 gene loci rs885821 (C>T), rs885822 (C>T), rs1889490 (G>A) in patients with lymphoma-associated hemophagocytic syndrome were 10.40%, 78.8% and 64.4%, respectively. The mutation frequencies of rs1800872 (A>C), rs1800871 (C>T) and rs1800896 (G>A) of IL-10 loci were 56.0%, 45.2% and 77.6%, respectively. CONCLUSION PRF1 and IL-10 gene loci were polymorphic in patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province. Alleles C and G of PRF1 and IL-10 were risk factors, and alleles T and A were protective factors.
Humans ; Genotype ; Interleukin-10/genetics* ; Lymphohistiocytosis, Hemophagocytic/genetics* ; Lymphoma/genetics* ; Perforin/genetics* ; Polymorphism, Genetic

OBJECTIVE: To analyze the clinical characteristics of hemophagocytic syndrome (HLH) children with different EB virus (EBV) DNA loads, and to explore the relationship between differential indicators and prognosis. METHODS: Clinical data of 73 children with HLH treated in our hospital from January 2015 to April 2022 were collected. According to EBV DNA loads, the children were divided into negative group (≤5×10² copies/ml), low load group (>5×10²-<5×10⁵ copies/ml) and high load group (≥5×10⁵copies/ml）. The clinical symptoms and laboratory indexes of the three groups were compared, and the ROC curve was used to determine the best cut-off value of the different indexes. Cox regression model was used to analyze the independent risk factors affecting the prognosis of children, and to analyze the survival of children in each group. RESULTS: The proportion of female children, the swelling rate of liver and spleen lymph nodes and the involvement rate of blood, liver, circulation and central nervous system in the high load group were higher than those in the negative group. The incidence of disseminated intravascular coagulation(DIC) and central nervous system(CNS) involvement in the high load group were higher than those in the low load group. The liver swelling rate and circulatory system involvement rate in the low load group were higher than those in the negative group(P<0.05). PLT counts in the high load group were significantly lower than those in the negative group, and the levels of GGT, TBIL, CK-MB, LDH, TG, SF, and organ involvement were significantly higher than those in the negative group. The levels of CK, LDH, SF and the number of organ involvement in the high load group were significantly higher than those in the low load group. The levels of GGT and TBIL in low load group were significantly higher than those in negative group. In terms of treatment, the proportion of blood purification therapy in the high and low load group was significantly higher than that in the negative group(P<0.01). ROC curve analysis showed that the best cut-off values of PLT, LDH, TG and SF were 49.5, 1139, 3.12 and 1812, respectively. The appellate laboratory indicators were dichotomized according to the cut-off value, and the differential clinical symptoms were included in the Cox regression model. Univariate analysis showed that LDH>1139 U/L, SF>1812 μg/L, dysfunction of central nervous system, number of organ damage, DIC and no blood purification therapy were the risk factors affecting the prognosis of children (P<0.05); Multivariate analysis shows that PLT≤49.5×10⁹/L and dysfunction of central nervous system were risk factors affecting the prognosis of children (P<0.05). Survival analysis showed that there was no significant difference in the survival rate among the three groups. CONCLUSION The incidence of adverse prognostic factors in children with HLH in the EBV-DNA high load group is higher, and there is no significant difference in the survival rate of the three groups after blood purification therapy. Therefore, early identification and application of blood purification therapy is of great significance for children with HLH in the high load group.
Humans ; Child ; Female ; Lymphohistiocytosis, Hemophagocytic ; Retrospective Studies ; Risk Factors ; DNA ; Prognosis

OBJECTIVE: To investigate the cytokine/chemokine profile in patients with Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH), and assess the prognostic value of survival. METHODS: Serum levels of thirty-eight cytokines/chemokines were measured by multiple cytokine assay kit in EBV-related HLH patients, EBV-infected patients, and controls. The expression profile of cytokines/chemokines was compared among groups. The changes of cytokine/chemokine expression in active and remission stage of EBV-related HLH patients were also compared, and the prognostic values for survival were evaluated. RESULTS: Serum levels of interferon-α2 (IFN-α2), interleukin (IL)-6, and IL-7 in EBV-related HLH patients were 33.67(23.23-68.78) pg/ml, (74.95±25.53) pg/ml, and 35.35(19.50-63.55) pg/ml, respectively, which were significantly higher than those in EBV-infected patients［IFN-α2: 16.07(9.87-29.63); IL-6: 55.91±20.29; IL-7: 20.40(13.35-31.40)］ and controls ［IFN-α2: 11.02(4.67-21.25); IL-6:42.64±13.41; IL-7: 16.95(14.95-33.78)］(all P<0.05). Serum levels of IL-8, IL-9, and marcophage-derived chemokine (MDC) in EBV-related HLH patients were 11.00(7.50-15.27) pg/ml, 81.30(40.79-111.0) pg/ml, and (512.6±128.7) pg/ml, respectively, which were significantly higher than those in controls ［IL-8: 6.80(5.56-8.38); IL-9: 41.30(29.82-67.91); MDC: 384.1±156.6］(all P<0.05), but there was no remarkable differences compared with EBV-infected patients (P>0.05). Serum IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC in survival and death groups of EBV-related HLH patients were analyzed by receiver operating characteristic curve with area under curve of 0.781, 0.778, 0.633, 0.805, 0.562, and 0.657, respectively (P=0.019, 0.021, 0.269, 0.015, 0.607, and 0.190). IFN-α2, IL-6, and IL-8 had good predictive effect on survival. Serum level of IFN-α2, IL-6, and MDC of EBV-related HLH patients in remission stage were significantly lower than those in active stage (P<0.05), while IL-7, IL-8, and IL-9 were not different (P>0.05). CONCLUSION IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC may take part in the pathogenesis of EBV-related HLH.
Humans ; Lymphohistiocytosis, Hemophagocytic/complications* ; Herpesvirus 4, Human ; Cytokines/metabolism* ; Epstein-Barr Virus Infections/complications* ; Interleukin-6 ; Clinical Relevance ; Interleukin-7 ; Interleukin-8 ; Interleukin-9 ; Chemokines ; Interferons