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

The acquired immunodeficiency syndrome patients with compromised immunity are prone to hemophagocytic syndrome secondary to opportunistic infections.This paper reports a rare case of hemophagocytic syndrome secondary to human parvovirus B19 infection in an acquired immunodeficiency syndrome patient,and analyzes the clinical characteristics,aiming to improve the diagnosis and treatment of the disease and prevent missed diagnosis and misdiagnosis.
Humans ; Lymphohistiocytosis, Hemophagocytic/drug therapy* ; Erythema Infectiosum/complications* ; Acquired Immunodeficiency Syndrome/complications* ; Parvoviridae Infections/diagnosis* ; Parvovirus B19, Human

Objective: To explore the clinical characteristics and outcomes of patients with non-Epstein-Barr virus (EBV) infection-associated hemophagocytic lymphohistiocytosis (IAHLH) . Methods: Clinical data of 48 patients diagnosed with non-EBV IAHLH in Beijing Friendship Hospital from January 2015 to March 2021 were collected, and the clinical characteristics, treatment, curative effect and prognosis of the patients were analyzed retrospectively. Results: This study included 48 patients, 28 males and 20 females, with a median (range) age of 34.5 (2-74) years. Pathogens that cause IAHLH were as follows: virus (16 cases, 33.3%) , bacteria (17 cases, 35.4%) , parasitic agents (13 cases, 27.1%) , and fungi (2 cases, 4.2%) . The median time from onset to diagnosis of hemophagocytic syndrome (HLH) was 40 (10-160) days. The median (range) time duration from prodrome to the definite diagnosis of IAHLH was 67 (23-270) days. The clinical characteristics were fever (48 cases, 100%) , splenomegaly (34 cases, 70.8%) , cytopenia (38 cases, 79.1%) , elevated ferritin (45 cases, 93.8%) , elevated fasting triglyceride levels (7 cases, 14.6%) , hypofibrinogenemia (17 cases, 35.4%) , decrease natural killer cell activity (26 in 44 cases, 59.1%) , and elevated sCD25 (35 cases, 74.5%) . Twenty-five patients (52.1%) had adenopathy. Once a certain pathogen was identified as the causative factor of hemophagocytic lymphohistiocytosis (HLH) , cytotoxic agents and glucocorticoids were withdrawn, and specific pathogen-directed treatment was initiated. After treatment, 36 cases (75.0%) achieved complete response, and 14 of 15 patients (93.3%) with parasitic and fungal HLH got a response; however, the response rate of patient with bacterial and viral HLH was only 66.7% (22 of 33 patients) . The estimated 5-year overall survival rate was 72.3% (95%CI 50.3%-69.8%) . The adverse prognostic factors were total bilirubin over the upper limit of normal (OR=20.0, 95%CI 1.1-378.3, P=0.046) and pathogenic infection not fully controlled (OR=19.9, 95%CI 2.9-134.5, P=0.002) . Conclusion: Non-EBV IAHLH has a good prognosis. When diagnosed, cytotoxic agents and glucocorticoids should be tapered off, and pathogen-targeted therapy should be critically administered to clear the triggering infection.
Adult ; Aged ; Epstein-Barr Virus Infections/complications* ; Female ; Herpesvirus 4, Human ; Humans ; Lymphohistiocytosis, Hemophagocytic/diagnosis* ; Male ; Middle Aged ; Prognosis ; Retrospective Studies

Hemophagocytic lymphohistiocytosis (HLH) was a life-threatening syndrome due to the uncontrolled immune activation of cytotoxic T lymphocytes, natural killer (NK) cells, and macrophages. HLH is characterized by primary and secondary causes, the early diagnosis and treatment of patients are closely related to the prognosis and clinical outcome of patients. The clinical presentation is variable but mostly includes prolonged fever, splenomegaly, coagulopathy, hypertriglyceridemia, and hemophagocytosis, none of them is specific and particular for HLH. Tuberculosis (TB) infection is one of the causes of HLH. HLH caused by TB is very rare clinically, but it has a high mortality. For patients with fever of unknown origin, HLH-related clinical manifestations sometimes present before the final diagnosis of TB, and HLH is associated with the most significant mortality rate. This article is mainly about a 28-year-old patient with HLH who suffered from severe TB infection. The patient attended a hospital with a history of 2 months of prolonged fever, 10 days booger and subcutaneous hemorrhage in lower limbs. Before this, he was in good health and denied any history of tuberculosis exposure. Combined with relevant laboratory test results (such as splenomegaly, hemoglobin, platelet count, and hypertriglyceridemia) and clinical manifestations (e.g. fever), the patient was diagnosed with hemophagocytic lymphohistiocytosis, but the etiology of HLH remained to be determined. To confirm the etiology, the patient was asked about the relevant medical history (intermittent low back pain) and was performed chest CT scan, bone marrow biopsy, and fundus photography. Finally, he was diagnosed with hemophagocytic lymphohistiocytosis caused by hematogenous disseminated pulmonary tuberculosis. In response to this, intravenous methylprednisolone and anti-tuberculosis treatment (isoniazid, pyrazinamide, moxifloxacin, and amikacin) were administered to the patient. After more than a month of treatment, the patient recovered from HLH caused by severe TB infection. Therefore, this case suggests that we should be vigilant to the patient who admitted to the hospital with fever for unknown reasons, to diagnose HLH as early as possible and clarify its cause, then perform interventions and treatment, especially HLH secondary to tuberculosis. Also, cases of atypical TB and severe TB should be carefully monitored to achieve early diagnosis and early intervention.
Male ; Humans ; Adult ; Lymphohistiocytosis, Hemophagocytic/diagnosis* ; Splenomegaly ; Tuberculosis, Pulmonary/diagnosis* ; Bone Marrow/pathology* ; Fever/etiology* ; Hypertriglyceridemia/complications*

OBJECTIVE: To present one patient initially diagnosed with dermatomyositis(DM) who was eventually revealed to be diffuse large B-cell lymphoma(DLBCL) complicated with hemophagocytic syndrome(HPS), and to improve the understanding of the disease. METHODS: The clinical characteristics, diagnostic approach, treatment of the patient were retrospectively analyzed, and some related literatures were reviewed. RESULTS: A 52-year-old female patient suffered from muscle weakness, elevated serum creatine kinase activity, electromyography changes and characteristic skin rashes and diagnosed as DM. The patient was treated with glucocorticoid therapy and the muscle strength, skin rashes, and creatine kinas index turns into remission. Subsequently, subcutaneous nodules appeared during treatment, and the patient was confirmed as DLBCL based on pathological biopsy; And the patient was considered HPS because of presenting with repeated fever, splenomegaly, cytopenias, hypofibrinogenemia, hypertriglyceridemia, hyperferritinemia, high levels of sCD25, low NK-cell activity and hemophagocytosis in bone marrow. But the patient refused chemotherapy, and only treated with "DXM+VP-16" to control hemophagocytic syndrome, and unfortunately died due to the disease progression. CONCLUSION Cutaneous involvement in diffuse large B-cell lymphoma and hemophagocytic syndrome patients with first presentation of dermatomyositis is relatively rare. Malignacy screening should be performed as soon as possible after newly diagnosed DM, so that the patient can get early diagnosis and effective treatment to improve survival rate.
Dermatomyositis/complications* ; Etoposide ; Female ; Humans ; Lymphohistiocytosis, Hemophagocytic/diagnosis* ; Lymphoma, Large B-Cell, Diffuse/complications* ; Middle Aged ; Retrospective Studies

PURPOSE: While there is an urgent need for diagnosis and therapeutic intervention in patients with primary immunodeficiency diseases (PIDs), current genetic tests have drawbacks. We retrospectively reviewed the usefulness of flow cytometry (FCM) as a quick tool for immunophenotyping and functional assays in patients suspected to have PIDs at a single tertiary care institute.METHODS: Between January 2001 and June 2018, patients suspected of having PIDs were subjected to FCM tests, including lymphocyte subset analysis, detection of surface- or intracellular-target proteins, and functional analysis of immune cells, at Samsung Medical Center, Seoul, Korea. The genetic diagnosis was performed using Sanger or diagnostic exome sequencing.RESULTS: Of 60 patients diagnosed with definite or probable PID according to the European Society of Immune Deficiencies criteria, 24 patients were provided with useful information about immunological dysfunction after initial FCM testing. In 10 patients, the PID diagnosis was based on abnormal findings in FCM testing without genetic tests. The FCM findings provided strong evidence for the diagnosis of severe combined immunodeficiency (n = 6), X-linked chronic granulomatous diseases (CGD) (n = 6), leukocyte adhesion deficiency type 1 (n = 3), X-linked agammaglobulinemia (n = 11), autoimmune lymphoproliferative syndrome-FASLG (n = 1), and familial hemophagocytic lymphohistiocytosis type 2 (n = 1), and probable evidence for autosomal recessive-CGD (n = 2), autosomal dominant-hyper-immunoglobulin E (IgE)-syndrome (n = 1), and STAT1 gain-of-function mutation (n = 1). In PIDs derived from PIK3CD (n = 2), LRBA (n = 2), and CTLA4 mutations (n = 3), the FCM test provided useful evidence of immune abnormalities and a tool for treatment monitoring.CONCLUSIONS: The initial application of FCM, particularly with known protein targets on immune cells, would facilitate the timely diagnosis of PIDs and thus would support clinical decisions and improve the clinical outcome.
Agammaglobulinemia ; Diagnosis ; Exome ; Flow Cytometry ; Genetic Testing ; Granulomatous Disease, Chronic ; Humans ; Immunophenotyping ; Korea ; Leukocytes ; Lymphocyte Subsets ; Lymphohistiocytosis, Hemophagocytic ; Phenotype ; Retrospective Studies ; Seoul ; Severe Combined Immunodeficiency ; Tertiary Healthcare

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by excessive activation of lymphocytes and macrophages, leading to cytokine storm. Infection-associated HLH is most common, and Epstein-Barr virus is the leading triggers. Quick diagnosis is essential for starting the treatment before irreversible damage. We report a case of 16-year-old boy who presented with unremitted fever, jaundice, and erythematous maculopapular rash all over the body. Investigations showed thrombocytopenia, hyperferritinemia, hypertriglycemia, and the bone marrow biopsy showed hemophagocytosis. Epstein-Barr virus antibody was positive. He responded to chemotherapy as per the HLH-2004 protocol and supportive treatment, and was discharged without complication on day 17.
Adolescent ; Biopsy ; Bone Marrow ; Diagnosis ; Drug Therapy ; Epstein-Barr Virus Infections ; Exanthema ; Ferritins ; Fever ; Herpesvirus 4, Human ; Humans ; Jaundice ; Lymphocytes ; Lymphohistiocytosis, Hemophagocytic ; Macrophages ; Male ; Thrombocytopenia

Central Nervous System Diseases ; etiology ; Child ; Female ; Humans ; Infant ; Lymphohistiocytosis, Hemophagocytic ; complications ; diagnosis ; genetics ; Magnetic Resonance Imaging ; Male ; Mutation ; Perforin ; genetics

Adult ; Ferritins ; blood ; Humans ; Leukocytes ; metabolism ; Lymphohistiocytosis, Hemophagocytic ; blood ; diagnosis ; Male ; Panniculitis ; blood ; diagnosis ; Triglycerides ; blood

Child, Preschool ; Humans ; Lymphohistiocytosis, Hemophagocytic ; diagnosis ; genetics ; therapy ; Male