جستجوی مقالات مرتبط با کلیدواژه "hemophagocytic lymphohistiocytosis" در نشریات گروه "پزشکی"

Hemophagocytic lymphohistiocytosis (HLH) is a fatal clinical syndrome. The most common cause of secondary HLH is Epstein-Barr virus (EBV) infection. EBV-HLH is a common clinical disease with high mortality, easy relapse, and poor prognosis. Therefore, treating EBV-HLH with T and B lymphocyte involvement is challenging, and selecting an appropriate treatment regimen is critical. Moreover, research on how to evaluate the recurrence index after remission is scarce. In this study, we reported a case of EBV-HLH successfully treated with programmed cell death protein-1 (PD-1) inhibitor in combination with rituximab. The regimen had a good curative effect, and we successfully detected the trend of early recurrence. Our findings indicated that PD-1 inhibitor in combination with rituximab may help to treat EBV-HLH and maintain EBV-infected T and B whole-line lymphocytes.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory clinical syndrome of uncontrolled immune response which results in hypercytokinemia due to underlying primary or secondary immune defects. HLH can be classified into familial (primary) and acquired (secondary) forms according to the underlying defect. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option in primary HLH, and the outcome of HSCT for HLH patients has improved over the last decades. However, HSCT for HLH still carries significant morbidity and mortality. Herein, we described three patients with primary HLH, including a 4.5 years old girl with Chédiak-Higashi Syndrome (CHS- LYST gene mutation), a 5.5 years old boy with Griscelli syndrome type 2 (GS2- Rab27a gene mutation), and an 8.9 years old girl with Hemophagocytic lymphohistiocytosis Syndrome type 5 (HLH 5- STXBP2 gene mutation). All three patients received allogeneic HSCT with a reduced-intensity conditioning (RIC) regimen, including Fludarabine, Melphalan, Rabbit Anti-thymocyte globulin (r-ATG), and graft versus host disease (GvHD) prophylaxis by Methylprednisolone and Cyclosporine. The outcome of HSCT for HLH patients has improved, and HSCT can provide long-term survival for familial HLH. Ongoing challenges in various aspects of HSCT remain to be elucidated, including donor selection, the timing of HSCT, the conditioning regimen, and mixed chimerism after HSCT.

Familial Hemophagocytic lymphohistiocytosis is an autosomal recessive lethal disorder caused by mutations in several genes. The immune system is overactivated in this disease and several organs such as liver and spleen are affected. Since Haematopoitic stem cell transplantation is essencial for surviving the patients with familial hemophagocytic lymphohistiocytosis, the easrly diagnosis is critical.

The aim of this study was to determine the probable genetic cause of disease in an infant with unclear primary diagnosis and suspected to suffer from blood cancer, Hemophagocytic lymphohistiocytosis or polycyctic liver disease.

Whole exome sequencing and Sanger sequencing were used to investigate the mutation and its confirmation respectively.

We found a compound heterozugous mutation in PRF1 gene including one novel nonsense and one previously reported missense mutations.

Due to the disease and clinical heterogeneity, next generation sequencing is the recommended method to find the disease causing mutations and confirm the disease.

Macrophage activation syndrome (MAS), a secondary hemophagocytic lymphohistiocytosis characterized by an excessive systemic inflammatory response, is a life-threatening and rare disease. Cardiovascular damage is a common and severe complication of the disease, however, it is easily ignored and not well studied. Herein, we report two cases of patients with MAS-associated heart damage and review the clinical characteristics, mechanism, and treatment. Case 1 along with systemic lupus erythematosus and Kikuchi necrotizing lymphadenitis occurred in fatal acute heart failure, and case 2 complicated adult-onset Still’s Disease began with atrial fibrillation and had some improvement with the treatment of high dose corticosteroids. MAS-associated heart damage is a critical issue in clinical settings, and the etiology and mechanisms of MAS-associated cardiovascular diseases are likely multifactorial. The manifestations were various and high levels of the cytokines and cardiac damage may contribute to poor prognosis. Therefore, early intensive immunosuppressive therapy probably improves the treatment outcome.

Due to uncontrolled lymphocyte reaction, the overproduction of cytokines in COVID-19 patients can cause sepsis-like symptoms, suggesting sepsis, cytokine release syndrome (CRS), and secondary hemophagocytic lymphohistiocytosis (sHLH). Since different therapeutic approaches are used for each diagnosis, differentiation is essential. This study aims to use H-score as a possible prognostic tool in COVID-19 patients.

A sample of 64 moderate and severe COVID-19 patients was enrolled in this study. Clinical and laboratory findings were assessed. H-score was initially calculated and reevaluated among severe cases 72 hours later and among moderate cases showing severe features of COVID-19.

Mortality of 31.3% was reported. Laboratory findings, including triglycerides (TG), ferritin, and aspartate aminotransferase (AST) showed significantly higher initial and follow-up laboratory assessment levels in severe cases than in moderate cases. Moreover, fibrinogen was significantly higher among severe cases than moderate cases at the initial assessment, but no significant difference was reported in the second fibrinogen assessment.

In this study, H-score was useful as a predictive tool for the initial evaluation of severe cases of COVID-19. H-score is much lower in these patients than in non-COVID-19 HLH patients may be due to the different underlying immunologic pathophysiology of COVID-19; thus, each H-score criterion must be evaluated for sensitivity and specificity in COVID-19 patients. The H-score cut-offs, H-score may be useful for diagnosing immune overreaction and determining the need for more exclusive immunomodulatory treatments

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of excessive immune activation, which is characterized by fever, hepatosplenomegaly, cytopenias, hyperferritinemia, hypertriglyceridemia, and/or hypofibrinogenemia, and evidence of hemophagocytosis. Secondary HLH is often seen in adults and categorized based on autoimmune, infections-related, and malignancy-associated etiologies such as A-HLH, I-HLH, and M-HLH, respectively. This study presented a rare case of HLH developing concurrently at the time of diagnosis of T-cell Acute Lymphoblastic Leukemia (T- ALL) with a unique presentation of membranous tonsillitis in a 10-year-old boy. In all of the cases of T-ALL reported in the pediatric age group, HLH develops post-therapy or at the relapse. The first presentation of leukemia as membranous tonsillitis and concurrent clinic laboratory findings of HLH is rare and can mislead the diagnosis. Therefore, prompt diagnosis is the mainstay of therapy and can considerably improve the prognosis.

Type 2 Griscelli syndrome (Type2 GS) is a primary inborn error of the immune system, classified in the immune dysregulation group.1,2 There are three different types of the disease, with different genetic causes responsible for the autosomal recessive inheritance pattern. Although hypopigmentation is common in all variants, neurological involvement or immunodeficiency with varying severity is seen in different types. Molecular motor protein myosin 5 an (MYo5A) [Type1GS], guanosine Triphosphate (GTP) binding protein (RAB27A) [Type2GS], and mutation in human melanophilin (MLPH) [Type 3GS] which is limited to hypopigmentation are reported as the known genetic defects in GS.3 Severe, ineffective, and uncontrolled inflammatory reactions are referred to as the pathogenesis of Hemophagocytic lymphohistiocytosis (HLH). HLH is a life-threatening condition that can be defined as either primary or secondary. Secondary causes happen in the context of autoimmunity, malignancy, spontaneous, or infections.4 Prenatal infections play an important role in causing long-term complications in the fetus. Some of them include toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and other organisms including syphilis, parvovirus, and Varicella zoster, known as TORCH syndrome (5).TORCH has been well described for a long time but there are limited reports of developing HLH in the context of prenatal infections. We described a type 2GS syndrome with neonatal-onset HLH triggered by a prenatal infection.

The coronavirus disease 2019 (COVID-19) pandemic has imposed a significant burden worldwide, manifesting as a severe disease and causing mortality even in children. Severe COVID-19 disease is characterized by cytokine storm with progression to secondary hemophagocytic lymphohistiocytosis (sHLH). We describe an 18-month-old boy in Iran, previously healthy, diagnosed with COVID19-induced sHLH. Three weeks after close contact with COVID-19 confirmed cases, he was admitted with high fever, lethargy, mild respiratory distress, skin rash, and conjunctivitis with swollen eyelids and lips. Laboratory data revealed elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and liver enzymes, and mild thrombocytopenia. His clinical condition rapidly deteriorated, with septic shock, hepatosplenomegaly, and respiratory failure. Laboratory tests showed cytopenia, coagulopathy, hyperferritinemia, and hypertriglyceridemia, which met the criteria for sHLH diagnosis. Chest computed tomography (CT) revealed bilateral infiltrations that suggested acute respiratory distress syndrome (ARDS) of COVID-19 that was confirmed by a positive realtime polymerase chain reaction (RT-PCR) test. Therefore, the child was treated with intravenous immunoglobulin (IVIG), glucocorticoid, hydroxychloroquine, lopinavir/ritonavir, and interferonβ-1a. This therapeutic strategy enabled complete recovery from fever, regaining consciousness, weaning from respiratory support, and resolving shock. Serial chest radiographs showed diminishing infiltrations. Sequential physical examinations revealed an overall significant reduction in spleen and liver span. Laboratory data showed rapid improvement from cytopenia and coagulopathy, normalization of liver enzyme levels, and reduction in hyperinflammation markers. Although ARDS is the most common cause of death from COVID-19, other complications such as sHLH may be lethal; thus, early diagnosis and appropriate treatment are necessary for saving patients’ lives.

Several reports have associated the severe Coronavirus disease-2019 (sCOVID-19) with secondary-hemophagocytic lymphohistiocytosis (sHLH) and proposed utilizing the hemophagocytic syndrome diagnostic score (HScore) for sCOVID-19 patients. We conducted a systematic review and meta-analysis to find the possible association of HScore parameters with severity in COVID-19 patients.

A systematic search was performed in Medline via PubMed, EMBASE, and Cochrane databases using all HScore and COVID-19 keywords. The studies were all from 2020, and the study language was limited to English. The records were screened based on inclusion/exclusion criteria. Random/fixed-effect models were employed for meta-analysis, based on the I2 index of parameters. The pooled mean differences were estimated for continuous parameters. The pooled odds-ratio was estimated for fever. The level of significance was set at 0.05.

Eighteen studies (comprising 2459 patients) out of 26151 screened studies were included in this meta-analysis. The results showed that the level of leukocyte, neutrophil, aspartate transaminase (AST), ferritin, and fibrinogen were significantly higher in sCOVID-19 patients than in non-severe ones. Significant lower levels of lymphocyte, platelet, and hemoglobin were also found in sCOVID-19 patients than non-severe patients. Fever was nearly associated with two times increased odds of sCOVID-19 (P=0.051).

Lymphopenia, thrombocytopenia, hypohemoglobinemia, hyperferritinemia, high levels of AST, and fever are common features of both sCOVID-19 and HLH. However, the leukocytosis, neutrophilia, and hyperfibrinogenemia found in sCOVID-19 are in contrast with HScore. Conclusively, HScore parameters could be risk factors for sCOVID-19. However, some parameters’ roles are contradictory, suggesting the need for further investigation and a new way of HScore interpretation in sCOVID-19 patients.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease with different causes. HLH has been categorized into two sub-groups; primary HLH which is associated with some gene mutations and secondary HLH that is developed by various causes, such as autoimmune disease, infections, and malignancies. However, the symptoms of both groups are identical and if left untreated, it will result in death.

In this study, we reported a 39 years old man had symptoms such as fever, weakness and chill for a month period of time. Firstly, due to pancytopenia in peripheral blood findings and clinical manifestations, he had been diagnosed with myelodysplastic syndrome (MDS) with an excess blast but the elevated liver enzymes and bilirubin were not consistent with this diagnosis. Hence, we recommended more investigation such as CT scan, bone marrow aspiration and bone marrow biopsy with immunohistochemistry tests. Finally, we found macrophages and histiocyte in bone marrow biopsy smear with Wright-Giemsa staining that engulfed the cells such as platelets and lymphocytes, so HLH syndrome was confirmed and treatment program with latest approved protocols started for the patient.

HLH syndrome is a life-threatening disease that can be saved if timely diagnosed. Therefore, more consideration of all the laboratory findings and clinical signs of the patient can help to diagnose the disease more accurately. Also, we did a review of its pathophysiology, symptoms and therapeutic treatments.

Griscelli syndrome (GS) is a rare autosomal recessive disease that affects hair, skin, and immune system. Here, we describe an 8.5-month-old infant with multiple admissions due to fever, petechial purpura, and several recurrent vomiting episodes with a presumptive diagnosis of recurrent sepsis. He was born from parents with consanguineous marriage. The initial examinations revealed huge splenomegaly and hepatomegaly without any source of infection. Laboratory tests revealed a hemophagocytic lymphohistiocytosis (HLH) like a picture with a high blood level of ferritin in all episodes, but the bone marrow test result was normal. Although he had normal hair and skin pigmentation on physical examination, the accumulation of melanosomes was found in his hair shafts on microscopic investigations. Eventually, a genetic test revealed a mutation in the RAB27A gene, which confirmed GS-II diagnosis. Our case is the first case of GS-II from Iran without any apparent clinical features of GS, such as hypopigmented skin and silvery-gray hair. Therefore, a genetic test, together with the microscopic examination of hair and skin, is necessary for the diagnosis and confirmation of GS-II. Since GS-II is an autosomal recessive disorder and consanguineous marriages are popular in Iran, premarital genetic counseling is recommended for this region.

Hemophagocytic lymphohistiocytosis (HLH) is the result of excessive cytokine release, leading to over-response by immune cells, such as macrophages and T lymphocytes. Here, we report a lethal case of HLH with a complete clinical course. The patient was a 45-year-old man with fever and chills since two months ago plus splenomegaly, hepatomegaly, and pancytopenia. The Anti-HBc IgM was positive, but the HBS antigen, anti-HCV, and HBS antibody were negative. Assessment for cirrhosis was carried out by FibroScan, which showed F4 grade. The biopsy sampling was impossible due to the low platelet count. During admission, generalized bleeding was developed and led to alveolar hemorrhage, which subsequently resulted in the patient's death. Liver necropsy certified the diagnosis of hemophagocytic syndrome. Overall, according to the reported case in this paper, it should be remembered that secondary HLH is an inflammatory phenomenon due to different conditions, such as latent newly-developed infections.

Hemophagocytic lymphohistiocytosis (HLH) is caused by overactivation of immune system. Gene mutations, infections, malignant, and autoimmune trigger the development of the disease.

Clinical data and peripheral blood samples of 21 patients suspected of HLH were collected in Shiraz Medical Centers 2017–2018. Peripheral blood samples were analyzed for soluble interleukin‑2 receptor alpha (sIL2Rα) marker (sCD25), and the results were compared with 36 normal controls as well as comparison with clinical findings and other laboratory parameters.

Twenty‑one patients (11 males and 10 females) with an average age of 5.2 were investigated. In this study, peripheral blood samples were taken from 16 newly diagnosed patients before treatment, and five were posttreatment blood samples. The mean sIL2Rα level before treatment in 16 patients was 9023 pg/ml. The mean peripheral blood sample of the 36 controls was 3025 pg/ml. The mean of the five posttreatment samples was 4198 pg/ml. Significant difference between pretreatment and the control group was observed. However, no significant difference was detected between after treatment samples and the control group. By comparing the sIL2Rα levels between patients with increased aspartate aminotransaminase (AST) and patients with normal AST level, there was a significant difference in the amount of IL2Rα level.

This study highlights the importance of IL2Rα marker in the diagnosis and follow‑up, during treatment and suppression. Furthermore, a significant difference with respect to AST level requires further investigation.

Brucellosis, with multi-organ involvement, is recognized as a zoonotic infection in Iran. This infection has multiple signs and symptoms. On the other hand, hemophagocytic lymphohistiocytosis (HLH) is described as an uncommon disorder. The secondary type of this disease may be associated with infection. However, the association between HLH and brucellosis has been rarely reported, especially in pediatric populations. Herein, we present a pediatric case of secondary HLH associated with brucellosis. Based on our findings, HLH should be considered in patients diagnosed with brucellosis with profound cytopenia and increased spleen size despite treatment.

Hemophagocytic lymphohistiocytosis (HLH) is an immune system disorder characterized by uncontrolled hyper-inflammation owing to hypercytokinemia from the activated but ineffective cytotoxic cells. Establishing a correct diagnosis for HLH patients due to the similarity of this disease with other conditions like malignant lymphoma and leukemia and similarity among its two forms is difficult and not always a successful procedure. Besides, the molecular characterization of HLH due to the locus and allelic heterogeneity is a challenging issue.

In this experimental study, whole exome sequencing (WES) was used for mutation detection in a four-member Iranian family with children suffering from signs and symptoms of HLH disease. Data analysis was performed by using a multi-step in-house WES approach on Linux OS.

In this study, a homozygous nucleotide substitution mutation (c.551G>A:p.W184*) was detected in exon number six of the UNC13D gene. W184* drives to a premature stop codon, so produce a truncated protein. This mutation inherited from parents to a four-month female infant with an autosomal recessive pattern. Parents were carrying out the heterozygous form of W184* without any symptoms. The patient showed clinical signs such as fever, diarrhea, hepatosplenomegaly, high level of ferritin, and a positive family history of HLH disease. W184* has a damaging effect on cytotoxic T lymphocytes, and natural killer cells. These two types of immune system cells without a healthy product of the UNC13D gene will be unable to discharge toxic granules into the synaptic space, so the inflammation in the immune response does not disappear.

According to this study, WES can be a reliable, fast, and cost-effective approach for the molecular characterization of HLH patients. Plus, WES specific data analysis platform introduced by this study potentially offers a high-speed analysis step. This cost-free platform doesn't require online data submission.

Hemophagocytic lymphohistiocytosis (HLH) is a disorder of the immune regulatory system with a high rate of mortality. The clinical presentation of HLH could be similar to those of many other conditions, making its diagnosis difficult. The current study was conducted on the children with HLH referred to the Pediatric Ward of Imam Reza Hospital, Mashhad, Iran during nine years from 2010 to 2018. The data collection tool included items on clinical presentations, physical examination, laboratory data, treatment strategy, and the disease outcome. The diagnosis of HLH was made based on the HLH-2004 Diagnostic Criteria. Data were analyzed using SPSS version 20. Among the 17 cases with HLH, the mean age at the onset of HLH was 4.671 ± 4.60 years with a male to female ratio of 11:6. Fever and splenomegaly were the most common findings. The study of the etiology revealed that about 30% of the children had the familial form of HLH, 17.5% were previously diagnosed with rheumatologic disorders (i.e., systemic lupus erythematosus and systemic-onset juvenile idiopathic arthritis), and the same rate was affected by infectious diseases. Idiopathic factors, the Chediak-Higashi syndrome, and the Griscelli syndrome were responsible for the occurrence of HLH in 17.5%, 12%, and 6% of the cases, respectively. According to the obtained results of the study, 35.3% of the patients were cured and about 64.7% died. Due to the high risk of mortality from this disorder, the recognition of HLH symptoms, especially atypical presentations of the disorder, is critical both for pediatricians and subspecialists.

Autoimmune lymphoproliferative Syndrome (ALPS) is a rare inherited disorder of apoptosis. It usually presents with chronic lymphadenopathy, splenomegaly, and symptomatic cytopenia in a child. Herein, we report a 14-year-old boy with symptoms misdiagnosed as hemophagocytic lymphohistiocytosis who was treated before ALPS was diagnosed for the patient. This case should alert pediatricians to consider ALPS in differential diagnosis of a child with lymphadenopathy, splenomegaly, and cytopenia.

We reported a typical brucellosis, which was diagnosed as hemophagocytic lymphohistiocytosis (HLH). Although some tumor markers (CEA, CYFRA21-1, NSE, CA19-9) in the patient’s serum were elevated, carcinomas were excluded by a variety of inspections including bone marrow aspirations, ultrasound examinations, and whole-body PET-CT scans. It was concluded that serum tumor markers are considered medically necessary as a screening test for brucellosis with HLH, however, detailed inspections were needed to make a final diagnosis. Moreover, combination of epidemiology investigations and laboratory inspections were helpful to determine the etiology of HLH and initiate the corresponding treatments