Disseminated histoplasmosis associated with acquired hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a potentially life‐threatening clinical syndrome caused by uncontrolled activation of lymphocytes and histiocytes resulting in high levels of cytokines. Acquired HLH occurs in autoimmune, inflammatory, infectious, and immunosuppressive disorders. Prompt identification and treatment of an underlying triggering cause improves clinical outcome.     

Trigger-dependent differences determine therapeutic outcome in murine primary hemophagocytic lymphohistiocytosis

Familial hemophagocytic lymphohistiocytosis (FHL) is a hyperinflammatory syndrome affecting patients with genetic cytotoxicity defects. Perforin-deficient (PKO) mice recapitulate the full clinical picture of FHL after infection with lymphocytic choriomeningitis virus (LCMV). Hyperactivated CD8⁺ T cells and IFN-γ have been identified as the key drivers of FHL and represent targets for therapeutic interventions. However, the response of patients is variable. This could be due to trigger-dependent differences in pathogenesis, which is difficult to address in FHL patients, since the trigger frequently escapes detection. We established an alternative FHL model using intravenous infection of PKO mice with murine CMV (MCMV)_Smith. PKO mice developed acute FHL after both infections and fulfilled HLH diagnostic criteria accompanied by excessive IFN-γ production by disease-inducing T cells, that enrich in the BM. However, direct comparison of the two infection models disclosed trigger-dependence of FHL progression and revealed a higher contribution of CD4 T cells and NK cells to IFN-γ production after MCMV infection. Importantly, therapeutic intervention by IFN-γ neutralization or CD8⁺ T-cell depletion had less benefit in MCMV-triggered FHL compared to LCMV-triggered FHL, likely due to MCMV-induced cytopathology. Thus, the context of the specific triggering viral infection can impact the success of targeted immunotherapeutic HLH control.     

噬血细胞综合征患者红细胞寿命的检测及其对患者贫血的影响分析

目的:通过一氧化碳呼气试验测定噬血细胞综合征患者红细胞寿命,分析其对噬血细胞综合征合并贫血患者的影响。方法:对20例初诊HLH患者进行一氧化碳呼气试验并测定红细胞寿命,并以20例健康人的检测作为对照,对比噬血细胞综合征患者与健康人2组间贫血相关指标的差异。结果:噬血细胞综合征患者的平均红细胞寿命为45.3 d,比健康人缩短65%。血红蛋白水平与红细胞寿命呈正相关,sCD25、呼气一氧化碳浓度和骨髓噬血现象与红细胞寿命呈负相关,胆红素、网织红细胞计数与红细胞寿命无相关性。新发噬血细胞综合征患者血清中IL-1β,IL-2,sCD25,IL-6,IL-10,IL-17A,GM-CSF,TNF-α和IFN-γ表达水平较健康人显著升高(P<0.05)。结论:一氧化碳呼气试验是一项快速测定红细胞寿命的方法。红细胞破坏增加是噬血细胞综合征合并贫血的重要发病机制。     

Miliary tuberculosis-associated hemophagocytic lymphohistiocytosis with a high level of soluble interleukin-2 receptor successfully treated with concomitant recombinant thrombomodulin: A case report

Hemophagocytic lymphohistiocytosis (HLH) is a fatal disease characterized by a highly inflammatory state due to the abnormal activation of T lymphocytes and macrophages. Miliary tuberculosis (MTB) is a rare cause of HLH and its clinical appearances occasionally resembles that of intravascular lymphoma (IVL). A 76-year-old woman presented with persistent fever and fatigue. Abnormal laboratory findings showing thrombocytopenia (13,000/μL), hypofibrinogenemia (101 mg/dL), hyperferritinemia (2,312 ng/mL), and markedly elevated soluble interleukin-2 receptor (sIL-2R) level (32,200 U/mL), in addition, hemophagocytosis in the bone marrow (BM) smear, were suggestive of IVL-associated HLH. The pathology of the BM biopsy specimen showed granuloma with non-caseous necrosis, and culture tests using sputum, gastric fluid, urine, and peripheral and bone marrow blood revealed the presence of Mycobacterium tuberculosis, leading to the final diagnosis of MTB-associated HLH. Anti-TB medications and corticosteroids were administered, but thrombocytopenia, hypofibrinogenemia, and hyperferritinemia persisted. Concomitant use of recombinant thrombomodulin (rTM) enabled regression of clinical status. In this case, BM biopsy served as the diagnosis of MTB-associated HLH, although IVL-associated HLH is initially suspected by an extremely high level of sIL-2R. Furthermore, this case report informs that using rTM could improve the outcomes of MTB-associated HLH.     

Haemophagocytic lymphohistiocytosis: Five years’ experience at tertiary hospitals in Free State Province,South Africa

Background Haemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome if not recognised and managed early. It involves an uncontrolled pathological activation of the immune system, and it is either genetic or acquired. It presents with clinical and laboratory features of severe inflammation. Early initiation of effective therapy may reduce mortality from 95% to 35%. ObjectivesTo raise awareness of HLH among healthcare professionals, particularly intensivists. MethodsWe report nine cases of secondary HLH seen at tertiary hospitals in Bloemfontein, South Africa. Results All patients presented with fever, hypertriglyceridaemia, hyperferritinaemia, transaminitis and cytopenia. Haemophagocytosis was noted on bone marrow biopsy in 66.7% (n=6/9) of the patients. More than one-third (44.4%; n=4/9) of the cases were triggered by a lymphoma, 44% (n=4/9) were associated with infection and 11% (n=1/9) were associated HIV. Finally, 11.1% (n=1) of the patients were triggered by an underlying autoimmune disease. More than half (55.6%; n=5/9) of the cases had a fatal outcome. Conclusion A high index of suspicion may promote the accurate diagnosis of HLH in patients presenting with fever, transaminitis and unexplained cytopenia. Contributions of the study HLH is a rare, life-threatening condition that may be missed in the intensive care setting. This report emphasises the importance of clinical suspicion, early diagnosis and appropriate intervention.     

Congenital dyserythropoietic anemia type II with a positive sucrose hemolysis test

Hemophagocytic syndrome (HPS) is a rare clinical presentation infrequently associated with lymphoproliferative disorders. We describe a 29-year-old male with aggressive HPS and T-cell lymphoma managed successfully with high-dose chemotherapy and autologous peripheral stem cell transplantation (APSCT), in remission at 41 months of follow-up. In reviewing the literature, this case illustrates the 2nd longest surviving individual post stem cell transplant for aggressive HPS.     

Reactive hemophagocytic syndrome as a presenting feature of Hodgkin's disease

We report the case of a 60-year-old man with febris of unknown origin, severe pancytopenia, and rapidly developing splenomegaly due to reactive hemophagocytic syndrome and Hodgkin's disease. Reactive hemophagocytic syndrome is often rapidly fatal and, once this diagnosis is considered, an underlying infection or malignancy should be treated promptly. An extensive search of the literature revealed only two other cases of reactive hemophagocytic syndrome and Hodgkin's disease. This is the only reported patient who survived after being diagnosed as having reactive hemophagocytic syndrome and Hodgkin's disease. Received: 12 October 1998 / Accepted: 4 November 1999     

Peripheral T-cell lymphoma associated consecutively with hemophagocytic lymphohistiocytosis and hypereosinophilic syndrome

Both hemophagocytic lymphohistiocytosis and hypereosinophilic syndrome have been associated with hematologic neoplasms and are respectively related to an overproduction of the cytokines Thelper 1 (Th1) and Th2 by tumor cells or reactive cells. To our knowledge, this is the first time a case of a peripheral T-cell lymphoma consecutively associated with both paraneoplastic conditions has been reported. Importantly, in this case when the lymphoma exclusively involved the bone marrow, severe paraneoplastic systemic damage, a CD8+ suppressor/cytotoxic phenotype and a hypereosinophilia not related to high levels of interleukin (IL)-5 was found. Interestingly, progression of the lymphoma coincided with an increase in the serum levels of several Th2 cytokines and IL-2, a decrease in tumor necrosis factor and granulocyte-macrophage colony-stimulating factor levels and the onset of a hypereosinophilic syndrome.