Secondary haemophagocytic lymphohistiocytosis: Experience from the Uppsala University Hospital

Background. Haemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by fever, hepatosplenomegaly, cytopenia, and progressive multiple-organ failure. HLH in adults is often secondary to autoimmune diseases, cancer, or infections in contrast to familial HLH. Treatment of secondary HLH is directed against the triggering disease in addition to immunosuppressive therapy, the latter commonly according to the HLH-2004 protocol.Methods. We conducted a retrospective study to identify triggering diseases, disease-specific and immunosuppressive therapy administered, and prognosis in adult patients with secondary HLH. Patient data were collected from October 2010 to January 2015.Results. Ten adult patients with secondary HLH were identified. Seven were men, and the median age at diagnosis was 62 years. Five cases were triggered by malignant disease and five by infection. The median patient fulfilled five of the eight HLH-2004 diagnostic criteria. All patients fulfilled the criteria fever, cytopenia, and ferritin >500 µg/L. Median time from hospital admission to HLH diagnosis was 20 days. Four patients received immunosuppressive therapy according to the HLH-2004 protocol. The prognosis was dismal, especially for the patients with malignancy-associated HLH, of whom all died.Conclusion. HLH should be suspected in patients who present with fever, cytopenia, and ferritin >500 µg/L. Secondary HLH has a dismal prognosis. None of the patients with HLH triggered by malignancy survived. Achieving remission of the triggering disease seems to be important for a favourable outcome as, in all surviving patients, the haemophagocytic syndrome resolved after remission of the underlying infection.     

Intracerebral vascular occlusion in familial erythrophagocytic lymphohistiocytosis: a case report of two siblings

Neuropathological findings in two siblings with familial erythrophagocytic lymphohistiocytosis (FEL) are reported. Case 1 showed the typical neuropathological findings of FEL with lymphohistiocytic infiltration of the leptomeninges and perivascular spaces. A characteristic erythrophagocytosis was detected in inguinal lymph nodes, lung and bone marrow. Case 2 revealed calcification and necrotic lesions in the brain. In the necrotic areas, parenchymal calcification, vascular medial calcification, and occlusion of many vessels due to subendothelial fibrosis were detected. The areas of necrosis correlated with the distribution of occluded vessels. These changes were most prominent in putamen, internal capsule, thalamus and dentate nucleus. Hypercytokinemia is suspected to be the underlying mechanism for the clinical and laboratory findings in patients with FEL, although the relationship to the vascular pathology is unclear.     

Sequential respiratory syncytial virus cytomegalovirus pneumonia following bone marrow transplantation

A 6-month-old child with familial hemophagocytic lymphohistiocytosis (FHL) experienced early sequential pneumonia due to respiratory syncytial virus (RSV) and cytomegalovirus (CMV) following bone marrow transplantation (BMT). The patient was deficient in natural killer (NK) cell activity (as found frequently in patients with FHL), and this risk factor may have played a major role in the concomitant infection by the two viral pathogens. Rapid diagnostic methods for both viruses are essential and early specific treatment may serve to ameliorate RSV- and CMV-induced lung injury in these life-threatening infections. © 1995 Wiley-Liss, Inc.     

采用噬血细胞综合征-04方案治疗噬血细胞综合征5例

目的观察噬血细胞综合征(HLH)-04方案治疗儿童HLH 5例的早期疗效。方法回顾性分析确诊为HLH患儿5例的临床特点,总结其对以鬼臼乙叉甙(VP16)为基础的免疫化学方案治疗的反应及转归。结果HLH患儿5例中4例在早期治疗阶段完全缓解(CR),CR时间17~22 d(平均18.8 d);另1例规则采用VP16治疗84 d未CR,改用鬼臼甲叉甙(VM26)于d130 CR;病例均存活9~11个月,目前仍CR。1例治疗14 d时出现手足震颤,怀疑为环孢素(CSA)不良反应,改用骁悉替代后手足震颤消失。结论儿童HLH可通过采用HLH-04方案的免疫化学治疗,早期得以有效控制。     

Risk for complications in patients with hemophagocytic lymphohistiocytosis who undergo hematopoietic stem cell transplantation: myeloablative versus reduced-intensity conditioning regimens

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option for patients with primary hemophagocytic lymphohistiocytosis (HLH) and for patients with secondary HLH who fail to respond to therapy. Advances in HSCT and supportive care measures have resulted in improved patient outcomes and decreased treatment-related mortality. Despite the overall improvement in outcome, HLH patients who undergo HSCT using myeloablative conditioning regimens are still at significant risk for complications. The HLH-94 study conducted by the Histiocyte Society reported a 30% TRM with increased pulmonary and hepatic complications. Recently, the use of reduced-intensity conditioning (RIC) regimens has shown favorable outcomes when compared to conventional HSCT and lower rate of acute complications. In this review we compare the potential complications of myeloablative and RIC regimens for HSCT in HLH patients.     

Spectrum of imaging appearances in Australian children with central nervous system hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem disorder characterised by the proliferation and infiltration of lymphocytes and histiocytes. Central nervous system (CNS) infiltration is particularly devastating. Neuroradiological findings have been reported predominantly as individual case reports due to the rarity of the condition. To our knowledge there have been no published studies of imaging in Australian patients. This study aimed to retrospectively describe and illustrate the MRI appearances of CNS involvement by HLH in a cohort of seven Australian children from two paediatric centres between 2000 and 2011. MRI appearances demonstrate intersubject and intrasubject variability over time, likely reflecting the severity of CNS infiltration and associated demyelination. Familiarity with MRI patterns is important for assessing and monitoring disease activity.     

Neuropsychological Assessment in a Case of Adult-Onset Hemophagocytic Lymphohistiocytosis (HLH)

We present a case of an individual diagnosed with hemophagocytic lymphohistiocytosis (HLH), an extremely rare and commonly fatal disorder characterized by rapid dysregulation of immune system processes. Typical age of onset is in childhood, with adult-onset occurring less frequently. The pathophysiology of this condition is characterized by a hyperinflammatory response with infiltration of visceral organs, lymph nodes, bone marrow, and the central nervous system. The clinical presentation has been documented in the extant medical literature. However, there appear to be no published reports of neuropsychological functioning in HLH patients. The patient we present here is a 28-year-old woman with 16 years of education who developed HLH subsequent to systemic lupus erythematosus flare-up. She was initially comatose for 3 weeks. Acute MRI reported multiple subcortical abnormalities, including the brainstem. The patient underwent chemotherapy, immunosuppresant, and steroid treatments. She underwent a neuropsychological evaluation at 2.5 and 7 months post initial presentation. Preliminary neuropsychological evaluation found impairments in motor abilities and aspects of executive functions. Subsequent evaluation showed improved executive function and relative sparing of higher-order cognitive abilities, but continued impairment on motor tests. To our knowledge this is the first study to report neuropsychological data for an adult diagnosed with HLH.