Secondary hemophagocytic syndrome in adults: a case series of 18 patients in a single institution and a review of literature

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is rare in adults and is usually fatal without treatment. We present a consecutive series of 18 adults with HLH diagnosed at our institution between 2004 and 2009. All diagnoses were confirmed by pathology. The median age at diagnosis was 56 years (range: 18-73 years), with a male: female ratio of 2:1. Patients uniformly presented with fever. Fifty-five per cent of the patients presented with evidence of hepatomegaly or splenomegaly. All of the patients had at least a bi- or trilineage cytopenia. Elevated liver enzymes, hyperferritinemia, hypertriglyceridemia and hyperfibrinogenemia were seen in 50, 100, 40 and 50% of patients, respectively. The presumed causes were as follows; haematological malignancies (n = 4), post-autologous stem cell transplant (n = 2), infection (n = 2), rheumatologic illness (n = 2), sickle cell disease (n = 1), post-orthotopic liver transplant (n = 1) and idiopathic (n = 3). The median time from suspicion to diagnosis was 5 days (1-27 days). Corticosteroids and/or cyclosporine were the most frequently used treatment regimen. Other agents used were etoposide, IVIG, cyclophosphamide and chemotherapy. The mortality rate was 72%, with multi-system organ failure being the most common cause of death. Median survival time from diagnosis was 35 days. Six patients are alive to date. In a univariate analysis, the presence of fever was the only factor that was statistically significant for predicting a poor prognosis (early mortality) (p = 0.05). In conclusion, a high index of suspicion is the critical factor for early diagnosis. Early treatment with immunosuppressant is warranted, and a thorough diagnostic evaluation to identify the underlying cause should be undertaken.

A Fatal Case of Pyrexia of Unknown Origin: Hemophagocytic Lymphohistiocytosis?

“…12,13 The HLH secondary to Epstein-Barr virus (EBV) infection with high EBV genome copy numbers is also considered to be related to poor prognosis, 14,15 which is attributed to delay in diagnosis as a result of similarity between its initial clinical presentation to that of common infective and inflammatory conditions. However, improved outcomes have been reported with the use of rituximab, etoposide, 16 and…”

Between a rock and a hard place

“…The mutations identified to date lead to abnormalities in the perforin cytotoxic pathway causing decreased function of NK-and/or cTC, indicating a pivotal role of this event in the pathogenesis of HLH [2]. Recently, there have been increasing reports of adult onset HLH in the context of conditions associated with immune dysregulation: hematologic malignancies, infections, autoimmune diseases, organ/ stem cell transplants and chemo-or immunosuppressive therapies [3][4][5][6][7]. Some of the cases affecting young adults represent attenuated familial forms of the disease due to partial loss of function of the HLH-causing genes [8], while in older adults (>60 yr.) malignancy associated HLH is most common.…”

“…The highest chance of therapeutic success is early diagnosis and identification of a treatable trigger condition. HLH diagnosis is difficult and requires a high level of clinical suspicion [3]. Consensus guidelines have helped increase the recognition of this rare entity [3][4][5].…”

“…HLH diagnosis is difficult and requires a high level of clinical suspicion [3]. Consensus guidelines have helped increase the recognition of this rare entity [3][4][5]. Peripheral blood hemophagocytosis is very rare, having been described only in a handful of case reports [9][10][11][12][13], always associated with HLH.…”

Causes of hyperferritinaemia classified by HIV status in a tertiary-care setting in South Africa

“…Acquired iron overload due to transfusion was accepted as being the cause of hyperferritinaemia in patients that had received at least four units of packed red cells within the preceding 6 months [3]. Haematological disease had to be confirmed by either bone marrow aspirate and/or biopsy or peripheral blood film [17]. Diagnosis of malignancy was only accepted when based on histological confirmation and haemophagocytosis based on bone marrow aspiration.…”