Contributions
Abstract: PB1825
Type: Publication Only
Background
Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition caused by highly stimulated but dysregulated and ineffective immune responses. Cardinal features of HLH are fever, hepatosplenomegaly, pancytopenia, and lymphohistiocytic proliferation. HLH is an underdiagnosed but potentially life-threatening clinicopathological syndrome often occurring in adults with hematological malignancies and autoimmune disorders.
Aims
To describe clinical characteristics of adults with reactive HLH/macrophage activation syndrome (MAS).
Methods
From Jan 2009 onwards, data on adults referred to the Rheumatology Department (2000 hospitalized patients per year) of the J. Dietl Specialist Hospital in Krakow (inhabited by approx. 1 million people) with suspected HLH/MAS were collected. The diagnosis of HLH was based on the HLH-2004 guidelines and HScore. In all patients, aspiration biopsy of bone marrow (BM) and/or lymph node was performed to evaluate a presence of hemophagocytosis. Connective tissue diseases were diagnosed according to international criterias. Infection as a possible additional trigger of HLH was carefully studied in all patients. EBV and CMV were routinely examined in whole blood; blood and urine cultures were performed in order to reveal any bacterial infections. The patient’s medical records were reviewed to collect relevant clinical data. The patients provided their informed consent. The study was performed according to the ethical guidelines of the Declaration of Helsinki.
Results
Seven adults (4 female, 3 male), aged 20–59 years (median age 31 years), were diagnosed with aggressive HLH during the 8.5-year period between Jan 2009 and Jul 2017. Of these, two patients suffered from adult onset Still disease, one from childhood onset ankylosing spondylitis, one from systemic lupus erythematosus, one from systemic onset juvenile idiopathic arthritis, one from connective tissue disease UNS, and one from Erdheim-Chester disease. All patients presented with unremitting fever, splenomegaly, and hyperferritinemia ≥500 μg/L (median 5731, range 1469-27760). Hemophagocytosis was present in all but one patient, though only in 3 patients on the first examination. A newly developed cytopenia was present in 3/7 patients according to HLH-2004 and in all patients according to HScore. HLH-2004 criterion of hypertriglyceridemia ≥3 mmol/L and/or hypofibrinogenemia ≤1.5 g/L was fulfilled in 5/7 patients. An inflammatory state was observed both from elevated CRP (median 49,4 mg/L, range 14-277) in all patients, and low ESR (median 17 mm, range 8-45) in all but one patient. In 3 patients, the HLH trigger was identified as an active EBV infection (IgG EBNA, VCA), and for one patient HSV was suspected. One patient presented with neuropsychiatric symptoms that were not accompanied at first by any MRI abnormalities, though CSF revealed hemophagocytosis.
Conclusion
Clinical and biological features of HLH (e.g., fever, splenomegaly, cytopenia, hyperferritinemia) are not specific and can also occur in other disorders. It may be difficult to distinguish HLH from other diseases such as severe sepsis, hematologic malignancies or exacerbation of rheumatic disease. Thus, the HLH/MAS diagnosis may be overlooked or delayed. Timely diagnosis is crucial since early administration of effective treatment (e.g., HLH-94 therapy) may improve survival. The knowledge of HLH-2004 and HScore diagnostic criteria among physicians is essential to increase a recognition of this syndrom.
Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Keyword(s): Ferritin, Fever, Pancytopenia, Spleen
Abstract: PB1825
Type: Publication Only
Background
Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition caused by highly stimulated but dysregulated and ineffective immune responses. Cardinal features of HLH are fever, hepatosplenomegaly, pancytopenia, and lymphohistiocytic proliferation. HLH is an underdiagnosed but potentially life-threatening clinicopathological syndrome often occurring in adults with hematological malignancies and autoimmune disorders.
Aims
To describe clinical characteristics of adults with reactive HLH/macrophage activation syndrome (MAS).
Methods
From Jan 2009 onwards, data on adults referred to the Rheumatology Department (2000 hospitalized patients per year) of the J. Dietl Specialist Hospital in Krakow (inhabited by approx. 1 million people) with suspected HLH/MAS were collected. The diagnosis of HLH was based on the HLH-2004 guidelines and HScore. In all patients, aspiration biopsy of bone marrow (BM) and/or lymph node was performed to evaluate a presence of hemophagocytosis. Connective tissue diseases were diagnosed according to international criterias. Infection as a possible additional trigger of HLH was carefully studied in all patients. EBV and CMV were routinely examined in whole blood; blood and urine cultures were performed in order to reveal any bacterial infections. The patient’s medical records were reviewed to collect relevant clinical data. The patients provided their informed consent. The study was performed according to the ethical guidelines of the Declaration of Helsinki.
Results
Seven adults (4 female, 3 male), aged 20–59 years (median age 31 years), were diagnosed with aggressive HLH during the 8.5-year period between Jan 2009 and Jul 2017. Of these, two patients suffered from adult onset Still disease, one from childhood onset ankylosing spondylitis, one from systemic lupus erythematosus, one from systemic onset juvenile idiopathic arthritis, one from connective tissue disease UNS, and one from Erdheim-Chester disease. All patients presented with unremitting fever, splenomegaly, and hyperferritinemia ≥500 μg/L (median 5731, range 1469-27760). Hemophagocytosis was present in all but one patient, though only in 3 patients on the first examination. A newly developed cytopenia was present in 3/7 patients according to HLH-2004 and in all patients according to HScore. HLH-2004 criterion of hypertriglyceridemia ≥3 mmol/L and/or hypofibrinogenemia ≤1.5 g/L was fulfilled in 5/7 patients. An inflammatory state was observed both from elevated CRP (median 49,4 mg/L, range 14-277) in all patients, and low ESR (median 17 mm, range 8-45) in all but one patient. In 3 patients, the HLH trigger was identified as an active EBV infection (IgG EBNA, VCA), and for one patient HSV was suspected. One patient presented with neuropsychiatric symptoms that were not accompanied at first by any MRI abnormalities, though CSF revealed hemophagocytosis.
Conclusion
Clinical and biological features of HLH (e.g., fever, splenomegaly, cytopenia, hyperferritinemia) are not specific and can also occur in other disorders. It may be difficult to distinguish HLH from other diseases such as severe sepsis, hematologic malignancies or exacerbation of rheumatic disease. Thus, the HLH/MAS diagnosis may be overlooked or delayed. Timely diagnosis is crucial since early administration of effective treatment (e.g., HLH-94 therapy) may improve survival. The knowledge of HLH-2004 and HScore diagnostic criteria among physicians is essential to increase a recognition of this syndrom.
Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Keyword(s): Ferritin, Fever, Pancytopenia, Spleen