Efficient management of secondary haemophagocytic lymphohistiocytosis with intravenous steroids and γ-immunoglobulin infusions

BACKGROUND: Secondary haemophagocytic lymphohistiocytosis (sHLH) is a rare life-threatening condition mainly associated with underlying infections, malignancies, and autoimmune or immune-mediated diseases. AIM: To analyse all sHLH cases that were diagnosed and managed under real-world circumstances in our department focusing on the treatment schedule and the outcome. METHODS: Prospectively collected data from all adult patients fulfilling the criteria of sHLH who diagnosed and managed from January 1, 2010 to June 1, 2018, in our department of the tertiary care university hospital of Larissa, Greece, were analysed retrospectively (n = 80; 52% male; median age: 55 years). The electronic records and/or written charts of the patients were reviewed for the demographic characteristics, clinical manifestations, underlying causes of sHLH, laboratory parameters, treatment schedule and 30-d-mortality rate. Most of patients had received after consent intravenous γ-immunoglobulin (IVIG) for 5 d (total dose 2 g/kg) in combination with intravenous steroid pulses followed by gradual tapering of prednisolone. RESULTS: Seventy-five patients (94%) reported fever > 38.5 °C, 47 (59%) had liver or spleen enlargement and 76 (95%) had ferritin > 500 ng/mL including 20 (25%) having considerably high levels (> 10000 ng/mL). Anaemia and thrombocytopenia occurred in 72% and leucopoenia in 47% of them. Underlying infections were diagnosed in 59 patients (74%) as follows: leishmaniasis alone in 15/80 (18.9%), leishmaniasis concurrently with Coxiella Burnetti or non-Hodgkin lymphoma in 2/80 (2.5%), bacterial infections in 14/80 (17.5%) including one case with concurrent non-Hodgkin lymphoma, viral infections in 13/80 (16.3%), fungal infections in 2/80 (2.5%), infections by mycobacteria in 1/80 (1.3%) and unidentified pathogens in 12/80 (15%). Seventy-two patients (90%) had received combination treatment with IVIG and intravenous steroids. Overall, sHLH resolved in 76% of patients, 15% died within the first month but 82.5% of patients were still alive 6 mo after diagnosis. Univariate analysis showed older age, anaemia, thrombocytopenia, low fibrinogen, disseminated intravascular coagulation (DIC), and delay of diagnosis as factors that negatively affected remission. However, multivariate analysis showed low platelets and DIC as the only independent predictors of adverse outcome. CONCLUSION: sHLH still carries a remarkable morbidity and mortality. Underlying infections were the major cause and therefore, they should be thoroughly investigated in patients with sHLH. Early recognition and combination treatment with IVIG and corticosteroids seem an efficient treatment option with successful outcome in this life-threatening condition.