Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Nov 6, 2019; 7(21): 3394-3406
Published online Nov 6, 2019. doi: 10.12998/wjcc.v7.i21.3394
Efficient management of secondary haemophagocytic lymphohistiocytosis with intravenous steroids and γ-immunoglobulin infusions
Sarah Georgiadou, Nikolaos K Gatselis, Aggelos Stefos, Kalliopi Zachou, Konstantinos Makaritsis, Eirini I Rigopoulou, George N Dalekos
Sarah Georgiadou, Nikolaos K Gatselis, Aggelos Stefos, Kalliopi Zachou, Konstantinos Makaritsis, Eirini I Rigopoulou, George N Dalekos, Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, Larissa 41110, Greece
Nikolaos K Gatselis, Kalliopi Zachou, Konstantinos Makaritsis, Eirini I Rigopoulou, George N Dalekos, Institute of Internal Medicine and Hepatology, University Hospital of Larissa, Larissa 41447, Greece
Author contributions: Makaritsis K, Rigopoulou EI, Dalekos GN made the conception and designed of the work, treated the patients, analyzed and interpreted of the data, critical revision of the manuscript and final approved of the version to be published; Georgiadou S, Gatselis NK, Stefos A, Zachou K treated the patients, made the collection, statistical analysis and interpretation of the data, wrote the first draft of the manuscript and final approved of the version to be published.
Institutional review board statement: The ethical committee of the University Hospital of Larissa approved the protocol which conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution's human research committee.
Informed consent statement: Patients were not required to give informed consent to the study because the retrospective analysis used anonymous clinical data that were obtained after each patient agreed to the treatment schedule by written consent.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: George N Dalekos, MD, PhD, Chairman, Full Professor, Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, Mezourlo, Larissa 41110, Greece. dalekos@med.uth.gr
Telephone: +30-241-3502285 Fax: +30-241-3501557
Received: June 5, 2019
Peer-review started: June 6, 2019
First decision: September 9, 2019
Revised: September 20, 2019
Accepted: October 15, 2019
Article in press: October 15, 2019
Published online: November 6, 2019
Processing time: 156 Days and 18.5 Hours
Abstract
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.

Keywords: Haemophagocytic syndrome; Haemophagocytic lymphohistiocytosis; γ-immunoglobulin; Leishmaniasis; Ferritin

Core tip: This retrospective study analysed all adult patients (n = 80) with secondary haemophagocytic lymphohistiocytosis (sHLH) diagnosed in our tertiary care hospital during 2010-2018 paying considerable attention on the treatment schedule and the outcome of patients. In our large cohort, infections were the major cause of sHLH (74% of patients) and therefore, they should be thoroughly investigated in such patients. sHLH still carries a remarkable morbidity and mortality as 15% of patients died within the first month. Early recognition and treatment with intravenous γ-immunoglobulin in association with intravenous corticosteroids seem an efficient treatment option for successful outcome in this life-threatening condition (resolution in 76%; 6-mo survival: 82.5%).