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
ARTICLE HIGHLIGHTS
Research background

Acquired or secondary haemophagocytic lymphohistiocytosis (sHLH) in adults is a heterogeneous disease triggered by infectious, autoimmune, or neoplastic disorders. sHLH is still associated with high morbidity and mortality. At the time of our study (January 2010-June 2018) the guidelines in use for the treatment of HLH, whether primary or secondary, included intensive immunosuppressive treatment.

Research motivation

As there are no randomized trials for the optimal management of sHLH in adults, treatment in every-day clinical practice varies widely among medical institutes. Nevertheless, several investigators are reluctant to treat patients with intense chemo-immune agents, particularly in cases with infection-associated sHLH.

Research objectives

To analyze all adult sHLH cases that were diagnosed and managed under real-world circumstances between 2010 and 2018 in our tertiary care hospital focusing on the treatment schedule and the outcome.

Research methods

All adult patients with well-established sHLH who were diagnosed and managed at the Department of Medicine of the Larissa University Hospital, Greece from January 1, 2010 to June 1, 2018, were assessed retrospectively. The electronic records and/or written charts of the patients were reviewed for demographic characteristics, clinical manifestations, underlying causes of sHLH, laboratory parameters, treatment schedule and the 30-d-mortality rate.

Research results

Over this 8-year study period, 80 patients (52.5% males; mean age 52.1 ± 19.2 years) with sHLH were identified. In the majority of cases (74%), the underlying cause of sHLH was infection followed by neoplastic disease (16.2%) and autoimmune disease (7.5%). Seventy-two patients (90%) received combination treatment of intravenous γ-immunoglobulin (IVIG) and intravenous steroids, 4 patients received corticosteroids only (due to IVIG short supply) and 4 patients received treatment only for their underlying disease (visceral leishmaniasis) with liposomal amphotericin B. The majority of patients (76%) were cured following treatment. Twelve patients (15%) died within the first month after diagnosis but the 6-mo survival was 82.5%. Although older age, anaemia, thrombocytopenia, low fibrinogen, disseminated intravascular coagulation (DIC), and delay of diagnosis were factors that negatively affected response to treatment in the univariate analysis, only the development of DIC and low platelets were independently associated with adverse outcome.

Research conclusions

Infections identified as the major cause of sHLH in our study and therefore, they should be thoroughly investigated in these patients. In addition, IVIG in combination with intravenous corticosteroids seems efficient and safe first-line treatment option for successful outcome of this life-threatening condition, avoiding in parallel overtreatment and unnecessary toxicity by using less immunosuppressive and less cytotoxic treatment modalities.

Research perspectives

Using a less cytotoxic and less immunosuppressive therapeutic schedule, we achieved a quite high remission rate (76%) and 6-mo survival (82.5%) albeit a 30-day mortality rate of 15%. Future prospective multicenter randomized control studies are needed in order to definitely address the potential therapeutic benefit of IVIG in patients with sHLH and particularly in those with infections- or autoimmunity-related sHLH.