Myelodysplastic syndrome (MDS) as a late stage of subclinical hemophagocytic lymphohistiocytosis (HLH): a putative role for Leptospira infection. A hypothesis

Abstract

It is proposed that hemophagocytic lymphohistiocytosis (HLH) and myelodysplastic syndromes (MDS) may be temporally distinct phases of pathophysiologically related disease processes. A significant subgroup of MDS may develop from subclinical HLH. In that case, HLH-like disease would chronically proceed with little disease activity or under occasional flares only, until it first becomes clinically apparent at the MDS stage. At the MDS stage, however, HLH activity may be easily overlooked by histological or cytogenetic means, since hemophagocytosis has fallen already largely silent. Current treatment options for HLH, like high-dose intravenous immunoglobulins (IVIG), may turn out to be helpful in MDS patients as well. In rare and extreme cases, Leptospira infection causes severe and life-threatening HLH. Thus, this proposal also implies that an insufficient, dysfunctional or misdirected immunological response to Leptospira infection may lead to MDS in the long run in a significant number of cases, which have not been recognized as Leptospira -triggered events in the first place. Infections by agents other than Leptospira may lead to subclinical HLH-like disease with MDS as a late stage as well.