Hemophagocytic lymphohistiocytosis syndrome

Authors: M. Suková 1;  E. Mejstříková 2;  E. Vodičková 3;  R. Špíšek 4;  R. Formánková 1;  D. Sumerauer 1;  T. Freiberger 5;  P. Sedláček 1;  J. Starý 1
Authors‘ workplace: Klinika dětské hematologie a onkologie 2. lékařské fakulty UK a FN Motol Praha, přednosta prof. MUDr. Jan Starý, DrSc. 1;  CLIP cytometrie Kliniky dětské hematologie a onkologie 2. lékařské fakulty UK a FN Motol Praha, vedoucí laboratorního centra prof. MUDr. Jan Trka, Ph. D. 2;  Oddělení klinické hematologie FN Motol Praha, přednostka prim. MUDr. Ivana Hochová 3;  Ústav imunologie 2. lékařské fakulty UK a FN Motol Praha, přednostka prof. MUDr. Jiřina Bartůňková, DrSc. 4;  Centrum kardiovaskulární a transplantační chirurgie Brno, ředitel doc. MUDr. Petr Němec, CSc. 5
Published in: Vnitř Lék 2010; 56(Supplementum 2): 157-169
Category: Langerhans cell histiocytosis and some other Hematology rare diseases


Hemophagocytic lymphohistiocytosis (HLH) represents a heterogenous group of specific immune-systeme deficiencies, characterized by uncontrolled proliferation of T lymphocytes and macrophages, resulting in overproduction of cytokines and inadequate hemophagocytic activity in lymphoreticular systeme and CNS. Cytokines overproduction plays a major role in a tissue damage and brings out typical clinical and laboratory features – persistant fever, hepatosplenomegaly, peripheral blood cytopenia, hypertriglyceridemia, hypofibrinogenemia and bone marrow hemophagocytosis. Full-blown HLH is a life-threatening disease rapidly progressing to multiorgan failure and death. Diagnostics of HLH is often difficult under the condition of absent specific diagnostic marker. Diagnostic guidelines proposed by The Histiocyte Society are based on combination of clinical, biochemical and immunological signs supported by morfological evidence of hemophagocyting macrophages in bone marrow. HLH comprises two different conditions that may be difficult to distinguish one from another: primary HLH – a heterogenous group of rare genetic disorders and a secondary form – HLH developing as a consequence of inadequate immune systeme activation initiated by infections, malignancies or systemic autoimmune diseases. According to HLH-2004 treatment proposal remission could be reached in both conditions by immunosuppression (dexamethasone, etoposide and steroids), but in primary HLH stem cell transplantation offers the only currative option. A series of 17 primary HLH patients diagnosed in the Czech Republic between 1999 and 2009, representing our experience with this rare disease, has outcome comparable to data published by European HLH group (4yrs OS 74%, EFS 56%). Diagnostic dilemma in HLH is demonstrated through several case reports of both primary and secondary HLH patients, revealing significance of clinical experience, awareness of differential diagnosis and application of modern immunological analyses in diagnostic procedure in HLH. All these parametres contribute to early onset of treatment determinating prognosis of HLH patients.

Key words:
hemophagocytic lymphohistiocytosis – immunodeficiency – lymphoproliferation – macrophage activation syndrome – immunosuppressive therapy – stem-cell transplantation


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