Clinical characteristics and disease course in children with haemophagocytic lymphohistiocytosis treated at the University children’s hospital in Belgrade

Abstract

Introduction. Haemophagocytic lymphohistiocytosis (HLH) is a disorder characterised by long-standing fever, splenomegaly and bicytopoenia or pancytopoenia. Lymphadenopathy, jaundice and neurological symptoms may also occur. HLH may ensue in various forms of innate or acquired immunodeficiency with impaired cytotoxic lymphocyte function resulting in excessive macrophage activation. Objective. To describe and analyse clinical characteristics of patients treated for HLH at the University Children?s Hospital of Belgrade from August 2000 to August 2010. Methods. Retrospective analysis of medical records. Results. Diagnosis of HLH was established in 13 children (five boys and eight girls) aged from one month to 14 years. In six children HLH was secondary (to visceral leishmaniasis in two, Ebstein-Barr virus infection in one, Langerhans? cell histiocytosis in one and systemic juvenile rheumatoid arthritis in two). Of the remaining seven patients, genes for perforin and syntaxin 11 were examined in two and no mutations were found. Of the remaining seven patients, genes encoding perforin and syntaxin 11 were analyzed in two, but no mutations were found. All children had fever, splenomegaly, cytopoenias, hyperferritinaemia and hypertriglyceridaemia, but haemophagocytosis was seen in only six (46.1%). Six children were cured (four with secondary HLH and two with primary HLH). Two children are undergoing treatment, while five succumbed (three before treatment could be administered and two due to complications). In four of the six cured children, HLH arose in the first year of life. Cure rate in those who underwent haematopoietic stem cell trans- plantation was 2/3. Conclusion. Results underscore the importance of timely diagnosis and treatment of HLH, warranting that in all children with fever, splenomegaly and/or cytopoenias, with or without haemophagocytosis, HLH be actively sought.Uvod. Hemofagocitna limfohistiocitoza (HLH) je patolosko stanje koje odlikuju dugotrajno povisena telesna temperatura, splenomegalija i bicitopenija ili pancitopenija. Takodje se javljaju limfadenopatija, zutica i neuroloski simptomi. U osnovi lezi hronican zapaljenjski proces nastao usled razlicitih oblika urodjene ili stecene imunodeficijencije sa smanjenom funkcijom citotoksicnih limfocita, sto dovodi do preterane aktivacije makrofaga. Cilj rada. Cilj rada bio je da se opisu i analiziraju klinicka obelezja bolesnika lecenih od HLH od avgusta 2000. do avgusta 2010. godine u Univerzitetskoj decjoj klinici u Beogradu. Metode rada. Retrospektivno je analizirana medicinska dokumentacija dece obolele od HLH. Rezultati. Dijagnoza HLH postavljena je kod pet decaka i osam devojcica (13 bolesnika) uzrasta od mesec dana do 14 godina. Kod sestoro dece HLH je bila sekundarna: po dva deteta bolovala su od visceralne lajsmanijaze i sistemskog juvenilnog reumatoidnog artritisa, a po jedno dete od infekcije Epstin-Bar virusom i histiocitoze Langerhansovih celija. Od ostalih sedmoro bolesnika geni za perforin i sintaksin 11 ispitivani su kod dva deteta, dok mutacije nisu nadjene. Kod sve dece dijagnostikovani su groznica, splenomegalija, citopenija, hiperferitinemija i hipertrigliceridemija, ali je kod samo sest bolesnika zabelezena hemofagocitoza. Sestoro dece je izleceno (cetvoro sa sekundarnom i dvoje sa primarnom HLH). Kod dvoje dece lecenje jos traje, dok je petoro bolesnika podleglo oboljenju (troje pre pocetka primene terapije, a dvoje usled komplikacija bolesti). Kod cetvoro od sestoro izlecene dece HLH se javila u prvoj godini po rodjenju. Od troje dece podvrgnute transplantaciji maticnih celija hematopoeze izleco je dvoje. Zakljucak. Rezultati naglasavaju znacaj blagovremenog postavljanja dijagnoze i otpocinjanja lecenja obolelih od HLH, isticuci znacaj aktivnog istrazivanja mogucnosti HLH kod sve dece sa groznicom, splenomegalijom i/ili citopenijama, bez obzira na to da li postoji hemofagocitoza ili ne.