| Abstract | Hemofagocitni sindrom (HS) ili hemofagocitna limfohistiocitoza (HLH) hiperinflamatorni je sindrom uzrokovan nekontroliranim otpuštanjem citokina i aktivacijom T-limfocita, makrofaga i histiocita. HLH obuhvaća dva osnovna oblika: primarni i sekundarni. Primarni oblik uzrokovan je poremećenom funkcijom citotoksičnih T-limfocita i prirodnoubilačkih (NK, prema engl. natural killer) stanica što je rezultat mutacije gena važnih za citotoksičnost ovih stanica. Sekundarni oblik potaknut je različitim stanjima poput infekcija, malignih novotvorina, autoimunih i autoinflamatornih bolesti. Tipični su simptomi i nalazi HLH-a vrućica, splenomegalija, citopenija, hemofagocitoza u koštanoj srži, koagulopatija i povišena razina feritina. Dijagnosticira se na temelju molekularnog nalaza koji je u skladu s dijagnozom HLH-a ili na temelju kliničko-laboratorijskih kriterija HLH-2004. Najčešći uzrok sekundarnog oblika u djece su infekcije, a u odraslih maligna bolest. Od infektivnih je uzročnika s HLH-om najčešće povezan Epstein-Barr virus (EBV). EBV je ubikvitaran virus kojim se tijekom života zarazi više od 90 % ukupne populacije. Uobičajeno uzrokuje kliničku sliku infektivne mononukleoze, ali je, zbog svoje sposobnosti uspostavljanja trajne infekcije, povezan s razvojem brojnih bolesti uključujući različite limfoproliferativne bolesti. EBV može biti okidač simptoma u osoba s primarnim HLH-om, može biti temeljni uzrok sekundarnog oblika ili uzrok NK/T-staničnih limfoproliferativnih bolesti koje su podloga za razvoj sekundarnog HLH-a. EBV-om induciran HLH dijagnosticira se ispunjavanjem dijagnostičkih kriterija za HLH uz dokazanu aktivnu infekciju EBV-om. Liječenje EBV-om induciranog HLH-a obuhvaća imunosupresivnu terapiju i kemoterapijske protokole. U slučaju primarnog HLH-a i drugih oblika koji ne odgovaraju na terapiju lijekovima jedina je učinkovita terapija alogenična transplantacija krvotvornih matičnih stanica. Poznavanje glavnih kliničkih i laboratorijskih značajki, pravovremeno dijagnosticiranje i liječenje temeljeno na kvalitetnim dijagnostičkim i terapijskim protokolima ključ su sprečavanja teških, često fatalnih posljedica EBV-om induciranog HLH-a. Istraživanja različitih lijekova, poput monoklonskih protutijela i ciljane terapije, kao i razvoj učinkovitog cjepiva protiv EBV-a, donose nove mogućnosti za uspješnije liječenje ovog rijetkog sindroma. |
| Abstract (english) | Hemophagocytic syndrome (HS) or hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by uncontrolled cytokine release and activation of T cells, macrophages, and histiocytes. HLH comprises two major forms: primary and secondary. The primary form is caused by impaired function of cytotoxic T cells and natural killer (NK) cells, as a result of mutations in genes that are important for the cytotoxicity of these cells. The secondary form is triggered by various conditions such as infections, malignancies, and autoimmune and autoinflammatory diseases. Typical findings of HLH include fever, splenomegaly, cytopenia, hemophagocytosis in the bone marrow, coagulopathy, and elevated ferritin levels. It is diagnosed based on a molecular finding consistent with HLH or on the clinical and laboratory criteria of HLH-2004. The leading cause of secondary HLH in children is infections, while in adults it is usually associated with malignancies. Among infectious agents associated with HLH, Epstein-Barr virus (EBV) is the most common trigger. EBV is a ubiquitous virus that infects over 90 % of the total population during their lifetime. Typically, the infection presents itself as infectious mononucleosis, but due to its ability to establish persistent infection, EBV is associated with the development of various diseases, including different lymphoproliferative disorders. EBV can act as a trigger for symptoms in individuals with primary HLH, it can be the sole cause of the secondary form; or can cause NK/T-cell lymphoproliferative diseases that serve as an underlying condition associated with the development of secondary HLH. EBV-induced HLH is diagnosed by the combination of HLH-2004 criteria and documented active EBV infection. The treatment of EBV-induced HLH involves immunosuppressive therapy and chemotherapy. In the case of primary HLH or other forms that do not respond to previous pharmacotherapy, the only effective therapy is allogeneic hematopoietic stem cell transplantation. Understanding the main clinical and laboratory features, timely diagnosis, and treatment based on high-quality diagnostic and therapeutic protocols are crucial in preventing the severe, often fatal consequences of EBV-induced HLH. Studies to evaluate different drugs, including monoclonal antibodies and targeted therapies, as well as the development of an effective vaccine against EBV, bring new options for the successful treatment of this rare syndrome. |
