Interna45

Limfohistiocytoza hemofagocytarna - kiedy nadmierna odpowiedź immunologiczna wymyka się mechanizmom kontrolnym

Hemophagocytic lymphohistiocytosis - when an exaggerated immune response escapes control mechanisms

Maciej Machaczka✉1Monika Klimkowska2

1Hematology Center Karolinska, and Department of Medicine at Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, SE–141 86 Stockholm, Sweden

2Department of Clinical Pathology and Cytology, Karolinska University Hospital Huddinge, SE–141 86 Stockholm, Sweden

✉Maciej Machaczka — maciej.machaczka@ki.se

Otrzymano: 23.02.2013Zaakceptowano: 24.02.2013Opublikowano: 23 marca 2013
e-ISSN: 2084-2708 (wersja pierwotna)p-ISSN: 2083-0033 (wersja drukowana)
Streszczenie (PDF)Pełny tekst (PDF)

Streszczenie

Wstęp

Limfohistiocytoza hemofagocytarna (ang. hemophagocytic lymphohistiocytosis, HLH), zwana dawniej także zespołem hemofagocytarnym (ang. hemophagocytic syndrome) jest ostrym, zagrażającym życiu chorego zaburzeniem immunoregulacji, powodowanym przez różne czynniki wrodzone i nabyte [1–3]. HLH jest zespołem objawów chorobowych wynikającym z wygórowanego odczynu zapalnego, który rozwija się na skutek nadmiernego uwalniania różnych mediatorów zapalenia, takich jak czynnik martwicy guza α (ang. tumor necrosis factor-α, TNF-α), interferon-γ, interleukina(IL)-6, IL-8, IL- 10, IL-12, IL-18, białko zapalne makrofagów 1α (ang. macrophage inflammatory protein-1α), czy hemopoetycznych czynników wzrostu (np. GM-CSF) przez aktywowane makrofagi/ histiocyty oraz limfocyty T [1, 3]. Niekontrolowana aktywacja oraz proliferacja limfocytów T i makrofagów spowodowana jest zwykle upośledzeniem mechanizmów wygaszania zapalenia, z powodu niedostatecznej aktywności cytotoksycznej komórek NK (ang. natural killer) oraz CD8+ cytotoksycznych limfocytów T. HLH to schorzenie rzadkie, ale które bez odpowiedniego leczenia prowadzi zazwyczaj do śmierci pacjenta [1, 3].

Opis przypadku

U 56-letniej pacjentki z m.in. celiaklią, wystąpiły wymioty i biegunka w ostatnim dniu pobytu na wczasach w Turcji. Przeprowadzone badania nie wykazały etiologii zakaźnej, stwierdzono natomiast HLH. W leczeniu zastosowano wysokie dawki deksametazonu, cyklosporynę A oraz dożylne immunoglobuliny. Po prawie 4 miesiącach leczenia chora uzyskała trwałą remisję HLH. Leczenie było trudne i powikłane m.in. niewydolnością przysadki mózgowej oraz obustronną martwicą głów kości udowych.

Wnioski

Leczenie HLH jest trudne, długotrwałe i nieraz obarczone wieloma komplikacjami. Szybkie rozpoznanie HLH oraz wdrożenie właściwej terapii jest decydujące dla uzyskiwanych wyników leczenia.
Słowa kluczowe:gorączkapowiększenie śledzionyzakażenielimfohistiocytoza hemofagocytarna

Abstract

Introduction

Hemophagocytic lymphohistiocytosis (HLH) lymphohistiocytosis (HLH), formerly also known as hemophagocytic syndrome hemophagocytic syndrome) is an an acute, life-threatening disorder of immunoregulation in the patient, caused by a variety of congenital and acquired [1-3]. HLH is a syndrome of disease symptoms resulting from an due to an exaggerated inflammatory reaction that develops due to the due to excessive release of various inflammatory mediators, such as tumor necrosis factor α (tumor necrosis factor-α (TNF-α), interferon-γ, interleukin(IL)-6, IL-8, IL- 10, IL-12, IL-18, macrophage inflammatory protein 1α (macrophage inflammatory protein-1α), or hemopoietic growth factors (e.g., GM-CSF) by activated macrophages/ histiocytes and T lymphocytes [1, 3]. Uncontrolled activation and proliferation of T lymphocytes and macrophages is usually due to is usually due to impaired mechanisms of extinguishing the inflammation, due to insufficient cytotoxic activity of NK (natural killer) cells and CD8+ cytotoxic T lymphocytes. HLH is a rare condition, but which, without appropriate treatment, usually leads to death of the patient [1, 3].

Case Report

A 56-year-old female patient with, among other things, celiac disease, developed vomiting and diarrhea on the last day of her vacation in Turkey. Tests performed did not reveal an infectious etiology, but HLH was found. The treatment high doses of dexamethasone, cyclosporine A and intravenous immunoglobulin were used. After almost 4 months of treatment, the patient achieved permanent remission of HLH. Treatment was difficult and complicated by, among other things. pituitary insufficiency and bilateral femoral head necrosis.

Conclusions

Treatment of HLH is difficult, lengthy and sometimes fraught with complications. Prompt diagnosis of HLH and implementation of appropriate therapy is critical to the treatment results obtained.
Keywords:5-HL protein, African swine fever virusspleen enlargement2019 Novel Coronavirus InfectionDehydrated hereditary stomatocytosis with or without pseudohyperkalemia and-or perinatal edema hemophagocytic lymphohistiocytosis

Piśmiennictwo

  1. 1.Machaczka M.. Limfohistiocytoza hemofagocytarna – współczesny problem medyczny. Polski Merkuriusz Lekarski 2012 ; 32 : 59–-63.
  2. 2.Kumakura S.. Hemophagocytic syndrome. Internal Medicine 2005 ; 44 : 278–-80.
  3. 3.Janka G.. Hemophagocytic lymphohistiocytosis: When the immune system runs amok. Klinische Pädiatrie 2009 ; 221 : 278–-85.
  4. 4.Rouphael N.G. and Talati N.J. and Vaughan C. et al.. Infections associated with haemophagocytic syndrome. The Lancet Infectious Diseases 2007 ; 7 : 814–-22.
  5. 5.Ishii E. and Ohga S. and Imashuku S. et al.. Nationwide survey of hemophagocytic lymphohistiocytosis in Japan. International Journal of Hematology 2007 ; 86 : 58–-65.
  6. 6.Gupta S. and Weitzman S.. Primary and secondary hemophagocytic lymphohistiocytosis: clinical features, pathogenesis and therapy. Expert Review of Clinical Immunology 2010 ; 6 : 137–-54.
  7. 7.Balwierz W. and Czogała M. and Pawińska-Wasikowska K. et al.. Limfocytoza hemofagocytarna: problemy diagnostyczne w pediatrii. Przegląd Lekarski 2010 ; 67 : 417–-24.
  8. 8.Machaczka M. and Vaktnäs J. and Klimkowska M. et al.. Malignancy-associated hemophagocytic lymphohistiocytosis in adults: a retrospective population-based analysis from a single center. Leukemia & Lymphoma 2011 ; 52 : 613–-19.
  9. 9.Machaczka M. and Vaktnäs J. and Klimkowska M. et al.. Acquired hemophagocytic lymphohistiocytosis associated with multiple myeloma. Medical Oncology 2011 ; 28 : 539–-43.
  10. 10.Machaczka M. and Nahi H. and Karbach H. et al.. Successful treatment of recurrent malignancy–associated hemophagocytic lymphohistiocytosis with a modified HLH–94 immunochemotherapy and allogeneic stem cell transplantation. Medical Oncology 2012 ; 29 : 1231–-36.
  11. 11.Abdelkefi A. and Jamil W.B. and Torjman L. et al.. Hemophagocytic syndrome after hematopoietic stem cell transplantation: a prospective observational study. International Journal of Hematology 2009 ; 89 : 368–-73.
  12. 12.Canna S.W. and Behrens E.M.. Not all hemophagocytes are created equally: appreciating the heterogeneity of the hemophagocytic syndromes. Current Opinion in Rheumatology 2012 ; 24 : 113–-8.
  13. 13.Reiner A.P. and Spivak J.L.. Hematophagic histiocytos. A report of 23 new patients and a review of the literature. Medicine (Baltimore) 1988 ; 67 : 369–-88.
  14. 14.Hasselblom S. and Linde A. and Ridell B.. Hodgkin’s lymphoma, Epstein-Barr virus reactivation and fatal haemophagocytic syndrome. Journal of Internal Medicine 2004 ; 255 : 289–-95.
  15. 15.Tong H. and Ren Y. and Liu H. et al.. Clinical characteristics of T–cell lymphoma associated with hemophagocytic syndrome: comparison of T–cell lymphoma with and without hemophagocytic syndrome. Leukemia & Lymphoma 2008 ; 49 : 81–-7.
  16. 16.Machaczka M. and Vaktnäs J.. Haemophagocytic syndrome associated with Hodgkin lymphoma and Pneumocystis jiroveci pneumonitis. British Journal of Haematology 2007 ; 138 : 672.
  17. 17.Machaczka M. and Vaktnäs J. and Chiang S.C. et al.. Alemtuzumab treatment for hemophagocytic lymphohistiocytosis. Nature Reviews Clinical Oncology 2010 ; 7 (10)
  18. 18.Henter J.-I. and Horne A. and Arico M. et al.. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatric Blood & Cancer 2007 ; 48 : 124–-31.
  19. 19.Shabbir M. and Lucas J. and Lazarchick J. et al.. Secondary hemophagocytic syndrome in adults: a case series of 18 patients in a single institution and a review of literature. Hematological Oncology 2011 ; 29 : 100–-6.
  20. 20.Strout M.P. and Seropian S. and Berliner N.. Alemtuzumab as a bridge to allogeneic SCT in atypical hemophagocytic lymphohistiocytosis. Nature Reviews Clinical Oncology 2010 ; 7 : 415–-20.
  21. 21.Castillo L. and Carcillo J.. Secondary hemophagocytic lymphohistiocytosis and severe sepsis/systemic inflammatory response syndrome/multiorgan dysfunction syndrome/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation. Pediatric Critical Care Medicine 2009 ; 10 : 387–-92.
  22. 22.Irwin R.S. and Rippe J.M.. Intensive Care Medicine. 6 wyd. Philadelphia (PA): Wolters Kluwer, Lippincott Williams & Wilkins; 2008. ISBN: 978-0-7817-9153-3.
  23. 23.Henter J.-I. and Arico M. and Egeler R.M. et al.. HLH Study Group of the Histiocyte Society. HLH-94: a treatment protocol for hemophagocytic lymphohistiocytosis. Medical and Pediatric Oncology 1997 ; 28 : 342–-47.
  24. 24.Machaczka M. and Sydor W. and Rucińska M. et al.. Autoimmune Disorders – Current Concepts and Advances from Bedside to Mechanistic Insights. 2011. [ISBN 978-953-307-653-9]
  25. 25.Horne A. and Janka G. and Maarten Egeler R. et al.. Haematopoietic stem cell transplantation in haemophagocytic lymphohistiocytosis. British Journal of Haematology 2005 ; 129 : 622–-30.
  26. 26.Jordan M.B. and Filipovich A.H.. Hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis: a journey of a thousand miles begins with a single (big) step. Bone Marrow Transplantation 2008 ; 42 : 433–-37.
  27. 27.Marsh R.A. and Jordan M.B. and Filipovich A.H.. Reduced–intensity conditioning haematopoietic cell transplantation for haemophagocytic lymphohistiocytosis: an important step forward. British Journal of Haematology 2011 ; 154 : 556–-63.
  28. 28.Ohga S. and Kudo K. and Ishii E. et al.. Hematopoietic stem cell transplantation for familial hemophagocytic lymphohistiocytosis and Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in Japan. Pediatric Blood & Cancer 2010 ; 54 : 299–-306.
  29. 29.Minegishi M. and Ohashi Y. and Kumaki S. et al.. Successful umbilical cord blood transplantation from an unrelated donor for a patient with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Bone Marrow Transplantation 2001 ; 27 : 883–-6.
  30. 30.Toubo T. and Suga N. and Ohga S. et al.. Successful unrelated cord blood transplantation for Epstein-Barr virus-associated lymphoproliferative disease with hemophagocytic syndrome. International Journal of Hematology 2004 ; 80 : 458–-62.
  31. 31.Sovinz P. and Schwinger W. and Lackner H. et al.. Severe Epstein-Barr virus encephalitis with hemophagocytic syndrome. Rapid clearance of virus following allogeneic hematopoietic stem cell transplantation from a seropositive donor. The Pediatric Infectious Disease Journal 2010 ; 29 : 553–-6.
  32. 32.Yoon H.S. and Im H.J. and Moon H.N. et al.. The outcome of hematopoietic stem cell transplantation in Korean children with hemophagocytic lymphohistiocytosis. Pediatric Transplantation 2010 ; 14 : 735–-40.
  33. 33.Bauer M.P. and van Burgel N.D. and Marijt W.A., et al.. Fever, shock and pancytopenia in a patient treated with alemtuzumab. Clinical Infectious Diseases 2009 ; 49 : 1540 and 1616–-17.
  34. 34.Makay B. and Yilmaz S. and Türkyilmaz Z. et al.. Etanercept for therapy-resistant macrophage activation syndrome. Pediatric Blood & Cancer 2008 ; 50 : 419–-21.
  35. 35.Sandhu C. and Chesney A. and Piliotis E. et al.. Macrophage activation syndrome after etanercept treatment. The Journal of Rheumatology 2007 ; 34 : 241–-2.
  36. 36.Sellmer A. and Stausbøl-Grøn B. and Krag-Olsen B. et al.. Successful use of infliximab in macrophage activation syndrome with severe CNS involvement. Scandinavian Journal of Rheumatology 2010 ; 40 : 156–-7.
  37. 37.Mougiakakos D. and Machaczka M. and Jitschin R. et al.. Treatment of familial haemophagocytic lymphohistiocytosis with third–party mesenchymal stromal cells. Stem Cells and Development 2012 ; 21 : 3147–-51.
  38. 38.Zhang K. and Jordan M.B. and Marsh R.A. et al.. Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial hemophagocytic lymphohistiocytosis. Blood 2011 ; 118 : 5794–-8.
  39. 39.Sanders J.W. and Frenck R.W. and Putnam S.D. et al.. Azithromycin and loperamide are comparable to levofloxacin and loperamide for the treatment of traveler’s diarrhea in United States military personnel in Turkey. Clinical Infectious Diseases 2007 ; 45 : 294–-301.
  40. 40.Porter C.K. and Riddle M.S. and Tribble D.R. et al.. The epidemiology of travelers’ diarrhea in Incirlik, Turkey: a region with a predominance of heat-stabile toxin producing enterotoxigenic Escherichia coli. Diagnostic Microbiology and Infectious Disease 2010 ; 66 : 241–-7.

Komentarze (0)

Brak komentarzy.

Zaloguj się aby dodać komentarz.
Publikacje