Advertisement

International Journal of Hematology

, Volume 79, Issue 5, pp 484–487 | Cite as

Fulminant Hemophagocytic Syndrome with a High Interferon γ Level Diagnosed as Macrophage Activation Syndrome

Case Report

Abstract

A 26-year-old woman presented with general fatigue, persistent fever, nuchal lymphadenitis, thrombocytopenia, and liver damage. From the bone marrow finding, we diagnosed her condition as hemophagocytic syndrome. Steroid pulse therapy, cyclosporin A treatment, and combined chemotherapy generated no response. The patient showed severe mucosal bleeding, rapidly experienced multiple organ failure, and finally died of a brain hemorrhage on the 13th hospital day. Epstein-Barr virus, cytomegalovirus, human herpes virus type 6, human parvovirus B19, and herpes simplex virus were not detected. Autopsied samples of the spleen, bone marrow, and liver showed extreme proliferation of activated macrophages, so-called histiocytes, without lymphoid malignancy. The interferon γ level at presentation was prominently high. The continuously elevated levels of ferritin and soluble interleukin 2 receptor were correlated with the catastrophic outcome. The disease in our case mimicked infantile hemophagocytic lymphohistiocytosis. However, there was neither a family history of the disease nor a mutation in the perforin gene. So, it is reasonable to categorize our case as macrophage activation syndrome. Although our patient lacked arthritis or eruption, we cannot deny the possibility that an oligoarthritis type of systemiconset juvenile rheumatoid arthritis or, considering the patient’s age, adult-onset Still disease lies at the base of our case.

Key words

HPS MAS 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Favara BE. Hemophagocytic lymphohistiocytosis: a hemophagocytic syndrome. Semin Diagn Pathol. 1992;9:63–74.PubMedGoogle Scholar
  2. 2.
    Tsuda H. Hemophagocytic syndrome in children and adults. Int J Hematol. 1997;65:215–226.CrossRefGoogle Scholar
  3. 3.
    Risdall RJ, McKenna RW, Nesbit ME, et al. Virus-associated hemophagocytic syndrome: a benign histiocytic proliferation distinct from malignant histiocytosis. Cancer. 1979;44:993–1002.CrossRefPubMedGoogle Scholar
  4. 4.
    Esumi N, Ikushima S, Todo S, Imashuku S. High serum level as a marker of malignant histiocytosis and virus-associated hemophagocytic syndrome. Cancer. 1988;61:2071–2076.CrossRefPubMedGoogle Scholar
  5. 5.
    Vespignani S, Sardeo G, Castronovo S, Galassi A, Venza E. A case of virus associated hemophagocytic syndrome and malignant histiocytosis: sometimes a difficult distinction. Recenti Prog Med. 1991;82:80–82.PubMedGoogle Scholar
  6. 6.
    Lasserre M, Huguet C, Terno O. Acute severe herpes simplex hepatitis with virus-associated hemophagocytic syndrome in an immunocompetent adult. J Hepatol. 1993;18:256–257.CrossRefPubMedGoogle Scholar
  7. 7.
    Takeoka Y, Hino M, Oiso N, et al. Virus-associated hemophagocytic syndrome due to rubella virus and varicella-zoster dual infection in patient with adult idiopathic thrombocytopenic purpura. Ann Hematol. 2001;80:361–364.CrossRefPubMedGoogle Scholar
  8. 8.
    Tsuda H, Shirono K. Successful treatment of virus-associated hemophagocytic syndrome in adults by cyclosporin A supported by granulocyte colony-stimulating factor. Br J Haematol. 1996;93:572–575.CrossRefPubMedGoogle Scholar
  9. 9.
    Huang LM, Lee CY, Lin KH, et al. Human herpes virus-6 associated with fatal hemophagocytic syndrome. Lancet. 1990;336:60–61.CrossRefPubMedGoogle Scholar
  10. 10.
    Levy J, Wodell RA, August CS, Bayever E, et al. Adenovirus-related hemophagocytic syndrome after bone marrow transplantation. Bone Marrow Transplant. 1990;6:349–352.PubMedGoogle Scholar
  11. 11.
    Marusawa H, Hamamoto K. Virus-associated hemophagocytic syndrome due to rubella virus in an adult [in Japanese]. Rinsho Ketsueki. 1994;35:576–580.PubMedGoogle Scholar
  12. 12.
    Kikuta H, Sakiyama Y, Matsumoto S, et al. Fatal Epstein-Barr virus-associated hemophagocytic syndrome. Blood. 1993;82:3259–3264.PubMedGoogle Scholar
  13. 13.
    Imashuku S, Kuriyama K, Sakai R, et al. Treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in young adults: a report from the HLH study center. Med Pediatr Oncol. 2003;41:103–109.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Henter JI, Elinder G, Ost A. Diagnostic guidelines for hemophagocytic lymphohistiocytosis. Semin Oncol. 1991;18:29–33.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Grom AA, Passo M. Macrophage activation syndrome in systemic juvenile rheumatoid arthritis. J Pediatr. 1996;129:630–632.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Marmont AM, Gualandi F, Lint MT, Bacigalupo A. Virus-associated hemophagocytic syndrome: interest of examination of fresh myeloaspirates. Blood. 1994;83:1711–1712.Google Scholar
  17. 17.
    Ueda I, Morimoto A, Inaba T, et al. Characteristic perforin gene mutations of haemophagocytic lymphohistiocytosis patients in Japan. Br J Haematol. 2003;121:503–510.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Allen M, Fusco CD, Legrand F, et al. Familial hemophagocytic lymphohistiocytosis: how late can the onset be? Haematologica. 2001;86:499–503.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Clementi R, Emmi L, Maccario R, et al. Adult onset and atypical presentation of hemophagocytic lymphohistiocytosis in siblings carrying PRF1 mutations. Blood. 2002;100:2266–2267.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Grom AA, Villanueva J, Lee S, Goldmuntz EA, Passo MH, Filipovich A. Natural killer cell dysfunction in patients with systemiconset juvenile rheumatoid arthritis and macrophage activation syndrome. J Pediatr. 2003;142:292–296.CrossRefPubMedGoogle Scholar
  21. 21.
    Grom AA. Macrophage activation syndrome and reactive hemophagocytic lymphohistiocytosis: the same entities? Curr Opin Rheumatol. 2003;15:587–590.CrossRefPubMedGoogle Scholar
  22. 22.
    Esdaile JM, Tannenbaum H, Hawkins D. Adult Still’s disease. Am J Med. 1980;68:825–830.CrossRefPubMedGoogle Scholar
  23. 23.
    Mert A, Ozaras R, Tabak F, et al. Fever of unknown origin: a review of 20 patients with adult-onset Still’s disease. Clin Rheumatol. 2003;22:89–93.CrossRefPubMedGoogle Scholar
  24. 24.
    Abbas AK, Lichtman AH, Pober JS. Cellular and Molecular Immunology. 4th ed. Philadelphia, Pa: W. B. Saunders; 1997:269.Google Scholar
  25. 25.
    Henter JI, Elinder G, Soder O, Hansson M, Andersson B, Andersson U. Hypercytokinemia in familial hemophagocytic lymphohistiocytosis. Blood. 1991;78:2918–2922.PubMedGoogle Scholar
  26. 26.
    Osugi Y, Hara J, Tagawa S, et al. Cytokine production regulation Th1 and Th2 cytokines in hemophagocytic lymphohistiocytosis. Blood. 1997;89:4100–4103.PubMedGoogle Scholar
  27. 27.
    Ohga S, Matsuzaki A, Nishizaki M, et al. Inflammatory cytokines in virus-associated hemophagocytic syndrome: interferon gamma as a sensitive indicator of disease activity. Am J Pediatr Hematol Oncol. 1993;15:291–298.PubMedGoogle Scholar
  28. 28.
    Imashuku S, Hibi S. Cytokines in hemophagocytic syndrome. Br J Haematol. 1991;77:438–440.CrossRefPubMedGoogle Scholar
  29. 29.
    Choi JH, Suh CH, Lee YM, et al. Serum cytokine profiles in patients with adult onset Still’s disease. J Rheumatol. 2003;30:2422–2427.PubMedGoogle Scholar
  30. 30.
    Esumi N, Ikushima S, Todo S, Imashuku S. Hyperferritinemia in malignant histiocytosis, virus-associated hemophagocytic syndrome and familial erythrophagocytic lymphohistiocytosis: a survey of pediatric cases. Acta Paediatr Scand. 1989;78:268–270.CrossRefPubMedGoogle Scholar
  31. 31.
    Emmenegger U, Frey U, Reimers A, et al. Hyperferritinemia as indicator for intravenous immunoglobulin treatment in reactive macrophage activation syndromes. Am J Hematol. 2001;68:4–10.CrossRefPubMedGoogle Scholar
  32. 32.
    Coffernils M, Soupart A, Pradier O, Feremans W, Neve P, Decaux G. Hyperferritinemia in adult onset Still’s disease and the hemophagocytic syndrome. J Rheumatol. 1992;19:1425–1427.PubMedGoogle Scholar
  33. 33.
    Komp DM, McNamara J, Buckley P. Elevated soluble interleukin-2 receptor in childhood hemophagocytic histiocytic syndromes. Blood. 1989;73:2128–2132.PubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2004

Authors and Affiliations

  1. 1.Department of Internal MedicineKyushu Kosei-Nenkin HospitalKitakyushuJapan
  2. 2.Department of HematologyHamanomachi HospitalFukuoka CityJapan

Personalised recommendations