Hemophagocytic lymfohistiocytosis in adults: review and case report


Authors: Jiří Šrámek 1;  Thomas Karvunidis 2;  Daniel Lysák 1;  Martin Harazim 2;  Michal Karas 1;  Pavel Jindra 1
Authors‘ workplace: Hematologicko-onkologické oddělení FN Plzeň 1;  Jednotka intenzivní péče I. interní kliniky LF UK a FN Plzeň 2
Published in: Vnitř Lék 2018; 64(3): 300-307
Category: Case Reports

Overview

Hemophagocytic lymfohistiocytosis (HLH) is rare, life-threatening condition, characterized by excessive activation of immune system with subsequent proinflammatory state resulting in multiorgan failure. Most frequently, it appears in infancy as a primary disorder caused by mutation of immune-regulatory genes. Increasingly, HLH is being diagnosed as a secondary – adult – form, which occurs as a result of aberrant immune response. Viral or bacterial systemic infections, malignancy with a predominance of lymphoproliferative disorders and autoimmune diseases are the most common triggers. Early diagnosis and initiation of therapy is crucial and increase the chance for recovery. HLH is usually presented as multisystem febrile illness, where an extensive differential diagnosis is needed. Diagnosis of HLH is defined by a combination of clinical and laboratory findings, eventually by a proof of specific mutation. The basic mechanism of therapy is an interruption of aberrant immune response by destruction and suppression of T-lymphocytes function. This is mostly achieved by corticosteroid and etoposide therapy. This review summarizes pathophysiology, diagnostics and therapy of HLH. Furthermore, a case-report of 22-years old patient with secondary HLH being manifested predominantly with acute respiratory failure is presented.

Key words:
acute respiratory failure – hemophagocytic lymphohistiocytosis – HLH-94 – macrophage activation syndrome – MODS


Sources

1. Scott RB, Robb-Smith AH. Histiocytic medullary reticulosis. Lancet 1939; 2(6047): 194–198.

2. Špíšek R, Mejstříková E, Formánková R et al. Familiární hemofagocytující lymfohistiocytóza na podkladě deficitu perforinu úspěšně léčená transplantací hematopoetických kmenových buněk – první diagnostikovaný případ v České republice. Čas Lék Čes 2006; 145(1): 50–54.

3. Schram AM, Berliner N. How I Treat Hemophagocytic Lymphohistiocytosis in the Adult Patient. Blood 2015; 125(19): 2908–2914. Dostupné z DOI: <http://dx.doi.org/10.1182/blood-2015–01–551622>.

4. Filipovich A, McClain K, Grom A. Histiocytic disorders: recent insights into pathophysiology and practical guidelines. Biol Blood Marrow Transplant 2010; 16(1 Suppl): S82-S89. Dostupné z DOI: <http://dx.doi.org/10.1016/j.bbmt.2009.11.014>.

5. Voskoboinik I, Smyth MJ, Trapani JA. Perforin-mediated target-cell death and immune homeostasis. Nat Rev Immunol 2006; 6(12): 940–952. Dostupné z DOI: <http://dx.doi.org/10.1038/nri1983>.

6. Ohadi M, Lalloz MR, Sham P et al. Localization of a gene for familial hemophagocytic lymphohistiocytosis at chromosome 9q21.3–22 by homozygosity mapping. Am J Hum Genet 1999; 64(1): 165–171. Dostupné z DOI: <http://dx.doi.org/10.1086/302187>.

7. Suková M, Mejstříková E, Vodičková E et al. Hemofagocytující lymfohistiocytóza. Vnitř Lék 2010; 56(Suppl 2): S157-S169.

8. Otrock ZK, Eby CS. Clinical characteristics, prognostic factors, and outcomes of adult patients with hemophagocytic lymphohistiocytosis. Am J Hematol 2015; 90(3): 220–224. Dostupné z DOI: <http://dx.doi.org/10.1002/ajh.23911>.

9. Ramos-Casals M, Brito-Zerón P, López-Guillermo A et al. Adult haemophagocytic syndrome. Lancet 2014; 383(9927): 1503–1516. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(13)61048-X>.Erratum in Lancet 2014; 383(9927): 1464.

10. Sawhney S, Woo P, Murray KJ Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders. Arch Dis Child 2001; 85(5): 421–426.

11. Zhang K, Jordan MB, Marsh RA et al. Hypomorphic mutations in PRF1, MUNC13–4, and STXBP2 are associated with adult-onset familial HLH. Blood 2011; 118(22): 5794–5798. Dostupné z DOI: <http://dx.doi.org/10.1182/blood-2011–07–370148>.

12. Voskoboinik I, Trapani JA. Perforinopathy: a spectrum of human immune disease caused by defective perforin delivery or function. Front Immunol 2013; 4: 441. Dostupné z DOI: <http://dx.doi.org/10.3389/fimmu.2013.00441>.

13. Trottestam H, Horne A, Arico M et al. Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol. Blood 2011; 118(17): 4577–4584. Dostupné z DOI: <http://dx.doi.org/10.1182/blood-2011–06–356261>.

14. Henter JI, Nennesmo I. Neuropathologic findings and neurologic symptoms in twenty-three children with hemophagocytic lymphohistiocytosis. J Pediatr 1997; 130(3): 358–365.

15. Rivière S, Galicier L, Coppo P et al. Reactive hemophagocytic syndrome in adults: a retrospective analysis of 162 patients. Am J Med 2014; 127(11): 1118–1125. Dostupné z DOI: <http://dx.doi.org/10.1016/j.amjmed.2014.04.034>.

16. Okamoto M, Yamaguchi H, Isobe Y et al. Analysis of triglyceride value in the diagnosis and treatment response of secondary hemophagocytic syndrome. Intern Med 2009; 48(10): 775–781.

17. Fukaya S, Yasuda S, Hashimoto T et al. Clinical features of haemophagocytic syndrome in patients with systemic autoimmune diseases: analysis of 30 cases. Rheumatology (Oxford) 2008; 47(11): 1686–1691. Dostupné z DOI: <http://dx.doi.org/10.1093/rheumatology/ken342>.

18. Henter JI, Horne A, Aricó M et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007; 48(2): 124–131. Dostupné z DOI: <http://dx.doi.org/10.1002/pbc.21039>.

19. Fardet L, Galicier L, Lambotte O et al. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheum (Munch) 2014; 66(9): 2613–2620. Dostupné z DOI: <http://dx.doi.org/10.1002/art.38690>.

20. Hejblum G, Lambotte O, Galicier L et al. A web-based delphi study for eliciting helpful criteria in the positive diagnosis of hemophagocytic syndrome in adult patients. PLoS ONE 2014; 9(4): e94024. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0094024>.

21. Marsh RA, Vaughn G, Kim MO et al. Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation. Blood 2010; 116(26): 5824–5831. Dostupné z DOI: <http://dx.doi.org/10.1182/blood-2010–04–282392>.

22. Cooper N, Rao K, Gilmour K et al. Stem cell transplantation with reduced-intensity conditioning for hemophagocytic lymphohistiocytosis. Blood 2006; 107(3): 1233–1236. Dostupné z DOI: <http://dx.doi.org/10.1182/blood-2005–05–1819>.

23. Henter JI, Samuelsson-Horne A, Aricò M et al. Histocyte Society. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood 2002; 100(7): 2367–2373. Dostupné z DOI: <http://d.doi.org/10.1182/blood-2002–01–0172>.

24. Jordan MB, Allen CE, Weitzman S et al. How I treat hemophagocytic lymphohistiocytosis. Blood 2011; 118(15): 4041–4052. Dostupné z DOI: <http://dx.doi.org/10.1182/blood-2011–03–278127>.

25. Jiang L, Yuan CM, Hubacheck J et al. Variable CD52 expression in mature T cell and NK cell malignancies: implications for alemtuzumab therapy. Br J Haematol 2009; 145(2): 173–179. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1365–2141.2009.07606.x>.

26. Strout MP, Seropian S, Berliner N. Alemtuzumab as a bridge to allogeneic SCT in atypical hemophagocytic lymphohistiocytosis. Nat Rev Clin Oncol 2010; 7(7): 415–420. Dostupné z DOI: <http://dx.doi.org/10.1038/nrclinonc.2010.40>.

27. Children‘s Hospital of Philadelphia. Tocilizumab and Hemophagocytic Lymphohistiocytosis (HLH). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). NLM Identifier: NCT02007239. Dostupné z WWW: <https://clinicaltrials.gov/ct2/show/NCT02007239>.

28. University of Michigan Cancer Center. A Pilot Study of Ruxolitinib in Secondary Hemophagocytic Syndrome. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). NLM Identifier: NCT02400463. Dostupné z WWW: https://clinicaltrials.gov/ct2/show/study/NCT02400463

29. Janka GE. Familial hemophagocytic lymphohistiocytosis. Eur J Pediatr 1983; 140(3): 221–230.

30. Parikh SA, Kapoor P, Letendre L et al. Prognostic factors and outcomes of adults with hemophagocytic lymphohistiocytosis. Mayo Clin Proc 2014; 89(4): 484–492. Dostupné z DOI: <http://dx.doi.org/10.1016/j.mayocp.2013.12.012>.

31. Li J, Wang Q, Zheng W et al. Hemophagocytic lymphohistiocytosis: clinical analysis of 103 adult patients. Medicine (Baltimore) 2014; 93(2): 100–105. Dostupné z DOI: <http://dx.doi.org/10.1097/MD.0000000000000022>.

32. Lin TF, Ferlic-Stark LL, Allen CE et al. Rate of decline of ferritin in patients with hemophagocytic lymphohistiocytosis as a prognostic variable for mortality. Pediatr Blood Cancer 2011; 56(1): 154–155. Dostupné z DOI: <http://dx.doi.org/10.1002/pbc.22774>.

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Diabetology Endocrinology Internal medicine
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