Advertisement

Pediatric Radiology

, Volume 33, Issue 6, pp 392–401 | Cite as

Imaging characteristics of hemophagocytic lymphohistiocytosis

  • Nancy E. FitzgeraldEmail author
  • Kenneth L. MacClain
Original Article

Abstract

Background

Hemophagocytic lymphohistiocytosis (HLH) is a nonmalignant disorder of immune regulation, with overproduction of cytokines and diminished immune surveillance. Symptoms are nonspecific and may affect multiple organs, including the central nervous system. Neuroimaging findings have been described in case reports and small series; body imaging findings have not been described extensively.

Objective

To summarize findings of the most frequently performed imaging studies of the brain, chest and abdomen in patients with HLH.

Materials and methods

Retrospective review of chest radiographs and CT, abdominal ultrasound and CT, brain CT and MRI, skeletal surveys, and autopsy data.

Results

Twenty-five patients were diagnosed and treated for HLH at our institution over an 11-year period; 15 patients (60%) died. Common chest radiograph findings included alveolar-interstitial opacities with pleural effusions, often with rapid evolution and resolution. Hepatosplenomegaly, gallbladder wall thickening, hyperechoic kidneys and ascites were common abdominal findings, which resolved after therapy in some cases. Brain-imaging studies revealed nonspecific periventricular white-matter abnormalities, brain-volume loss and enlargement of extra-axial fluid spaces. Three infant cases, one with intracranial hemorrhage, one with multiple pathologic rib fractures and one with diaphyseal periosteal reaction involving multiple long bones on skeletal survey, raised suspicion of child abuse at presentation. Abuse was not substantiated in any case.

Conclusions

Clinicians and radiologists should be aware of the radiographic manifestations of HLH, which are nonspecific and overlap with infectious, inflammatory and neoplastic disorders. Findings in the chest (similar to acute respiratory distress syndrome) and abdomen may progress rapidly and then regress with institution of appropriate anti-HLH therapy. CNS findings may be progressive. In some infants, initial imaging findings may mimic nonaccidental trauma.

Keywords

Bone-marrow transplant Epstein-Barr virus (EBV) Gallbladder wall thickening Hemophagocytic lymphohistiocytosis Hepatosplenomegaly Kawasaki disease Periportal echogenicity Ultrasound Abdomen Periventricular white matter 

Notes

Acknowledgements

Gracious thanks are due to Dr. Alan Schlesinger for his imaging expertise and to Dr. Richard Braverman for editorial assistance.

References

  1. 1.
    Fujiwara F, Hibi S, Imashiku S (1993) Hypercytokinemia in hemophagocytic syndrome. Am J Pediatr Hematol Oncol 15:92–98Google Scholar
  2. 2.
    Arico M, Janka G, Fischer A, et al (1996) Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. Leukemia 10:197–203PubMedGoogle Scholar
  3. 3.
    Henter J-I, Elinder G (1991) Incidence in Sweden and clinical features of familial hemophagocytic lymphohistiocytosis. Acta Paediatr Scand 80:428–435PubMedGoogle Scholar
  4. 4.
    Ladisch S, Jaffe ES (2002) The histiocytoses. In: Pizzo PA, Poplack DG (eds) Principles and practice of pediatric oncology, 4th edn. Lippincott Williams & Wilkins, Philadelphia, pp 744–747Google Scholar
  5. 5.
    Al-Eid W, Al-Jefri A, Bahabri S (2000) Hemophagocytosis complicating Kawasaki disease. Pediatr Hematol Oncol 17:323–329CrossRefPubMedGoogle Scholar
  6. 6.
    Writing group of the Histiocyte Society (Chu T, D'Angelo GJ, Favara B, Ladisch S, Nesbit M, Pritchard J) (1987) Lancet 1:208–209Google Scholar
  7. 7.
    Henter J-I, Elinder G, Ost A (1991) Diagnostic guidelines for hemophagocytic lymphohistiocytosis: The FHL Study Group of the Histiocyte Society. Semin Oncol 18:29–33Google Scholar
  8. 8.
    Kikuta H (1995) Epstein-Barr virus-associated hemophagocytic syndrome. Leukemia and lymphoma 16:425–429PubMedGoogle Scholar
  9. 9.
    Hallahan AR, Carpenter PA, O'Gorman-Hughes DW, et al (1999) Haemophagocytic lymphohistiocytosis in children. J Paediatr Child Health 35:55–59PubMedGoogle Scholar
  10. 10.
    Kieslich M, Vecchi M, Driever PH, et al (2001) Acute encephalopathy as a primary menifestation of hemophagocytic lymphohistiocytosis. Dev Med Child Neurol 43:555–558PubMedGoogle Scholar
  11. 11.
    Henter J-I, Elinder G (1992) Cerebromeningeal haemophagocytic lymphohistiocytosis. Lancet 339:104–107PubMedGoogle Scholar
  12. 12.
    Egeler RM, Shapiro R, Loechelt B, et al (1996) Characteristic immune abnormalities in hemophagocytic lymphohistiocytosis. J Pediatr Hematol Oncol 18:340–345CrossRefPubMedGoogle Scholar
  13. 13.
    McClain K, Gehrz R, Grierson H, et al (1988) Virus-associated histiocytic proliferation in children. Frequent associations with Epstein-Barr virus and congenital or acquired immunodeficiencies. Am J Pediatr Hematol Oncol 10:196–203PubMedGoogle Scholar
  14. 14.
    Henter J-I, Samuelsson-Horne A, Arico M, et al (2002) Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunotherapy and bone marrow transplantation. Blood 100:2367–2373Google Scholar
  15. 15.
    Akinbami LJ, Selby DM, Slonim AD (2001) Grand rounds: hepatosplenomegaly and pulmonary infiltrates in an infant. J Pediatr 139:124–129CrossRefPubMedGoogle Scholar
  16. 16.
    Gauvin F, Toledan B, Champagne J, et al (2000) Reactive hemophagocytic syndrome presenting as a component of multiple organ dysfunction syndrome. Crit Care Med 28:3341–3345Google Scholar
  17. 17.
    Ohga S, Matsuzuki A, Nishizaki M, et al (1993) Inflammatory cytokines in virus-associated hemophagocytic syndrome. Am J Pediatr Hematol/Oncol 15:291–298Google Scholar
  18. 18.
    Chateil J-F, Brun M, Perel Y, et al (1999) Abdominal ultrasound findings in children with hemophagocytic lymphohistiocytosis. Eur Radiol 9:474–477CrossRefPubMedGoogle Scholar
  19. 19.
    deKergenac C, Hillaire S, Molinie V, et al (2001) Hepatic manifestations of hemophagocytic syndrome: a study of 30 cases. Am J Gastroenterol 96:852–857CrossRefPubMedGoogle Scholar
  20. 20.
    Haddad E, Sulis M-L, Jabado N, et al (1997) Frequency and severity of central nervous system lesions in hemophagocytic lymphohistiocytosis. Blood 89:794–800PubMedGoogle Scholar
  21. 21.
    Takahashi S, Oki J, Miyamoto A, et al (1999) Encephalopathy associated with haemophagocytic lymphohistiocytosis following rotavirus infection. Eur J Pediatr 158:133–137CrossRefPubMedGoogle Scholar
  22. 22.
    Vasishta RK, Kakkar N, Barjee AK, et al (1999) Pathologic case of the month. Arch Pediatr Adolesc Med 153:545–547PubMedGoogle Scholar
  23. 23.
    Appen RE, Weber SW, DeVenecia G, et al (1976) Ocular and cerebral involvement in familial lymphohistiocytosis. Am J Ophthalmology 82:758–766Google Scholar
  24. 24.
    Akima M, Sumi SM (1984) Neuropathology of familial erythrocytic lymphohistiocytosis. Six cases and review of the literature. Human Pathol 15:161–168Google Scholar
  25. 25.
    Forbes KPN, Collie DA, Parker A (2000) CNS involvement of virus-associated hemophagocytic syndrome: MR imaging appearance. AJNR 21:1248–1250Google Scholar
  26. 26.
    Henter J-I, Nennesmo I (1997) Neuropathological findings and neurological symptoms in 23 children with hemophagocytic lymphohistiocytosis. Pediatrics 130:358–365Google Scholar
  27. 27.
    Casey SO, Sampaio RC, Michel E, et al (2000) Posterior reversible leukoencephalopathy syndrome: utility of fluid-attenuated inversion recovery MR imaging in the detection of cortical and subcortical lesions. AJNR 21:1199–1206Google Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  1. 1.E. B. Singleton Department of Diagnostic ImagingTexas Children's HospitalHoustonUSA
  2. 2.Texas Children's Cancer Center6701 FanninHoustonUSA

Personalised recommendations