Haematologica (Jul 2015)

The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis

  • Sebastian FN Bode,
  • Sandra Ammann,
  • Waleed Al-Herz,
  • Mihaela Bataneant,
  • Christopher C Dvorak,
  • Stephan Gehring,
  • Andrew Gennery,
  • Kimberly C Gilmour,
  • Luis I Gonzalez-Granado,
  • Ute Groß-Wieltsch,
  • Marianne Ifversen,
  • Jenny Lingman-Framme,
  • Susanne Matthes-Martin,
  • Rolf Mesters,
  • Isabelle Meyts,
  • Joris M van Montfrans,
  • Jana Pachlopnik Schmid,
  • Sung-Yun Pai,
  • Pere Soler-Palacin,
  • Uta Schuermann,
  • Volker Schuster,
  • Markus G. Seidel,
  • Carsten Speckmann,
  • Polina Stepensky,
  • Karl-Walter Sykora,
  • Bianca Tesi,
  • Thomas Vraetz,
  • Catherine Waruiru,
  • Yenan T. Bryceson,
  • Despina Moshous,
  • Kai Lehmberg,
  • Michael B Jordan,
  • Stephan Ehl

DOI
https://doi.org/10.3324/haematol.2014.121608
Journal volume & issue
Vol. 100, no. 7

Abstract

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Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome defined by clinical and laboratory criteria. Current criteria were created to identify patients with familial hemophagocytic lmyphohistiocytosis in immediate need of immunosuppressive therapy. However, these criteria also identify patients with infection-associated hemophagocytic inflammatory states lacking genetic defects typically predisposing to hemophagocytic lymphohistiocytosis. These patients include those with primary immunodeficiencies, in whom the pathogenesis of the inflammatory syndrome may be distinctive and aggressive immunosuppression is contraindicated. To better characterize hemophagocytic inflammation associated with immunodeficiencies, we combined an international survey with a literature search and identified 63 patients with primary immunodeficiencies other than cytotoxicity defects or X-linked lymphoproliferative disorders, presenting with conditions fulfilling current criteria for hemophagocytic lymphohistiocytosis. Twelve patients had severe combined immunodeficiency with