The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis.
Haematologica. 2015 May 28;
Authors: Bode SF, Ammann S, Al-Herz W, Bataneant M, Dvorak CC, Gehring S, Gennery A, Gilmour KC, Gonzalez-Granado LI, GroB-Wieltsch U, Ifversen M, Lingman-Framme J, Matthes-Martin S, Mesters R, Meyts I, van Montfrans JM, Pachlopnik Schmid J, Pai SY, Soler-Palacin P, Schuermann U, Schuster V, Seidel MG, Speckmann C, Stepensky P, Sykora KW, Tesi B, Vraetz T, Waruiru C, Bryceson YT, Moshous D, Lehmberg K, Jordan MB, Ehl S
Abstract
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. This includes patients with primary immunodeficiencies, in whom pathogenesis of the inflammatory syndrome may be distinctive and aggressive immunosuppression 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 <100/ml T-cells, 18 had partial T-cell deficiencies; episodes of hemophagocytic lymphohistiocytosis were mostly associated with viral infections. Twenty-two patients had chronic granulomatous disease with hemophagocytic episodes mainly associated with bacterial infections. Compared to patients with cytotoxicity defects, patients with T-cell deficiencies had lower soluble CD25 and higher ferritin. Other criteria for hemophagocytoc lymphohistiocytosis were not discriminative. Thus, (i) a hemophagocytic inflammatory syndrome fulfilling criteria for hemophagocytic lymphohistiocytosis can be the initial manifestation of primary immunodeficiencies. (ii) this syndrome can develop despite severe deficiency of T- and NK-cells, implicating that pathophysiology is distinct and not appropriately described as Lympho-Histiocytosis in these patients (iii) current criteria for hemophagocytoc lymphohistiocytosis are insufficient to differentiate hemophagocytic inflammatory syndromes with different pathogenesis. This is important because of implications for therapy, in particular for protocols targeting T-cells.
PMID: 26022711 [PubMed – as supplied by publisher]
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