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

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The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis. / Bode, Sebastian Fn; Ammann, Sandra; Al-Herz, Waleed; Bataneant, Mihaela; Dvorak, Christopher C; Gehring, Stephan; Gennery, Andrew; Gilmour, Kimberly C; Gonzalez-Granado, Luis I; Groß-Wieltsch, Ute; Ifversen, Marianne; Lingman-Framme, Jenny; Matthes-Martin, Susanne; Mesters, Rolf; Meyts, Isabelle; van Montfrans, Joris M; Pachlopnik Schmid, Jana; Pai, Sung-Yun; Soler-Palacin, Pere; Schuermann, Uta; Schuster, Volker; Seidel, Markus G; Speckmann, Carsten; Stepensky, Polina; Sykora, Karl-Walter; Tesi, Bianca; Vraetz, Thomas; Waruiru, Catherine; Bryceson, Yenan T; Moshous, Despina; Lehmberg, Kai; Jordan, Michael B; Ehl, Stephan; Inborn Errors Working Party of the EBMT.

In: HAEMATOLOGICA, Vol. 100, No. 7, 06.2015, p. 978-88.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Bode, SF, Ammann, S, Al-Herz, W, Bataneant, M, Dvorak, CC, Gehring, S, Gennery, A, Gilmour, KC, Gonzalez-Granado, LI, Groß-Wieltsch, U, Ifversen, M, Lingman-Framme, J, Matthes-Martin, S, Mesters, R, Meyts, I, van Montfrans, JM, Pachlopnik Schmid, J, Pai, S-Y, Soler-Palacin, P, Schuermann, U, Schuster, V, Seidel, MG, Speckmann, C, Stepensky, P, Sykora, K-W, Tesi, B, Vraetz, T, Waruiru, C, Bryceson, YT, Moshous, D, Lehmberg, K, Jordan, MB, Ehl, S & Inborn Errors Working Party of the EBMT 2015, 'The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis', HAEMATOLOGICA, vol. 100, no. 7, pp. 978-88. https://doi.org/10.3324/haematol.2014.121608

APA

Bode, S. F., Ammann, S., Al-Herz, W., Bataneant, M., Dvorak, C. C., Gehring, S., Gennery, A., Gilmour, K. C., Gonzalez-Granado, L. I., Groß-Wieltsch, U., Ifversen, M., Lingman-Framme, J., Matthes-Martin, S., Mesters, R., Meyts, I., van Montfrans, J. M., Pachlopnik Schmid, J., Pai, S-Y., Soler-Palacin, P., ... Inborn Errors Working Party of the EBMT (2015). The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis. HAEMATOLOGICA, 100(7), 978-88. https://doi.org/10.3324/haematol.2014.121608

Vancouver

Bode SF, Ammann S, Al-Herz W, Bataneant M, Dvorak CC, Gehring S et al. The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis. HAEMATOLOGICA. 2015 Jun;100(7):978-88. https://doi.org/10.3324/haematol.2014.121608

Bibtex

@article{0b82bfb5c3464614951c0c95f08f731e,
title = "The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis",
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. 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 <100/μL 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 levels of soluble CD25 and higher ferritin concentrations. 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, implying that the pathophysiology is distinct and not appropriately described as {"}lympho{"}-histiocytosis in these patients; and (iii) current criteria for hemophagocytoc lymphohistiocytosis are insufficient to differentiate hemophagocytic inflammatory syndromes with different pathogeneses. This is important because of implications for therapy, in particular for protocols targeting T cells.",
keywords = "Adolescent, Adult, Bacterial Infections, Child, Child, Preschool, Diagnosis, Differential, Europe, Female, Humans, Immunoglobulins, Intravenous, Immunologic Deficiency Syndromes, Immunologic Factors, Infant, Infant, Newborn, Killer Cells, Natural, Leishmaniasis, Lymphohistiocytosis, Hemophagocytic, Lymphoproliferative Disorders, Male, Mycoses, Opportunistic Infections, Registries, Steroids, T-Lymphocytes, Terminology as Topic, Virus Diseases",
author = "Bode, {Sebastian Fn} and Sandra Ammann and Waleed Al-Herz and Mihaela Bataneant and Dvorak, {Christopher C} and Stephan Gehring and Andrew Gennery and Gilmour, {Kimberly C} and Gonzalez-Granado, {Luis I} and Ute Gro{\ss}-Wieltsch and Marianne Ifversen and Jenny Lingman-Framme and Susanne Matthes-Martin and Rolf Mesters and Isabelle Meyts and {van Montfrans}, {Joris M} and {Pachlopnik Schmid}, Jana and Sung-Yun Pai and Pere Soler-Palacin and Uta Schuermann and Volker Schuster and Seidel, {Markus G} and Carsten Speckmann and Polina Stepensky and Karl-Walter Sykora and Bianca Tesi and Thomas Vraetz and Catherine Waruiru and Bryceson, {Yenan T} and Despina Moshous and Kai Lehmberg and Jordan, {Michael B} and Stephan Ehl and {Inborn Errors Working Party of the EBMT}",
note = "Copyright{\textcopyright} Ferrata Storti Foundation.",
year = "2015",
month = jun,
doi = "10.3324/haematol.2014.121608",
language = "English",
volume = "100",
pages = "978--88",
journal = "HAEMATOLOGICA",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",
number = "7",

}

RIS

TY - JOUR

T1 - The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis

AU - Bode, Sebastian Fn

AU - Ammann, Sandra

AU - Al-Herz, Waleed

AU - Bataneant, Mihaela

AU - Dvorak, Christopher C

AU - Gehring, Stephan

AU - Gennery, Andrew

AU - Gilmour, Kimberly C

AU - Gonzalez-Granado, Luis I

AU - Groß-Wieltsch, Ute

AU - Ifversen, Marianne

AU - Lingman-Framme, Jenny

AU - Matthes-Martin, Susanne

AU - Mesters, Rolf

AU - Meyts, Isabelle

AU - van Montfrans, Joris M

AU - Pachlopnik Schmid, Jana

AU - Pai, Sung-Yun

AU - Soler-Palacin, Pere

AU - Schuermann, Uta

AU - Schuster, Volker

AU - Seidel, Markus G

AU - Speckmann, Carsten

AU - Stepensky, Polina

AU - Sykora, Karl-Walter

AU - Tesi, Bianca

AU - Vraetz, Thomas

AU - Waruiru, Catherine

AU - Bryceson, Yenan T

AU - Moshous, Despina

AU - Lehmberg, Kai

AU - Jordan, Michael B

AU - Ehl, Stephan

AU - Inborn Errors Working Party of the EBMT

N1 - Copyright© Ferrata Storti Foundation.

PY - 2015/6

Y1 - 2015/6

N2 - 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 <100/μL 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 levels of soluble CD25 and higher ferritin concentrations. 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, implying that the pathophysiology is distinct and not appropriately described as "lympho"-histiocytosis in these patients; and (iii) current criteria for hemophagocytoc lymphohistiocytosis are insufficient to differentiate hemophagocytic inflammatory syndromes with different pathogeneses. This is important because of implications for therapy, in particular for protocols targeting T cells.

AB - 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 <100/μL 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 levels of soluble CD25 and higher ferritin concentrations. 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, implying that the pathophysiology is distinct and not appropriately described as "lympho"-histiocytosis in these patients; and (iii) current criteria for hemophagocytoc lymphohistiocytosis are insufficient to differentiate hemophagocytic inflammatory syndromes with different pathogeneses. This is important because of implications for therapy, in particular for protocols targeting T cells.

KW - Adolescent

KW - Adult

KW - Bacterial Infections

KW - Child

KW - Child, Preschool

KW - Diagnosis, Differential

KW - Europe

KW - Female

KW - Humans

KW - Immunoglobulins, Intravenous

KW - Immunologic Deficiency Syndromes

KW - Immunologic Factors

KW - Infant

KW - Infant, Newborn

KW - Killer Cells, Natural

KW - Leishmaniasis

KW - Lymphohistiocytosis, Hemophagocytic

KW - Lymphoproliferative Disorders

KW - Male

KW - Mycoses

KW - Opportunistic Infections

KW - Registries

KW - Steroids

KW - T-Lymphocytes

KW - Terminology as Topic

KW - Virus Diseases

U2 - 10.3324/haematol.2014.121608

DO - 10.3324/haematol.2014.121608

M3 - SCORING: Journal article

C2 - 26022711

VL - 100

SP - 978

EP - 988

JO - HAEMATOLOGICA

JF - HAEMATOLOGICA

SN - 0390-6078

IS - 7

ER -