Zusammenfassung
Die hämophagozytische Lymphohistiozytose (HLH) ist ein hyperferritinämisches Hyperinflammationssyndrom. Es wird eine hereditäre von einer erworbenen Form unterschieden. Bei Erwachsenen ist in erster Linie die erworbene, sekundäre HLH anzutreffen. Infektionen, Malignome und Autoimmunerkrankungen sind häufige Auslöser der sekundären HLH. Zunehmend wird auch über Fälle von HLH im Zusammenhang mit Immuntherapien berichtet, etwa unter Einsatz von CAR-T-Zellen (CAR: chimärer Antigenrezeptor). Bei kritisch kranken Patienten auf der Intensivstation stellt die Sepsis aufgrund des oft ähnlichen klinischen Erscheinungsbilds die wichtigste Differenzialdiagnose zur HLH dar. Teilweise liegen HLH und Sepsis zeitgleich vor. Eine frühzeitige Diagnosestellung und der rasche Beginn einer immunsuppressiven Therapie spielen für den weiteren Verlauf und die Prognose der HLH eine wichtige Rolle. Daher sollte bei kritisch kranken Patienten mit persistierendem Fieber, entsprechender Symptomatik (etwa Splenomegalie und neurologische Auffälligkeiten) und typischen Laborauffälligkeiten (beispielsweise Hyperferritinämie, Zytopenie von 2 oder 3 Zellreihen, erhöhte Transaminasen) an das mögliche Vorliegen einer HLH gedacht werden. Die Diagnose der HLH wird anhand der HLH-2004-Kriterien gestellt. Die Wahrscheinlichkeit für das Vorliegen einer HLH kann mithilfe des HScores ermittelt werden. Hoch dosierte Kortikosteroide stellen den Grundpfeiler der Therapie dar. Darüber hinaus werden je nach Trigger Immunglobuline, Etoposid, Anakinra oder Ruxolitinib ergänzt. Der Verlauf hängt neben der frühzeitigen Einleitung der Therapie vom Auslöser sowie dem Ansprechen auf die Behandlung ab. Trotz Fortschritten im Hinblick auf die Diagnostik und den Einsatz zielgerichteter Therapien haben kritisch kranke Patienten mit HLH weiterhin eine ungünstige Prognose.
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome characterized by hyperferritinemia. A differentiation is made between hereditary and acquired forms. In contrast to children, almost all cases in adult patients consist of acquired secondary HLH. Infections, malignancies and autoimmune diseases are frequent triggers of secondary HLH. More recently, cases of HLH have also been described in association with immunotherapy, e.g., when using chimeric antigen receptor (CAR) T‑cell treatment. In critically ill patients in the intensive care unit (ICU), sepsis represents the major differential diagnosis of HLH due to the frequently similar clinical presentation. Sometimes both sepsis and HLH are present at the same time. An early diagnosis and timely initiation of immunosuppressive treatment are essential for the further course and prognosis of HLH. Therefore, HLH should be considered as a possible diagnosis in critically ill patients with persistent fever and additional compatible symptoms (e.g., splenomegaly, neurological symptoms) or laboratory parameters (e.g., hyperferritinemia, cytopenia of two or three cell lines, increased transaminases). The diagnosis of HLH is made on the basis of the HLH-2004 criteria. The HScore can be used to estimate the probability of the presence of HLH. Corticosteroids given at high doses are the cornerstone of HLH treatment. Furthermore, immunoglobulins, etoposide, anakinra or ruxolitinib can complement treatment depending on the HLH trigger. The course of HLH depends on the timely initiation of treatment, the underlying trigger and the response to treatment. Despite progress in terms of diagnostics and targeted treatment, the prognosis of critically ill HLH patients is still poor.
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D.A. Eichenauer und P. La Rosée geben an, dass kein Interessenkonflikt besteht.
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Eichenauer, D.A., La Rosée, P. Behandlung der hämophagozytischen Lymphohistiozytose bei Patienten auf der Intensivstation. Innere Medizin 64, 955–960 (2023). https://doi.org/10.1007/s00108-023-01584-0
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DOI: https://doi.org/10.1007/s00108-023-01584-0
Schlüsselwörter
- Hämophagozytische Lymphohistiozytose/Prognose
- Hyperferritinämie
- Immunsuppressive Therapie
- Kortikosteroide
- Sepsis