Zusammenfassung:
Die hämophagozytische Lymphohistiozytose (HLH) ist ein Hyperinflammations-Syndrom, welchem neben genetischen Defekten insbesondere in Genen der die Immunsynapse regulierenden Proteine auch erworbene Defekte der effektiven Pathogen-Elimination zugrunde liegen. Das rasche Erkennen und zielgerichtete Diagnostizieren einer HLH ist bei weiterhin hoher Mortalitätsrate zwischen 40%–70% essentiell, um Therapieverbesserungen zu erreichen. Hierfür ist der wichtigste Schritt für den Kliniker, an eine HLH zu denken. Prolongiertes Fieber unklarer Genese, eine Hepatosplenomegalie und eine Bi- oder Panzytopenie sind die führende Symptomentrias. Bei bekannter Familienanamnese oder bekanntem Gendefekt sind rasche bestätigende Untersuchungen einzuleiten, um die häufig notwendige Stammzelltransplantation nicht zu verzögern. Insbesondere bei Erwachsenen, bei denen auch genetische Defekte mit verzögerter Manifestation vorliegen können (v.a. bei de novo EBV-Infektion), muss eine breite Diagnostik zur Ursachenforschung einer HLH angestrengt werden. Die HLH ist keine eigenständige Erkrankung. Sie ist gemeinsame Endstrecke eines Immundefekts, welcher genetisch bedingt, oder durch infektiöse, autoimmune, autoinflammatorische, maligne oder auch iatrogene Trigger (Immunsuppression, Stammzelltransplantation) erworben werden kann. Diesem breiten Spektrum der Pathogenese der HLH muss die labormedizinische Diagnostik Rechnung tragen, um dem Kliniker sehr zeitnah die klinisch zu stellende Verdachtsdiagnose zu erhärten und schnellstmöglich die Therapie einleiten zu können.
Abstract:
Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by genetic and acquired defects of the molecular machinery, which regulate the cellular immune synapse. Rapid recognition of symptoms resembling HLH, and a targeted diagnostic approach are essential in improving outcome. The condition is associated with a mortality rate between 40% and 70%. For the clinician, the most important step towards diagnosing HLH is to include it in the list of potential differential diagnoses. The leading triad of symptoms consists of prolonged fever of unknown origin, hepatosplenomegaly, and bi- or pancytopeniae. A known family history or known gene mutations require rapid confirmatory testing, which facilitates the initiation of a life saving risk-adapted treatment that includes stem cell transplantation. In adults with de-novo infection with Epstein-Barr virus, a broad diagnostic approach is required to identify potential late-onset hereditary HLH. HLH is not a diagnosis, per se, but represents a common terminal pathway of diseases with the ability to trigger HLH. Such diseases include infections, malignant disorders, autoimmune or autoinflammatory diseases, and iatrogenic triggers such as immunosuppressive treatment or stem cell transplantation itself. This broad spectrum of HLH pathogenesis must be considered in order to achieve rapid diagnosis, which is a prerequisite for the initiation of rationale treatment.
Reviewed Publication:
Nebe C.T.
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