Differentialdiagnose der Eosinophilie aus hämatologischer Sicht

Zusammenfassung

Obwohl eosinophile Granulozyten nur einen kleinen Anteil der Leukozyten im Blut ausmachen (weniger als 5%), können erhöhte Werte auf schwerwiegende Erkrankungen hinweisen. Dabei bedarf nicht jede Eosinophilie einer weiteren Diagnostik - anhaltend erhöhte Werte über 1,5 x 10⁹ /L sollten jedoch differenzialdiagnostisch abgeklärt werden. Die häufigsten Ursachen für eine Eosinophilie sind reaktiver Natur und umfassen Allergien, Medikamente, Autoimmunerkrankungen oder parasitäre Infektionen. Auch solide Tumore oder Lymphome können mit einer begleitenden reaktiven Eosinophilie einhergehen. Davon abzugrenzen sind die seltenen (<5%) klonalen Eosinophilien, deren Identifikation prognostisch und therapeutisch relevant ist. Nach Ausschluss klassisch reaktiver und klonaler Ursachen, bleibt das idiopathische Hypereosinophilie-Syndrom (iHES) als Differentialdiagnose, bei dem es zur Organschädigung durch eine persistierende Eosinophilie kommt. Das klinische Erscheinungsbild eosinophiler Erkrankungen ist oft unspezifisch und erlaubt keine eindeutige Diagnose. Daher ist neben einer sorgfältigen Anamnese, einer ausgedehnten Labor- und bildgebenden Diagnostik auch eine molekulargenetische Abklärung unbedingt notwendig. Eine frühzeitige Diagnose kann die Prognose erheblich verbessern. Während Steroide bei reaktiven Ursachen und dem iHES sehr gut wirksam sind, können bei klonalen Eosinophilien keine dauerhaften Remissionen mit Steroiden erreicht werden. Stattdessen kommen hier je nach zugrundeliegender genetischer Veränderung Tyrosinkinasehemmer zum Einsatz.

Abstract

Although eosinophilic granulocytes constitute only a small proportion of leukocytes in peripheral blood (less than 5%), elevated levels can indicate serious illnesses. Not every case of eosinophilia should prompt further diagnostic investigations; however, persistently elevated levels above 1.5 x 10⁹ /L should be thoroughly examined. The most common causes of eosinophilia are reactive and include allergies, medication, autoimmune diseases, or parasitic infections. Additionally, solid tumours or lymphomas may be accompanied by reactive eosinophilia. Distinguishing reactive forms from the rare clonal eosinophilias (<5%) is essential for prognosis and treatment. After secondary reactive and clonal causes have been ruled out, idiopathic hypereosinophilic syndrome (iHES), characterized by organ damage due to persistent non-clonal eosinophilia, may be considered. The clinical presentation of eosinophilic disorders is often non-specific, making a definitive diagnosis challenging. Therefore, molecular genetic testing, along with a comprehensive medical history and extensive laboratory and imaging tests, is essential. Early diagnosis can significantly improve prognosis. While steroids are effective for reactive causes and iHES, they do not achieve durable remissions in clonal eosinophilia. Tyrosine kinase inhibitors have shown promising responses and should be used instead, based on the underlying genetic alteration.

Schlüsselwörter

Hypereosinophilie - klonale Eosinophilie - MLN mit Tk - Hypereosinophiles Syndrom

Keywords

MLN TK - clonal eosinophilia - hypereosinophilic syndrome - hypereosinophilia

Publication History

Article published online:
16 May 2024

• Literatur

• 1 Valent P, Klion AD, Horny HP. et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol. 2012 S0091-6749(12)00348-X
• 2 Valent P, Gleich GJ, Reiter A. et al. Pathogenesis and classification of eosinophil disorders: a review of recent developments in the field. Expert Rev Hematol 2012; 5: 157-176
• 3 Varricchi G, Galdiero MR, Loffredo S. et al. Eosinophils: The unsung heroes in cancer?. Oncoimmunology 2018; 7: e1393134
• 4 El-Osta H, El-Haddad P, Nabbout N. Lung carcinoma associated with excessive eosinophilia. J Clin Oncol 2008; 26: 3456-3457
• 5 Kaur P, Khan WA. Myeloid/Lymphoid Neoplasms with Eosinophilia and Platelet Derived Growth Factor Receptor Alpha (PDGFRA) Rearrangement. In: Li W, editor. Leukemia [Internet]. Brisbane (AU): Exon Publications; 2022. Chapter 8. Available from https://www.ncbi.nlm.nih.gov/books/NBK586201/
• 6 Schwaab J, Umbach R, Metzgeroth G. et al. KIT D816V and JAK2 V617F mutations are seen recurrently in hypereosinophilia of unknown significance. Am J Hematol 2015; 90: 774-777
• 7 Helbig G, Stella-Hołowiecka B, Majewski M. et al. A single weekly dose of imatinib is sufficient to induce and maintain remission of chronic eosinophilic leukaemia in FIP1L1-PDGFRA-expressing patients. Br J Haematol 2008; 141: 200-204
• 8 Helbig G, Kyrcz-Krzemień S. Cessation of imatinib mesylate may lead to sustained hematologic and molecular remission in FIP1L1-PDGFRA-mutated hypereosinophilic syndrome. Am J Hematol 2014; 89: 115
• 9 Metzgeroth G, Schwaab J, Naumann N. et al. Treatment-free remission in FIP1L1-PDGFRA-positive myeloid/lymphoid neoplasms with eosinophilia after imatinib discontinuation. Blood Adv 2020; 4: 440-443
• 10 Bradeen HA, Eide CA, O‘Hare T. et al. Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (NEU)-based mutagenesis screen: high efficacy of drug combinations. Blood 2006; 108: 2332-2338
• 11 Freyer CW, Hughes ME, Carulli A. et al. Pemigatinib eh ave treatment of myeloid/lymphoid neoplasms with FGFR1 rearrangement. Expert Rev Anticancer Ther 2023; 23: 351-359
• 12 Schwaab J, Cabral do O, Hartmann N. et al. Importance of Adequate Diagnostic Workup for Correct Diagnosis of Advanced Systemic Mastocytosis. J Allergy Clin Immunol Pract 2020; 8: 3121-3127
• 13 Yao J, Xu L, Aypar U. et al. Myeloid/lymphoid neoplasms with eosinophilia/ basophilia and ETV6-ABL1 fusion: cell-of-origin and response to tyrosine kinase inhibition. Haematologica 2021; 106: 614-618
• 14 Metzgeroth G, Steiner L, Naumann N. et al. Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions: reevaluation eh av defining characteristics in a registry-based cohort. Leukemia 2023; 37: 1860-1867
• 15 Kluin-Nelemans HC, Reiter A, Illerhaus A. et al. Prognostic impact of eosinophils in mastocytosis: analysis of 2350 patients collected in the ECNM Registry. Leukemia 2020; 34: 1090-1101
• 16 Gotlib J, Castells M, Elberink HO. et al. Avapritinib versus Placebo in Indolent Systemic Mastocytosis. NEJM Evid. 2023; 2: EVIDoa2200339
• 17 Gotlib J, Reiter A, Radia DH. et al. Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis eh av phase 2 PATHFINDER trial. Nat Med 2021; 27: 2192-2199
• 18 Gotlib J, Kluin-Nelemans HC, George TI. et al. Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. N Engl J Med 2016; 374: 2530-2541
• 19 Roufosse F, Garaud S, de Leval L. Lymphoproliferative disorders associated with hypereosinophilia. Semin Hematol 2012; 49: 138-148
• 20 Shomali W, Gotlib J. World Health Organization-defined eosinophilic disorders: 2022 update on diagnosis, risk stratification, and management. Am J Hematol 2022; 97: 129-148
• 21 Shi Y, Wang C. What eh ave learned about lymphocytic variant hypereosinophilic syndrome: A systematic literature review. Clin Immunol 2022; 237: 108982
• 22 Ledoult E, Groh M, Meresse B. et al. Mogamulizumab for Refractory CD3-CD4+ Lymphocytic-Variant Hypereosinophilic Syndrome. Blood 2023; 142: 4444
• 23 Faguer S, Groh M, Vergez F. et al. JAK inhibition for CD3- CD4+ lymphocytic-variant hypereosinophilic syndrome. Clin Immunol 2023; 251: 109275