Hypereosinophilia
The medical term " hypereosinophilia " ( HE ) describes a prolonged prolonged increase in eosinophilic granulocytes ( eosinophils for short) above 1.5 × 10 9 / L in the peripheral blood and / or a higher level of tissue infiltration by eosinophilic granulocytes.
definition
The term 'hypereosinophilia' was precisely defined by the International consensus group definitions for Hypereosinophilia and Hypereosinophilic Syndromes in 2012. According to this definition, hypereosinophilia is present if:
- more than 1.5 × 10 9 / L (1.5 / nl) eosinophilic granulocytes can be detected in two blood samples that were taken more than a month apart (in life-threatening situations, the one-month interval can also be shortened ),
and / or - a tissue eosinophilia is present, which is characterized by the following features:
- Percentage of eosinophils on histological examination of bone marrow accounts for over 20% of all nucleated cells;
and or - Tissue eosinophil infiltration judged by a pathologist to be extensive;
and or - clear deposits of proteins from eosinophil granules are detectable in the tissue (simultaneous tissue infiltration by eosinophils is not mandatory).
- Percentage of eosinophils on histological examination of bone marrow accounts for over 20% of all nucleated cells;
Forms of hypereosinophilia
The group of experts quoted above suggested the following classification of hypereosinophilia:
| designation | abbreviation | Pathogenesis / definition |
|---|---|---|
| Hereditary (familial) HE | HE FA | Unknown pathogenesis, familial accumulation, no evidence of a congenital immunodeficiency, no evidence of a reactive or underlying neoplastic cause |
| HE of undetermined significance | HE US | No recognizable underlying cause of HE, no familial accumulation, no evidence of a reactive or underlying neoplastic cause, no organ damage from hypereosinophilia |
| Primary (clonal / neoplastic) HE | HE N | Underlying haematopoietic stem cell disease, the eosinophils are part of the neoplastic clone |
| Secondary (reactive) HE | HE R | Non-clonal hypereosinophilia, mostly due to increased cytokine release in other underlying diseases |
| Hypereosinophilic syndrome | HES | Criteria for peripheral blood hypereosinophilia met and at the same time present organ damage from eosinophil infiltration or deposition of proteins from eosinophil granules. |
In the case of clonal or reactive hyperososinophilia, it should be emphasized that the final diagnosis here should not simply be “hypereosinophilia”, but that more detailed research must be carried out into the underlying cause. For example, a genetic analysis should be carried out in the case of clonal HE, and in the case of reactive eosinophils, a search must be made for the causative diseases (allergic reactions, infections, autoimmune diseases, etc.).
causes
Reactive hypereosinophilia
The reactive hypereosinophilias are mostly mediated by cytokines - especially by interleukin-3 (IL-3), interleukin-5 (IL-5), granulocyte-macrophage-colony-stimulating factor (GM-CSF). However, these cytokines are not measurably increased in all reactive HE. Reactive HE can be found in atopy , allergic reactions, some infections (especially worm and parasite infections), certain medications, or autoimmune diseases. Concomitant, non-clonal eosinophils are rarely found in hematological neoplasms or solid tumors.
Drug reactions rarely lead to (hyper) eosinophilia and when they do, it is usually mild. A very rare form of systemic reaction with (hyper) eosinophilia is the so-called DRESS syndrome (syndrome of drug reaction with eosinophilia and systemic symptoms). Examples of causative drugs are phenytoin , carbamazepine, and phenobarbital .
Clonal hypereosinophilias
| change | therapy |
|---|---|
|
PDGFRA fusion genes (e.g. FIP1L1-PDGFRA ) |
z. B. Imatinib |
|
PDGFRB fusion genes (e.g. ETV6-PDGFRB ) |
z. B. Imatinib |
|
FGFR1 fusion genes (e.g. BCR-FGFR1 ) |
(experimental) |
|
JAK2 fusion genes (e.g. PCM1-JAK2 ) |
z. B. ruxolitinib |
Clonal hypereosinophils are malignant or at least premalignant eosinophil proliferation, ie the eosinophils are part of the malignant cell clone. Clonal eosinophils are most common in chronic myeloid diseases: in myeloproliferative neoplasias (MPN) or mixed forms of myelodysplasias and MPN. They occur less frequently in acute myeloid leukemia (AML) or acute lymphocytic leukemia / lymphomas of the B or T cell series.
Since 2008, the classification of hematopoietic neoplasms by the World Health Organization (WHO) has included an entity Myeloid or lymphatic neoplasms with eosinophilia and aberrations of the genes PDGFRA, PDGFRB or FGFR1 . In the new edition of the WHO classification, the cases with detection of a fusion gene PCM1-JAK2 were added.
If clonal hypereosinophilia is suspected, an attempt should be made to prove the clonality by demonstrating corresponding genetic changes using cytogenetic or molecular genetic methods. This is also useful because some of these changes can be treated therapeutically with specific tyrosine kinase inhibitors.
Relative versus absolute eosinophil levels
It should be noted that absolute eosinophil values are required for the diagnosis of hypereosinophilia . In everyday clinical practice, however, relative values are often given. The normal value for peripheral blood leukocytes is around 4–10 / nl (or 4000–10,000 / µl). With a white blood cell count of 4 / nl, 1.5 / nl eosinophils correspond to an eosinophil content of 37.5%, but with a white blood cell count of 10 / nl only 15%.
Individual evidence
- ↑ a b P. Valent, AD Klion, HP Horny, F. Roufosse, J. Gotlib, PF Weller, A. Hellmann, G. Metzgeroth, KM Leiferman, M. Arock, JH Butterfield, WR Sperr, K. Sotlar, P Vandenberghe, T. Haferlach, HU Simon, A. Reiter, GJ Gleich: Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. In: J Allergy Clin Immunol. 130 (3), 2012, pp. 607-612.e9. doi: 10.1016 / j.jaci.2012.02.019
- ↑ a b c A. Reiter, J. Gotlib: Myeloid neoplasms with eosinophilia. In: Blood. 129 (6), 2017, pp. 704-714. doi: 10.1182 / blood-2016-10-695973
- ↑ M. Ebnöther, R. Schoenenberger: Eosinophilia - what comes into question? In: Switzerland Med Forum . tape 5 , 2005, p. 735-741 ( medicalforum.ch [PDF]).
- ↑ Werner J. Pichler, Thomas Wendland, Oliver Hausmann, Benno Schnyder, Michael Fricker, Christiane Pichler, Arthur Helbling: DRESS (Drug Rash with Eosinophilia and Systemic Symptoms): A serious, often misunderstood drug allergy . In: Switzerland Med Forum . tape 11 , no. 48 , 2011, p. 879-884 ( medicalforum.ch [PDF]).
