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Health Sciences · Medicine

Eosinophilic Disorders and Syndromes
Research Guide

What is Eosinophilic Disorders and Syndromes?

Eosinophilic disorders and syndromes are a cluster of conditions characterized by hypereosinophilic syndrome and related disorders, involving sustained eosinophilia, molecular pathogenesis such as fusion genes like FIP1L1-PDGFRA, cardiac manifestations, and therapeutic management with agents like imatinib mesylate.

This field encompasses 37,340 works on the classification, molecular pathogenesis, and treatment of eosinophilic disorders. Key topics include fusion genes such as FIP1L1-PDGFRA and the use of imatinib mesylate for therapeutic management. Research addresses cardiac manifestations and precise classification of these syndromes.

Topic Hierarchy

100%
graph TD D["Health Sciences"] F["Medicine"] S["Rheumatology"] T["Eosinophilic Disorders and Syndromes"] D --> F F --> S S --> T style T fill:#DC5238,stroke:#c4452e,stroke-width:2px
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37.3K
Papers
N/A
5yr Growth
325.4K
Total Citations

Research Sub-Topics

FIP1L1-PDGFRA Fusion in Hypereosinophilic Syndrome

This sub-topic examines the molecular detection, functional consequences, and prognostic significance of the FIP1L1-PDGFRA fusion gene in patients with hypereosinophilic syndrome. Researchers study its role in driving eosinophil proliferation and its implications for targeted therapies.

15 papers

Imatinib Mesylate Treatment for PDGFRA-Associated Eosinophilia

This area investigates the efficacy, resistance mechanisms, and long-term outcomes of imatinib mesylate in treating PDGFRA-rearranged eosinophilic disorders. Studies focus on dosing regimens, response predictors, and combination therapies.

15 papers

Cardiac Manifestations in Hypereosinophilic Syndrome

Researchers explore eosinophil-mediated endomyocardial damage, diagnostic imaging, and therapeutic interventions for cardiac involvement in hypereosinophilic syndrome. This includes histopathological studies and risk stratification models.

15 papers

Classification of Eosinophilic Disorders

This sub-topic covers updated WHO classifications, clinicopathologic criteria, and molecular subtyping of idiopathic, clonal, and reactive eosinophilic disorders. Researchers develop diagnostic algorithms integrating genetics and cytology.

15 papers

Molecular Pathogenesis of Idiopathic Hypereosinophilia

Studies investigate cytokine dysregulation, eosinophil activation pathways, and novel genetic drivers in idiopathic hypereosinophilic syndrome excluding known fusions. Research includes omics profiling and signaling pathway analyses.

15 papers

Why It Matters

Eosinophilic disorders impact patients through organ damage from persistent eosinophilia, with imatinib mesylate targeting fusion genes like FIP1L1-PDGFRA to achieve hematologic responses. In chronic myeloid leukemia, a related myeloproliferative condition with eosinophilic features, imatinib demonstrated superiority over interferon alfa plus low-dose cytarabine, yielding higher hematologic and cytogenetic responses and lower progression rates (O’Brien et al. (2003) in "Imatinib Compared with Interferon and Low-Dose Cytarabine for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia"). Five-year follow-up showed durable responses in a high proportion of chronic-phase CML patients on continuous imatinib (Druker et al. (2006) in "Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia"). These findings support targeted tyrosine kinase inhibition in eosinophil-driven pathologies, reducing mortality and improving survival.

Reading Guide

Where to Start

"Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr–Abl positive cells" (1996) by Druker et al., as it establishes the mechanism of tyrosine kinase inhibition foundational to treatments like imatinib for PDGFRA-driven eosinophilic disorders.

Key Papers Explained

Druker et al. (1996) in "Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr–Abl positive cells" introduced selective Abl kinase inhibition, which O’Brien et al. (2003) in "Imatinib Compared with Interferon and Low-Dose Cytarabine for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia" applied clinically to show imatinib's superiority in CML with eosinophilic overlaps; Druker et al. (2006) in "Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia" then confirmed long-term durability, informing eosinophilic syndrome management.

Paper Timeline

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graph LR P0["Effects of a selective inhibitor...
1996 · 3.6K cites"] P1["Imatinib Compared with Interfero...
2003 · 3.5K cites"] P2["A Gain-of-Function Mutation of <...
2005 · 3.4K cites"] P3["Acquired mutation of the tyrosin...
2005 · 3.4K cites"] P4["Activating mutation in the tyros...
2005 · 3.0K cites"] P5["Five-Year Follow-up of Patients ...
2006 · 3.5K cites"] P6["A Phase 3 Trial of Pirfenidone i...
2014 · 3.8K cites"] P0 --> P1 P1 --> P2 P2 --> P3 P3 --> P4 P4 --> P5 P5 --> P6 style P6 fill:#DC5238,stroke:#c4452e,stroke-width:2px
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Most-cited paper highlighted in red. Papers ordered chronologically.

Advanced Directions

Current frontiers emphasize molecular classification of hypereosinophilic syndrome subtypes responsive to imatinib, with focus on PDGFRA fusion detection; no recent preprints available, but ongoing needs include biomarkers for cardiac risk stratification.

Papers at a Glance

# Paper Year Venue Citations Open Access
1 A Phase 3 Trial of Pirfenidone in Patients with Idiopathic Pul... 2014 New England Journal of... 3.8K
2 Effects of a selective inhibitor of the Abl tyrosine kinase on... 1996 Nature Medicine 3.6K
3 Imatinib Compared with Interferon and Low-Dose Cytarabine for ... 2003 New England Journal of... 3.5K
4 Five-Year Follow-up of Patients Receiving Imatinib for Chronic... 2006 New England Journal of... 3.5K
5 A Gain-of-Function Mutation of <i>JAK2</i> in Myeloproliferati... 2005 New England Journal of... 3.4K
6 Acquired mutation of the tyrosine kinase JAK2 in human myelopr... 2005 The Lancet 3.4K
7 Activating mutation in the tyrosine kinase JAK2 in polycythemi... 2005 Cancer Cell 3.0K
8 Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin A... 2018 New England Journal of... 2.7K
9 Activity of a Specific Inhibitor of the BCR-ABL Tyrosine Kinas... 2001 New England Journal of... 2.7K
10 HISTOPATHOLOGY OF THE SKIN 1950 Plastic & Reconstructi... 2.6K

Frequently Asked Questions

What are the main molecular drivers in eosinophilic disorders?

Fusion genes such as FIP1L1-PDGFRA represent key molecular drivers in hypereosinophilic syndrome. These genetic alterations contribute to sustained eosinophilia and organ involvement. Targeted therapies like imatinib mesylate inhibit the associated tyrosine kinase activity.

How does imatinib mesylate treat eosinophilic disorders?

Imatinib mesylate acts as a selective inhibitor of tyrosine kinases, including those activated by fusion genes in eosinophilic conditions. It induces hematologic and cytogenetic responses in patients with PDGFRA rearrangements. Long-term use sustains durable responses with an acceptable safety profile.

What cardiac manifestations occur in eosinophilic syndromes?

Cardiac manifestations in eosinophilic disorders include endomyocardial fibrosis and thrombosis due to eosinophil-mediated damage. These complications arise from persistent eosinophilia. Early therapeutic intervention with kinase inhibitors can mitigate progression.

What is the classification of eosinophilic disorders?

Classification of eosinophilic disorders distinguishes idiopathic hypereosinophilic syndrome from clonal variants driven by fusion genes like FIP1L1-PDGFRA. Myeloproliferative subtypes overlap with conditions responsive to imatinib. Accurate classification guides targeted therapy selection.

What role do tyrosine kinase inhibitors play in management?

Tyrosine kinase inhibitors like imatinib target aberrant signaling in eosinophilic disorders with PDGFRA fusions. Druker et al. (1996) in "Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr–Abl positive cells" demonstrated growth inhibition in kinase-driven cells. This approach extends to eosinophil-related pathologies for clinical benefit.

Open Research Questions

  • ? How do FIP1L1-PDGFRA fusion genes precisely contribute to cardiac damage in hypereosinophilic syndrome?
  • ? What criteria best classify idiopathic versus clonal eosinophilic disorders for imatinib responsiveness?
  • ? Can imatinib mesylate dosing be optimized to prevent long-term cardiac manifestations?
  • ? Which additional fusion genes beyond PDGFRA drive refractory eosinophilia?

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