Clonal eosinophil and mast cell diseases: different in the same way?

Wilde, Virginie De; Roufosse, Florence; Hermine, Olivier

doi:10.1080/17474086.2016.1254036

Cited by 4 publications

(2 citation statements)

References 22 publications

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“…Eosinophils may also contribute to symptoms and complications in certain indolent hematological disorders, such as mastocytosis and cutaneous T cell lymphoma, that need not necessarily be treated aggressively. One patient with unrecognized cutaneous mastocytosis associated with hypereosinophilia responded to prolonged treatment with mepolizumab (750 mg IV), before the correct diagnosis was made more than 10 years after initial presentation ( 90 ). Eosinophil counts normalized and she experienced symptomatic improvement (pruritus, erythematous eruptions, and chronic cough) with repeated mepolizumab infusions.…”

Section: Anti-il-5 Treatment In Other Inflammatory Disorders Associatmentioning

confidence: 99%

Targeting the Interleukin-5 Pathway for Treatment of Eosinophilic Conditions Other than Asthma

2018

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Improved understanding of the contribution of eosinophils to various chronic inflammatory conditions, most notably allergic asthma, has encouraged development of monoclonal antibodies specifically targeting mediators and surface receptors involved in eosinophil expansion and activation. The pivotal role of interleukin-5 (IL-5) in eosinophil biology, its high specificity for this leukocyte subset, and its involvement in the majority of eosinophilic conditions make it a very enticing target for treatment of eosinophil-mediated disorders. Two types of antibodies have been developed to target eosinophils: antibodies against IL-5 (mepolizumab and reslizumab), and an antibody against the IL-5-receptor-alpha-chain (IL-5Rα) (benralizumab). Both types of antibodies prevent IL-5 from engaging its receptor and in addition, anti-IL-5Rα antibodies induce target-cell lysis. They have been shown to reduce circulating eosinophil counts rapidly in humans with various disorders. Herein, a brief overview of the role of IL-5 in eosinophil biology will be presented, followed by a description of the development and characteristics of antibodies targeting IL-5 or its receptor. Results of clinical trials evaluating the efficacy and safety of these new antibodies in diseases (other than eosinophilic asthma) with prominent tissue eosinophilia are reviewed, followed by safety considerations and potential future applications.

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Section: Anti-il-5 Treatment In Other Inflammatory Disorders Associatmentioning

confidence: 99%

Targeting the Interleukin-5 Pathway for Treatment of Eosinophilic Conditions Other than Asthma

2018

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“…Indeed, mast cells and eosinophils may be found in both disorders; however, when present, genetic mutations (KIT mutations and FIP1L1-PDGFRa rearrangement) are the diseases distinctive signature (58). Only a few patients carry both KITD816V and FIP1L1-PDGFRa rearrangement (59).…”

Section: Treatment Of Advanced Smmentioning

confidence: 99%

Targeted Treatment Options in Mastocytosis

2017

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Mastocytosis refers to a heterogeneous group of disorders resulting from the clonal proliferation of abnormal mast cells and their accumulation in the skin (cutaneous mastocytosis when only in the skin, CM) or in various organs (systemic mastocytosis, SM). This leads to a wide variety of clinical manifestations resulting from excessive mediator release in CM and benign forms of SM (indolent SM, ISM) and from tissue mast cell infiltration causing multiorgan dysfunction and failure in more aggressive subtypes (aggressive SM, ASM, or mast cell leukemia). In addition, SM may be associated with hematological neoplasms (AHN). While treatment of ISM primarily aims at symptom management with anti-mediator therapies, cytoreductive and targeted therapies are needed to control the expansion of neoplastic mast cells in advanced forms of SM, in order to improve overall survival. Mast cell accumulation results from a gain-of-function mutation (mostly the D816V mutation) within the KIT tyrosine kinase domain expressed by mast cells and additional genetic and epigenetic mutations may further determine the features of the disease (ASM and AHN). Consequently, tyrosine kinase inhibitors and targeted therapies directed against the oncogenic signaling machinery downstream of KIT are attractive therapeutic approaches. A better understanding of the relative contribution of these genetic and epigenetic events to the molecular pathogenesis of mastocytosis is of particular interest for the development of targeted therapies and therefore to better choose patient subgroups that would best benefit from a given therapeutic strategy.

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Gastrointestinal Manifestations of Hypereosinophilic Syndromes and Mast Cell Disorders: a Comprehensive Review

Nanagas

Kovalszki

2018

Clinic Rev Allerg Immunol

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Hypereosinophilic syndrome and mastocytosis are relatively rare proliferative diseases encountered in the general population. However, allergists frequently consider these disorders in the differential of patients presenting with gastrointestinal, pulmonary, cutaneous, and allergic symptoms. Gastrointestinal symptoms are some of the most frequent and/or debilitating aspects of both disease states and in many cases lead to poor quality of life and functional limitation for the patient. They are the third most common clinical manifestation in hypereosinophilic syndrome and have been found to be the most distressful aspect of the disorder in those with systemic mastocytosis. Both eosinophils and mast cells play integral parts in normal gut physiology, but when and how exactly their effector functionality translates into clinically significant disease remains unclear, and the available literature regarding their pathophysiology remains sparse. Eosinophils and mast cells even, in fact, may not necessarily function in isolation from each other but can participate in bidirectional crosstalk. Both are affected by similar mediators and can also influence one another in a paracrine fashion. Their interactions include both production of soluble mediators for specific eosinophil and mast cell receptors (for example, eosinophil recruitment and activation by mast cells releasing histamine and eotaxin) as well as direct physical contact. The mechanistic relationship between clonal forms of hypereosinophilia and systemic mastocytosis has also been explored. The nature of gastrointestinal symptomatology in the setting of both hypereosinophilic syndrome and mast cell disease is frequently manifold, heterogeneous, and the lack of better targeted therapy makes diagnosis and management challenging, especially when faced with a substantial differential. Currently, the management of these gastrointestinal symptoms relies on the treatment of the overall disease process. In hypereosinophilia patients, systemic corticosteroids are mainstay, although steroid-sparing agents such as hydroxyurea, IFN-α, methotrexate, cyclosporine, imatinib, and mepolizumab have been utilized with varying success. In mastocytosis patients, anti-mediator therapy with antihistamines and mast cell stabilization with cromolyn sodium can be considered treatments of choice, followed by other therapies yet to be thoroughly studied, including the role of the low-histamine diet, corticosteroids, and treatment of associated IBS symptoms. Given that both eosinophils and mast cells may have joint pathophysiologic roles, they have the potential to be a combined target for therapeutic intervention in disease states exhibiting eosinophil or mast cell involvement.

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Clonal eosinophil and mast cell diseases: different in the same way?

Cited by 4 publications

References 22 publications

Targeting the Interleukin-5 Pathway for Treatment of Eosinophilic Conditions Other than Asthma

Targeting the Interleukin-5 Pathway for Treatment of Eosinophilic Conditions Other than Asthma

Targeted Treatment Options in Mastocytosis

Gastrointestinal Manifestations of Hypereosinophilic Syndromes and Mast Cell Disorders: a Comprehensive Review

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