Clinical Profile and Treatment in Hypereosinophilic Syndrome Variants: A Pragmatic Review.

BACKGROUND: Hypereosinophilic syndrome (HES) is a group of rare hematologic disorders leading to eosinophil-driven tissue damage and dysfunction. Better understanding of HES variants may facilitate improved patient management. OBJECTIVE: To describe disease characteristics, treatment, and outcomes of patients with idiopathic (I-HES), myeloproliferative (M-HES), lymphocytic (L-HES), and chronic eosinophilic leukemia, not otherwise specified (CEL-NOS) among HES case reports and aggregate data where available. METHODS: Relevant articles published between January 1, 2000, and March 20, 2020, were retrieved via PubMed; those reporting secondary, associated/reactive, overlap/single-organ, or familial HES were excluded. RESULTS: Of 188 articles included, 171 contained data on 347 separate HES cases (152 I-HES, 121 M-HES, 62 L-HES, 12 CEL-NOS). Based on individual data, mean age at diagnosis was 43 to 48 years for patients with all HES variants. Males accounted for 90% to 91% of M-HES/CEL-NOS and 55% to 65% of I-HES/L-HES cases. Cardiac symptoms were frequently observed for all HES variants (13%-22% of patients). Respiratory symptoms (I-HES), splenomegaly (M-HES and CEL-NOS), and skin conditions (L-HES) were also frequently observed. Bone marrow, heart, lung, spleen, liver, skin, and lymph nodes were commonly involved. Most patients with I-HES, L-HES, and CEL-NOS received corticosteroids (65%-85%), whereas most with M-HES received imatinib (81%); those with CEL-NOS also received interferon alpha (42%). CONCLUSIONS: Collective analysis of HES case reports supports and extends current understanding of HES variants, highlighting differences in signs and symptoms, organ involvement, and treatment approaches. Improved characterization of HES variants may facilitate the development of novel treatments.

Gene Expression Comparison between Sézary Syndrome and Lymphocytic-Variant Hypereosinophilic Syndrome Refines Biomarkers for Sézary Syndrome.

Sézary syndrome (SS), an aggressive cutaneous T-cell lymphoma (CTCL) with poor prognosis, is characterized by the clinical hallmarks of circulating malignant T cells, erythroderma and lymphadenopathy. However, highly variable clinical skin manifestations and similarities with benign mimickers can lead to significant diagnostic delay and inappropriate therapy that can lead to disease progression and mortality. SS has been the focus of numerous transcriptomic-profiling studies to identify sensitive and specific diagnostic and prognostic biomarkers. Benign inflammatory disease controls (e.g., psoriasis, atopic dermatitis) have served to identify chronic inflammatory phenotypes in gene expression profiles, but provide limited insight into the lymphoproliferative and oncogenic roles of abnormal gene expression in SS. This perspective was recently clarified by a transcriptome meta-analysis comparing SS and lymphocytic-variant hypereosinophilic syndrome, a benign yet often clonal T-cell lymphoproliferation, with clinical features similar to SS. Here we review the rationale for selecting lymphocytic-variant hypereosinophilic syndrome (L-HES) as a disease control for SS, and discuss differentially expressed genes that may distinguish benign from malignant lymphoproliferative phenotypes, including additional context from prior gene expression studies to improve understanding of genes important in SS.

Hypereosinophilic Syndrome.

Hypereosinophilic syndrome consists of a group of disorders characterized by abnormal accumulation of eosinophils in the blood or peripheral tissues, independent of known secondary causes of eosinophilia such as parasitic infection. Clinical manifestations of the condition are highly variable, ranging from asymptomatic eosinophilia to severe tissue damage and end-organ failure. This entity has been recognized for decades, with early studies identifying distinct groups of patients with differing symptoms, exam findings, laboratory abnormalities, and prognosis. In the past, these patients were treated with non-targeted immunosuppressive agents, often with limited efficacy. More recently, advances in the knowledge of eosinophil biology and molecular diagnostics have allowed for more specific delineation of the many disease subgroups that characterize hypereosinophilic syndrome. Identification of these groups has led to a personalized management approach to the condition, with improved diagnostic techniques as well as stratification of patients into more effective treatment groups. This review will discuss the evolution of the definition of hypereosinophilic syndrome, outline current disease classifications, provide a guide for evaluation and monitoring, and discuss current and future therapeutic modalities.

Evaluation and Differential Diagnosis of Persistent Marked Eosinophilia.

Peripheral blood eosinophilia is commonly encountered in clinical practice. The causes of peripheral blood eosinophilia are varied, ranging from benign eosinophilia to malignancy. A careful history and physical examination along with directed clinical evaluation may help determine the cause. When uncontrolled, peripheral blood eosinophilia may result in end-organ damage and life-threatening complications. This article summarizes the differential diagnosis and evaluation of persistent marked eosinophilia.