Management of Hypereosinophilic Syndromes

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Key points

  • Clinical manifestations in a patient with persistent hypereosinophilia may be related to underlying disease, organ damage and dysfunction provoked by eosinophils, or both. Pathologic assessment is key to establishing a direct role for eosinophils in signs and symptoms, thereby defining a hypereosinophilic syndrome.

  • Most patients presenting with hypereosinophilia have an underlying disease or condition driving polyclonal eosinophil expansion. Many of these conditions are treatable, and the causal

Assessment for the presence of eosinophil-mediated complications

Activated eosinophils are prone to infiltrate various tissues and release a wide array of mediators, inducing organ or system damage and dysfunction, as developed in detail by Weller and Akuthota elsewhere in this issue. According to the currently accepted definition, diagnosis of a HES can be proposed in the presence of documented persistent HE (ie, in routine practice: [1] blood eosinophil count greater than 1.5 × 109/L on at least 2 occasions, ideally at minimum 1 month apart, and/or [2]

Diagnostic evaluation of hypereosinophilia

The search for an underlying cause of HE, developed in detail by Ogbogu and Curtis elsewhere in this issue, is conducted simultaneously with assessment for eosinophil-mediated damage. In most patients, an underlying disease or condition (eg, drug allergy, parasitic infections, or cancer) is found after clinical examination and a limited series of relatively routine investigations. When these first-line investigations are negative, further testing is warranted. Diagnostic evaluation of HE is

Treatment of hypereosinophilic syndromes associated with a known underlying condition

In most situations where HE is reactive (secondary) and judged deleterious, systemic corticosteroid therapy represents the most effective and rapid means of reducing eosinophils. By contrast, primary HE that can accompany various myeloid neoplasms (including FIP1L1-PDGFRA–associated disease) is typically corticosteroid resistant, and treatment should target the underlying hematologic disorder or cytogenetic abnormality.

Specific management of lymphocytic variant hypereosinophilic syndrome

L-HES is an indolent and benign lymphoproliferative disorder that generally responds to oral corticosteroid therapy.42 However, patients often require second-line agents for corticosteroid-sparing purposes (see Table 2). Interferon-α,42 mepolizumab,43 and cyclosporin A42 are the most effective, and isolated responses to hydroxyurea and alemtuzumab have been reported. Modalities for administering these agents are discussed in the section on idiopathic HES.

It is essential that patients with L-HES

Treatment of symptomatic and unexplained hypereosinophilia

From a practical standpoint, when eosinophil-mediated organ damage or dysfunction occurs in the absence of a detectable cause or condition associated with HE (ie, idiopathic HES, including organ-restricted eosinophilic disorders), eosinophil-targeted treatment is justified to control symptoms, restore vital organ function, and prevent further deterioration with development of irreversible damage. Although controlling eosinophilia is the therapeutic end point, eosinophils need not necessarily be

Summary and future considerations

With the recognition more than 40 years ago that chronic HE could be deleterious and the subsequent identification of pathogenic mechanisms underlying HE in specific disease variants, management of patients has improved significantly, resulting in less morbidity and better survival. However, because most available therapeutic agents for HES deplete eosinophils through nonspecific mechanisms, long-term iatrogenic toxicity and treatment-refractory disease remain subjects of concern. This

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      Citation Excerpt :

      The goal of the therapy is to mitigate hypereosinophilia mediated organ damage. For patients with idiopathic HES, corticosteroids are the first-line therapy and are effective in producing rapid reductions in the eosinophil count [11], but the maintenance dose and the duration of therapy are different because of individual difference [12,13]. Corticosteroids can inhibit the production of the inflammatory mediators such as eosinophil cationic protein, major essential protein, eosinophil peroxidase and eosinophil-derived neurotoxin, which are thought to cause hypercoagulation [14].

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    Disclosure Statement: F. Roufosse has received consultancy fees from GlaxoSmithKline.

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