Treatment of lymphocyte‐variant hypereosinophilic syndrome (L‐HES): what to consider after confirming the elusive diagnosis

Summary Lymphocyte‐variant hypereosinophilic syndrome (L‐HES) is a rare disease driven by immunophenotypically aberrant T cells producing eosinophilopoetic cytokines such as interleukin‐5 (IL‐5). Treatment is challenging because L‐HES is relatively steroid resistant and not amenable to tyrosine kinase inhibitors. We searched the literature for clinical trials and observational studies, including case reports, of patients treated for L‐HES. In all, 25 studies were selected; two were randomised controlled trials of IL‐5 blockade, which included some patients with L‐HES, and the rest were observational studies. Corticosteroids are often used as first‐line therapy, but patients with L‐HES have lower response rates than other types of HES. Treatments that reduce symptoms and steroid dependence in some patients include interferon‐alpha (IFN‐α), anti‐IL‐5 monoclonal antibodies, cyclosporine and mycophenolate. These drugs target T‐cell activation and proliferation, or IL‐5 directly. Although effective, IFN‐α and cyclosporine were commonly reported to cause side‐effects resulting in discontinuation. Alemtuzumab can induce remissions, but these are generally short lived. The anti‐IL‐5 monoclonal antibodies mepolizumab and benralizumab are effective and well tolerated, but with a high rate of relapse once withdrawn. Hydroxyurea, methotrexate, imatinib were unsuccessful in most patients studied. More prospective clinical trials are needed for patients with L‐HES.