Refractory hemophagocytic syndrome in systemic lupus erythematosus successfully treated with intermittent intravenous cyclophosphamide: three case reports and literature review

We experienced three patients with refractory or severe hemophagocytic syndrome associated with the activity of systemic lupus erythematosus, so-called acute lupus hemophagocytic syndrome (ALHS). All patients were successfully treated with intermittent intravenous injections of cyclophosphamide (IVCY). In each patient, hemophagocytosis was found during bone marrow examination, and infectious causes of hemophagocytic syndrome were carefully excluded. Patients 1 and 2 were refractory to combination therapy with a high-dose corticosteroid and rituximab or cyclosporine and were successfully treated with additive IVCY. Patient 3 had very severe ALHS that developed after cardiac surgery but was successfully treated with a high-dose corticosteroid and IVCY. We conducted a literature review of adult ALHS and analyzed 54 cases reported from 2006 to 2013. Although the clinical and laboratory features were diverse, fever, bicytopenia or pancytopenia, and hyperferritinemia were almost universal. Including our 3 patients, a total of 16 have reportedly been treated with IVCY-containing regimens, and ALHS was successfully controlled in most of them without switching or adding other therapies. We suggest that combination therapy with IVCY and corticosteroids may be useful to treat severe or refractory ALHS.