Severe Aplastic Anemia Associated With Eosinophilic Fasciitis

Abstract

Diffuse eosinophilic fasciitis (Shulman disease) is a rare sclerodermiform syndrome that, in most cases, resolves spontaneously or after corticosteroid therapy. It has been associated with hematologic disorders, such as aplastic anemia. The clinical features and long-term outcomes of patients with eosinophilic fasciitis and associated aplastic anemia have been poorly described. We report the cases of 4 patients with eosinophilic fasciitis and associated severe aplastic anemia. For 3 of these patients, aplastic anemia was refractory to conventional immunosuppressive therapy with antithymocyte globulin and cyclosporine. One of the patients received rituximab as a second-line therapy with significant efficacy for both the skin and hematologic symptoms. To our knowledge, this report is the first to describe rituximab used to treat eosinophilic fasciitis with associated aplastic anemia.In a literature review, we identified 19 additional cases of eosinophilic fasciitis and aplastic anemia. Compared to patients with isolated eosinophilic fasciitis, patients with eosinophilic fasciitis and associated aplastic anemia were more likely to be men (70%) and older (mean age, 56 yr; range, 18–71 yr). Corticosteroid-containing regimens improved skin symptoms in 5 (42%) of 12 cases but were ineffective in the treatment of associated aplastic anemia in all but 1 case. Aplastic anemia was profound in 13 cases (57%) and was the cause of death in 8 cases (35%). Only 5 patients (22%) achieved long-term remission (allogeneic hematopoietic stem cell transplantation: n = 2; cyclosporine-containing regimen: n = 2; high-dose corticosteroid-based regimen: n = 1).

Guideline for the investigation and management of eosinophilia

“…There are no universally accepted diagnostic criteria but, in a recent review (Pinal-Fernandez et al, 2014), peripheral blood eosinophilia formed one of four minor criteria for the diagnosis. There is an association with aplastic anaemia (de Masson et al, 2013).…”

Rituximab as a therapeutic consideration for refractory eosinophilic fasciitis

“…In the patient who had EF in association with aplastic anemia, IV rituximab was delivered at a dose of 375 mg/m 2 per week for 4 weeks and resulted in subsequent cytopenic regression, followed by relapse of disease. A second course of four rituximab infusions delivered at the same dose and infusion schedule in this patient resulted in another cytopenic regression as well as complete resolution of skin abnormalities . Rituximab failure has been reported in a patient who received two 1 g IV infusions of rituximab for treatment‐refractory EF.…”

“…As a chimeric monoclonal antibody, rituximab targets the CD‐20 antigen present on the cell surface of mature B‐lymphocytes . Using rituximab, successful outcomes have been observed in a patient with EF and hypergammaglobulinemia and in a patient with EF associated with aplastic anemia . In the patient with EF and hypergammaglobulinemia, skin lesions resolved, peripheral eosinophilia normalized, and immunoglobulin G (IgG) levels decreased with a 375 mg/m 2 IV rituximab infusion delivered for four consecutive weeks or two doses of 1g of IV rituximab given 2 weeks apart.…”

Diagnostic criteria, severity classification and guidelines of eosinophilic fasciitis

“…Explanation: Multiple reports have evaluated the complications that are associated with eosinophilic fasciitis, including: autoimmune diseases such as localized scleroderma (30%), autoimmune thyroiditis, systemic lupus erythematosus, and rheumatoid arthritis; blood diseases such as aplastic anemia, thrombocytopenic purpura, autoimmune hemolytic anemia, malignant lymphoma, leukemia, multiple myeloma and myelodysplastic syndrome; peripheral neuropathy; and visceral malignant tumors including prostate cancer and breast cancer . Muscle pain and weakness can sometimes occur due to perimyositis with the spread of fasciitis, but myositis is not normally seen …”