We previously have reported success in treating patients with moderate aplastic anemia with daclizumab, a humanized monoclonal antibody that recognizes the interleukin-2 receptor (

Blood.
2003
;
102
(10):
3584
–6
). Since our first report we have treated eighty-eight patients with moderate aplastic anemia, pure red cell aplasia and relapsed severe aplastic anemia with 1 mg/kg of monoclonal antibody every 2 weeks for 3 months. Although this drug has been used extensively in the management of solid organ rejection, erythroderma has not been reported. In our study, five patients developed a severe generalized erythema in a period of 20 to 70 days following the last dose of treatment. The cutaneous eruptions were characterized by severe pruritis and intense erythematous inflammation with spongiotic papules and plaques. Pathologic evaluation was possible for four of five patients and described focal spongiosis, dermal lymphocytic infiltration including some eosinophils, and no evidence of infection. All patients were negative for anti-nuclear antibody and had no arthritis, fever, or other systemic signs. HLA types were available on 83 of the 88 patients. HLA DR13 was more common in the patients that developed a rash; 80% versus 18% in those who did not develop rash (p = .0071, Fisher’s Exact Test). The rash was associated with a two to ten fold increase in the proportion of CD25-positive CD4 cells compared to pre-drug levels (p<0.05). All patients required treatment with oral corticosteroids for periods of 2–6 weeks. Three patients who had partial or minimal responses to daclizumab elected to undergo a second course. The three patients who had a mild rash after the first course of treatment developed a more severe eruption with subsequent administration of the drug; rashes were delayed after each therapeutic administration of daclizumab. Two additional patients developed other autoimmune symptoms including inflammatory arthritis about three months following daclizumab administration. The absence of autoimmune complications following use of daclizumab in solid organ or allogeneic stem cell transplant recipients may be related to additional immunosuppression frequently administered to these patients. Our working hypothesis is that daclizumab associated rash is caused by an immune phenomenon. This is supported by the findings that CD4+CD25+ (effector) T cells are expanded at the time of the rash, the presence of a lymphocytic dermal infiltrate, and the relative preponderance of HLA-DR13 in the affected group. It is possible that treatment with daclizumab (an anti-CD25 antibody) results in a relative depletion of CD4+CD25+ regulatory T cells thereby permitting expansion of CD4+CD25+ effector T cells.

Topics:
antigens, cd25, aplastic anemia, cd4 positive t-lymphocytes, daclizumab, exfoliative dermatitis, pure red-cell aplasia, exanthema, human leukocyte antigens, arthritis, monoclonal antibodies

Corresponding author

2005, The American Society of Hematology
2005
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