BACKGROUND: Lenalidomide is a thalidomide analogue that may serve as an adjunctive therapy for treatment-refractory cutaneous lupus erythematosus (CLE). OBJECTIVES: We evaluate the use of lenalidomide in CLE and describe the skin and circulating leukocyte profile of treatment-refractory patients before and after treatment. METHODS: Five subjects were treated with lenalidomide in an unblinded open-label study. Immunohistochemistry of skin was performed for T-cell markers, glycosaminoglycans, and CXCL10, an interferon-inducible chemokine, before and after treatment. Immunophenotyping and measurement of interferon-inducible genes from peripheral blood mononuclear cells was also performed before and after treatment. RESULTS: Four subjects demonstrated clinical improvement of their skin, however one of these responders subsequently developed symptoms of systemic lupus erythematosus. Small changes in rare circulating leukocyte subsets, plasmacytoid dendritic cells, and regulatory T cells were observed with treatment and may correlate with clinical response. Treatment was associated with increased circulating HLA-DR expression and decreased markers of interferon-mediated pathways, regardless of clinical response. LIMITATIONS: Our results are limited by small sample size and the measurement of rare populations of circulating cell subsets. CONCLUSIONS: Lenalidomide may have usefulness as therapy for severe, treatment-refractory CLE. However, our preliminary data suggest that lenalidomide may activate T cells and trigger systemic disease in some patients with CLE. We also saw a different histologic and circulating leukocyte phenotype in the nonresponding subject. Further characterization of the skin and circulating leukocyte profile of treatment-refractory patients will improve our understanding of CLE.
BACKGROUND:Lenalidomide is a thalidomide analogue that may serve as an adjunctive therapy for treatment-refractory cutaneous lupus erythematosus (CLE). OBJECTIVES: We evaluate the use of lenalidomide in CLE and describe the skin and circulating leukocyte profile of treatment-refractory patients before and after treatment. METHODS: Five subjects were treated with lenalidomide in an unblinded open-label study. Immunohistochemistry of skin was performed for T-cell markers, glycosaminoglycans, and CXCL10, an interferon-inducible chemokine, before and after treatment. Immunophenotyping and measurement of interferon-inducible genes from peripheral blood mononuclear cells was also performed before and after treatment. RESULTS: Four subjects demonstrated clinical improvement of their skin, however one of these responders subsequently developed symptoms of systemic lupus erythematosus. Small changes in rare circulating leukocyte subsets, plasmacytoid dendritic cells, and regulatory T cells were observed with treatment and may correlate with clinical response. Treatment was associated with increased circulating HLA-DR expression and decreased markers of interferon-mediated pathways, regardless of clinical response. LIMITATIONS: Our results are limited by small sample size and the measurement of rare populations of circulating cell subsets. CONCLUSIONS:Lenalidomide may have usefulness as therapy for severe, treatment-refractory CLE. However, our preliminary data suggest that lenalidomide may activate T cells and trigger systemic disease in some patients with CLE. We also saw a different histologic and circulating leukocyte phenotype in the nonresponding subject. Further characterization of the skin and circulating leukocyte profile of treatment-refractory patients will improve our understanding of CLE.
Authors: Sven Klunker; Axel Trautmann; Mübeccel Akdis; Johan Verhagen; Peter Schmid-Grendelmeier; Kurt Blaser; Cezmi A Akdis Journal: J Immunol Date: 2003-07-15 Impact factor: 5.422
Authors: Macrene R Alexiades-Armenakas; Marisa Baldassano; Benji Bince; Victoria Werth; Jean-Claude Bystryn; Hideko Kamino; Nicholas A Soter; Andrew G Franks Journal: Arthritis Rheum Date: 2003-08-15
Authors: Tiina M Järvinen; Anna Hellquist; Sari Koskenmies; Elisabet Einarsdottir; Lotta L E Koskinen; Leila Jeskanen; Linda Berglind; Jaana Panelius; Taina Hasan; Annamari Ranki; Juha Kere; Ulpu Saarialho-Kere Journal: Exp Dermatol Date: 2009-09-16 Impact factor: 3.960
Authors: Christian Termeer; Frauke Benedix; Jonathon Sleeman; Christina Fieber; Ursula Voith; Thomas Ahrens; Kensuke Miyake; Marina Freudenberg; Christopher Galanos; Jan Christoph Simon Journal: J Exp Med Date: 2002-01-07 Impact factor: 14.307