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Journal of the American Academy of Dermatology
Volume 66, n° 4
pages 571-582 (avril 2012)
Doi : 10.1016/j.jaad.2011.01.015
accepted : 19 January 2011
Original Articles

Lenalidomide therapy in treatment-refractory cutaneous lupus erythematosus: Histologic and circulating leukocyte profile and potential risk of a systemic lupus flare

Inbal Braunstein, MD a, b, Noah G. Goodman, MPH c, Misha Rosenbach, MD b, Joyce Okawa, RN a, b, Asha Shah, MD a, b, Michael Krathen, MD a, b, Carrie L. Kovarik, MD a, b, Eline Luning Prak, MD, PhD c, Victoria P. Werth, MD a, b,
a Dermatology Section, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania 
b Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania 
c Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 

Reprint requests: Victoria P. Werth, MD, Department of Dermatology, Hospital of the University of Pennsylvania, PCAM Suite 1-330S, 3400 Civic Center Blvd, Philadelphia, PA 19104.

Lenalidomide is a thalidomide analogue that may serve as an adjunctive therapy for treatment-refractory cutaneous lupus erythematosus (CLE).


We evaluate the use of lenalidomide in CLE and describe the skin and circulating leukocyte profile of treatment-refractory patients before and after treatment.


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.


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.


Our results are limited by small sample size and the measurement of rare populations of circulating cell subsets.


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.

The full text of this article is available in PDF format.

Key words : cutaneous lupus erythematosus, lenalidomide, lupus erythematosus, subacute cutaneous, lupus erythematosus, discoid, lupus erythematosus, tumid

Abbreviations used : CLA, CLASI, CLE, DLE, GAG, IFN, IHC, pDCs, SCLE, SLE, TLE, Tregs

 Supported in part by the Alliance for Lupus Research, a Merit Review Grant from the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, and by the National Institutes of Health (K24-AR 02207) to Dr Werth. Celgene Corporation provided the drug free of charge.
 Conflicts of interest: None declared.

© 2011  American Academy of Dermatology, Inc.@@#104156@@
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