title: Lenalidomide therapy in treatment-refractory cutaneous lupus erythematosus: histologic and circulating leukocyte profile and potential risk of a systemic lupus flare.
abstract: BACKGROUND
  Lenalidomide is a thalidomide analogue that may serve as an adjunctive therapy for treatment-refractory cutaneous lupus erythematosus (CLE).
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Dermatology Section, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.
authors.forename: Inbal
authors.initials: I
authors.lastname: Braunstein
authors.forename: Noah G
authors.initials: NG
authors.lastname: Goodman
authors.forename: Misha
authors.initials: M
authors.lastname: Rosenbach
authors.forename: Joyce
authors.initials: J
authors.lastname: Okawa
authors.forename: Asha
authors.initials: A
authors.lastname: Shah
authors.forename: Michael
authors.initials: M
authors.lastname: Krathen
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Kovarik
authors.forename: Eline
authors.initials: E
authors.lastname: Luning Prak
authors.forename: Victoria P
authors.initials: VP
authors.lastname: Werth
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D007962:Leukocytes; D008178:Lupus Erythematosus, Cutaneous / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D013792:Thalidomide; D000077269:Lenalidomide