American Journal of Clinical Dermatology

, Volume 17, Issue 2, pp 135–146 | Cite as

Cutaneous Lupus Erythematosus: An Update on Pathogenesis, Diagnosis and Treatment

  • Emily Z. Hejazi
  • Victoria P. Werth
Review Article


Cutaneous lupus erythematosus (CLE) includes a broad range of dermatologic manifestations, which may or may not be associated with systemic disease. Recent studies in this area continue to shape our understanding of this disease and treatment options. Epidemiologic studies have found an incidence of CLE of 4.30 per 100,000, which approaches similar analysis for systemic lupus erythematosus (SLE). Although there have been extensive efforts to define SLE, the classification of CLE and its subgroups remains a challenge. Currently, diagnosis relies on clinical and laboratory findings as well as skin histology. The Cutaneous Lupus Area and Severity Index™ (CLASI™) is a validated measure of disease activity and damage. CLE pathogenesis is multifactorial and includes genetic contributions as well as effects of ultraviolet (UV) light. Immune dysregulation and aberrant cell signaling pathways through cytokine cascades are also implicated. Patient education and avoidance of triggers are key to disease prevention. Antimalarials and topical steroids continue to be the standard of care; however, immunosuppressants, thalidomide analogs and monoclonal antibodies are possible systemic therapies for the treatment of recalcitrant disease.


Systemic Lupus Erythematosus Human Leukocyte Antigen Systemic Lupus Erythematosus Patient Thalidomide Lenalidomide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This project is supported by the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development.

We acknowledge Majid Zeidi, MD, for providing the H & E figure.

Compliance with Ethical Standards


No funding was received in the preparation of this review.

Conflict of interest

VPW has received grants from Celgene and Janssen; consulting fees and/or honoraria from Celgene, Janssen, Medimmune, Pfizer, Biogen and Sanofi-Aventis; stock in UV Therapeutics; and royalties from licensing of the CLASI™ from the University of Pennsylvania. EZH has no conflicts of interest to declare.


  1. 1.
    Gilliam JN, Sontheimer RD. Distinctive cutaneous subsets in the spectrum of lupus erythematosus. J Am Acad Dermatol. 1981;4(4):471–5.CrossRefPubMedGoogle Scholar
  2. 2.
    Pons-Estel GJ, Alarcon GS, Scofield L, Reinlib L, Cooper GS. Understanding the epidemiology and progression of systemic lupus erythematosus. Semin Arthritis Rheum. 2010;39(4):257–68. doi: 10.1016/j.semarthrit.2008.10.007.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Petri M. Epidemiology of systemic lupus erythematosus. Best Pract Res Clin Rheumatol. 2002;16(5):847–58.CrossRefPubMedGoogle Scholar
  4. 4.
    Durosaro O, Davis MD, Reed KB, Rohlinger AL. Incidence of cutaneous lupus erythematosus, 1965–2005: a population-based study. Arch Dermatol. 2009;145(3):249–53. doi: 10.1001/archdermatol.2009.21.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Gronhagen CM, Fored CM, Granath F, Nyberg F. Cutaneous lupus erythematosus and the association with systemic lupus erythematosus: a population-based cohort of 1088 patients in Sweden. Br J Dermatol. 2011;164(6):1335–41. doi: 10.1111/j.1365-2133.2011.10272.x.CrossRefPubMedGoogle Scholar
  6. 6.
    Jarukitsopa S, Hoganson DD, Crowson CS, Sokumbi O, Davis MD, Michet CJ Jr, et al. Epidemiology of systemic lupus erythematosus and cutaneous lupus erythematosus in a predominantly white population in the United States. Arthritis Care Res (Hoboken). 2015;67(6):817–28. doi: 10.1002/acr.22502.CrossRefPubMedGoogle Scholar
  7. 7.
    McCarty DJ, Manzi S, Medsger TA Jr, Ramsey-Goldman R, LaPorte RE, Kwoh CK. Incidence of systemic lupus erythematosus. Race and gender differences. Arthritis Rheum. 1995;38(9):1260–70.CrossRefPubMedGoogle Scholar
  8. 8.
    Chiu YM, Lai CH. Nationwide population-based epidemiologic study of systemic lupus erythematosus in Taiwan. Lupus. 2010;19(10):1250–5. doi: 10.1177/0961203310373780.CrossRefPubMedGoogle Scholar
  9. 9.
    Mok CC, To CH, Ho LY, Yu KL. Incidence and mortality of systemic lupus erythematosus in a southern Chinese population, 2000–2006. J Rheumatol. 2008;35(10):1978–82.PubMedGoogle Scholar
  10. 10.
    Albrecht J, Berlin JA, Braverman IM, Callen JP, Connolly MK, Costner MI, et al. Dermatology position paper on the revision of the 1982 ACR criteria for systemic lupus erythematosus. Lupus. 2004;13(11):839–49.CrossRefPubMedGoogle Scholar
  11. 11.
    Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677–86. doi: 10.1002/art.34473.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Schultz HY, Dutz JP, Furukawa F, Goodfield MJ, Kuhn A, Lee LA, et al. From pathogenesis, epidemiology, and genetics to definitions, diagnosis, and treatments of cutaneous lupus erythematosus and dermatomyositis: a report from the 3rd International Conference on Cutaneous Lupus Erythematosus (ICCLE) 2013. J Investig Dermatol. 2015;135(1):7–12. doi: 10.1038/jid.2014.316.
  13. 13.
    Merola JF, Nyberg F, Furukawa F, Goodfield MJ, Hasegawa M, Marinovic B, et al. Redefining cutaneous lupus erythematosus: a proposed international consensus approach and results of a preliminary questionnaire. Lupus Sci Med. 2015;2(1):e000085. doi: 10.1136/lupus-2015-000085.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Walling HW, Sontheimer RD. Cutaneous lupus erythematosus: issues in diagnosis and treatment. Am J Clin Dermatol. 2009;10(6):365–81. doi: 10.2165/11310780-000000000-00000.CrossRefPubMedGoogle Scholar
  15. 15.
    Tebbe B, Mansmann U, Wollina U, Auer-Grumbach P, Licht-Mbalyohere A, Arensmeier M, et al. Markers in cutaneous lupus erythematosus indicating systemic involvement. A multicenter study on 296 patients. Acta Derm Venereol. 1997;77(4):305–8.PubMedGoogle Scholar
  16. 16.
    Rothfield N, Sontheimer RD, Bernstein M. Lupus erythematosus: systemic and cutaneous manifestations. Clin Dermatol. 2006;24(5):348–62. doi: 10.1016/j.clindermatol.2006.07.014.CrossRefPubMedGoogle Scholar
  17. 17.
    Fonseca E, Alvarez R, Gonzalez MR, Pascual D. Prevalence of anticardiolipin antibodies in subacute cutaneous lupus erythematosus. Lupus. 1992;1(4):265–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Garcia-Martin P, Garcia-Garcia C, Fraga J, Garcia-Diez A. Prevalence of antiphospholipid antibodies in patients with subacute and chronic cutaneous lupus erythematosus. Actas Dermosifiliogr. 2013;104(3):232–8. doi: 10.1016/ Scholar
  19. 19.
    Albrecht J, Taylor L, Berlin JA, Dulay S, Ang G, Fakharzadeh S, et al. The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index): an outcome instrument for cutaneous lupus erythematosus. J Investig Dermatol. 2005;125(5):889–94. doi: 10.1111/j.0022-202X.2005.23889.x.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Krathen MS, Dunham J, Gaines E, Junkins-Hopkins J, Kim E, Kolasinski SL, et al. The Cutaneous Lupus Erythematosus Disease Activity and Severity Index: expansion for rheumatology and dermatology. Arthritis Rheum. 2008;59(3):338–44. doi: 10.1002/art.23319.CrossRefPubMedGoogle Scholar
  21. 21.
    Klein R, Moghadam-Kia S, LoMonico J, Okawa J, Coley C, Taylor L, et al. Development of the CLASI as a tool to measure disease severity and responsiveness to therapy in cutaneous lupus erythematosus. Arch Dermatol. 2011;147(2):203–8. doi: 10.1001/archdermatol.2010.435.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Braunstein I, Klein R, Okawa J, Werth VP. The interferon-regulated gene signature is elevated in subacute cutaneous lupus erythematosus and discoid lupus erythematosus and correlates with the Cutaneous Lupus Area And Severity Index score. Br J Dermatol. 2012;166(5):971–5. doi: 10.1111/j.1365-2133.2012.10825.x.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Nabatian AS, Bashir MM, Wysocka M, Sharma M, Werth VP. Tumor necrosis factor alpha release in peripheral blood mononuclear cells of cutaneous lupus and dermatomyositis patients. Arthritis Res Ther. 2012;14(1):R1. doi: 10.1186/ar3549.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Vasquez R, Wang D, Tran QP, Adams-Huet B, Chren MM, Costner MI, et al. A multicentre, cross-sectional study on quality of life in patients with cutaneous lupus erythematosus. Br J Dermatol. 2013;168(1):145–53. doi: 10.1111/j.1365-2133.2012.11106.x.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Jolly M, Kazmi N, Mikolaitis RA, Sequeira W, Block JA. Validation of the Cutaneous Lupus Disease Area and Severity Index (CLASI) using physician- and patient-assessed health outcome measures. J Am Acad Dermatol. 2013;68(4):618–23. doi: 10.1016/j.jaad.2012.08.035.CrossRefPubMedGoogle Scholar
  26. 26.
    Salphale P, Danda D, Chandrashekar L, Peter D, Jayaseeli N, George R. The study of Cutaneous Lupus Erythematosus Disease Area and Severity Index in Indian patients with systemic lupus erythematosus. Lupus. 2011;20(14):1510–7. doi: 10.1177/0961203311418789.CrossRefPubMedGoogle Scholar
  27. 27.
    Ishiguro M, Hashizume H, Ikeda T, Yamamoto Y, Furukawa F. Evaluation of the quality of life of lupus erythematosus patients with cutaneous lesions in Japan. Lupus. 2014;23(1):93–101. doi: 10.1177/0961203313509293.CrossRefPubMedGoogle Scholar
  28. 28.
    Kuhn A, Meuth AM, Bein D, Amler S, Beissert S, Bohm M, et al. Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI): a modified outcome instrument for cutaneous lupus erythematosus. Br J Dermatol. 2010;163(1):83–92. doi: 10.1111/j.1365-2133.2010.09799.x.PubMedGoogle Scholar
  29. 29.
    Wahie S, McColl E, Reynolds NJ, Meggitt SJ. Measuring disease activity and damage in cutaneous lupus erythematosus. Br J Dermatol. 2011;164(1):221–2. doi: 10.1111/j.1365-2133.2010.10072.x (author reply 2–4).CrossRefPubMedGoogle Scholar
  30. 30.
    Yu C, Chang C, Zhang J. Immunologic and genetic considerations of cutaneous lupus erythematosus: a comprehensive review. J Autoimmun. 2013;41:34–45. doi: 10.1016/j.jaut.2013.01.007.CrossRefPubMedGoogle Scholar
  31. 31.
    Osmola A, Namysl J, Jagodzinski PP, Prokop J. Genetic background of cutaneous forms of lupus erythematosus: update on current evidence. J Appl Genet. 2004;45(1):77–86.PubMedGoogle Scholar
  32. 32.
    Fischer GF, Pickl WF, Fae I, Anegg B, Milota S, Volc-Platzer B. Association between chronic cutaneous lupus erythematosus and HLA class II alleles. Hum Immunol. 1994;41(4):280–4.CrossRefPubMedGoogle Scholar
  33. 33.
    Jarvinen TM, Hellquist A, Koskenmies S, Einarsdottir E, Koskinen LL, Jeskanen L, et al. Tyrosine kinase 2 and interferon regulatory factor 5 polymorphisms are associated with discoid and subacute cutaneous lupus erythematosus. Exp Dermatol. 2010;19(2):123–31. doi: 10.1111/j.1600-0625.2009.00982.x.CrossRefPubMedGoogle Scholar
  34. 34.
    Lee-Kirsch MA, Gong M, Schulz H, Ruschendorf F, Stein A, Pfeiffer C, et al. Familial chilblain lupus, a monogenic form of cutaneous lupus erythematosus, maps to chromosome 3p. Am J Hum Genet. 2006;79(4):731–7. doi: 10.1086/507848.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Lee-Kirsch MA, Chowdhury D, Harvey S, Gong M, Senenko L, Engel K, et al. A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus. J Mol Med. 2007;85(5):531–7. doi: 10.1007/s00109-007-0199-9.CrossRefPubMedGoogle Scholar
  36. 36.
    Jarvinen TM, Hellquist A, Koskenmies S, Einarsdottir E, Panelius J, Hasan T et al. Polymorphisms of the ITGAM gene confer higher risk of discoid cutaneous than of systemic lupus erythematosus. PLoS One. 2010;5(12):e14212. doi: 10.1371/journal.pone.0014212.CrossRefGoogle Scholar
  37. 37.
    Lin JH, Dutz JP, Sontheimer RD, Werth VP. Pathophysiology of cutaneous lupus erythematosus. Clin Rev Allergy Immunol. 2007;33(1–2):85–106. doi: 10.1007/s12016-007-0031-x.CrossRefPubMedGoogle Scholar
  38. 38.
    Kuhn A, Herrmann M, Kleber S, Beckmann-Welle M, Fehsel K, Martin-Villalba A, et al. Accumulation of apoptotic cells in the epidermis of patients with cutaneous lupus erythematosus after ultraviolet irradiation. Arthritis Rheum. 2006;54(3):939–50. doi: 10.1002/art.21658.CrossRefPubMedGoogle Scholar
  39. 39.
    Reefman E, de Jong MC, Kuiper H, Jonkman MF, Limburg PC, Kallenberg CG, et al. Is disturbed clearance of apoptotic keratinocytes responsible for UVB-induced inflammatory skin lesions in systemic lupus erythematosus? Arthritis Res Ther. 2006;8(6):R156. doi: 10.1186/ar2051.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Bashir MM, Sharma MR, Werth VP. UVB and proinflammatory cytokines synergistically activate TNF-alpha production in keratinocytes through enhanced gene transcription. J Invest Dermatol. 2009;129(4):994–1001. doi: 10.1038/jid.2008.332.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Kuhn A, Wenzel J, Weyd H. Photosensitivity, apoptosis, and cytokines in the pathogenesis of lupus erythematosus: a critical review. Clin Rev Allergy Immunol. 2014;47(2):148–62. doi: 10.1007/s12016-013-8403-x.CrossRefPubMedGoogle Scholar
  42. 42.
    Kuhn A, Wozniacka A, Szepietowski JC, Glaser R, Lehmann P, Haust M, et al. Photoprovocation in cutaneous lupus erythematosus: a multicenter study evaluating a standardized protocol. J Investig Dermatol. 2011;131(8):1622–30. doi: 10.1038/jid.2011.101.CrossRefPubMedGoogle Scholar
  43. 43.
    Ruland V, Haust M, Stilling RM, Metze D, Amler S, Ruzicka T, et al. Updated analysis of standardized photoprovocation in patients with cutaneous lupus erythematosus. Arthritis Care Res (Hoboken). 2013;65(5):767–76. doi: 10.1002/acr.21867.CrossRefPubMedGoogle Scholar
  44. 44.
    Calderon C, Zucht HD, Kuhn A, Wozniacka A, Szepietowski JC, Nyberg F, et al. A multicenter photoprovocation study to identify potential biomarkers by global peptide profiling in cutaneous lupus erythematosus. Lupus. 2015;. doi: 10.1177/0961203315596077.Google Scholar
  45. 45.
    Biazar C, Sigges J, Patsinakidis N, Ruland V, Amler S, Bonsmann G, et al. Cutaneous lupus erythematosus: first multicenter database analysis of 1002 patients from the European Society of Cutaneous Lupus Erythematosus (EUSCLE). Autoimmun Rev. 2013;12(3):444–54. doi: 10.1016/j.autrev.2012.08.019.CrossRefPubMedGoogle Scholar
  46. 46.
    Li PH, Wong WH, Lee TL, Lau CS, Chan TM, Leung AM, et al. Relationship between autoantibody clustering and clinical subsets in SLE: cluster and association analyses in Hong Kong Chinese. Rheumatology (Oxford). 2013;52(2):337–45. doi: 10.1093/rheumatology/kes261.CrossRefPubMedGoogle Scholar
  47. 47.
    Fredi M, Cavazzana I, Quinzanini M, Taraborelli M, Cartella S, Tincani A, et al. Rare autoantibodies to cellular antigens in systemic lupus erythematosus. Lupus. 2014;23(7):672–7. doi: 10.1177/0961203314524850.CrossRefPubMedGoogle Scholar
  48. 48.
    Zahn S, Rehkamper C, Ferring-Schmitt S, Bieber T, Tuting T, Wenzel J. Interferon-alpha stimulates TRAIL expression in human keratinocytes and peripheral blood mononuclear cells: implications for the pathogenesis of cutaneous lupus erythematosus. Br J Dermatol. 2011;165(5):1118–23. doi: 10.1111/j.1365-2133.2011.10479.x.CrossRefPubMedGoogle Scholar
  49. 49.
    Toberer F, Sykora J, Gottel D, Hartschuh W, Werchau S, Enk A, et al. Apoptotic signal molecules in skin biopsies of cutaneous lupus erythematosus: analysis using tissue microarray. Exp Dermatol. 2013;22(10):656–9. doi: 10.1111/exd.12216.CrossRefPubMedGoogle Scholar
  50. 50.
    Kanda N, Shimizu T, Tada Y, Watanabe S. IL-18 enhances IFN-gamma-induced production of CXCL9, CXCL10, and CXCL11 in human keratinocytes. Eur J Immunol. 2007;37(2):338–50. doi: 10.1002/eji.200636420.CrossRefPubMedGoogle Scholar
  51. 51.
    Wang D, Drenker M, Eiz-Vesper B, Werfel T, Wittmann M. Evidence for a pathogenetic role of interleukin-18 in cutaneous lupus erythematosus. Arthritis Rheum. 2008;58(10):3205–15. doi: 10.1002/art.23868.CrossRefPubMedGoogle Scholar
  52. 52.
    Lin YJ, Wan L, Lee CC, Huang CM, Tsai Y, Tsai CH, et al. Disease association of the interleukin-18 promoter polymorphisms in Taiwan Chinese systemic lupus erythematosus patients. Genes Immun. 2007;8(4):302–7. doi: 10.1038/sj.gene.6364387.CrossRefPubMedGoogle Scholar
  53. 53.
    Wenzel J, Uerlich M, Worrenkamper E, Freutel S, Bieber T, Tuting T. Scarring skin lesions of discoid lupus erythematosus are characterized by high numbers of skin-homing cytotoxic lymphocytes associated with strong expression of the type I interferon-induced protein MxA. Br J Dermatol. 2005;153(5):1011–5. doi: 10.1111/j.1365-2133.2005.06784.x.CrossRefPubMedGoogle Scholar
  54. 54.
    Wenzel J, Worenkamper E, Freutel S, Henze S, Haller O, Bieber T, et al. Enhanced type I interferon signalling promotes Th1-biased inflammation in cutaneous lupus erythematosus. J Pathol. 2005;205(4):435–42. doi: 10.1002/path.1721.CrossRefPubMedGoogle Scholar
  55. 55.
    Fett N, Werth VP. Systemic lupus erythematosus treatment: a guide to photoprotection. CML Rheumatol. 2010;29(2):33–41.Google Scholar
  56. 56.
    Kuhn A, Gensch K, Haust M, Meuth AM, Boyer F, Dupuy P, et al. Photoprotective effects of a broad-spectrum sunscreen in ultraviolet-induced cutaneous lupus erythematosus: a randomized, vehicle-controlled, double-blind study. J Am Acad Dermatol. 2011;64(1):37–48. doi: 10.1016/j.jaad.2009.12.053.CrossRefPubMedGoogle Scholar
  57. 57.
    Klein RS, Werth VP, Dowdy JC, Sayre RM. Analysis of compact fluorescent lights for use by patients with photosensitive conditions. Photochem Photobiol. 2009;85(4):1004–10. doi: 10.1111/j.1751-1097.2009.00540.x.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Klein RS, Sayre RM, Dowdy JC, Werth VP. The risk of ultraviolet radiation exposure from indoor lamps in lupus erythematosus. Autoimmun Rev. 2009;8(4):320–4. doi: 10.1016/j.autrev.2008.10.003.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Fenton L, Dawe R, Ibbotson S, Ferguson J, Silburn S, Moseley H. Impact assessment of energy-efficient lighting in patients with lupus erythematosus: a pilot study. Br J Dermatol. 2014;170(3):694–8. doi: 10.1111/bjd.12719.CrossRefPubMedGoogle Scholar
  60. 60.
    Heine G, Lahl A, Muller C, Worm M. Vitamin D deficiency in patients with cutaneous lupus erythematosus is prevalent throughout the year. Br J Dermatol. 2010;163(4):863–5. doi: 10.1111/j.1365-2133.2010.09948.x.CrossRefPubMedGoogle Scholar
  61. 61.
    Cutillas-Marco E, Marquina-Vila A, Grant WB, Vilata-Corell JJ, Morales-Suarez-Varela MM. Vitamin D and cutaneous lupus erythematosus: effect of vitamin D replacement on disease severity. Lupus. 2014;23(7):615–23. doi: 10.1177/0961203314522338.CrossRefPubMedGoogle Scholar
  62. 62.
    Schoindre Y, Jallouli M, Tanguy ML, Ghillani P, Galicier L, Aumaitre O, et al. Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up. Lupus Sci Med. 2014;1(1):e000027. doi: 10.1136/lupus-2014-000027.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Terrier B, Derian N, Schoindre Y, Chaara W, Geri G, Zahr N, et al. Restoration of regulatory and effector T cell balance and B cell homeostasis in systemic lupus erythematosus patients through vitamin D supplementation. Arthritis Res Ther. 2012;14(5):R221. doi: 10.1186/ar4060.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Kuhn A, Ruland V, Bonsmann G. Cutaneous lupus erythematosus: update of therapeutic options part I. J Am Acad Dermatol. 2011;65(6):e179–93. doi: 10.1016/j.jaad.2010.06.018.CrossRefPubMedGoogle Scholar
  65. 65.
    Kuhn A, Sigges J, Biazar C, Ruland V, Patsinakidis N, Landmann A, et al. Influence of smoking on disease severity and antimalarial therapy in cutaneous lupus erythematosus: analysis of 1002 patients from the EUSCLE database. Br J Dermatol. 2014;171(3):571–9. doi: 10.1111/bjd.13006.CrossRefPubMedGoogle Scholar
  66. 66.
    Gallego H, Crutchfield CE 3rd, Lewis EJ, Gallego HJ. Report of an association between discoid lupus erythematosus and smoking. Cutis. 1999;63(4):231–4.PubMedGoogle Scholar
  67. 67.
    Miot HA, Bartoli Miot LD, Haddad GR. Association between discoid lupus erythematosus and cigarette smoking. Dermatology. 2005;211(2):118–22. doi: 10.1159/000086440.CrossRefPubMedGoogle Scholar
  68. 68.
    Wahie S, Daly AK, Cordell HJ, Goodfield MJ, Jones SK, Lovell CR, et al. Clinical and pharmacogenetic influences on response to hydroxychloroquine in discoid lupus erythematosus: a retrospective cohort study. J Investig Dermatol. 2011;131(10):1981–6. doi: 10.1038/jid.2011.167.CrossRefPubMedGoogle Scholar
  69. 69.
    Piette EW, Foering KP, Chang AY, Okawa J, Ten Have TR, Feng R, et al. Impact of smoking in cutaneous lupus erythematosus. Arch Dermatol. 2012;148(3):317–22. doi: 10.1001/archdermatol.2011.342.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Chasset F, Frances C, Barete S, Amoura Z, Arnaud L. Influence of smoking on the efficacy of antimalarials in cutaneous lupus: a meta-analysis of the literature. J Am Acad Dermatol. 2015;72(4):634–9. doi: 10.1016/j.jaad.2014.12.025.CrossRefPubMedGoogle Scholar
  71. 71.
    Tzung TY, Liu YS, Chang HW. Tacrolimus vs. clobetasol propionate in the treatment of facial cutaneous lupus erythematosus: a randomized, double-blind, bilateral comparison study. Br J Dermatol. 2007;156(1):191–2. doi: 10.1111/j.1365-2133.2006.07595.x.CrossRefPubMedGoogle Scholar
  72. 72.
    Kuhn A, Gensch K, Haust M, Schneider SW, Bonsmann G, Gaebelein-Wissing N, et al. Efficacy of tacrolimus 0.1 % ointment in cutaneous lupus erythematosus: a multicenter, randomized, double-blind, vehicle-controlled trial. J Am Acad Dermatol. 2011;65(1):54–64, e1–2. doi: 10.1016/j.jaad.2010.03.037.
  73. 73.
    Avgerinou G, Papafragkaki DK, Nasiopoulou A, Arapaki A, Katsambas A, Stavropoulos PG. Effectiveness of topical calcineurin inhibitors as monotherapy or in combination with hydroxychloroquine in cutaneous lupus erythematosus. J Eur Acad Dermatol Venereol. 2012;26(6):762–7. doi: 10.1111/j.1468-3083.2011.04161.x.CrossRefPubMedGoogle Scholar
  74. 74.
    James JA, Kim-Howard XR, Bruner BF, Jonsson MK, McClain MT, Arbuckle MR, et al. Hydroxychloroquine sulfate treatment is associated with later onset of systemic lupus erythematosus. Lupus. 2007;16(6):401–9. doi: 10.1177/0961203307078579.CrossRefPubMedGoogle Scholar
  75. 75.
    Frances C, Cosnes A, Duhaut P, Zahr N, Soutou B, Ingen-Housz-Oro S, et al. Low blood concentration of hydroxychloroquine in patients with refractory cutaneous lupus erythematosus: a French multicenter prospective study. Arch Dermatol. 2012;148(4):479–84. doi: 10.1001/archdermatol.2011.2558.CrossRefPubMedGoogle Scholar
  76. 76.
    Chang AY, Piette EW, Foering KP, Tenhave TR, Okawa J, Werth VP. Response to antimalarial agents in cutaneous lupus erythematosus: a prospective analysis. Arch Dermatol. 2011;147(11):1261–7. doi: 10.1001/archdermatol.2011.191.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Cavazzana I, Sala R, Bazzani C, Ceribelli A, Zane C, Cattaneo R, et al. Treatment of lupus skin involvement with quinacrine and hydroxychloroquine. Lupus. 2009;18(8):735–9. doi: 10.1177/0961203308101714.CrossRefPubMedGoogle Scholar
  78. 78.
    Wenzel J, Brahler S, Bauer R, Bieber T, Tuting T. Efficacy and safety of methotrexate in recalcitrant cutaneous lupus erythematosus: results of a retrospective study in 43 patients. Br J Dermatol. 2005;153(1):157–62. doi: 10.1111/j.1365-2133.2005.06552.x.CrossRefPubMedGoogle Scholar
  79. 79.
    Gammon B, Hansen C, Costner MI. Efficacy of mycophenolate mofetil in antimalarial-resistant cutaneous lupus erythematosus. J Am Acad Dermatol. 2011;65(4):717–21. doi: 10.1016/j.jaad.2010.08.011.CrossRefPubMedGoogle Scholar
  80. 80.
    Kreuter A, Tomi NS, Weiner SM, Huger M, Altmeyer P, Gambichler T. Mycophenolate sodium for subacute cutaneous lupus erythematosus resistant to standard therapy. Br J Dermatol. 2007;156(6):1321–7. doi: 10.1111/j.1365-2133.2007.07826.x.CrossRefPubMedGoogle Scholar
  81. 81.
    Pisoni CN, Obermoser G, Cuadrado MJ, Sanchez FJ, Karim Y, Sepp NT, et al. Skin manifestations of systemic lupus erythematosus refractory to multiple treatment modalities: poor results with mycophenolate mofetil. Clin Exp Rheumatol. 2005;23(3):393–6.PubMedGoogle Scholar
  82. 82.
    Ruzicka T, Sommerburg C, Goerz G, Kind P, Mensing H. Treatment of cutaneous lupus erythematosus with acitretin and hydroxychloroquine. Br J Dermatol. 1992;127(5):513–8.CrossRefPubMedGoogle Scholar
  83. 83.
    Al-Mutairi N, Rijhwani M, Nour-Eldin O. Hypertrophic lupus erythematosus treated successfully with acitretin as monotherapy. J Dermatol. 2005;32(6):482–6.CrossRefPubMedGoogle Scholar
  84. 84.
    D’Erme AM, Milanesi N, Difonzo EM, Lotti T, Gola M. Treatment of refractory subacute cutaneous lupus erythematosus with oral isotretinoin: a valid therapeutic option. Dermatol Ther. 2012;25(3):281–2. doi: 10.1111/j.1529-8019.2012.01461.x.CrossRefPubMedGoogle Scholar
  85. 85.
    Kuhn A, Patsinakidis N, Luger T. Alitretinoin for cutaneous lupus erythematosus. J Am Acad Dermatol. 2012;67(3):e123–6. doi: 10.1016/j.jaad.2011.10.030.CrossRefPubMedGoogle Scholar
  86. 86.
    Klebes M, Wutte N, Aberer E. Dapsone as second-line treatment for cutaneous lupus erythematosus? A retrospective analysis of 34 patients and a review of the literature. Dermatology. 2015. doi: 10.1159/000441054.
  87. 87.
    De Pita O, Bellucci AM, Ruffelli M, Girardelli CR, Puddu P. Intravenous immunoglobulin therapy is not able to efficiently control cutaneous manifestations in patients with lupus erythematosus. Lupus. 1997;6(4):415–7.CrossRefPubMedGoogle Scholar
  88. 88.
    Lampropoulos CE, Hughes GR. DP DC. Intravenous immunoglobulin in the treatment of resistant subacute cutaneous lupus erythematosus: a possible alternative. Clin Rheumatol. 2007;26(6):981–3. doi: 10.1007/s10067-006-0222-5.CrossRefPubMedGoogle Scholar
  89. 89.
    Espirito Santo J, Gomes MF, Gomes MJ, Peixoto L, Pereira SC, Acabado A, et al. Intravenous immunoglobulin in lupus panniculitis. Clin Rev Allergy Immunol. 2010;38(2–3):307–18. doi: 10.1007/s12016-009-8162-x.CrossRefPubMedGoogle Scholar
  90. 90.
    Ky C, Swasdibutra B, Khademi S, Desai S, Laquer V, Grando SA. Efficacy of intravenous immunoglobulin monotherapy in patients with cutaneous lupus erythematosus: results of proof-of-concept study. Dermatol Rep. 2015;7(1):5804. doi: 10.4081/dr.2015.5804.CrossRefGoogle Scholar
  91. 91.
    Cortes-Hernandez J, Torres-Salido M, Castro-Marrero J, Vilardell-Tarres M, Ordi-Ros J. Thalidomide in the treatment of refractory cutaneous lupus erythematosus: prognostic factors of clinical outcome. Br J Dermatol. 2012;166(3):616–23. doi: 10.1111/j.1365-2133.2011.10693.x.CrossRefPubMedGoogle Scholar
  92. 92.
    Frankel HC, Sharon VR, Vleugels RA, Merola JF, Qureshi AA. Lower-dose thalidomide therapy effectively treats cutaneous lupus erythematosus but is limited by neuropathic toxicity. Int J Dermatol. 2013;52(11):1407–9. doi: 10.1111/j.1365-4632.2011.05200.x.CrossRefPubMedGoogle Scholar
  93. 93.
    Braunstein I, Goodman NG, Rosenbach M, Okawa J, Shah A, Krathen M, et al. Lenalidomide therapy in treatment-refractory cutaneous lupus erythematosus: histologic and circulating leukocyte profile and potential risk of a systemic lupus flare. J Am Acad Dermatol. 2012;66(4):571–82. doi: 10.1016/j.jaad.2011.01.015.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Cortes-Hernandez J, Avila G, Vilardell-Tarres M, Ordi-Ros J. Efficacy and safety of lenalidomide for refractory cutaneous lupus erythematosus. Arthritis Res Ther. 2012;14(6):R265. doi: 10.1186/ar4111.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Manzi S, Sanchez-Guerrero J, Merrill JT, Furie R, Gladman D, Navarra SV, et al. Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials. Ann Rheum Dis. 2012;71(11):1833–8. doi: 10.1136/annrheumdis-2011-200831.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Strand V, Levy RA, Cervera R, Petri MA, Birch H, Freimuth WW, et al. Improvements in health-related quality of life with belimumab, a B-lymphocyte stimulator-specific inhibitor, in patients with autoantibody-positive systemic lupus erythematosus from the randomised controlled BLISS trials. Ann Rheum Dis. 2014;73(5):838–44. doi: 10.1136/annrheumdis-2012-202865.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Ginzler EM, Wallace DJ, Merrill JT, Furie RA, Stohl W, Chatham WW, et al. Disease control and safety of belimumab plus standard therapy over 7 years in patients with systemic lupus erythematosus. J Rheumatol. 2014;41(2):300–9. doi: 10.3899/jrheum.121368.CrossRefPubMedGoogle Scholar
  98. 98.
    Cobo-Ibanez T, Loza-Santamaria E, Pego-Reigosa JM, Marques AO, Rua-Figueroa I, Fernandez-Nebro A, et al. Efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus: a systematic review. Semin Arthritis Rheum. 2014;44(2):175–85. doi: 10.1016/j.semarthrit.2014.04.002.CrossRefPubMedGoogle Scholar
  99. 99.
    Vital EM, Wittmann M, Edward S, Md Yusof MY, MacIver H, Pease CT, et al. Brief report: responses to rituximab suggest B cell-independent inflammation in cutaneous systemic lupus erythematosus. Arthritis Rheumatol. 2015;67(6):1586–91. doi: 10.1002/art.39085.CrossRefPubMedGoogle Scholar
  100. 100.
    Petri M, Wallace DJ, Spindler A, Chindalore V, Kalunian K, Mysler E, et al. Sifalimumab, a human anti-interferon-alpha monoclonal antibody, in systemic lupus erythematosus: a phase I randomized, controlled, dose-escalation study. Arthritis Rheum. 2013;65(4):1011–21. doi: 10.1002/art.37824.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Furie R MJ, Werth V, Khamashta M, Kalunian K, Brohawn P, Illei G, Drappa J, Wang L, Yoo S. Anifrolumab, an anti-interferon alpha receptor monoclonal antibody, in moderate to severe systemic lupus erythematosus (SLE) [abstract]. Arthritis Rheumatol. 2015;67:(suppl 10).Google Scholar
  102. 102.
    Khamashta MMJ, Werth VP, Furie R, Kalunian K, Illeis GG, Drappas J, Wang L, Greth W. Safety and efficacy of sifilmumab, an anti IFN-alpha monoclonal antibody, in a phase 2b study of moderate to severe systemic lupus erythematosus (SLE) [abstract]. Arthritis Rheum. 2014;66:3530–1 (L4).Google Scholar

Copyright information

© Springer International Publishing Switzerland (Outside the USA) 2016

Authors and Affiliations

  1. 1.Corporal Michael J. Crescenz Veterans Affairs Medical Center (Philadelphia)PhiladelphiaUSA
  2. 2.Department of Dermatology, Perelman Center for Advanced Medicine, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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