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

Abstract

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.

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References

  1. Gilliam JN, Sontheimer RD. Distinctive cutaneous subsets in the spectrum of lupus erythematosus. J Am Acad Dermatol. 1981;4(4):471–5.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Petri M. Epidemiology of systemic lupus erythematosus. Best Pract Res Clin Rheumatol. 2002;16(5):847–58.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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. 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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  17. Fonseca E, Alvarez R, Gonzalez MR, Pascual D. Prevalence of anticardiolipin antibodies in subacute cutaneous lupus erythematosus. Lupus. 1992;1(4):265–8.

    CAS  Article  PubMed  Google Scholar 

  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/j.ad.2012.10.017.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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).

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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. 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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  55. Fett N, Werth VP. Systemic lupus erythematosus treatment: a guide to photoprotection. CML Rheumatol. 2010;29(2):33–41.

    Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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. 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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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. 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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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).

  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).

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Acknowledgments

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.

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Correspondence to Victoria P. Werth.

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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.

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Hejazi, E.Z., Werth, V.P. Cutaneous Lupus Erythematosus: An Update on Pathogenesis, Diagnosis and Treatment. Am J Clin Dermatol 17, 135–146 (2016). https://doi.org/10.1007/s40257-016-0173-9

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Keywords

  • Systemic Lupus Erythematosus
  • Human Leukocyte Antigen
  • Systemic Lupus Erythematosus Patient
  • Thalidomide
  • Lenalidomide