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Pathogenesis and targeted treatment of skin injury in SLE

Nature Reviews Rheumatology volume 11, pages 663–669 (2015)Cite this article

Subjects

Key Points

  • Skin injury is the second most common manifestation of systemic lupus erythematosus (SLE), yet its pathogenesis remains unclear

  • Ultraviolet light triggers activation of immune cells in areas where IgG has been deposited, which induces skin injury and disease flare

  • Mouse models of intradermal injection of lupus serum IgG develop skin inflammation and represent a useful tool to investigate the pathogenesis of skin injury in SLE

  • TNF receptor superfamily member 1A, tyrosine-protein kinase SYK, calcium/calmodulin-dependent protein kinase type IV and nuclear factor of activated T cells might be useful therapeutic targets to control skin injury in SLE

Abstract

Skin is the second most common organ (after the kidney) to be affected in patients with systemic lupus erythematosus (SLE), yet the aetiology of skin injury and the mechanisms involved in the development of dermal manifestations of SLE remain unclear. Ultraviolet light (UV), immune cells, cytokines and deposition of immunoglobulins all seem to have a role in the development of skin inflammation and damage in SLE. UV represents the most important environmental factor, and exposure to UV triggers the development of skin lesions in areas where immunoglobulin has been deposited and various other components of the immune system have accumulated. In addition, a number of intracellular kinases and transcription factors have also been demonstrated to be involved in the generation of skin lesions in lupus-prone mice. These molecules can be targeted by small-molecule inhibitors, leading to the prospect that treatments suitable for topical application, and with limited adverse effects, could be developed. Further studies to eliminate the burden of skin inflammation in patients with SLE are clearly required.

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Figure 1: Classification of skin injury in patients with SLE.
Figure 2: Mechanisms of skin injury in SLE.

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Acknowledgements

The authors acknowledge Health & Human Sciences–NIH–National Institute of Allergy and Infectious Diseases (NIAID) grant R01 AI 42269 to G.C.T.

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Authors and Affiliations

  1. Key Laboratory of Antibody Technology of Ministry of Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, Jiangsu, China

    Guo-Min Deng

  2. Division of Rheumatology, Beth Israel Deaconess Medical Centre, Harvard Medical School, Harvard University, 330 Brookline Avenue, CLS937, Boston, 02215, MA, USA

    George C. Tsokos

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Both authors contributed equally to all aspects of the manuscript (researching data for the article, discussions of its content, writing, review and editing of the manuscript before submission).

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Correspondence to George C. Tsokos.

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Deng, GM., Tsokos, G. Pathogenesis and targeted treatment of skin injury in SLE. Nat Rev Rheumatol 11, 663–669 (2015). https://doi.org/10.1038/nrrheum.2015.106

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