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Clinical Treatment Options in Scleroderma: Recommendations and Comprehensive Review

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Abstract

There are two major clinical subsets of scleroderma: (i) systemic sclerosis (SSc) is a complex systemic autoimmune disorder characterized by inflammation, vasculopathy, and excessive fibrosis of the skin and multiple internal organs and (ii) localized scleroderma (LoS), also known as morphea, is confined to the skin and/or subcutaneous tissues resulting in collagen deposition and subsequent fibrosis. SSc is rare but is associated with significant morbidity and mortality compared with other rheumatic diseases. Fatal outcomes in SSc often originate from organ complications of the disease, such as lung fibrosis, pulmonary artery hypertension (PAH), and scleroderma renal crisis (SRC). Current treatment modalities in SSc have focused on targeting vascular damage, fibrosis, and regulation of inflammation as well as autoimmune responses. Some drugs previously used in an attempt to suppress fibrosis, like D-penicillamine (D-Pen) or colchicine, have been disappointing in clinical practice despite anecdotal evidence of their advantages. Some canonical medications, including glucocorticoids, immunosuppressants, and vasodilators, have had some success in treating various manifestations in SSc patients. Increasing evidence suggests that some biologic agents targeting collagen, cytokines, and cell surface molecules might have promising therapeutic effects in SSc. In recent years, hematopoietic stem cell transplantation (HSCT), mostly autologous, has made great progress as a promising treatment option in severe and refractory SSc. Due to the complexity and heterogeneity of SSc, there are currently no optimal treatments for all aspects of the disease. As for LoS, local skin-targeted therapy is generally used, including topical application of glucocorticoids or other immunomodulatory ointments and ultraviolet (UV) irradiation. In addition, systemic immunosuppressants are also utilized in several forms of LoS. Here, we comprehensively discuss current treatment options for scleroderma, encompassing old, new, and future potential treatment options. In addition, we summarize data from new clinical trials that have the potential to modify the disease process and improve long-term outcomes in SSc.

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Funding

The present research was supported by the Key project for international and regional cooperation in science and technology innovation of Hunan province (2019WK2081), the Project for leading talents in science and technology in Hunan province (2019RS3003), and CAMS Innovation Fund for Medical Sciences (2019-I2M-5-033).

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Authors and Affiliations

  1. Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, China

    Ming Zhao, Jiali Wu, Haijing Wu & Qianjin Lu

  2. Research Unit of Key Technologies of Immune-Related Skin Diseases Diagnosis and Treatment, Chinese Academy of Medical Sciences, Changsha, China

    Ming Zhao, Jiali Wu, Haijing Wu & Qianjin Lu

  3. Departments of Pediatrics, Medicine, and Immunology, and Lupus Center of Excellence, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Amr H. Sawalha

  4. Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China

    Qianjin Lu

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Concept and design: Qianjin Lu, Amr H Sawalha, Ming Zhao, Jiali Wu; drafting of the manuscript: Ming Zhao, Jiali Wu; revising of the manuscript: Qianjin Lu, Amr H Sawalha, Ming Zhao, Jiali Wu, Haijing Wu.

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Zhao, M., Wu, J., Wu, H. et al. Clinical Treatment Options in Scleroderma: Recommendations and Comprehensive Review. Clinic Rev Allerg Immunol 62, 273–291 (2022). https://doi.org/10.1007/s12016-020-08831-4

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