Review Article Role of Vitamin D in Systemic Sclerosis: A Systematic Literature Review Alexandra-Diana Diaconu , 1 Iustina Ostafie , 1 Alexandr Ceasovschih , 2,3 Victorița Șorodoc , 2,3 Cătălina Lionte , 2,3 Codrina Ancuța , 1,3 and Laurențiu Șorodoc 2,3 1 2nd Rheumatology Department, Clinical Rehabilitation Hospital, 700661 Iasi, Romania 2 2nd Internal Medicine Department, “Sf. Spiridon” Emergency Clinic County Hospital, 700111 Iasi, Romania 3 Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania Correspondence should be addressed to Alexandr Ceasovschih; alexandr.ceasovschih@yahoo.com and Codrina Ancuța; codrina_ancuta@yahoo.com Received 6 August 2021; Accepted 29 October 2021; Published 29 November 2021 Academic Editor: Vlad Padureanu Copyright © 2021 Alexandra-Diana Diaconu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Systemic sclerosis (SSc) is a chronic multisystem autoimmune condition defined by a complex pathobiology, comprising excessive fibrosis of skin and internal organs, peripheral vasculopathy with endothelial cell dysfunction, inadequate vascular repair and neovascularization, and aberrant immunity. Vitamin D is a steroid hormone with pleiotropic effects beyond its traditional role in calcium and bone homeostasis. Since vitamin D has immunomodulatory, cardioprotective, and antifibrotic properties, it could potentially interfere with SSc pathogenesis. Suboptimal vitamin D levels are classically recognized in scleroderma, irrespective of clinical and serological phenotype. Aim. This systematic review is aimed at investigating and clarifying the role of vitamin D in SSc and emphasizing the association of vitamin D status with different clinical settings. Methods and Results. A systematic online search was performed, using PubMed databases to collect articles on the topic of vitamin D in SSc. The final analysis included 40 eligible articles. Conclusions. Hypovitaminosis D is common in SSc patients and could be associated with clinical and serologic patterns of the disease. Intervention for low serum vitamin D levels in SSc pathogenesis remains controversial, as well as the significance of vitamin D supplementation in such patients. 1. Introduction 1.1. Systemic Sclerosis. Classified as an orphan disease, sys- temic sclerosis (SSc) remains a chronic multisystem autoim- mune condition driven by a multifaceted link between excessive fibrosis of the skin and internal organs, peripheral vasculopathy with endothelial cell dysfunction succeeded by inadequate vascular repair and neovascularization, and aber- rant immunity. The clinical picture ranges from peripheral vasculopathy (Raynaud’s phenomenon, digital ulcers, and critical digital ischemia) and skin involvement, to a broad spectrum of manifestations depending on the presence and degree of internal organ (gastrointestinal, lung, kidney, and heart) involvement, resulting in specific phenotypes charac- terized by precise antibodies, distinct prognoses, and specific management [1, 2]. Although the complex pathobiology of SSc is still not well understood, immunological, vascular, and fibrotic abnormal- ities remain key events, including (i) fibroproliferative vascu- lar injuries of small arteries and arterioles; (ii) increased production of profibrotic growth factors such as trans- former-β growth factor (TGF-β), connective tissue growth factor, and insulin-like growth factor, leading to fibrosis of the skin and various internal organs; and (iii) various modi- fications of innate, humoral, and cellular immunity, promot- ing immune cell trafficking into the affected tissues and Hindawi Journal of Immunology Research Volume 2021, Article ID 9782994, 15 pages https://doi.org/10.1155/2021/9782994