A systematic review of therapeutic procedures for the treatment of morphea and systemic sclerosis

Considering the challenges involved in managing morphea and systemic sclerosis—especially the risks of disease reactivation and inflammation following treatment—and the limited evidence on the effectiveness and safety of treatment methods like energy-based devices and intralesional injections, it is essential to conduct a systematic review to compile and critically evaluate the available data comprehensively. This review aims to evaluate the effectiveness and safety of energy-based devices and intralesional injections in managing morphea and systemic sclerosis, to provide critical evidence that informs clinical decision-making and ultimately enhances patients’ quality of life. This study was conducted as a systematic review following established guidelines and checklists for such reviews. The PRISMA flow diagram was employed to illustrate the identification, screening, eligibility, and inclusion of studies. Comprehensive searches were performed from different scientific databases, including PubMed, Scopus, Web of Science, and Embase, to identify all relevant studies evaluating the effectiveness and safety of energy-based devices and intralesional injections in treating morphea and systemic sclerosis. We managed the retrieved records using EndNote reference management software. After a thorough screening process, we extracted relevant data based on predefined study variables and then analyzed it. This study reviewed 28 articles published between 2010 and 2025. Of these, 17 articles (60.7%) were clinical trials, 4 (14.3%) were retrospective studies, 4 (14.3%) were cohort studies, 2 (7.1%) were cross-sectional studies, and 1 (3.6%) was a case series, encompassing a total of 732 patients. Among the patients, 114 (15.6%) were men and 618 (84.4%) were women, ranging from 6 to 70 years. Of the studies reviewed, 14 articles (50%) focused on morphea, 12 articles (42.9%) on systemic sclerosis, and 2 articles (7.1%) examined both conditions. A total of 15 studies (53.6%) evaluated the efficacy and safety of energy-based devices, with UVA-1 phototherapy being the most frequently studied modality, appearing in 9 articles (60%). Other energy-based treatments included ablative fractional CO₂ laser (2 studies, 13.3%), a comparison of UVA-1 and CO₂ laser (1 study, 6.7%), Water-Filtered Infrared A plus Visible Light (1 study, 6.7%), LEDs emitting at 850 nm (infrared), 660 nm (red), and 405 nm (violet) (1 study, 6.7%), and Fibroblast Activation Protein Targeted Photodynamic Therapy (1 study, 6.7%). The remaining 13 studies (46.4%) investigated intralesional injections, with stromal vascular fraction (SVF) gel (2 studies, 15.4%), injecting fat micrografts along with fat-derived SVF (1 study, 7.7%), Botulinum toxin (BTX) (4 studies, 30.8%), injection of ozone/oxygen (1 study, 7.7%), hyaluronic acid filler (2 studies, 15.4%), PRP combined with autologous SVF (1 study, 7.7%), Hydrodissection + injection of 80 mg of triamcinolone acetonide (1 study, 7.7%), and autologous fat grafting (1 study, 7.7%) being the most common intralesional treatments. Follow-up durations varied from 5 days to 37 months. Positive therapeutic outcomes were reported in two studies involving energy-based devices and in all but one study involving intralesional injections. Furthermore, none of the studies reported any life-threatening adverse events from these treatments. The promising therapeutic efficacy and lack of severe adverse effects reported in the literature regarding energy-based devices and intralesional injections for managing morphea and systemic sclerosis suggest a favorable outlook for their clinical use, particularly in patients with refractory forms of the disease. Further clinical trials and genetic research in this field could strengthen the methodological rigor of future studies, support the development of innovative treatment strategies, and help identify patients most likely to benefit from specific therapies.