Retinoids in Skin Health and Disease — Mechanisms, Clinical Applications, and Safety: Scoping Review with ☸️SAIMSARA

To map and synthesize original research on retinoids in skin, identifying the dominant biological mechanisms, clinical applications, formulation strategies, safety signals, and evidence gaps relevant to retinoid use and retinoid signaling in cutaneous health and disease. The review uses 320 references and builds its evidence map from 796 original studies with 21358 total participants/sample observations (topic-deduplicated ΣN). This scoping review indicates that retinoids act as pleiotropic regulators of skin biology, with recurrent signals linking RAR/RXR signaling to epidermal proliferation, dermal matrix remodeling, and tightly regulated local metabolism that together explain both therapeutic benefit and characteristic irritation. Across diverse formulations and populations, retinoids were consistently associated with improvements in photoaging, acne, and psoriasis, including long-term reductions in lentigines and substantial lesion clearance, while mucocutaneous dryness and barrier disruption remained the dominant tolerability barriers. A practical implication is that tolerability can often be improved through barrier-supportive adjuncts and targeted delivery systems without clearly sacrificing efficacy. However, much of this evidence derives from small or lower-level study designs, so confidence in comparative effectiveness remains limited. Future head-to-head trials with standardized efficacy, irritation, and tolerability endpoints—particularly in underrepresented skin types—are needed to clarify which retinoid strategies optimize the therapeutic index.