Scleroderma disease mechanism in adults
Scleroderma, also known as systemic sclerosis, is a complex autoimmune disease characterized by abnormal immune responses leading to fibrosis, vascular damage, and immune dysregulation. In adults, the disease manifests through a multifaceted mechanism involving genetic predisposition, environmental triggers, immune system abnormalities, and progressive tissue fibrosis.
The initiation of scleroderma often begins with immune system activation. Immune cells, particularly T lymphocytes and B cells, become dysregulated, producing autoantibodies and cytokines that target the body’s own tissues. These autoantibodies, such as anti-topoisomerase I and anti-centromere antibodies, serve not only as diagnostic markers but also contribute to the disease process. The immune activation leads to persistent inflammation within the skin and internal organs, setting the stage for subsequent tissue changes.
Vascular damage is a hallmark of scleroderma and plays a critical role in disease progression. Endothelial cell injury, triggered by immune-mediated attacks and environmental factors like silica exposure or certain chemicals, results in endothelial dysfunction. This damage causes narrowing and obliteration of small blood vessels, leading to poor blood flow and ischemia. The compromised vasculature can induce Raynaud’s phenomenon, a common early symptom, and contribute to tissue hypoxia, further promoting fibrosis.
Fibrosis, the hallmark feature of scleroderma, results from an imbalance between collagen production and degradation. Fibroblasts, the primary cells responsible for producing extracellular matrix components, become abnormally activated under the influence of cytokines such as transforming growth factor-beta (TGF-β), platelet-derived growth factor (PDGF), and interleukins. These cyt
okines are released by immune cells in response to vascular injury and inflammation. The persistent activation of fibroblasts leads to excessive collagen and extracellular matrix deposition in the skin and internal organs like the lungs, heart, and kidneys, causing stiffening and functional impairment.
Another critical aspect of the disease mechanism involves the interplay between the immune system and tissue repair pathways. Instead of resolving inflammation, the ongoing immune response perpetuates tissue injury and fibrosis. Additionally, genetic factors contribute to susceptibility, with certain HLA haplotypes and gene polymorphisms influencing immune regulation and fibrotic responses.
Environmental factors also contribute by acting as triggers in genetically predisposed individuals. Exposure to silica dust, organic solvents, and certain medications has been linked to increased risk. These elements may initiate or exacerbate immune dysregulation and vascular injury, accelerating disease progression.
Overall, scleroderma in adults results from a complex interplay of immune activation, vascular injury, and fibrotic processes. The disease progression varies widely among individuals, with some experiencing limited skin involvement and others developing severe internal organ fibrosis. Advances in understanding these mechanisms have facilitated the development of targeted therapies aimed at modulating immune responses, protecting vascular integrity, and inhibiting fibrosis, offering hope for better management and outcomes.
