Author: Shelley Ensz. Scleroderma is highly variable. See Types of Scleroderma. Read Disclaimer

Causes of Scleroderma

Advanced Glycation
B and T Cells
Cluster South Boston
Dendritic Cells
Artificial Joints/Implants
Mercury (Amalgam)
Vinyl Chloride
Fetal Cells
Molecular Defect
Mucosal Immune System
Natural Killer Cells
Oxidative Stress, Lipids
Platelet Aggregation
Vitamin D Deficiency


The cause of scleroderma is generally unknown, however areas being investigated include autoimmunity, environmental exposures, genetics, and infections. Many researchers feel that several factors work together to induce scleroderma, such as a genetic inclination along with exposure to a toxin or infection which triggers the illness. (Also see What is Scleroderma?, Types of Scleroderma, and Systemic Sclerosis)

Scleroderma is not believed to be contagious; you cannot get it by hugging or kissing someone or other intimate contact. There is an increased incidence of certain types other autoimmune diseases and cancer among scleroderma patients. (Also see Associated Conditions and Cancer and Scleroderma)

Transcriptional insights into pathogenesis of cutaneous systemic sclerosis using pathway driven meta-analysis assisted by machine learning methods. Our analysis unveiled an important 80 pathway signatures that differentiated SSc patients into 8 unique subtypes. PubMed, PLoS One, 2020 Nov 30;15(11):e0242863.

Older age onset of systemic sclerosis (SSc) - accelerated disease progression in all disease subsets. In this large registry, 25% of patients developed SSc at an age above 60 years with an increased frequency of limited cutaneous systemic sclerosis. PubMed, Rheumatology (Oxford), 04/24/2020.

Scleroderma: An insight into causes, pathogenesis and treatment strategies. Current review is an effort to reflect scleroderma in provisions of its pathogenesis, causative factors, and therapeutic approaches. PubMed, Pathophysiology, 05/18/2019.

Advanced Glycation Endproducts (AGES)

Noninvasive measurement of skin autofluorescence is increased in patients with systemic sclerosis: an indicator of increased advanced glycation endproducts? Autofluorescence is increased in patients with dcSSc compared to primary RP and to healthy controls. This suggests increased oxidative stress and the potential for autofluorescence as a biomarker. J Rheumatol.

Molecular Defect - TGF Dysregulation

Causes of Scleroderma: Molecular Defect in TGFbeta/SMAD may play a role in the development of scleroderma fibrosis. ISN.

Mucosal Immune System

Researchers Discover New Immune System. A San Diego State University biology researcher discovered immunity defense in an unlikely place: Mucus. Stanford Report.

Natural Killer Cells

Natural killer cells are cells in the immune system that destroy cancer cells and virus-infected cells. ISN.

Oxidative Stress, Lipid Peroxidation

Oxidative Stress is an imbalance between pro-oxidants and antioxidants that can result in cellular degeneration. ISN.

Platelet Aggregation

Platelet aggregation is the clumping of platelets together, using fibrin (a protein involved in the clotting of blood) as the connecting agent. Widipedia.


CCN proteins as potential actionable targets in scleroderma (SSc). We discuss the possible implication of CCN proteins in SSc pathogenesis, with a special focus on skin features, and identify the potential actionable CCN targets. PubMed, Exp Dermatol, 10/17/2018. (Also see Skin Fibrosis)

Increased expression of S100A8 and S100A9 in patients with diffuse cutaneous systemic sclerosis (dcSSc). A correlation with organ involvement and immunological abnormalities. These two proteins may play important roles in the development of systemic sclerosis. PubMed, Clin Rheumatol.

Go to Cause of Scleroderma: Autoimmunity

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