[Skip to Content]
Home > Medical Directory > Scleroderma Symptoms > Causes of Scleroderma

What Causes Scleroderma?

Author: Shelley Ensz. Scleroderma is highly variable. See Types of Scleroderma. Read Disclaimer
Causes of Scleroderma?
Advanced Glycation Endproducts
B Cells and T Cells
Cluster Studies (Main Page)
Cluster in South Boston
Dendritic Cells
Drugs and Medications
Environmental (Main Page)
Artificial Joints & Breast Implants
Drugs and Medications
Mercury (Dental Amalgam)
Silica Exposure
Vinyl Chloride
Fetal Cells
Gluten Sensitivity
Hormones and Chromosomes
Molecular Defect
Mucosal Immune System
Natural Killer Cells
Oxidative Stress, Lipid Peroxidation
Platelet Aggregation
Serum TIMP-2
Tissue Kallikrein
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)
Prevention of autoimmune rheumatic disease: state of the art and future perspectives. The road map towards prevention of autoimmune rheumatic diseases includes increased understanding of how genes, environment and immunity interact. Klareskog L. (PubMed) Ann Rheum Dis, 2010 Dec. (Also see: Autoimmunity)

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, 2012 Aug;39(8):1654-8.

Artificial Joints and Silicone Breast Implants

Causes of Scleroderma: Artificial Joints and Silicone Breast Implants. Are some cases of connective tissue disease, such as scleroderma, related to artificial joints or silicone breast implants? Contradictory findings continue to plague research into this area. ISN.
Device Implantation Research
Media Stories
Personal Stories Related to Implants


Causes of Scleroderma: Autoimmunity Scleroderma appears to be an autoimmune disease, in which the immune system attacks the body itself, causing an overproduction of collagen. ISN.
What is Autoimmunity?
B Cells and T Cells
Autoimmunity and Scleroderma

Autoimmunity: B Cells and T Cells

Autoimmunity: B Cells and T Cells. T Cells are white blood cells that help stimulate an immune response to infections. ISN.
Overview of B Cells and T Cells
B Cells and T-Cells and Autoimmunity
B Cells and T Cells and Systemic Sclerosis

Cluster Studies

Causes of Scleroderma: Cluster Studies Cluster studies can help pinpoint some of the causes of scleroderma. ISN.
Australian Clusters
Canadian Clusters
United States Clusters
South Boston, Massachusetts


Cytokines are small secreted proteins which mediate and regulate immunity, inflammation, and hematopoiesis. ISN.
Cytokines and Interleukins
Cytokines and Scleroderma
Cytokines and Sleep

Dendritic Cells

Dendritic cells are involved in the regulation of the body's immune system response, and are thought to be a key to preventing or treating autoimmune diseases. ISN.

Drugs and Medications

Causes of Scleroderma: Drugs and Medications Some medications and street drugs are known or thought to induce scleroderma or Raynaud's, such as Bleomycin, Cocaine, Marijuana, and Paclitaxel (Taxanes). ISN.
5HTP w/ Carbidopa
Bleomycin-Induced Scleroderma
Chemotherapy-induced Scleroderma
Cocaine-Induced Scleroderma
Collagen and Liquid Silicone Injections
Interferon Alpha
Marijuana and Raynaud's
Paclitaxel (Taxanes)


Endothelin and Systemic Scleroderma. Endothelin is a protein that helps to regulate contraction and relaxation of the smooth muscle found in the walls of blood vessels and internal organs (except the heart). ISN.
Endothelin and Systemic Scleroderma Endothelin Receptor Antagonists


Causes of Scleroderma: Environmental Topics covered include exposure to cadmium, mercury (dental amalgam), solvents (such as paint thinners), radiation, and silica as either known or suspected causes of autoimmune disease or scleroderma. ISN.
Artificial Joints and Implants
Drugs and Medications
Environmental Toxins
Mercury Exposure (Dental Amalgam)
Vinyl Chloride Disease

Fetal Cells and Scleroderma

Causes of Scleroderma: Fetal Cells Fetal cells as a cause of  scleroderma is a hot topic of research and discussion lately. And since the topic is filled with intriguing possibilities, cutting-edge science, and unanswered questions, there is likewise some inescapable controversy. ISN.
Overview of Fetal Cells
Research: Scleroderma
Research: Autoimmune


Fibroblast. Fibroblasts are the most common cells of connective tissue. They produce the fibrous protein called collagen. "The major source of fibrosis in SSc is over production of collagens from fibroblasts."(2) ISN.

Genetics and Scleroderma

Causes of Scleroderma: Genetics includes information on DNA, Familial CRST with Sicca Syndrome, Familial Progressive Systemic Sclerosis (FPSS), studies of twins, Choctaw genetic study, and human genome project. ISN.
Birth Order
Choctaw Study
Ethnicity, Race, Geography
Familial CRST w/ Sicca
Genetics and Scleroderma
Homocysteine/MTHFR C677T Gene Mutation
Human Genome Project
Scleroderma Registries
Shared Autoimmunity
Twins and Siblings Study

Gluten Sensitivity

Celiac Disease and Gluten Sensitivity. Gluten sensitivity is a known cause of dozens of autoimmune diseases, including Hashimoto's thyroiditis, Sjogren's syndrome, and scleroderma. ISN.
Overview of Gluten Sensitivity
What is Celiac Disease?
CD and Scleroderma
CD and Autoimmunity
Diets and Celiac Disease
Media Articles
Personal Stories

Hormones and Chromosomes

Hormones and Chromosomes have been found to attribute to the development of autoimmune diseases. This may explain why women are more susceptible to autoimmune diseases than men. ISN.
Adrenocortical Function
Gender Differences
Prempro Lawsuit
X Chromosome, Mosaicism


Causes of Scleroderma: Infections Researchers have long suspected an infection component may be involved as the trigger of some cases of scleroderma and there is an ongoing study about persistent infection as a possible cause of scleroderma. ISN.
Infection (General)
Bacterial Infections
Borrelia Burgdorferi

Persistent Infection Study
Viral Infection


Causes of Scleroderma: Interleukins. Interleukins are a vital part of the pathway that regulates inflammation in the body. There are many different types of interleukins. ISN.
Anti-TNF-a Therapies

Mercury Exposure (Dental Amalgam)

Causes of Scleroderma: Mercury Exposure (Dental Amalgam) covers recent research indicating that there may be a link between mercury exposure and autoimmune diseases. ISN.
Overview of Mercury Exposure
Dental Amalgam
Media Stories

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, 06/18/2013.

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.


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, 2013 Jun 11.
Researchers implicate well-known protein in fibrosis. We now know that TLR4 plays a role in scleroderma, but much research remains to be done to develop safe and effective drugs to inhibit this pathway. EurekAlert, 11/20/12.
Researchers identify molecular gatekeeper of arthritis. The protein, researchers noted, determines the fate of damaging cells that mistakenly attack the body's own tissues and lead to autoimmune disorders such as rheumatoid arthritis. The finding could help researchers explore new types of treatments for patients whose arthritis has not been effectively treated by other means. OrthoSuperSite. 09/10/10.


Radiation and Scleroderma. There is an increased rate of cancer among scleroderma patients. ISN.
What is Radiation?
Immune System and Radiation
What is Scleroderma?
Radiation and Scleroderma
Radiation Complications in Scleroderma
Radiation Port Scleroderma
Personal Stories About Radiation

Serum TIMP-2

Serum Levels of Tissue Inhibitors of Metalloproteinase 2 in Patients With Systemic Sclerosis (SSc). This study confirms the probable role of TIMP-2 in inducing fibrosis in the course of SSc, and suggests a possible role of TIMP-2 in the development of pulmonary involvement in diffuse scleroderma (dSSc) patients, and cardiac lesions in limited scleroderma (lSSc) patients, with disease duration equal to or more than 2 years. Amira Shahin. (PubMed) Mediators Inflamm. 2006; 2006(6): 38458.

Serum sCD40

Increased Serum Soluble CD40 Levels in Patients with Systemic Sclerosis. Elevated serum sCD40 levels were associated with lcSSc. These results suggest that the blockade of CD40/CD40 ligand interaction could be a potential therapeutic strategy in SSc. J Rheumatol 2007 February;34:353–8. (Also see: Limited Scleroderma)


Causes of Scleroderma: Silica. Silica exposure can cause autoimmune diseases such as lupus, scleroderma, and vasculitis. ISN. (Also see: Causes of Scleroderma: Silicone Breast Implants)
Overview of Silica Exposure
Diseases Caused by Silica Exposure
Materials Containing Silica
Silica and Silicosis
Silica and Scleroderma
Silica Occupational Exposures

Sleep Disorders

Overview of Sleep and Scleroderma
Restless Leg Syndrome
Sleep and Illness
Sleep and Medications
Sleep Apnea
Personal Stories


Stress can cause hormonal and cellular changes in our bodies which can lead to a variety of medical problems. ISN.

Tissue Kallikrein (t-kallikrein)

Increased circulating levels of tissue kallikrein in systemic sclerosis correlate with microvascular involvement. T-kallikrein levels are increased in patients with SSc, particularly in lSSc, and are associated with early and active capillaroscopic patterns. T-kallikrein may play a part in SSc microvascular changes. PubMed, Ann Rheum Dis. 2005 Mar;64(3):382-7. (Also see: Raynaud's)


Thyroid Disease. It is common for people to develop thyroid diseases, such as hyperthyroidism (hyper means "too much") and hypothyroidism (hypo means "too little.) ISN.
With Scleroderma
With Other Diseases
Graves' Disease
Personal Stories

Vitamin D Deficiency

Vitamin D 's major biological function is to maintain normal blood levels of calcium and phosphorus. ISN.
Autoimmune Diseases
Deficiencies of Vit D
Scleroderma and Vit D
Sunshine Exposure


(1) Medscape requires (free) sign up and password. You do not need to be a medical professional to use Medscape. However this makes for slower access to the site for first-time users.
(2) Xiong M, Arnett FC, Guo X, Xiong H, Zhou X (2008) Differential Dynamic Properties of Scleroderma Fibroblasts in Response to Perturbation of Environmental Stimuli. PLoS ONE 3(2): e1693. doi:10.1371/journal.pone.0001693.
Go to Cause of Scleroderma: Autoimmunity

SCLERO.ORG is operated by the International Scleroderma Network, which is a full-service U.S. nonprofit 501(c)(3) established in 2002. We provide stellar worldwide research, support, education and awareness for scleroderma and related illnesses, such as pulmonary hypertension. Donate or Shop Now.

Questions? Post a message in Sclero Forums or email us directly at isn@sclero.org. Or call our Scleroderma Hotline (English only), Toll Free in U.S. 1-800-564-7099 or Direct at 1-952-831-3091. Ask for our Welcoming Email.

Our headquarters postal mailing address is: International Scleroderma Network (ISN), 7455 France Ave So #266, Edina, MN 55435-4702, United States.

The most important thing in the world to know about scleroderma...is sclero.org!
Home   Medical  News  Sclero Forums  Support  Translations  Donate or Shop
Copyright 1998-2015, International Scleroderma Network. AKA Scleroderma from A to Z and SCLERO.ORG. All Rights Reserved.