| What Causes Scleroderma? | | The cause of scleroderma is largely unknown, but here is some interesting research. | |
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| What Causes Scleroderma? |
| 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. |
| 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) |
| The Immunobiology of Systemic Sclerosis. The SSc hallmarks of vascular damage, immunologic activation, and collagen deposition can be traced to 4 major factors: T-cells, fibroblasts, B-cells, and cytokines/chemokines. Significant variations in laboratory data among patients suggest that the pathology reflects a heterogeneous disease. (Science Direct) Seminars in Arthritis and Rheumatism. 02/13/08. (Also see: B and T cells, Fibroblasts, and Cytokines) |
| How Cells Die Determines Whether Immune System Mounts Response. Every moment we live, cells in our bodies are dying. One type of cell death activates an immune response while another type doesn't. This finding eventually could have important implications in the treatment of autoimmune diseases and cancer. NewsWire. 07/15/08. (Also see: Autoimmunity) |
| Scientists Closer to Cracking the Autoimmune Mystery. "Almost every autoimmune disease, with the exception of rheumatoid arthritis, seems to be going up," says immunologist Noel Rose, director of the Johns Hopkins Autoimmune Diseases Research Center. But whether that's because of an increase in disease or better recognition of cases is not certain. MedIndia.com. 09/06/07. (Also see: Autoimmunity) |
| Impact of Autoimmune Disease Diagnosis on Clinical Laboratory. The interplay of various genes determines an individual's susceptibility to an antigen and, by extension, the type of autoimmune disease the patient may suffer. Express Healthcare March 2007. |
| When The Body Attacks Itself. According to the National Institutes of Health in the United States, approximately 23.5 million Americans have 24 of the 80 recognised autoimmune disorders, making the prevalence of autoimmune disease greater than cancer and roughly equal to heart disease. The Jamaica Observer. 01/28/07. (Also see: Autoimmunity) |
| Low levels of activated factor VII in systemic sclerosis. Reduced activated factor VII activity might be involved in the pathogenesis of the ischemic complications, by modulating apoptotic and angiogenetic processes. PubMed. J Thromb Thrombolysis. 2006 Oct;22(2):133-8. |
| Infection, vaccines and other environmental triggers of autoimmunity. Most often autoimmunity is not followed by clinical symptoms unless an additional event such as an environmental factor favors an overt expression. Many environmental factors are known to affect the immune system and may play a role as triggers of the autoimmune mosaic. PubMed. Autoimmunity. 2005 May;38(3):235-45. |
| Aberrant serum hyaluronan and hyaluronidase levels in scleroderma. Scleroderma is characterized by aberrations of extracellular matrix deposition. This study represents the first time that hyaluronidase activity levels have been determined in scleroderma patients. PubMed. Br J Dermatol. 2004 Mar;150(3):469-76. |
| Advanced Glycation Endproducts (AGES) |
| Advanced Glycation Endproducts (AGES) as Potential Mediators in Vascular Disease in Systemic Sclerosis (SSc). These data indicate increased AGE formation in SSc, also featuring increased homocysteine levels. AGE formation in SSc may be involved, along with increased homocysteinemia, in endothelial injury favoring both micro- and macrovascular disease. O. Kaloudi. FRI0322 EULAR 2004. |
| 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. |
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| Autoimmunity |
| 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. |
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| 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. Sometimes T cells become overactive, which is suspected as being part of the process that leads to autoimmune diseases. ISN. |
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| Cluster Studies |
| Causes of Scleroderma: Cluster Studies Cluster studies can help pinpoint some of the causes of scleroderma. ISN. |
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| Cytokines |
| Cytokines are small secreted proteins which mediate and regulate immunity, inflammation, and hematopoiesis. Cytokines can cause inflammation associated with a variety of autoimmune diseases. ISN. |
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| 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. |
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| 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. |
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| Endothelin |
| When healing turns to scarring: Research reveals why it happens and how to stop it. During tissue repair, specialized cells called myofibroblasts migrate to the wound where they generate the adhesive and tensile forces required for wound closure. Normally, these myofibroblasts then disappear from the wound. But if they persist and continue to make connective tissue, it can become too thick, preventing the organ from functioning properly. EurekAlert! 09/18/08. (Also see: Causes of Scleroderma: Fibroblasts) |
| Simvastatin Reduces Endothelial Activation and Damage But Is Partially Ineffective in Inducing Endothelial Repair in Systemic Sclerosis (SSc). Treatment with simvastatin results in rapid and significant improvement of measures of endothelial activation, suggesting a potential role of statins in the treatment of peripheral vascular disease in SSc. Journal of Rheumatology. June 2008. (Also see: Medications,and Raynaud's) |
| How does endothelial cell injury start? The role of endothelin in systemic sclerosis. This article reviews the role of endothelin as an example of a pleiotropic mediator with effects on various aspects of SSc pathogenesis, such as inflammation, vasculopathy and tissue remodelling. Arthritis Research & Therapy 2007, 9(Suppl 2):S2. |
| Systemic Sclerosis Patients Have Activating Antibodies Targeting Both Endothelin Receptor Type A And Angiotensin Ii Type 1 Receptor Predicting Worse Prognosis. Anti-AT1R and anti-ETAR antibodies are a biomarker for severe disease and worse prognosis and could explain pathogenic features found in systemic sclerosis. The detection of these antibodies could identify SSc patients that might benefit from a receptor blockade or from a specific modulation of the antibody-receptor interaction. G. Riemekasten OP0162 EULAR 2007. (Also see: Antibodies,and Prognosis) |
| Environmental |
| 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. |
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| 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. |
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| Fibroblasts |
| Fibroblasts. Fibroblasts provide a structural framework (stroma) for many tissues, and play a critical role in wound healing. They are the most common cells of connective tissue in animals. Wikipedia. |
| When healing turns to scarring: Research reveals why it happens and how to stop it. During tissue repair, specialized cells called myofibroblasts migrate to the wound where they generate the adhesive and tensile forces required for wound closure. Normally, these myofibroblasts then disappear from the wound. But if they persist and continue to make connective tissue, it can become too thick, preventing the organ from functioning properly. EurekAlert! 09/18/08. (Also see: Causes of Scleroderma: Endothelin) |
| 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. |
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| 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. |
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| 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. |
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| Homocysteine and MTHFR C677T Gene Mutation |
| Plasma Homocysteine Levels and the Prevalence of Methylenetetrahydrofolate Reductase Gene C677T Polymorphism in Systemic Sclerosis. The presence of MTHFR C677T mutation influences the incidence of macrovascular abnormalities in SSc. Elevated Hcy levels may be associated with disease duration and the evolution of macrovascular disorders and pulmonary hypertension in SSc. Gabriella Szücs. FRI0288 EULAR 2004. |
| Infection |
| 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. |
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| Interleukins |
| Causes of Scleroderma: Interleukins Interleukin-10 gene is associated with scleroderma; interleukin-1 may upregulate scleroderma fibroblasts; interleukin-13 is associated with localized scleroderma. ISN. |
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| 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. |
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| Molecular Defect - TGF Dysregulation |
| Causes of Scleroderma: Molecular Defect in TGFbeta/SMAD may play a role in the development of scleroderma fibrosis. ISN. |
| Natural Killer Cells |
| Natural Immune-control System May Aid Treatment Of Autoimmune Disease And Tissue Rejection. "Our findings suggest that it is possible to use antibodies to trigger the body's own mechanism for suppressing the immune response," Cantor remarks. "The results serve as a proof of principle that this approach can be applied to the treatment of conditions characterized by an excessive or unwanted immune response." Science Daily. 05/17/07. |
| Study reveals how production of interferon gamma (IFNg) is controlled in natural killer (NK) cells. IFNg, produced by NK cells and other cell types, plays a critical role in killing pathogen-infected cells and in defending against tumor cells. However, overproduction of IFNg is also dangerous to the body and can cause autoimmune diseases. News Medical.Net 05/31/06. |
| Neuropeptides and Substance P |
| Levels of Neuropeptides in Bronchoalveolar Lavage (BAL) Fluids of Patients with Systemic Sclerosis (SSc). Our results indicate that VIP (vasoactive intestinal peptide) and SP (substance P) may be involved in the pathogenesis of SLD (scleroderma lung disease) and that they may play a role in the development of skin and interstitial lung fibrosis. A. Del Rosso. FRI0302 EULAR 2004. (Also see: Pulmonary Fibrosis and Skin Fibrosis) |
| Oxidative Stress, Lipid Peroxidation |
| Abnormal exhaled ethane concentrations in scleroderma. Scleroderma is a chronic multisystem autoimmune disease in which oxidative stress is suspected to play a role in the pathophysiology. It was postulated that patients with scleroderma would have abnormally high breath ethane concentrations, a volatile product of free-radical-mediated lipid peroxidation. PubMed. Biomarkers. 2006 Jan-Feb;11(1):70-84. |
| Lipid peroxidation and trace elements in systemic sclerosis (SSc). Oxidative stress appears to be important in the causation and perpetuation of tissue injury and fibrosis in SSc. There is evidence that lipid peroxidation increase and antioxidant capacity reduces in SSc. The gradual decline in MDA levels suggests that antioxidant therapy, if to be useful in SSc, is most likely to be effective early in the course of the disease. PubMed. Clin Rheumatol. 2005 Oct 25;:1-5. (Also see: Alternative Treatments) |
| 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. |
| A Polymorphism In The Human Serotonin 5-HT2A Receptor Gene May Protect Against Systemic Sclerosis By Reducing Platelet Aggregation. Platelet aggregation may contribute to the pathogenesis of systemic sclerosis: following activation platelets release significant amounts of serotonin which promotes vasoconstriction, fibrosis and further enhances aggregation. L, Beretta. Arthritis Research & Therapy 2008, 10:R103. |
| Proteins |
| Antitransforming growth factor (Anti-TGF) -[beta] therapy in fibrosis: recent progress and implications for systemic sclerosis. Anti-TGF-[beta] therapies promise to have a major impact in systemic sclerosis. Significant concerns regarding efficacy and safety need to be addresed. The identification of optimal candidates for therapy, and of biomarkers of safety and efficacy, are critical challenges ahead. J.Varga. Current Opinion in Rheumatology. 20(6):720-728, November 2008. |
| Inflammation's trigger finger. A molecule found in nearly all cells plays a vital role in kick-starting the production of key biological molecules involved in inflammation. The finding may lead to new strategies for blocking the devastating inflammation that lies at the heart of autoimmune disorders such as multiple sclerosis, arthritis, lupus as well as some cancers. innovations report. Salk Institute 07/20/04. |
| Radiation |
| Radiation and Scleroderma. There is an increased rate of cancer among scleroderma patients. Furthermore, scleroderma patients have an increased sensitivity to radiation treatments. In addition, radiation can cause scleroderma including Radiation Port Scleroderma. ISN. |
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| Serum TIMP-2 |
| Clue To Systemic Sclerosis Cited In Preliminary Study. Tissue inhibitor of metalloproteinases 2 may well play a role in systemic sclerosis. In spirometric testing serum concentration of TIMP-2 was found to be higher in patients with restrictive pulmonary dysfunction. Doctor's Guide 3/26/02. |
| 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) |
| Silica |
| Causes of Scleroderma: Silica. Silica exposure can cause autoimmune diseases such as lupus, scleroderma, and vasculitis. It can also cause silicosis, kidney disease, lung cancer, tuberculosis, and other airways diseases. Environmental exposure to silica can occur in workers and bystanders in many industries, including agriculture, construction, and pottery. ISN. (Also see: Causes of Scleroderma: Silicone Breast Implants) |
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| Sleep Disorders |
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| Sleep-Disordered Breathing Among Women With Fibromyalgia Syndrome. A large proportion of women with fibromyalgia in a general rheumatology practice had sleep-disordered breathing, which can be detected using sleep polysomnograms. Journal of Clinical Rheumatology. 12(6):277-281, December 2006.(Also see: Fibromyalgia) |
| Stress |
| Stress can cause hormonal and cellular changes in our bodies which can lead to a variety of medical problems. Chronic stress is thought to be a trigger for the development or exacerbation of autoimmune diseases. 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 |
| Thyroid at Root of Many Symptoms. The most common single disorder is an autoimmune problem (in which the body "fights" itself) called Hashimoto's disease, which results in underactive thyroid. Women with other autoimmune disorders are at prime risk for some form of thyroid dysfunction. WebMD. (Also see: Associated Conditions: Thyroid) |
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| Vascular and Microvascular |
| Reduced Aerobic Capacity in Systemic Sclerosis (SSc) Patients Without Pulmonary Involvement. Abnormal vascular response to exercise may account for this finding since the vascular system is one of the major target organs in this pathologic condition. Natalia C. Oliveira. 1866/538 ACR 2006. |
| Bone marrow endothelial progenitors are defective in systemic sclerosis (SSc). This study showed there is a complex impairment in the bone marrow microenvironment involving both the endothelial and mesenchymal stem cell compartments and that this impairment might play a role in defective vasculogenesis in scleroderma. PubMed. Arthritis Rheum. 2006 Jul 25;54(8):2605-2615. |
| Hyperplasia of dermal microvascular pericytes in scleroderma. The observed pericytes increase in the peripheral zones of active disease supports the hypothesis of a vascular pathogenesis of scleroderma and directs the focus to microvascular PC. PubMed. J Cutan Pathol. 2004 Jul;31(6):431-40. |
| Defective vasculogenesis in systemic sclerosis. Insufficient vascular repair machinery due to defective vasculogenesis might contribute to vasculopathy in systemic sclerosis. Circulating endothelial precursors could be a novel target for therapeutic strategies for ischaemic complications in patients with systemic sclerosis. PubMed. Lancet. 2004 Aug 14;364(9434):603-10. |
| (Also see: Raynaud's Phenomenon) |
| Vitamin D Deficiency |
| Vitamin D 's major biological function is to maintain normal blood levels of calcium and phosphorus. Recent studies have demonstrated that individuals with low blood levels of vitamin D are at a higher risk of developing autoimmune diseases. ISN. |
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| Related Books |
| Donna Jackson Nakazawa: Autoimmune diseases hazards. My paralysis was caused by Guillain-Barre syndrome, in which body's immune system destroys the nerves' myelin sheaths, short-circuiting messages from the brain to the muscles. Opinion. The Sacramento Bee. 03/19/08. (Also see: Guillain-Barre Syndrome) |
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