| 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) |
| 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) |
| Epidemiology
of connective tissue disorders. The reported prevalence
and incidence of connective tissue disorders are quite variable,
depending on differences in study methodology. The prevalence
of systemic sclerosis is lower, however, varying significantly
between different studies and countries. PubMed. Rheumatology
(Oxford). 2006 Oct;45 Suppl 3:iii3-iii4. |
| 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. |
|
| 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. |
|
|
| 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. |
|
|
| Cluster Studies |
| Causes
of Scleroderma: Cluster Studies Cluster studies can help
pinpoint some of the causes of scleroderma. ISN. |
|
| 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 |
|
|
| 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 |
|
| Endothelin |
| 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 |
|
| 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 |
|
|
| 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. |
| 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: Causes of Scleroderma, B and T cells, and Cytokines) |
| 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 |
|
| 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. |
|
|
| 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. |
|
| 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. |
|
|
| 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. |
|
| 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. |
| Saving Your Self From Yourself. Being able to better tune the body's defenses offers the possibility of a wide range of novel therapies to treat diseases like arthritis and diabetes, to combat transplant rejection, and, perhaps, to fight cancer. In autoimmune diseases, T cells attack the self, rather than the non-self. Harvard University Gazette. 02/08/07. (Also see: Causes of Scleroderma: B Cells and T Cells ) |
| 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. |
| Abnormal
natural killer cell function in systemic sclerosis: altered
cytokine production and defective killing activity. Natural
killer (NK) cells are innate immune effectors that produce
various immunoregulatory cytokines. Recent studies have shown
that NK cells are involved in the initiation of autoimmunity.
In this study results suggested that altered NK cell function
contributes to immunological abnormalities in SSc. PubMed.
J Invest Dermatol. 2005 Oct;125(4):731-7. |
| 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) |
| Proteins |
| Protein May Form Target in Autoimmune Therapy. Researchers here have isolated what they think may be a new therapeutic target in autoimmune diseases. Medpage Today. 01/28/08. |
| 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. |
|
|
| 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) |
|
| Sleep Disorders |
|
|
| 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) |
| Differential
expression of tissue kallikrein in the skin of systemic sclerosis. Immunohistochemical
and biomolecular results indicate that t-kallikrein is decreased
in the skin of SSc patients and decreases progressively from
the early to advanced phase of lSSc and dSSc. The decreased
expression of t-kallikrein may be involved in the impairment
of the sweating process, vessel functionality and angiogenesis. PubMed.
Histol Histopathol. 2005 Apr;20(2):415-22. |
| 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) |
|
|
| 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. |
|
|
| 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) |
| Footnotes |
| (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. |
. Despite the prevalence of autoimmune disease, surveys show that more than 90 percent of people cannot summon the name of a single autoimmune disease when asked to name one specifically. Excerpt from book by Donna Nakazawa. Alert.net. 03/19/08. (Also see: