Scleroderma

Scleroderma is a disabling disease characterized by fibrosis, an excessive production of connective tissue proteins, such as collagen. Its name is derived from the Greek words “sklerosis” (which means hardness) and “derma” (which means skin), because a major symptom is hard skin due to fibrosis. The cause of the disease is not known, but one of the reasons is believed to be autoimmunity (a condition in which the body mistakenly detects its own tissue as foreign and attacks itself), which may trigger molecular events leading to fibrosis.


Types of Scleroderma

Scleroderma has many different forms that are placed in two major categories: localized and systemic. Localized scleroderma is generally limited to skin, underlying tissues, and, in some cases, underlying muscle. Systemic sclerosis affects many parts of the body, such as skin, internal organs, and blood vessels.

Approximately 50,000 Americans are affected by systemic sclerosis and it is 2-3 times more common in women than men. Although it strikes patients of all ages, including children, incidence is most likely between the ages of 40-60. There is a higher prevalence in some Native American populations.
Raynaud’s phenomenon—an intensified reaction to cold or anxiety, including numbness in fingers, toes, and sometimes other extremities—affects approximately 90% of people with scleroderma at some point in their life. By contrast, only about 3% of the general population has Raynaud’s phenomenon.


YESTERDAY

  • In the past, scleroderma frequently went undiagnosed because of its rarity. Patients were usually referred to orthopaedic surgeons to treat shortening of tendons and muscles (a permanent condition known as “contracture”), as well as complications from infections that might require an amputation or the removal of dead or damaged tissue.

Photograph, from Primer on the Rheumatic Diseases, 11th edition (courtesy of Springer) shows severe scleroderma of the hand, with depigmentation, ulceration, and finger contractures due to skin fibrosis.

    • Although there were no known treatments, a published description from 18th century Italy did report the successful resolution of symptoms following 11 months of warm milk and vapor baths, bleeding from the foot, and small doses of mercury.

TODAY

  • We have learned that scleroderma is not contagious. Patients are usually referred to dermatologists and rheumatologists who have expertise in autoimmune diseases and musculoskeletal disorders.

  • Patients are still treated by orthopaedic surgeons to manage health issues related to the disease, such as those associated with infections. While the amputation of fingers and toes is sometimes still unavoidable, these procedures are rarely necessary because of the availability of many new treatments that target specific tissues and nerves.

  • In order to manage the activities of daily living and to intervene in problems of contracture, occupational and physical therapists are also often involved in a patient’s care. In addition, other health specialists become involved if particular organs are affected: for example, cardiologists for heart problems, pulmonologists for lung complications, and gastroenterologists for digestive tract issues.

  • The majority of treatments address symptoms in specific, affected organs and not the underlying cause of scleroderma, which is the excessive production of connective tissue proteins.

  • NIH-funded research has shown that the immunosuppressive drug cyclophosphamide may improve lung function and quality-of-life in scleroderma patients.

  • Genetic factors that may contribute to the disease have been identified and are an important focus of NIH investigation.

  • The NIH-funded National Family Registry for Scleroderma is collecting biological samples from patients and, when possible, their parents, so that genetic differences between patients and healthy individuals can be detected and potentially traced to a parent. Further research based on this registry may reveal genes that contribute to the development of scleroderma.

TOMORROW

  • Categorizing the severity of the disease by distinct patterns of gene expression, or “gene signatures,” may guide personalized treatment for scleroderma patients.

  • Antibodies are molecules that attack the body’s invaders, such as bacteria or viruses. In the case of scleroderma, autoantibodies (antibodies that attack a person’s own tissues) may carry out some of the tissue damage seen in this disease. Therefore, monitoring these scleroderma-associated autoantibodies may help characterize patients’ conditions and predict the future course of their disease.

  • New therapies may prevent the development of scleroderma by interrupting the process of fibrosis or immune system dysfunction that leads to attacks on a patient’s own tissues. NIH-supported researchers have developed several mouse models that mimic these biological pathways in humans. Additional insights from these models could be pivotal to the development of new scleroderma treatments.

  • Scleroderma susceptibility genes discovered by the National Family Registry may identify new targets for treatment.

  • Participation of patients in clinical research is one of the best ways to advance new knowledge and contribute to the development of new treatments.

Contact: NIAMS Information Clearinghouse toll free: 877-22-NIAMS (226-4267); email: NIAMSInfo@mail.nih.gov

National Institute on Arthritis and Musculoskeletal and Skin Diseases (NIAMS): http://www.niams.nih.gov

 

 

 

 

Systemic scleroderma

Other Names:

Systemic sclerosis; Scleroderma, systemic; Progressive systemic sclerosis

Categories:

Skin Diseases

Subtypes:

Diffuse cutaneous systemic sclerosis; Limited cutaneous systemic sclerosis; Limited systemic sclerosis

This disease is grouped under:

Scleroderma

Systemic scleroderma is an autoimmune disorder that affects the skin and internal organs. It is characterized by the buildup of scar tissue (fibrosis) in the skin and other organs. The fibrosis is caused by the body's production of too much collagen, which normally strengthens and supports connective tissues. The signs and symptoms of systemic scleroderma usually begin with episodes of Raynaud's phenomenon, which can occur weeks to years before fibrosis. This may be followed by puffy or swollen hands before the skin becomes thickened and hard. Fibrosis can also affect internal organs and can lead to impairment or failure of the affected organs. The most commonly affected organs are the esophagus, heart, lungs, and kidneys.[1]

There are three types of systemic scleroderma, defined by the tissues affected in the disorder.[1][2]

  • Diffuse cutaneous systemic sclerosis

  • Limited cutaneous systemic sclerosis (which includes CREST syndrome)

  • Limited systemic sclerosis (systemic sclerosis sine scleroderma)

Treatment depends on the symptoms that are present and the organs that are affected in the disease, and may include immunosupressive therapy.[3]  

Last updated: 4/26/2018

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing 1-5 of 56 |

Medical Terms

Other Names

Learn More:

HPO ID

80%-99% of people have these symptoms

Abnormality of the gastric mucosa

Abnormality of the mucous membrane layer of stomach

0004295

Arthralgia

Joint pain

0002829

Arthritis

Joint inflammation

0001369

Atypical scarring of skin

Atypical scarring

0000987

Autoimmunity

Autoimmune disease

[ more ]

0002960

Showing 1-5 of 56 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 10/1/2019

Do you have updated information on this disease? We want to hear from you.

The exact, underlying cause of systemic sclerosis is unknown. The cause appears to involve some injury to the cells that line blood vessels, resulting in excessive activation of dermal connective tissue cells, called fibroblasts. Fibroblasts normally produce collagen and other proteins.[4] Build-up of collagen in the skin and other organs causes the signs and symptoms of the condition.[5]

It is suspected that scleroderma may develop from a variety of factors, which may include:[6][4][7]

  • Abnormal immune or inflammatory activity

  • Genetic susceptibility: while no specific genes are thought to cause scleroderma, certain variations in genes or combination of genes  may increase a person's risk to be affected. These genes include  several human leukocyte antigen (HLA) complex genes, and also non-HLA genes such as the TNFAIP3, CD247, IRF5, STAT4, and PTPN22 genes. However, while the risk of being affected by the disease is increased when a relative is affected, the condition is not passed directly from parents to children.

  • Environmental triggers: suspected triggers may include infections; injury; drugs (e.g. vitamin K, cocaine, penicillamine, appetite suppressants and some chemotherapeutic agents); and chemicals (e.g. silica, organic solvents, pesticides, aliphatic hydrocarbons and epoxy resin).

  • Hormones: because women develop scleroderma more often than men, researchers suspect that hormones may play a role, but  the role of female hormones has not been proven.

Widespread scleroderma can also occur in association with other autoimmune diseases, including systemic lupus erythematosus and polymyositis.[5]

It is thought that the disease is triggered from the exposure to the environmental factors in people who are genetically susceptible. In some people, genetic factors may be sufficiently strong to lead to the disease. 

Last updated: 4/26/2018

Most cases of systemic scleroderma are not inherited, but instead, occur in people with no history of the condition in their family.  However, several studies show that the risk of systemic scleroderma in first-degree relatives of people with the disease is increased and and a few cases of the condition have been reported to run in families, but there is no clear pattern of inheritance. Also, some people with systemic scleroderma have relatives with other autoimmune disorders.[8][7]


Last updated: 4/26/2018

Because systemic scleroderma is not caused by a mutation in any one specific gene, clinical genetic testing to confirm a diagnosis or identify a "carrier" is not currently available.  Even if someone is known to carry a version of a gene that may make them susceptible to the condition, it does not mean they will definitely develop the condition.

You can view a list of centers that may be involved in research projects on systemic scleroderma on Orphanet's Web site.

You can also view a list of clinical trials involving people with systemic scleroderma on ClinicalTrials.gov.

People interested in learning more about genes and genetic testing for systemic scleroderma should speak with a genetics professional.

Last updated: 4/9/2014

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Systemic scleroderma. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Systemic scleroderma. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Systemic scleroderma:
    CONQUER Registry?

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

  • International Scleroderma Network (ISN)
    7455 France Ave So #266
    Edina, MN 55435-4702
    Toll-free: 1-800-564-7099
    Telephone: +1-952-831-3091
    E-mail: isn@sclero.org
    Website: https://www.sclero.org/index.html

  • Scleroderma & Raynaud's UK (SRUK)
    18-20 Bride Lane
    London, EC4Y 8EE United Kingdom
    Toll-free: 0800 311 2756 (Helpline)
    Telephone: 020 7000 1925 (Office)
    E-mail: info@sruk.co.uk
    Website: https://www.sruk.co.uk

  • Scleroderma Foundation
    300 Rosewood Drive, Suite 105
    Danvers, MA 01923
    Toll-free: 1-800-722-4673 (HOPE)
    Telephone: +1-978-463-5843
    Fax: +1-978-463-5809
    E-mail: sfinfo@scleroderma.org
    Website: https://www.scleroderma.org

  • Scleroderma Research Foundation
    220 Montgomery Street, Suite 484
    San Francisco, CA 94104
    Telephone: +1-415-834-9444
    E-mail: info@srfcure.org
    Website: https://srfcure.org/

  • Scleroderma Society of Ontario
    41 King William Street, Suite 202
    Hamilton, ON, L8R 1A2 Canada
    Toll-free: 1-888-776-7776 (Helpline)
    Telephone: +1-905-544-0343
    E-mail: info@sclerodermaontario.ca
    Website: https://www.sclerodermaontario.ca/

Do you know of an organization? We want to hear from you.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.

  • Genetics Home Reference (GHR) contains information on Systemic scleroderma. This website is maintained by the National Library of Medicine.

  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.

  • The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. Click on the link to view information on this topic.

  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.

  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 

  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.