Rare Cardiology News

Disease Profile

Systemic scleroderma

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-5 / 10 000

33,100 - 165,500

US Estimated

1-5 / 10 000

51,350 - 256,750

Europe Estimated

Age of onset

Adult

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ICD-10

M34.0 M34.1 M34.2 M34.8 M34.9

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Systemic sclerosis; Scleroderma, systemic; Progressive systemic sclerosis

Categories

Skin Diseases

Summary

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]

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

Symptoms

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.

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
Autoimmune disorder

[ more ]

0002960
Chest pain
0100749
Chondrocalcinosis
Calcium deposits in joints
0000934
Cough
Coughing
0012735
Edema
Fluid retention
Water retention

[ more ]

0000969
Fatigue
Tired
Tiredness

[ more ]

0012378
Gastroparesis
Delayed gastric emptying
0002578
Hyperkeratosis
0000962
Lack of skin elasticity
0100679
Myalgia
Muscle ache
Muscle pain

[ more ]

0003326
Nausea and vomiting
0002017
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

0003202
30%-79% of people have these symptoms
Cachexia
Wasting syndrome
0004326
Carious teeth
Dental cavities
Tooth cavities
Tooth decay

[ more ]

0000670
Gangrene
Death of body tissue due to lack of blood flow or infection
0100758
Malabsorption
Intestinal malabsorption
0002024
Mucosal telangiectasiae
0100579
Myocardial fibrosis
0001685
Myositis
Muscle inflammation
0100614
Papule
0200034
Pericarditis
Swelling or irritation of membrane around heart
0001701
Pulmonary fibrosis
0002206
Pulmonary infiltrates
Lung infiltrates
0002113
Respiratory insufficiency
Respiratory impairment
0002093
Skin ulcer
Open skin sore
0200042
Telangiectasia of the skin
0100585
Xerostomia
Dry mouth
Dry mouth syndrome
Reduced salivation

[ more ]

0000217
5%-29% of people have these symptoms
Angina pectoris
0001681
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat

[ more ]

0011675
Bowel incontinence
Loss of bowel control
0002607
Erectile dysfunction
Abnormal erection
Erectile abnormalities

[ more ]

0100639
Feeding difficulties in infancy
0008872
Hypertensive crisis
0100735
Irregular hyperpigmentation
0007400
Joint dislocation
Joint dislocations
Recurrent joint dislocations

[ more ]

0001373
Migraine
Intermittent migraine headaches
Migraine headache
Migraine headaches

[ more ]

0002076
Narrow mouth
Small mouth
0000160
Osteolysis
Breakdown of bone
0002797
Osteomyelitis
Bone infection
0002754
Peripheral neuropathy
0009830
Pulmonary arterial hypertension
Increased blood pressure in blood vessels of lungs
0002092
Seizure
0001250
Tendon rupture
Rupture of tendons
Ruptured tendon

[ more ]

0100550
Tetralogy of Fallot with atrioventricular canal defect
0011677
Percent of people who have these symptoms is not available through HPO
Abnormal abdomen morphology
Abnormality of abdomen structure
0001438
Abnormality of chromosome stability
0003220
Autosomal dominant inheritance
0000006
Calcinosis
Calcium buildup in soft tissues of body
0003761
Chromosome breakage
0040012
Sclerodactyly
0011838
Scleroderma
0100324
Telangiectasia
0001009

Cause

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. 

Diagnosis

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.

Treatment

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Organizations

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

    Learn more

    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.
    • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
    • Genetics Home Reference (GHR) contains information on Systemic scleroderma. This website is maintained by the National Library of Medicine.
    • 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.

        References

        1. Systemic scleroderma. Genetics Home Reference (GHR). 2015; https://ghr.nlm.nih.gov/condition/systemic-scleroderma.
        2. Denton CP. Overview and classification of scleroderma disorders. UpToDate. 2016; https://www.uptodate.com/contents/overview-and-classification-of-scleroderma-disorders.
        3. Denton CP. Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults. UpToDate. February 05, 2018; https://www.uptodate.com/contents/overview-of-the-treatment-and-prognosis-of-systemic-sclerosis-scleroderma-in-adults.
        4. Ngan V. Systemic sclerosis. DermNet NZ. 2018; https://dermnetnz.org/immune/systemic-sclerosis.html.
        5. Scleroderma. MedlinePlus. April, 2018; https://www.nlm.nih.gov/medlineplus/ency/article/000429.htm.
        6. Handout on Health: Scleroderma. NIAMS. 2016; https://www.niams.nih.gov/Health_Info/Scleroderma/default.asp#4.
        7. Varga J. Risk factors for and possible causes of systemic sclerosis (scleroderma). UpToDate. November 07, 2017; https://www.uptodate.com/contents/risk-factors-for-and-possible-causes-of-systemic-sclerosis-scleroderma.
        8. Systemic scleroderma. Genetics Home Reference. 2015; https://ghr.nlm.nih.gov/condition/systemic-scleroderma.

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