Scleroderma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2] Ayesha A. Khan, MD[3]

Scleroderma is an autoimmune connective tissue disease. The hallmark of the disease is the presence of autoantibodies against various cellular antigens, which results in small vessel vasculopathy, excessive collagen deposition and fibrosis of skin and internal organs. Growth factors and cytokines play an important role in the underlying pathogenesis. The word scleroderma is greek in origin and translates in to hard skin, describing the skin fibrosis. Scleroderma is classified into 2 subtype, limited cutaneous scleroderma and diffuse cutaneous scleroderma. CREST syndrome is a variant of limited cutaneous scleroderma. Choctaw native Americans have a much higher prevalence of scleroderma than the general population. Scleroderma must be differentiated from other diseases that cause skin thickening, sclerodactyly, edema and symptoms of gastroesophageal reflux disease. Common risk factors for scleroderma that have been described in literature are exposure to silica, chlorinated and aromatic solvents and welding fumes. Since there is a possibility of internal organ involvement, screening for fatal complications such as scleroderma renal crisis, pulmonary arterial hypertension, and cardiovascular involvement must be carried out in patients with scleroderma. Scleroderma is mainly diagnosed based on clinical presentation and the new American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification criteria has been published. The new criteria is more sensitive and is better for detecting disease earlier, so that the fatal renal and pulmonary complications can be screened for and prevented. Nailfold video capillaroscopy is the diagnostic study of choice to confirm Raynaud’s phenomenon and scleroderma microangiopathy. The mainstay of treatment for scleroderma is medical therapy. Pharmacologic medical therapies for scleroderma include topical tacrolimus for morphea, methotrexate for diffuse sclerosis of the skin, minocycline for calcinosis cutis, nifedipine for Raynaud’s phenomenon, captopril for scleroderma renal crisis.

The word scleroderma comes from greek words; skleros (hard) and derma (skin). Scleroderma was first described by Carlo Curzio in Naples, Italy in 1753. The association between abnormal vasoconstriction and diffuse scleroderma was made in 1865 by Raynaud.

Scleroderma (systemic sclerosis) is classified into 2 subtypes, limited cutaneous scleroderma and diffuse cutaneous scleroderma. Morphea and CREST syndrome are variants of limited cutaneous scleroderma. Scleroderma was previously classified according to American College of Rheumatology (ACR) 1980 preliminary scleroderma criteria. Scleroderma (systemic sclerosis) is now classified according to the new American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) criteria.

Scleroderma is an autoimmune connective tissue disease. The hallmark of the underlying pathophysiology is production of autoantibodies against various cellular antigens, small vessel vasculopathy, fibrosis of skin and internal organs, and excess collagen deposition in the skin and internal organs. Circulating autoantibodies found in patients with scleroderma are anti-topoisomerase I (Scl-70) antibody, anti-centromere antibody, anti-RNA polymerase III antibody, anti-nucleolar antibody. Growth factors and cytokines play an important role in the underlying pathogenesis of scleroderma. Increased fibroblast activity leads to the excessive collagen deposition in scleroderma. Although the hallmark of this disease is skin fibrosis, internal organ involvement is a fatal complication and includes, esophageal dysmotility, interstitial lung disease, pulmonary arterial hypertension, scleroderma renal crisis, myocardial fibrosis, pericardial fibrosis and pericardial effusion. Although scleroderma occurs in a sporadic pattern in the general population, variations in the human leukocyte antigen (HLA) genes can predispose an individual to developing scleroderma. On gross pathology, sclerodactyly, skin fibrosis, edema and calcinosis are characteristic findings of scleroderma. On microscopic histopathological analysis, characteristic findings of scleroderma include microvascular damage, perivascular infiltrates of immune cells, loss of microvasculature, perivascular edema, fibrosis, densely packed collagen in the lower dermis and upper subcutaneous layer, atrophy and loss of cells in the later stages of the disease. The endothelial cell dysfunction allows the chemokine– and cytokine-mediated attraction of inflammatory cells and fibroblast precursors (fibrocytes) from the bloodstream and bone marrow and their transmigration into the surrounding tissues, resulting in the establishment of a chronic inflammatory process with participation of macrophages and T and B lymphocytes, with further production and secretion of cytokines and growth factors from these cells.The immunological alterations include innate immunity abnormalities, tissue infiltration with macrophages and T and B lymphocytes; production of numerous disease-specific autoantibodies; and dysregulation of cytokine, chemokine, and growth factor production. The released cytokines and growth factors induce the activation and phenotypic conversion of various cellular types, including resident fibroblasts, epithelial cells, endothelial cells, and pericytes into activated myofibroblasts, the cells ultimately responsible for initiation and establishment of the fibrotic process.

The cause of scleroderma has not been identified. There is a possibility of an underlying immunologic abnormality. To review risk factors for the development of scleroderma click here.

Scleroderma must be differentiated from other diseases that cause skin thickening, sclerodactyly, edema and symptoms of GERD such as scleredema, scleromyxedema, eosinophilic fasciitis, chronic graft-versus-host disease, drug induced scleroderma, scleroderma overlap syndromes, diabetic cheiroarthropathy, myxedema and nephrogenic systemic fibrosis.

The majority of cases of scleroderma have been reported from the United States. The prevalence of scleroderma is approximately 24 cases per 100,000 individuals in the United States. Scleroderma commonly affects individuals between 20 to 50 years of age. Choctaw native Americans have a much higher prevalence of scleroderma than the general population. Females are more commonly affected than males. Familial clustering of scleroderma has been reported in United States and Australia.

Common risk factors in the development of scleroderma include occupational and environmental exposure to certain chemicals, certain genetic variations and infectious agents. Most commonly implicated occupational and environmental risk factors are exposure is to silica, chlorinated and aromatic solvents as well as welding fumes.

There is insufficient evidence to recommend routine screening for scleroderma, however screening is recommended for pulmonary arterial hypertension and malignancy in scleroderma patients. Regular blood pressure monitoring at home is encouraged in patients with scleroderma to screen for renal involvement and prevention of scleroderma renal crisis

If left untreated, patients with scleroderma may progress to develop pulmonary arterial hypertension (PAH), interstitial lung disease and severe gastrointestinal disease. Common complications of scleroderma include pulmonary fibrosis, pulmonary arterial hypertension, interstitial lung disease and scleroderma renal crisis. The 10-year survival rate of patients with scleroderma is approximately 70%-80%.

There is no single diagnostic study of choice for the diagnosis of scleroderma. Scleroderma is mainly diagnosed based on clinical presentation, though scleroderma (systemic sclerosis) maybe diagnosed based on the new American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification criteria. The new criteria is more sensitive and is better for detecting disease earlier, so that the fatal renal and pulmonary complications can be screened for and prevented.

The hallmark of scleroderma is sclerodactyly. A positive history of progressive skin tightening and hardening is suggestive of scleroderma. The most common symptoms of scleroderma include skin tightening or induration, Raynaud’s phenomenon, and symptoms of gastroesophageal reflux disease (GERD). Less common symptoms of scleroderma include shiny skin appearance and restricted movement of affected areas of the skin.

Patients with scleroderma usually appear anxious. Physical examination of patients with scleroderma is usually remarkable for sclerodactyly, Raynaud’s phenomenon, digital ulcers, skin fibrosis and telangiectasias.

An ECG may be helpful in the diagnosis of scleroderma heart disease. Findings on an ECG suggestive of scleroderma heart disease include left bundle branch block, right bundle branch block and septal infarction pattern. It is recommended to screen for myocardial fibrosis with an annual electrocardiogram in patients with scleroderma.

An x-ray of the chest may be helpful in the diagnosis of scleroderma interstitial lung disease and pulmonary fibrosis.Although it is usually not as sensitive as HRCT, findings on an x-ray suggestive of scleroderma interstitial lung disease include, interstitial opacification, reticular areas of attenuation, ground glass opacity greatest at lung bases.

High-resolution CT (HRCT) scan of the chest may be helpful in the diagnosis of scleroderma interstitial lung disease and pulmonary hypertension. Findings on HRCT suggestive of interstitial lung disease include architectural distortion due to pulmonary fibrosis, reticular interlobular interstitial thickening, increased ground glass opacity and accentuated reticular markings on juxtapleural, posterior and basilar portion of the lungs, traction bronchiectasis, and honeycomb cystic change

There are no MRI findings associated with scleroderma.

There are no echocardiography/ultrasound findings associated with scleroderma. However, a transthoracic echocardiography (TTE) may be helpful in the diagnosis of complications of scleroderma, which include pulmonary arterial hypertension (PAH).

Nail-fold video capillaroscopy (NVC) may be helpful in the diagnosis of scleroderma. Findings on nail-fold video capillaroscopy diagnostic of raynaud’s phenomenon (RP) and scleroderma microangiopathy include nail-fold capillary abnormalities, capillary dilatation, and capillary loop drop-out. Findings on nail-fold video capillaroscopy diagnostic of scleroderma microangiopathy are graded into 3 phases; early, active and late.

There are no other diagnostic study associated with scleroderma.

The mainstay of treatment for scleroderma is medical therapy. Pharmacologic medical therapies for scleroderma include topical tacrolimus for morphea, methotrexate for diffuse sclerosis of the skin, minocycline for calcinosis cutis, nifedipine for Raynaud’s phenomenon, captopril for scleroderma renal crisis, treatment of gastroesophageal reflux disease and pulmonary hypertension. Localized phototherapy with ultraviolet light is preferred for the treatment of morphea.

Surgical intervention is not recommended for the management of scleroderma. However, surgical procedures such as debulking and lung transplantation are needed to treat complications of scleroderma which include calcinosis cutis and pulmonary hypertension.

Effective measures for the primary prevention of scleroderma include avoiding occupational and environmental exposure to crystalline silica, epoxy resins, welding fumes and hand-arm vibration.

There are no established measures for the secondary prevention of scleroderma. However, effective measures for the secondary prevention of pulmonary arterial hypertension and scleroderma renal crisis in patients with scleroderma include screening.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

The word scleroderma comes from greek words; skleros (hard) and derma (skin). Scleroderma was first described by Carlo Curzio in Naples, Italy in 1753. The association between abnormal vasoconstriction and diffuse scleroderma was made in 1865 by Raynaud.

• The word scleroderma comes from greek words; skleros (hard) and derma (skin).^[1]
• Hippocrates, in his literature has also described scleroderma as a patient having hard skin.^[2]
• Scleroderma was first described by Carlo Curzio in Naples, Italy in 1753.^[3]
• The term scleroderma was first used by Fantonetti in 1837.
• The association between abnormal vasoconstriction and diffuse scleroderma was made in 1865 by Raynaud.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

Scleroderma (systemic sclerosis) is classified into 2 subtypes, limited cutaneous scleroderma and diffuse cutaneous scleroderma. Morphea and CREST syndrome are variants of limited cutaneous scleroderma. Scleroderma was previously classified according to American College of Rheumatology (ACR) 1980 preliminary scleroderma criteria. Scleroderma (systemic sclerosis) is now classified according to the new American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria.

Scleroderma (systemic sclerosis) is classified into 2 main subtypes:^[1][2][3]

• Limited cutaneous scleroderma:
  • Fibrosis is restricted to hands, arms and face.
  • Raynaud’s phenomenon is present for many years before the onset of fibrosis.
  • Pulmonary hypertension often occurs.
  • Anti-centromere antibodies are present in more than half of the patients.
  • Anti-centromere antibodies are associated with CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) syndrome.^[4][5]
  • Morphea is a type of localized scleroderma limited to the skin and subcutaneous tissues.^[6]
  • Patients with internal organ involvement with out the skin manifestations are known to have systemic sclerosis sine scleroderma.
• Diffuse cutaneous scleroderma:
  • It progresses rapidly.
  • Large area of the skin is affected.
  • One or more internal organs are affected.
  • It is associated with Anti-Scl-70 antibody (Anti-DNA topoisomerase I antibody).

Scleroderma was previously classified according to American College of Rheumatology (ACR) 1980 preliminary scleroderma criteria:^[7]

• Major criteria:
  • Proximal cutaneous sclerosis (skin thickening-nonpitting) of fingers that also extended proximally to the metacarpophalangeal joints (MCPs)
• Minor criteria:
  • Sclerodactyly
  • Digital pitting scars of fingertips or loss of substance of the distal finger pad (digital tuft resorption)
  • Bibasilar pulmonary fibrosis

• Scleroderma is classified if either one major criteria or 2 of 3 minor criteria are present.

Scleroderma (systemic sclerosis) is now classified according to the new American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) criteria:^[8][9]

Item	Sub-item(s)	Weight/score
Skin thickening of the fingers of both hands extending proximal to the metacarpophalangeal joints (sufficient criterion)	–	9
Skin thickening of the fingers (only count higher score)	Puffy fingers Sclerodactyly of the fingers (distal to the metacarpophalangeal joints but proximal to the proximal interphalangeal joints)	2 4
Fingertip lesions (only count the higher score)	Digital tip ulcers Fingertip pitting scars	2 3
Telangiectasia	–	2
Abnormal nail fold capillaries	–	2
Pulmonary arterial hypertension and/or interstitial lung disease		2
Raynaud’s phenomenon (RP)	–	3
Any of the scleroderma related autoantibodies	Anti-centromere antibodies Anti-topoisomerase I (anti-SCL-70) Anti-RNA polymerase-3	3

• The total score is determined by adding only the highest weight/score in each category.
• Patients with a total score ≥ 9 are classified as having scleroderma.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

Scleroderma is an autoimmune connective tissue disease. The hallmark of the underlying pathophysiology is production of autoantibodies against various cellular antigens, small vessel vasculopathy, fibrosis of skin and internal organs, and excess collagen deposition in the skin and internal organs. Circulating autoantibodies found in patients with scleroderma are anti-topoisomerase I (Scl-70) antibody, anti-centromere antibody, anti-RNA polymerase III antibody, anti-nucleolar antibody. Growth factors and cytokines play an important role in the underlying pathogenesis of scleroderma. Increased fibroblast activity leads to the excessive collagen deposition in scleroderma. Although the hallmark of this disease is skin fibrosis, internal organ involvement is a fatal complication and includes, esophageal dysmotility, interstitial lung disease, pulmonary arterial hypertension, scleroderma renal crisis, myocardial fibrosis, pericardial fibrosis and pericardial effusion. Although scleroderma occurs in a sporadic pattern in the general population, variations in the human leukocyte antigen (HLA) genes can predispose an individual to developing scleroderma. On gross pathology, sclerodactyly, skin fibrosis, edema and calcinosis are characteristic findings of scleroderma. On microscopic histopathological analysis, characteristic findings of scleroderma include microvascular damage, perivascular infiltrates of immune cells, loss of microvasculature, perivascular edema, fibrosis, densely packed collagen in the lower dermis and upper subcutaneous layer, atrophy, and loss of cells in the later stages of the disease.

• Scleroderma, also known as systemic sclerosis (SSc) is an autoimmune connective tissue disease.^[1][2]
• Important features of scleroderma include:^[3]
  • Production of autoantibodies against various cellular antigens
  • Small vessel vasculopathy
  • Fibrosis of the skin and internal organs
  • Excess of collagen deposition in the skin and internal organs
• Other features of Scleroderma include:
  • Sclerodactyly (thickened skin of the fingers) is common
  • Extensive skin fibrosis may be present
  • Raynaud phenomenon
  • Esophageal dysmotility
  • Pulmonary arterial hypertension
  • Cardiac involvement
  • Interstitial lung disease
  • Inflamatory arthritis
  • Digital ulcers
• There is an association between scleroderma and malignancy:^[4]
  • Patients with RNA polymerase III autoantibodies are at high risk for scleroderma associated malignancy
  • Patients with an older age of onset of scleroderma are at higher risk for cancer
  • Screening for malignancy is recommended in these patients at risk
• An increase in alpha2-adrenergic activity in vascular smooth muscle is responsible for vasospasm in scleroderma.^[5]
• Circulating autoantibodies found in patients with scleroderma include:
  • Anti-topoisomerase I (Scl-70) antibody^[6][7][8]
    • Associated with higher risk of interstitial lung disease
    • Increased disease activity
  • Anti-centromere antibody
    • Present in limited cutaneous scleroderma (CREST syndrome)
  • Anti-RNA polymerase III antibody^[9]
    • Associated with higher prevalence of malignancy in scleroderma patients
  • Anti-nuclear antibody (ANA)
• Growth factors and cytokines play a role in the underlying mechanism of disease:^[1]
  • Transforming growth factor-beta (TGF-beta)^[10]
  • Platelet-derived growth factor^[11]
  • Interleukins^[12]
    • IL-1, IL-6, IL-8, IL-17
  • Basic fibroblast growth factor (bFGF)^[13]
  • Interferon-gamma
  • Tumor necrosis factor (TNF) alpha
• Increased fibroblast activity leads to excess collagen deposition^[14]
  • The mechanism responsible is thought to be increased transcription of collagen specific mRNA^[15]
  • The transformation of fibroblasts to myofibroblasts leads to the over expression of cytokines and growth factors^[16][10]
  • Reactive oxygen species also play a role in the differentiation of fibroblasts^[17]
• Internal organ involvement:
  • Gastrointestinal system^[18][19][20]
    • Esophageal dysmotility
    • Lower esophageal sphincter incompetence
  • Pulmonary system
    • Interstitial lung disease (pulmonary fibrosis)^[21]
    • Pulmonary arterial hypertension
  • Renal system
    • Scleroderma renal crisis^[22][23]
      • Microalbuminuria
      • Elevated plasma creatinine
      • Hypertension
  • Cardiovascular system^[24]
    • Pericarditis^[25]
    • Pericardial effusion
    • Myocardial fibrosis^[26]
    • Myocardial ischemia leading to myocardial infarction^[27][28]
    • Arrhythmia
      • Ventricular arrhythmias
      • Due to fibrosis of the myocardium and conduction system

Genetics associated with the development of scleroderma include:^[29]

• Scleroderma occurs in a sporadic pattern in the general population.
• Variations in human leukocyte antigen (HLA) genes can predispose an individual to developing scleroderma.
• Other genes that increase the risk of developing scleroderma include:
  • IRF5
  • STAT4
• Genetic variation in the IRF5 gene predisposes an individual to developing diffuse cutaneous systemic scleroderma.
• Genetic variation in the STAT4 gene predisposes an individual to developing limited cutaneous systemic scleroderma.

Conditions that are associated with scleroderma include:^[2]

• Nephrogenic sclerosing fibrosis
• Scleroderma diabeticorum
• Scleromyxedema
• Erythromyalgia
• Porphyria
• Lichen sclerosis
• Diabetic cheiroarthropathy
• Primary biliary cirrhosis^[30]

• Systemic lupus erythematosus (SLE)
• Rheumatoid arthritis
• Polymyositis
• Sjögren’s syndrome
• Graft-versus-host disease^[31]
• Mixed connective tissue disease
• Malignancy^[32][4]

• On gross pathology, sclerodactyly, skin fibrosis, edema and calcinosis are characteristic findings of scleroderma.^[33][34][2]

• On microscopic histopathological analysis characteristic findings of scleroderma include:
  • Microvascular damage^[35]
    • Arterioles are primarily affected
    • Perivascular edema
    • Large gaps between endothelial cells
    • Loss of integrity of the endothelial lining
    • Platelet aggregation in the vessels
    • Vacuolization of the cytoplasm of endothelial cells
    • Perivascular infiltrates of mononuclear immune cells in the walls of arterioles^[36]
    • Obliterative microvascular lesions
    • Rarefaction of capillaries
    • Small vessel effacement^[37]
  • Fibrosis^[38]
    • Densely packed collagen in the lower dermis
    • Upper subcutaneous layer also affected
    • Loss of reticular structure
    • Accumulation of proteoglycans, fibrillar and elastic fibers^[39]
    • Accumulation of type I collagen^[40]
  • Atrophy and loss of cells in later stages

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

The cause of scleroderma has not been identified. There is a possibility of an underlying immunologic abnormality. To review risk factors for the development of scleroderma click here.

The cause of scleroderma remains unknown. Although there is thought to be an underlying immunologic abnormality evident by present of certain autoantibodies including:^[1]

• Antinuclear antibody (ANA)
• Anti-centromere antibody
• Anti-scl-70 antibody

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

Scleroderma must be differentiated from other diseases that cause skin thickening, sclerodactyly, edema, and symptoms of GERD such as scleredema, scleromyxedema, eosinophilic fasciitis, chronic graft-versus-host disease, drug induced scleroderma, scleroderma overlap syndromes, diabetic cheiroarthropathy, myxedema, and nephrogenic systemic fibrosis.

Scleroderma must be differentiated from other diseases that cause skin thickening, sclerodactyly, edema, and symptoms of GERD such as scleredema, scleromyxedema, eosinophilic fasciitis, chronic graft-versus-host disease, drug induced scleroderma, scleroderma overlap syndromes, diabetic cheiroarthropathy, myxedema, and nephrogenic systemic fibrosis.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

The majority of cases of scleroderma have been reported from the United States. The prevalence of scleroderma is approximately 24 cases per 100,000 individuals in the United States. Scleroderma commonly affects individuals between 20 to 50 years of age. Choctaw native Americans have a much higher prevalence of scleroderma than the general population. Females are more commonly affected than males. Familial clustering of scleroderma has been reported in United States and Australia.

• The incidence of scleroderma is approximately 0.23 to 2.28 cases per 100,000 individuals worldwide.^[1]
• The incidence of scleroderma is approximately 2 per 100,000 individuals in the United States.^[2]

• The prevalence of scleroderma is approximately 5 to 30 cases per 100,000 individuals worldwide.^[1]
• In 1990, the prevalence of scleroderma was estimated to be 27.6 cases per 100,000 individuals in the united states.^[1]
• The prevalence of scleroderma is approximately 24 cases per 100,000 individuals in the United States.^[2]

• The standardized mortality ratio of scleroderma is approximately 1.5 to 7.2.^[3]

• Scleroderma commonly affects individuals between 20 to 50 years of age.^[4]
• Scleroderma may also occur in patients younger than 20 years or older than 50 years.

• Choctaw native Americans from southeastern Oklahoma were reported to have much higher prevalence of scleroderma than the general population.^[5]
• Scleroderma usually affects individuals of the African-American race more than the caucasian race.^[6][7]

• Females are more commonly affected by scleroderma than males. The female to male ratio is approximately ranging from 3:1 to 14:1.^[7][8]

• Scleroderma cases are more frequently reported in the United States than in continental Europe.^[2]
• Familial clustering of scleroderma has been reported in United States and Australia.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

Common risk factors in the development of scleroderma include occupational and environmental exposure to certain chemicals, certain genetic variations, and infectious agents. Most commonly implicated occupational and environmental risk factors are exposure to silica, chlorinated and aromatic solvents as well as welding fumes.

• Common risk factors in the development of scleroderma include occupational and environmental exposure to certain chemicals, certain genetic variations, and infectious agents.

Common risk factors in the development of scleroderma may be occupational, environmental, genetic, and infectious.

• Occupational and environmental exposure to:^[1][2][3][4]
  • Crystalline silica
  • Trichlorethylene
  • Chlorinated solvents
  • Toluene
  • Aromatic solvents
  • Ketones
  • White spirit
  • Epoxy resins
  • Welding fumes
• Genetic variations in:^[5]
  • Human leukocyte antigen (HLA) genes
  • IRF5 gene
  • STAT4 gene
• Infectious agents:^[6][7]
  • Cytomegalovirus (CMV)
  • Hepatitis B virus (HBV)
  • Toxoplasma gondii infection (toxoplasmosis)

Less common risk factors in the development of scleroderma include:

• Occupational exposure to hand-arm vibration^[3][8]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

There is insufficient evidence to recommend routine screening for scleroderma, however screening is recommended for pulmonary arterial hypertension and malignancy in scleroderma patients. Regular blood pressure monitoring at home is encouraged in patients with scleroderma to screen for renal involvement and prevention of scleroderma renal crisis.

There is insufficient evidence to recommend routine screening for scleroderma, however screening is recommended for pulmonary arterial hypertension and malignancy in scleroderma patients:

• According to the ACCF/AHA expert consensus document, screening for pulmonary arterial hypertension (PAH) by transthoracic echocardiogram (TTE) and pulmonary function tests (PFTs) is recommended every year among patients with scleroderma.^[1][2]
• Enhanced screening for malignancy is recommended in scleroderma patients at high risk.^[3]
• Regular blood pressure monitoring at home is encouraged in patients with scleroderma to screen for renal involvement and prevention of scleroderma renal crisis.^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

The symptoms of scleroderma usually develop in the third decade of life, and start with symptoms such as skin thickening and edema of the hands and feet. Common complications of scleroderma include pulmonary fibrosis, pulmonary arterial hypertension, interstitial lung disease and scleroderma renal crisis. The 10-year survival rate of patients with scleroderma is approximately 70%-80%.

• The symptoms of scleroderma usually develop in the third decade of life, and start with symptoms such as skin thickening and edema of the hands and feet.^[1][2]
• If left untreated, patients with scleroderma may progress to develop pulmonary arterial hypertension (PAH), interstitial lung disease, and severe gastrointestinal disease.^[1]

• Common complications of scleroderma include:^[3][4][5][6]
  • Scleroderma renal crisis
  • Pulmonary fibrosis
  • Pulmonary arterial hypertension
  • Interstitial lung disease
  • Malignancy^[7]

• The 10-year survival rate of patients with scleroderma is approximately 70%-80%.^[8]
• The presence of pulmonary arterial hypertension is associated with a particularly poor prognosis among patients with scleroderma.^[9]
• The survival rate of patients with scleroderma is negatively affected by older age of onset.^[3]
• The mean survival of patients with scleroderma is approximately 12 years from diagnosis.^[10]

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