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Systemic Sclerosis

Updated : January 31, 2024





Background

Systemic sclerosis, also known as scleroderma, is a rare autoimmune disorder that causes the skin to harden and tighten and can also affect the blood vessels, internal organs, and immune system. The cause of systemic sclerosis is not fully understood, but it is thought to be related to a combination of genetic, environmental, and immune factors.

The disease can range from mild to severe, and treatment typically involves medications to manage symptoms and prevent complications. There is no cure for systemic sclerosis, but early diagnosis and treatment can help improve the quality of life and slow the progression of the disease.

Epidemiology

Systemic sclerosis is a rare autoimmune disorder, with an estimated prevalence of between 20 and 240 cases per million people worldwide. The disease affects women more commonly than men, with a female-to-male ratio of approximately 3:1. The onset of systemic sclerosis can occur at any age. However, it is most commonly diagnosed in people between 30 and 50.

The disease is more common in non-Hispanic white ethnicity and is also more common in developed countries. The mortality rate for systemic sclerosis varies depending on the disease’s severity and complications. In general, the mortality rate is higher for individuals with severe systemic sclerosis and is also higher with certain complications, such as pulmonary arterial hypertension or renal crisis.

A review of published studies shows that the overall mortality rate for people with systemic sclerosis is approximately 5-15%. However, this rate may be higher for people with severe disease and lower for people with mild disease. It is important to note that the mortality rate for systemic sclerosis has decreased over time due to improvements in treatment and management of the disease.

Anatomy

Pathophysiology

Systemic sclerosis is a complex autoimmune disorder involving multiple body systems, including the immune system, blood vessels, and skin. It is thought that the disease may be triggered by an environmental factor, such as an infection or exposure to certain chemicals, in individuals who have a genetic predisposition to the disease. This initial trigger leads to inflammation and scarring in the body, which can cause the skin to harden and tighten and affect the blood vessels, internal organs, and immune system.

The inflammation and scarring can cause complications such as pulmonary arterial hypertension, renal crisis, and gastrointestinal problems. The scarring and inflammation can also lead to tissue hypoxia and oxidative stress, which can cause further damage to the body. It is characterized by immune dysregulation and inflammation, which play a crucial role in the development of the disease.

There is an imbalance in the levels of specific immune system cells (T-helper 1 and T-helper 2) and the cytokines they produce, leading to an increase in fibrosis. This fibrosis is caused by the activation and differentiation of mesenchymal cells, fibroblasts, and myofibroblasts and the accumulation of extra-cellular matrix in the body. The production of certain autoantibodies and the presence of humoral autoimmunity are also characteristic and can contribute to the development of the disease.

Etiology

Systemic sclerosis has been found to occur more commonly in families with a history of the disease. There is evidence that other autoimmune disorders, such as systemic lupus erythematosus and rheumatoid arthritis, are also common in individuals with a family history of systemic sclerosis.

Genetic studies have identified specific genetic regions, including the major histocompatibility complex (MHC) region, and specific human leukocyte antigens (HLA) such as HLA DRB11104, DQA10501, and DQB1*0301, as being associated with an increased risk. Other genetic factors implicated in the development of systemic sclerosis include NLRP1, PTPN22, STAT4, and IRF5.

Genetics

Prognostic Factors

The prognosis for systemic sclerosis varies depending on the disease’s severity and complications. The long-term prognosis has improved in recent years due to advances in the treatment and management of the disease. Individuals with mild disease may have a good prognosis, an average life expectancy, and a good quality of life. However, even in mild cases, systemic sclerosis can progress over time.

Individuals need routine medical care to monitor for changes in the disease and manage any complications that may arise. People with severe disease may have a poorer prognosis, as the disease can cause serious and life-threatening complications. The most common cause of death in severe systemic sclerosis is pulmonary arterial hypertension, followed by renal crisis. Other complications that can affect the prognosis of the severe disease include gastrointestinal, cardiac, and neurological problems.

Clinical History

Clinical History

Raynaud phenomenon is a condition that is often one of the first symptoms to appear in people with systemic sclerosis. It is characterized by a triphasic color change of the fingers and toes in response to cold temperatures or stress. The digits, especially of the upper extremities, become white as blood flow is restricted, blue due to a lack of oxygen in the skin and tissues and red as blood flow returns to normal. This condition occurs in over 95% of individuals and is caused by vasospasm or a narrowing of the blood vessels.

During the initial phase, individuals may experience inflammation in the hands, which can cause the fingers to appear puffy. This phase may last for several months and can be accompanied by symptoms such as itching, burning pain, and redness of the skin. The swelling can also compress underlying structures and lead to the development of conditions such as carpal tunnel syndrome.

The skin may also become dry and thickened, and the loss of skin appendages may occur. Oropharyngeal involvement may include tight skin around the mouth, the reduced opening of the mouth leads to difficulty in chewing and swallowing, gum disease, and inflammation of the gums. A dry mouth can result in scarring in the salivary glands.

Physical Examination

Physical Examination

The modified Rodnan skin score is used to evaluate skin thickness in systemic sclerosis, with scores ranging from 0 (uninvolved areas) to 3 (severe skin thickening). This score should be regularly monitored because the progression rate of skin thickness can be a prognostic indicator. Nail fold capillary exams should be performed in all patients with the Raynaud phenomenon suspected of having systemic sclerosis.

Video capillaroscopy track changes over time and detects signs of organ involvement in systemic sclerosis. Dermatoscopy effectively identifies specific changes in the nail fold capillary pattern characteristic of systemic sclerosis. It is typically performed on all fingers except the thumbs.

Both of these techniques may be useful in diagnosing and managing systemic sclerosis. Blood pressure should be closely monitored, especially in patients with diffuse cutaneous systemic sclerosis who have new-onset hypertension or significant worsening of baseline hypertension, as this can be a sign of a scleroderma renal crisis.

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Differential Diagnoses

Eosinophilic Fasciitis (EF)

Scleromyxedema

Scleredema

Eosinophilia Myalgia Syndrome

Lichen Sclerosus

Nephrogenic Systemic Fibrosis (NSF)

Toxic Oil Syndrome

Dermatomyositis

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

There is currently no cure for systemic sclerosis and no treatment that can universally alter the course of the disease. However, effective management of the symptoms and complications can improve the quality of life and outcomes for people with the disease. Early diagnosis is important for successful management.

Corticosteroids should generally be avoided in the treatment of systemic sclerosis due to their potential to exacerbate the disease and cause complications such as scleroderma renal crisis. If corticosteroids are necessary, they should be used at the lowest possible dose for the shortest possible period and only in the case of specific indications such as inflammatory myositis, refractory inflammatory arthritis, or active inflammatory alveolitis.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

 

 

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

Media Gallary

References

Systemic Sclerosis

Updated : January 31, 2024




Systemic sclerosis, also known as scleroderma, is a rare autoimmune disorder that causes the skin to harden and tighten and can also affect the blood vessels, internal organs, and immune system. The cause of systemic sclerosis is not fully understood, but it is thought to be related to a combination of genetic, environmental, and immune factors.

The disease can range from mild to severe, and treatment typically involves medications to manage symptoms and prevent complications. There is no cure for systemic sclerosis, but early diagnosis and treatment can help improve the quality of life and slow the progression of the disease.

Systemic sclerosis is a rare autoimmune disorder, with an estimated prevalence of between 20 and 240 cases per million people worldwide. The disease affects women more commonly than men, with a female-to-male ratio of approximately 3:1. The onset of systemic sclerosis can occur at any age. However, it is most commonly diagnosed in people between 30 and 50.

The disease is more common in non-Hispanic white ethnicity and is also more common in developed countries. The mortality rate for systemic sclerosis varies depending on the disease’s severity and complications. In general, the mortality rate is higher for individuals with severe systemic sclerosis and is also higher with certain complications, such as pulmonary arterial hypertension or renal crisis.

A review of published studies shows that the overall mortality rate for people with systemic sclerosis is approximately 5-15%. However, this rate may be higher for people with severe disease and lower for people with mild disease. It is important to note that the mortality rate for systemic sclerosis has decreased over time due to improvements in treatment and management of the disease.

Systemic sclerosis is a complex autoimmune disorder involving multiple body systems, including the immune system, blood vessels, and skin. It is thought that the disease may be triggered by an environmental factor, such as an infection or exposure to certain chemicals, in individuals who have a genetic predisposition to the disease. This initial trigger leads to inflammation and scarring in the body, which can cause the skin to harden and tighten and affect the blood vessels, internal organs, and immune system.

The inflammation and scarring can cause complications such as pulmonary arterial hypertension, renal crisis, and gastrointestinal problems. The scarring and inflammation can also lead to tissue hypoxia and oxidative stress, which can cause further damage to the body. It is characterized by immune dysregulation and inflammation, which play a crucial role in the development of the disease.

There is an imbalance in the levels of specific immune system cells (T-helper 1 and T-helper 2) and the cytokines they produce, leading to an increase in fibrosis. This fibrosis is caused by the activation and differentiation of mesenchymal cells, fibroblasts, and myofibroblasts and the accumulation of extra-cellular matrix in the body. The production of certain autoantibodies and the presence of humoral autoimmunity are also characteristic and can contribute to the development of the disease.

Systemic sclerosis has been found to occur more commonly in families with a history of the disease. There is evidence that other autoimmune disorders, such as systemic lupus erythematosus and rheumatoid arthritis, are also common in individuals with a family history of systemic sclerosis.

Genetic studies have identified specific genetic regions, including the major histocompatibility complex (MHC) region, and specific human leukocyte antigens (HLA) such as HLA DRB11104, DQA10501, and DQB1*0301, as being associated with an increased risk. Other genetic factors implicated in the development of systemic sclerosis include NLRP1, PTPN22, STAT4, and IRF5.

The prognosis for systemic sclerosis varies depending on the disease’s severity and complications. The long-term prognosis has improved in recent years due to advances in the treatment and management of the disease. Individuals with mild disease may have a good prognosis, an average life expectancy, and a good quality of life. However, even in mild cases, systemic sclerosis can progress over time.

Individuals need routine medical care to monitor for changes in the disease and manage any complications that may arise. People with severe disease may have a poorer prognosis, as the disease can cause serious and life-threatening complications. The most common cause of death in severe systemic sclerosis is pulmonary arterial hypertension, followed by renal crisis. Other complications that can affect the prognosis of the severe disease include gastrointestinal, cardiac, and neurological problems.

Clinical History

Raynaud phenomenon is a condition that is often one of the first symptoms to appear in people with systemic sclerosis. It is characterized by a triphasic color change of the fingers and toes in response to cold temperatures or stress. The digits, especially of the upper extremities, become white as blood flow is restricted, blue due to a lack of oxygen in the skin and tissues and red as blood flow returns to normal. This condition occurs in over 95% of individuals and is caused by vasospasm or a narrowing of the blood vessels.

During the initial phase, individuals may experience inflammation in the hands, which can cause the fingers to appear puffy. This phase may last for several months and can be accompanied by symptoms such as itching, burning pain, and redness of the skin. The swelling can also compress underlying structures and lead to the development of conditions such as carpal tunnel syndrome.

The skin may also become dry and thickened, and the loss of skin appendages may occur. Oropharyngeal involvement may include tight skin around the mouth, the reduced opening of the mouth leads to difficulty in chewing and swallowing, gum disease, and inflammation of the gums. A dry mouth can result in scarring in the salivary glands.

Physical Examination

The modified Rodnan skin score is used to evaluate skin thickness in systemic sclerosis, with scores ranging from 0 (uninvolved areas) to 3 (severe skin thickening). This score should be regularly monitored because the progression rate of skin thickness can be a prognostic indicator. Nail fold capillary exams should be performed in all patients with the Raynaud phenomenon suspected of having systemic sclerosis.

Video capillaroscopy track changes over time and detects signs of organ involvement in systemic sclerosis. Dermatoscopy effectively identifies specific changes in the nail fold capillary pattern characteristic of systemic sclerosis. It is typically performed on all fingers except the thumbs.

Both of these techniques may be useful in diagnosing and managing systemic sclerosis. Blood pressure should be closely monitored, especially in patients with diffuse cutaneous systemic sclerosis who have new-onset hypertension or significant worsening of baseline hypertension, as this can be a sign of a scleroderma renal crisis.

Differential Diagnoses

Eosinophilic Fasciitis (EF)

Scleromyxedema

Scleredema

Eosinophilia Myalgia Syndrome

Lichen Sclerosus

Nephrogenic Systemic Fibrosis (NSF)

Toxic Oil Syndrome

Dermatomyositis

There is currently no cure for systemic sclerosis and no treatment that can universally alter the course of the disease. However, effective management of the symptoms and complications can improve the quality of life and outcomes for people with the disease. Early diagnosis is important for successful management.

Corticosteroids should generally be avoided in the treatment of systemic sclerosis due to their potential to exacerbate the disease and cause complications such as scleroderma renal crisis. If corticosteroids are necessary, they should be used at the lowest possible dose for the shortest possible period and only in the case of specific indications such as inflammatory myositis, refractory inflammatory arthritis, or active inflammatory alveolitis.