Scleroderma


Scleroderma is a group of autoimmune diseases that may result in changes to the skin, blood vessels, muscles, and internal organs. The disease can be either localized to the skin or involve other organs as well. Symptoms may include areas of thickened skin, stiffness, feeling tired, and poor blood flow to the fingers or toes with cold exposure. One form of the condition, known as CREST syndrome, classically results in calcium deposits, Raynaud's syndrome, esophageal problems, thickening of the skin of the fingers and toes, and areas of small dilated blood vessels.
The cause is unknown; however, some suspect it may be due to an abnormal immune response. Risk factors include family history, certain genetic factors, and exposure to silica. The underlying mechanism involves the abnormal growth of connective tissue which is believed to be the result of the immune system attacking healthy tissues. Diagnosis is based on symptoms, supported by a skin biopsy or blood tests.
While there is no cure, treatment may improve symptoms. Medications used include corticosteroids, methotrexate, and non-steroidal anti-inflammatory drugs. Outcome depends on the extent of disease. Those with localized disease generally have a normal life expectancy. In those with systemic disease typical life expectancy is about 11 years from onset. Death is often due to lung, gastrointestinal, or heart complications.
About 3 out of 100,000 people per year develop the systemic form. The condition most often begins in middle age. Women are more often affected than men. Scleroderma symptoms were first described in 1753 by Carlo Curzio and then well documented in 1842. The term is from the Greek "sklerosis" meaning "hardness" and "derma" meaning "skin".

Signs and symptoms

Potential signs and symptoms include:
Scleroderma is caused by genetic and environmental factors. Mutations in HLA genes seem to play a crucial role in the pathogenesis of some cases, likewise silica, aromatic and chlorinated solvents, ketones, trichloroethylene, welding fumes and white spirits exposure seems to contribute to the condition in a small proportion of affected persons.

Pathophysiology

It is characterised by increased synthesis of collagen, damage to small blood vessels, activation of T lymphocytes and production of altered connective tissues. Its proposed pathogenesis is the following:
Vitamin D is implicated in the pathophysiology of the disease. An inverse correlation between plasma levels of vitamin D and scleroderma severity has been noted and vitamin D is known to play a crucial role in regulating the actions of the immune system.

Diagnosis

Typical scleroderma is classically defined as symmetrical skin thickening, with about 70% of cases also presenting with Raynaud's phenomenon, nail-fold capillary changes and antinuclear antibodies. Affected individuals may or may not experience systemic organ involvement. There is no single test for scleroderma that works all of the time and hence the diagnosis is often a matter of exclusion. Atypical scleroderma may show any variation of these changes without skin changes or with finger swelling only.
Laboratory testing can show antitopoisomerase antibodies, like anti-scl70, or anticentromere antibodies. Other autoantibodies can be seen, such as anti-U3 or anti-RNA polymerase.
Anti-double-stranded DNA autoantibodies likely to be present in serum.

Differential

Diseases that are often in the differential include:
Scleroderma is characterised by the appearance of circumscribed or diffuse, hard, smooth, ivory-colored areas that are immobile and which give the appearance of hidebound skin, a disease occurring in both localised and systemic forms:
There is no cure for scleroderma, although relief of symptoms is often achieved. These include the following:
Systemic disease-modifying treatment with immunosuppressants is often used. Immunosuppressants used in its treatment include azathioprine, methotrexate, cyclophosphamide, mycophenolate, intravenous immunoglobulin, rituximab, sirolimus, alefacept and the tyrosine kinase inhibitors, imatinib, nilotinib and dasatinib.
Experimental therapies under investigation include endothelin receptor antagonists, tyrosine kinase inhibitors, beta-glycan peptides, halofuginone, basiliximab, alemtuzumab, abatacept and haematopoietic stem cell transplantation.

Prognosis

The five-year survival rate for systemic scleroderma is about 85%, whereas the 10-year survival rate is just under 70%. This varies according to the subtype; while localized scleroderma rarely results in death, the systemic form can, and the diffuse systemic form carries a worse prognosis than the limited form. The major scleroderma-related causes of death are: pulmonary hypertension, pulmonary fibrosis, and scleroderma renal crisis. People with scleroderma are also at a heightened risk for contracting cancers and, perhaps, cardiovascular disease.
According to a study of an Australian cohort, between 1985 and 2015, the average life expectancy of a person with scleroderma increased from 66 years to 74 years.

Epidemiology

Scleroderma most commonly first presents between the ages of 20 and 50 years, although any age group can be affected. Women are four to nine times more likely to develop scleroderma than men.
This disease is found worldwide. In the United States, prevalence is estimated at 240 per million and the annual incidence of scleroderma is 19 per million people. Likewise in the United States, it is slightly more common in African Americans than in their white counterparts, Scleroderma occurs much more often in women than it does in men. Choctaw Native Americans are more likely than Americans of European descent to develop the type of scleroderma that affects internal organs. In Germany, the prevalence is between 10 and 150 per million people, and the annual incidence is between 3 and 28 per million people. In South Australia, the annual incidence is 23 per million people, and the prevalence 233 per million people. Scleroderma is less common in the Asian population.

Pregnancy

Scleroderma in pregnancy is a complex situation; it increases the risk to both mother and child. Overall scleroderma is associated with reduced fetal weight for gestational age. The treatment for scleroderma often includes known teratogens such as cyclophosphamide, methotrexate, mycophenolate, etc. and hence careful avoidance of such drugs during pregnancy is advised. In these cases hydroxychloroquine and low-dose corticosteroids might be used for disease control.