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 (especially liver, lung, haematologic, and bladder 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 (around 8 years less than the average Australian life expectancy of 82 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. 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 three 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.
Dysregulated transforming growth factor β (TGF-β) signalling in fibroblasts and myofibroblasts has been observed in multiple studies of scleroderma-affected individuals. Activation of fibroblasts and myofibroblasts leads to excessive deposition of collagen and other related proteins, leading to fibrosis. B cells are implicated in this stage, IL-6 and TGF-β produced by the B cells decrease collagen degradation and increase extracellular matrix production. Endothelin signalling is implicated in the pathophysiology of fibrosis.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 (usually suppressing) the actions of the immune system. Diagnosis
Typical scleroderma is classically defined as symmetrical skin thickening, with about 70% of cases also presenting with Raynauds phenomenon, nail-fold capillary changes, and antinuclear antibodies. Affected individuals may experience systemic organ involvement. No single test for scleroderma works all of the time, hence 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 (causing a diffuse systemic form), or anticentromere antibodies (causing a limited systemic form and the CREST syndrome). Other autoantibodies can be seen, such as anti-U3 or anti-RNA polymerase. Antidouble-stranded DNA  autoantibodies are likely to be present in serum.