In 1945 Goetz, emphasizing the widespread and generally worsening visceral involvement seen in some individuals with scleroderma, proposed the term “progressive systemic sclerosis.” Today we recognize that progressive systemic sclerosis, a whole-body disease, can have both diffuse cutaneous involvement and limited cutaneous involvement. Either form has the potential to cause major morbidity.
Progressive systemic sclerosis occurs more frequently in females, especially during the peak incidence years of 30 to 55, where the female-to-male ratio may be as high as 12 to 1. Major mechanisms accounting for the pathological changes in progressive systemic sclerosis include generalized fibrosis, systemic microangiopathy, and immunoregulatory abnormalities. Pain symptoms are common in patients with systemic sclerosis and are independently associated with more frequent episodes of Raynaud phenomenon, active ulcers, and worsening synovitis. Among the various concepts entertained for the pathophysiology of scleroderma, the role of hypoxia, cellular stress, and a concert of interacting cytokines has been highlighted. Tyrosine kinases are involved in transforming growth factor-beta and platelet-derived growth factor, which play a central role in the pathophysiology of systemic sclerosis. Clear understanding of these mechanisms might pave the way for novel therapies for systemic sclerosis.
In this article, Dr. Richard Keating of Scripps Clinic/Scripps Green Hospital and Dr. Kavitta Allem of WakeMed Physician Practices discuss the clinical manifestations, diagnosis, and management of this multi-system, complex disease.
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