Progressive systemic sclerosis
Systemic sclerosis (also known as Scleroderma) is a chronic autoimmune CT disease of unknown cause, although women are affected 5x more than men. The hallmark is thickening and hardening of the skin, although commonly the GI tract, kidneys and heart are also affected. Over time, structural alterations in small vessels and fibrosis in multiple organs can cause failure.
This question is asking us about systemic sclerosis, there are two types of systemic sclerosis: limited scleroderma and diffuse scleroderma. Don’t confuse this with the fact there is also localized scleroderma, this is not a subtype of systemic sclerosis, rather its own group within which sits morphea, pansclerotic morphea and linear scleroderma.
Limited scleroderma typically affects the face and distal extremities. One can often see calcinosis, sclerodactyly and telangiectasia, often with Raynaud's syndrome presenting - this is the so called CREST syndrome. The course of the limited form is slow and indolent. On the other hand, diffuse scleroderma has a more rapid progression, involvement of the proximal elbows and knees and trunk is common, with fibrosis of internal organs such as lung, kidney, GI tract and heart leading to symptoms in all of these systems. Limited scleroderma is associated with anti-centrometere autoantibodies, while diffuse scleroderma is associated with anti-Scl-70 antibodies.
Image: “Raynaud-Syndrom” by Niklas D, CC BY-SA 3.0, via Wikimedia Commons.
Limited cutaneous systemic scleroderma is also known as CREST syndrome, so called after the main symptoms (Calcinosis, Raynauds, Esophageal dysmotility, Sclerodactyly and Telangiectasia). Interestingly in the limited form pulmonary hypertension can develop subclinically and can become life threatening so should be looked for.
Image: “Calcinosis of CREST syndrome” by Mikael Häggström , M.D. Author info - Reusing images - Conflicts of interest: None Mikael Häggström , M.D. Consent note , CC0, via Wikimedia Commons.
Systemic sclerosis occurs based on three interrelated processes - autoimmunity and inflammation, vascular injury and obliteration, and fibrosis and excessive matrix accumulation in multiple tissues and organs. Simply put, an autoimmune process is activated against the endothelium, this leads to cell damage and tissue hypoxia, which leads to cellular repair, which causes fibrosis.
The diagnostic process for patients should be as follows:
- 1. Obtain bloods - FBC, U&Es, ESR, CRP
- 2. Arrange auto-antibody testing
- a. Anti-nuclear (90%)
- b. Anti-centromere (limited form only)
- c. Anti Scl-70 or anti topoisomerase I (diffuse form only)
- d. Anti-RNA polymerase III (associated with an increased risk of renal crisis)