What causes scleroderma? It may be caused by abnormal blood vessels!

Scleroderma is a very common systemic connective tissue disease. Many people don’t know what causes scleroderma. This condition is generally closely related to genetics and autoimmunity. It is also possible that the abnormality of the connective tissue band is the cause.

(1) Vascular injury theory:

Raynaud's phenomenon is often an early manifestation of SSc, which means that the early lesions are obvious vascular damage, which occurs not only at the finger (toe) ends, but also in internal organs. Recently, some people believe that SSc is the result of repeated damage to vascular endothelial cells. Endothelial cell damage causes changes in capillary permeability, and damage to the arteriolar walls leads to platelet aggregation and endothelial cell proliferation. Endothelial cell damage is diverse, with swelling, hyperplasia, followed by thrombosis causing lumen narrowing and tissue ischemia. These vascular lesions are seen in multiple blood vessels such as skin, skeletal muscle, digestive tract, lungs, heart, kidneys and brain. Although there are significant vascular lesions in the early stages of the disease, immunoglobulins, complement and immune complexes are rarely found in the blood vessel walls, which also shows that endothelial damage is the basis of the disease.

(2) Immunology:

This disease often coexists simultaneously or successively with autoimmune diseases such as systemic lupus erythematosus, dermatomyositis, Sjögren's syndrome, rheumatoid arthritis, etc. In addition, idiopathic thrombocytopenic purpura, autoimmune anemia, etc. may often occur during the course of the disease. This disease contains multiple autoantibodies in the serum, and often has multicellular hypergammaglobulinemia, immune complexes, etc., indicating that it is an autoimmune disease.

(3) Abnormal fibrous proliferation:

The disease causes extensive fibrosis of the skin and internal organs because newly synthesized collagen replaces most or all of the subcutaneous tissue, thus making the skin tight and hardened. Certain subtypes of fibroblasts isolated from the skin of SSc patients can synthesize excessive amounts of collagen (mainly types I and III), glycoproteins, etc. in culture. Experiments have also shown that local collagen decomposition is reduced. Current studies have shown that TGF-B (transforming growth factor) can not only directly stimulate but also secrete PDGF-β (platelet-derived growth factor) to indirectly stimulate the growth of fibroblasts.

(4) Abnormal connective tissue metabolism (10%):

The patients showed extensive connective tissue lesions, with a significantly increased collagen content in the skin. In the skin lesions during the active phase of the virus, there was a large amount of soluble collagen and unstable intermolecular side chains. Culture of the patients' fibroblasts showed a significantly increased activity of collagen synthesis.