Scleroderma

Definitions & Key takeaways

Scleroderma, also known as systemic sclerosis, is a chronic systemic autoimmune disease characterized by progressive fibrosis of skin and internal organs such as the gastrointestinal tract, lungs, heart, and kidneys. The exact cause is unknown but is associated with autoimmune processes that lead to excessive collagen production in individuals with a genetic predisposition. Scleroderma can be either limited or diffuse, with symptoms varying according to the organs involved. Treatment options involve immunosuppressants and medications to relieve symptoms and slow the progression of the disease.

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Scleroderma refers to systemic sclerosis, a rare autoimmune disorder in which a normal tissue is replaced with thick dense connective tissue.
It affects the skin, blood vessels and internal organs. Now, there are two main types of scleroderma, limited cutaneous systemic scleroderma, better known as crest syndrome and diffuse cutaneous systemic scleroderma.
The word scleroderma comes from the Greek words sclero, meaning hard and derma meaning skin, which points to the hard skin as its most visible feature.
So normally when there is an infection in the body macrophages will eat some of the invading organisms and break them down.
In addition to destroying the pathogen, they also present a fragment of the pathogen called an antigen to naive T cells.
When the naive T cells bind to this presented antigen, they mature into T helper cells also called CD four positive T cells and they go on to help and recruit more immune cells.
The T helper cells release cytokines which increase the activity of macrophages and attract nearby neutrophils. Macrophages also release cytokines like TGF beta that tell fibroblasts to repair damaged tissue after the infection by laying down collagen, scleroderma affects women three times more often than men.
The exact pathology of scleroderma is not completely understood, but generally, it's thought that some individuals have a genetic predisposition to scleroderma which is triggered by external triggers.
Some known triggers include viral infection by cytomegalovirus and Parvovirus B 19 exposure to silica dust, organic solvents and vinyl chloride and drugs and medications like cocaine, bleomycin and pentazine.
It's thought that there's initially an injury to endothelial cells lining the small arteries. These cells then start expressing adhesion molecules that attach to T cells floating by T cells attach and then migrate outside of the blood vessel into the surrounding tissue and start releasing cytic like TGF beta which causes inflammation and further damages small blood vessels.
Cytokines also activate fibroblasts that produce and deposit collagen which builds up and forms a highly stable matrix that is responsible for the stiffness of the tissue.
This build up of excessive connective tissue is called fibrosis. Finally, blood vessel damage and fibrosis, reduce blood flow to the tissue and cause ischemic tissue damage.
There is another type of immune cell that plays a role in scleroderma and that's B cells. It's not known how they are activated or if they cause any damage.
But activated B cells do produce antinuclear antibodies or ana which bind to the content of the cell nucleus. Some ana are highly specific to scleroderma and can help make the diagnosis.
These include anti SCL 70 which targets DNA topoisomerase. One, anti RNA polymerase three antibodies called A ra and anti centromere antibodies called ac scleroderma can affect any organ but it usually involves the skin, gastrointestinal tract, lungs, heart and kidneys.
Skin lesions start in the fingers and move up across the arm to the shoulders, neck and face. At first, the affected skin is swollen and dewy later, when fibrosis develops, the skin becomes tight, shiny, smooth and stiff.
When it happens on the fingers, it's called sclerodactyly, which can cause ulcerations and can also cause the fingers to curl inward so that the hand becomes shaped like a claw on the face.
The mouth can become narrow called microstomia and the nose becomes beaked due to the damage in the small vessels. There is Raynaud phenomenon in which fingers turn white when exposed to cold.
Then the color changes to blue and finally red as the blood vessels expand to get enough oxygen rich blood to the fingers.
In the gastrointestinal tract. There can be esophageal dysfunction and gastroesophageal reflux, which is when the content of the stomach flows up to the esophagus and damages it.
And also the intestine can be damaged, which leads to malabsorption. Blood vessels of the lungs can be damaged and cause pulmonary arterial hypertension and pulmonary fibrosis, which can be seen as coughing and difficulty breathing.
Lung damage can lead to hypertrophy of the heart's right ventricle and heart failure. Finally, kidney damage can cause hypertension and kidney failure.
In limited scleroderma or crest syndrome. The first symptom in most individuals is Raynaud phenomenon.
The skin of the fingers and face can be affected while internal organ damage comes much later in the disease. The syndrome itself is named after its most common symptoms, calcinosis, Raynaud phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia.
In the diffuse scleroderma, skin of the arms legs, trunk and face are affected and organ damage occurs earlier, diagnosis of scleroderma is based on its symptoms.
The presence of specific antibodies like anti SCL 70 A ra and AC and sometimes additional tests like BP, upper endoscopy for gastrointestinal symptoms, complete blood count to detect anemia due to malabsorption and pulmonary function tests to assess for lung damage.
In terms of treatment, immunosuppressants are used to slow down the disease. Other medication can be used to relieve the symptoms.
Proton pump inhibitors for gastroesophageal reflux calcium channel blockers for Raynaud phenomenon, non steroid antiinflammatory medication for the pain and ace inhibitors for hypertension.
All right, as a quick recap scleroderma is a rare autoimmune disorder in which normal tissue is replaced with thick dense connective tissue.
It affects the skin blood vessels and internal organs. There are two main types diffuse, which affects a larger area of the skin progresses quicker and involves internal organs earlier and limited or crest syndrome, which affects a smaller area of the skin progresses slower and involves internal organs.
Later, the precise cause is not known but the autoimmune process leads to excessive collagen production in individuals with a genetic predisposition, scleroderma most commonly affects the skin, gastrointestinal tract, lungs, heart and kidneys.
Its diagnosed based on the symptoms, antinuclear antibody finding and additional findings related to the disease like hypertension and gastroesophageal reflux.
The treatment includes immunosuppressants and medications to relieve the symptoms. Thanks for watching.
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