Limited systemic sclerosis (CREST syndrome)

Definitions & Key takeaways

CREST syndrome, also known as the limited cutaneous form of systemic sclerosis is a multisystem connective tissue disorder. The acronym "CREST" refers to the five main features: calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia. It is associated with detectable antibodies against centromeres, and usually spares the kidneys. If the lungs are involved, it is usually in the form of pulmonary arterial hypertension.

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Introduction0:00–0:38

CREST syndrome, also known as limited cutaneous systemic sclerosis, is an autoimmune condition, and its name is an acronym that stands for calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias.
Calcinosis is the deposition of calcium in the skin, Raynaud’s is spasm of the arteries in the fingers, esophageal dysmotility refers to difficulty swallowing, sclerodactyly is tightening of the skin over the fingers, and telangiectasias are small dilated blood vessels on the skin surface.

Physiology0:38–1:20

So, normally, when there’s 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 CD4+ T-cells, and 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. They also release cytokines, like TGF-β, that tells fibroblasts to repair damaged tissue after the infection by laying down collagen.

Pathology1:20–3:04

The cause of CREST syndrome isn’t known exactly, but individuals in the first two years of the disease have a higher than normal number of T-helper cells in the skin on their hands and face, particularly near small blood vessels.
The T-helper cells release cytokines to attract other immune cells, like macrophages and neutrophils, which cause a lot of inflammation in the skin.
There is so much inflammation that the tissue dies, in a process called necrosis. When the cells die, calcium in the cytosol binds to fragments of cell membrane and builds up in the skin, which is called calcinosis.
It’s not clear why it happens, but individuals with CREST often experience Raynaud’s phenomenon, which is an episodic, dramatic vasoconstriction of arterial blood vessels in the hands.
It’s not quite clear what is going on, but in CREST syndrome there is often difficulty in swallowing food, which we esophageal dysmotility.
The inflammation in the skin, also damages the blood vessels, which eventually results in poor blood flow, called ischemia.
This causes more damage to the skin, particularly in the hands and fingers. The severe ischemia and tight skin in the fingers can cause ischemic ulcers and even finger loss if left untreated.
The body tries to repair the damage by activating fibroblasts which lay down bundles of collagen. The T-helper cells also release more cytokines, like TGF-β, which keep these fibroblasts switched on.
This collagen builds up in the skin of the fingers and hands, causing sclerodactyly, with “sclero-” referring to thickening and “-dactyly” referring to the fingers.
The vascular damage also causes telangiectasia, which are tiny dilated capillaries, usually on the skin of the hands. People with CREST syndrome might report hard bumps on their hands or fingers if they have calcinosis.

Symptoms3:04–3:48

They might also say that their fingers change color or turn white from time to time, especially if they’re cold. Raynaud’s phenomenon is typically the first thing individuals with CREST syndrome notice.
The sensation of food getting stuck in the esophagus, or difficulty swallowing is a symptom of esophageal dysmotility. They may have to drink water with every bite to make sure that food goes down properly.
Early on in the disease, the skin of the fingers might be swollen and painful, but later on will be thicker and tighter than usual.
They might also notice red spots or dots on their hands and sometimes on their face or neck. CREST is diagnosed by thorough history and physical examination.

Diagnosis3:48–4:07

There is an association between CREST syndrome and an autoantibody called anti centromere antibody. A serum blood test for anti centromere antibody will confirm the diagnosis of CREST syndrome in about 60% of people.

Treatment4:07–4:16

There’s no cure for CREST syndrome but it can be managed with steroids initially and with stronger immunosuppressants like cyclosporin if the disease progresses.
All right, as a quick recap…CREST syndrome stands for calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly and telangiectasias.

Review4:16–4:45

It is a less severe form of systemic sclerosis and is caused by T-helper cell activation causing damage to skin and blood vessels and then causing fibrosis.
Anti-centromere antibody can be used to confirm diagnosis and it is treated with steroids and sometimes with immunosuppressants.