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Scleroderma

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Scleroderma

14 flashcards
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USMLE® Step 1 style questions USMLE

5 questions
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A 41-year-old woman comes to her outpatient provider for evaluation of fatigue and dyspnea on exertion that started five months ago. The patient previously enjoyed biking on the weekends, but she has been unable to do so because of her symptoms. Past medical history is notable for seasonal allergies. She is currently not taking any medications. In the office, her temperature is 37.1°C (98.8°F), blood pressure is 128/88 mmHg, and pulse is 73/min. Physical examination is notable for diffuse skin thickening and telangiectasias. On cardiac examination, there is a loud S2 at the left upper sternal border. A chest x-ray is ordered, and the results are as follows:  



Image reproduced from Radiopedia 

Which of the following findings is most likely to be seen in this patient?  

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Rishi Desai, MD, MPH

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Scleroderma refers to systemic sclerosis, a rare autoimmune disorder in which 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’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 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-β, 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 B19; exposure to silica dust, organic solvents, and vinyl chloride; and drugs and medications like cocaine, bleomycin, and pentazocine.

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 cytokines like TGF-β 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 buildup 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 is 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’s are highly specific to scleroderma and can help make the diagnosis. These include anti-Scl 70 which targets DNA topoisomerase I, anti-RNA polymerase III antibodies called ARA, and anti-centromere antibodies called ACA.

Summary
Scleroderma, also known as systemic sclerosis, is a chronic systemic autoimmune disease characterised by hardening of the skin. There are two forms, limited scleroderma, also referred to as CREST syndrome and diffuse scleroderma. Diffuse scleroderma is rapidly progressing form and affects a large area of the skin and one or more internal organs, frequently the kidneys, esophagus, heart and/or lungs.