Sarcoidosis

Definitions & Key takeaways

Sarcoidosis is a chronic inflammatory disease whereby inflammatory cells called granulomas get abnormally collected in multiple organs in the body, most commonly the lungs, lymph nodes, eyes, skin, and liver. Its causes are not fully understood, it is believed to be caused by an immune reaction continuing after the initial infection or causative antigen is cleared from the body. Symptoms vary depending on which organs are affected, but they may include shortness of breath, cough, fatigue, weight loss, joint pain, vision changes, and skin rashes. Treatment for sarcoidosis depends on the severity and can involve supportive treatment and steroids.

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Introduction0:00–0:23

With sarcoidosis, sarcoid refers to the flesh and osis means disorder - and the reason we called it that, is that sarcoidosis is an immunologic disorder that results in lots of small nodules forming throughout the body.
The disease is actually poorly understood though we know it’s most common among African American females.Normally, the trusty cells of the immune system are ready to spot and destroy any foreign pathogens that could cause the body harm.

Physiology0:23–2:01

To help with this mission, there’s a category of cells in the body called antigen-presenting cells, and these include macrophages, B-cells, and dendritic cells.The most common member of the antigen presenting cell club is the dendritic cell which is named after its long beautiful branch-like arms called dendrites.
When a dendritic cell comes into contact with a pathogen, it latches onto it and with its dendrites pulls and engulfs it.
The pathogen is then broken down and the dendritic cell presents a piece of it, called an antigen, on something called a major histocompatibility complex class II molecule, or MHC-class II for short.The dendritic cell then carries the antigen to the lymph node to find some naive helper T-cells which are T-cells that have never seen an antigen before.
Eventually, it runs into a naive helper T-cell with a T-cell receptor that recognizes and binds to the antigen. Then, Cytokines get released by the dendritic cell and this helps to activate the helper T-cell which then begins to divide or proliferate.The new T-cells then leave the comfort of their lymph node to fulfill their destiny in the great fight against infection.
These brave T-cells start secreting proinflammatory cytokines, or signaling molecules, and they then recruit more immune cells like additional T-cells and macrophages.In sarcoidosis though, this process unfolds over and over throughout the body without the presence of a specific pathogen that the body is trying to destroy.

Causes2:01–2:45

In other words, the immune system seems to be going a bit haywire in the absence of a pathogen. Now, the precise trigger isn’t actually known, but there are some known genetic and environmental risk factors.Genetic risk factors include being African American and having a family member with sarcoidosis.
Environmental risk factors include a prior infection with Mycobacterium tuberculosis and Borrelia burgdorferi, but to be specific, these pathogens are long gone when the autoimmune problem sets in.So when sarcoidosis is triggered, T cells and macrophages get attracted to a particular spot of healthy tissue.

Pathology2:45–4:11

Now, Sarcoidosis can involve nearly every organ, but they most often involve hilar lymph nodes which are the lymph nodes that are near the point where the bronchi meets the lung.As more and more immune cells gather at a particular spot, they form small nodules called granulomas.
These granulomas have T cells on the periphery and macrophages at the center. The granulomas in sarcoidosis are noncaseating which means that there is no tissue necrosis at the center of the granuloma, unlike some other granulomatous diseases like tuberculosis.Often, macrophages fuse together to form a single large multinucleated cell called a Langhans giant cell.
Within the Langhans giant cell, there are cytoplasmic inclusions called Schaumann bodies which are made of calcium and protein deposits.There are also things called asteroid bodies which look like tiny stars.
What they are made of is controversial; some scientists think that they are pieces of the cytoskeleton, while others think that they are made up of lipids.
Over time, the granulomas cause the lymph nodes to enlarge and that can cause bilateral hilar lymphadenopathy.Sarcoidosis is a systemic disease; meaning that the granulomas can sometimes form in other organs beside the lymph nodes.

Symptoms4:11–5:08

Skin nodules are called erythema nodosum and typically develop on the lower legs, along the tibias. These nodules are caused by inflammation of the fat within the skin layer, and they’re typically red, hard, and painful.Sarcoidosis can also cause uveitis which is inflammation in the pigmented layer of the eye beneath the cornea and sclera.
It can also take effect in the heart - leading to problems like arrhythmias.Sarcoidosis can cause a variety of generalized symptoms like fevers, weight loss, and fatigue.
In addition, there can be specific symptoms depending on which part of the body is most affected. This range from shortness of breath and coughing, to tender leg nodules, to vision changes.A diagnosis of sarcoidosis usually involves a chest x-ray or CT scan of the chest to look for bilateral hilar lymphadenopathy.

Diagnosis5:08–6:00

In blood tests, individuals typically also have an increased level of calcium which is caused by excess vitamin D produced by macrophages.
There’s also usually an increased level of angiotensin converting enzyme or ACE, which is produced by T cells. Another helpful clue, using bronchoalveolar lavage, is finding elevated levels of T cells in the lungs.
In that procedure, a bronchoscope is passed through the mouth or nose into the lungs where fluid is squirted out, and then recollected, and examined.
Now finally, the best way to diagnose sarcoidosis is to do a biopsy.People with sarcoidosis who have minimal symptoms don’t need treatment because most symptoms resolve spontaneously within a few weeks, and complete remission from sarcoidosis typically happens within a few years.

Treatment6:00–6:17

But if there are severe symptoms, steroids can be really helpful.Okay, so that’s Sarcoidosis. Let’s just quickly go over the main points.

Review6:17–7:03

Sarcoidosis is a system-wide disease with noncaseating granulomas. These have T cells on the periphery and macrophages in the center.
Sometimes, there are large multinucleated cells called Langhans giant cells which contain Schaumann and asteroid bodies.
In most cases of Sarcoidosis, individuals develop bilateral hilar lymphadenopathy, erythema nodosum, and have elevated levels of ACE or angiotensin converting enzyme, as well as raised calcium levels.
Fortunately, the disease tends to resolve spontaneously.