Systemic lupus erythematosus (SLE) – causes, symptoms, diagnosis & pathology

Systemic lupus erythematosus (SLE) – causes, symptoms, diagnosis & pathology

Alright, “systemic lupus erythematosus,”
k we totally got this. “Systemic” is easy, and refers to affecting multiple organs in
the body. “Erythematosus” means reddening of the skin, alright alright. “Lupus”
is latin for “wolf”. So affects multiple organs wolf…reddening of the skin? Not exactly,
the modern use of lupus usually refers to a variety of diseases that affect the skin…which
was possibly originally used since these diseases resemble a wolf bite on the patients’ skin.
Is that true? Who knows. At any rate, systemic lupus erythematosus, or SLE, sometimes just
lupus, is a disease that’s systemic, and affects a wide variety of organs, but notably
often causes red lesions on the skin. But how does lupus affect all these organs?
Well usually the immune system protects the body’s tissues from invaders, but lupus
is an autoimmune disease, which means that immune cells start attacking the very tissues
their supposed to protect. With lupus, essentially any tissue or organ can be targeted. And just
like a ton of other autoimmune diseases though, it’s not completely clear why it develops,
and like most diseases it’s the result of both genetics and the environment. Alright so let’s go over a specific scenario
to show how this plays out. Let’s say this guy has susceptibility genes—genes that
make him susceptible to getting lupus, and he’s exposed to UV radiation in sunlight,
which we know is an environmental risk factor for lupus. Well, given enough UV rays, think
like sunburn, the cell’s DNA can become so badly damaged, that the cell undergoes
programmed cell death, or apoptosis, and it dies. This produces all these little apoptotic
bodies, and exposes the insides of the cell, including parts of the nucleus, like DNA,
histones, and other proteins, to the rest of the body. Well those susceptibility genes
specifically have an effect on this person’s immune system such that their immune cells
are more likely to think that these are foreign, or antigens, and since they’re from the
nucleus, we call them nuclear antigens, and immune cells try to attack them. Not only
that though, susceptibility genes also cause this person to have less effective clearance,
essentially they aren’t as good at getting rid of the apoptotic bodies and so they end
up having more nuclear antigens floating around. This means that B cells might swing by, see
them, and start the production of antibodies against these pieces of nucleus, which are
called antinuclear antibodies, and these guys are present in almost all cases of lupus.
Alright so those antinuclear antibodies bind to the nuclear antigens, forming antigen-antibody
complexes. These complexes can get into the blood and then drift away and deposit or stick
to the vessel wall in all sorts of different organs and tissues like the kidneys, skin,
joints, heart. Deposited complexes then initiate a local inflammatory reaction, which causes
damage through the activation of the complement system, which, after a huge cascade of enzyme
activation, leaves cell membranes with channels that let fluid and molecules go in and out
all willy nilly, causing the cell to burst and die, usually though you’d want this
to happen to foreign cell or an infected cell, not healthy cells. When tissues become damaged
as a result of these immune complexes, it’s known as a type III hypersensitivity reaction.
UV radiation isn’t the only way to damage cells, though, right? It therefore isn’t
the only trigger that’s thought to be associated with lupus—other potential triggers that
have been associated with SLE include cigarette smoking, viruses, bacteria, use of certain
medications like procainamide, hydralazine, and isoniazid, as well as sex hormones, particularly
estrogen, which might be partly why lupus is more common in women, especially considering
it’s about 10 times more common in women than men during reproductive years, but only
about 2 or 3 times more common in childhood or past the age of 65. Okay okay, as a quick recap, the model that’s
generally thought to be what leads to SLE starts with some environmental trigger, which
damages cells, and causes apoptosis and the release of nuclear antigens. At this point,
the genetic components come in, and the person likely has certain genes that make them not
so good at clearing these apoptotic bodies and nuclear antigens, so you end up with a
lot of nuclear antigens floating around. In combination, they probably also have genes
that cause their immune cells to recognize these nuclear antigens as foreign, which initiates
an immune response, creates antinuclear antibodies that bind to antigens and then float around
and deposit in various tissues, which causes inflammation. These deposits and inflammation seem to be
the cause of most of the symptoms of lupus, which remember is a type III hypersensitivity
reaction. Many patients, though, also develop antibodies targeting other cells like red
and white blood cells, and molecules like various phospholipids, which can mark them
for phagocytosis and destruction, leading to additional symptoms. This is considered
a type II hypersensitivity reaction, although it isn’t fully understood why some of these
antibodies targeting specific cells and molecules develop. So the classic presentation of lupus is fever,
joint pain, and a rash in a woman of childbearing age, but the actual diagnosis is difficult
because it can affect a variety of people of different genders and ages, and there’re
also a wide variety of symptoms. There are general symptoms like fever and weight loss,
as well as specific symptoms depending on the specific organ system being affected and
damaged. In fact, it’s so unpredictable that a diagnosis is given only when 4 or more
out of eleven diagnostic criteria are met. The first few have to do with the skin and
often happen to sun-exposed areas; the first is a Malar rash, meaning a rash over the cheeks
that spares the nasolabial folds, sometimes just called a “butterfly rash” and this
appears after sun exposure. Second is a discoid rash, which is chronic rash in sun-exposed
areas that are plaque-like or forms a sort of patchy redness and can scar. Finally, a
general photosensitivity of the skin—essentially a catch-all category for other rashes that
happen to sun-exposed areas—typically only lasting a couple of days. Another type of tissue that can be damaged
is the mucosa, or the the inner membrane of various tissues can become damaged as well,
so the fourth criteria is ulcers in the mucus membrane of the mouth or the nose. Lupus can
also affect the serosa, which is like the outer membrane of an organ or tissue, so if
it gets inflamed, people get get serositis, which could manifest as something like pleuritis,
which is inflammation of the lining around the lungs and chest cavity, or as pericarditis,
inflammation of the lining of the heart. Although this isn’t strictly a criteria, it’s worth
noting that lupus can affect any layer of the heart—meaning in addition to inflammation
of the pericardium, they might also have inflammation of the endocardium and myocardium, leading
to endocarditis and myocarditis, of which the former presents as Libman-Sacks endocarditis,
where vegetations form, which are essentially clumps of fibrin, a blood-clotting protein
and immune cells, around the mitral valve. Next, if the joints get inflamed, patients
may also develop arthritis, specifically two or more joints to meet the criteria. If the
kidneys are affected, patients might develop renal disorders, like abnormal amounts of
urine protein or diffuse proliferative glomerulonephritis, inflammation of the glomeruli. For reasons
that aren’t completely understood, some autoantibodies that target receptors in the
brain have been implicated as well, and this can cause neurologic disorders like seizures
and psychosis. Sort of along the same lines, patients can have autoantibodies against components
of the blood, causing various hematologic disorders, for example they’ll get anemia
if red blood cells are targeted, thrombocytopenia if platelets are targeted, and leukopenia
if white blood cells or immune cells are targeted. That last one is really a mind-bender because
it means that your immune system is attacking your immune system. Alright so the last two
have to do with specific antibodies being found in the blood, the first one being antinuclear
antibody, which we already went through. Now a large proportion of patients with lupus
have these, meaning this test is very sensitive, but this test isn’t very specific, since
these are seen in other autoimmune diseases. Finally, they can have some other self-directed
antibody that isn’t antinuclear antibody, which can be one of three types. It could
be anti-Smith, which is an antibody against small ribonucleoproteins, or it could be anti-dsDNA
which is against double stranded DNA and is often seen more during periods of active disease.
These two are relatively specific for lupus. A third type of antibody though is anti-phospholipid
which is actually against proteins that are bound to the phospholipids, and is less specific
for lupus, meaning that it can pop up in other situations. There are three types of antiphospholipid
antibodies – anticardiolipin, which can cause a false-positive test for syphilis since anticardiolipin
antibodies are also sometimes involved in syphilis, the other two are lupus anticoagulant
also known as lupus antibody, and anti-beta2 glycoprotein I. Sometimes, because of these,
patients with lupus develop an antiphospholipid syndrome, where the antiphospholipid antibodies
cause a hypercoagulable state, meaning they’re more prone to developing clots and having
complications like deep vein thrombosis, hepatic vein thrombosis, and stroke. These patients
often end up needing lifelong anticoagulation therapy. So lupus is characterized by periods of flare-ups
and periods of remittance, so treatment is often aimed at preventing flares or limiting
how severe they are when they do happen. To help prevent flares, some patients may have
to avoid sunlight exposure with hats and long-sleeved clothes. To reduce severity of flares, corticosteroids
may be used to help limit the immune response, and finally, if symptoms are really severe,
certain immunosuppressive drugs might be used.

100 Replies to “Systemic lupus erythematosus (SLE) – causes, symptoms, diagnosis & pathology”

  1. Lupus is fucking crazy af. I have kidney lupus and it still blows my mind how much has happened to me in the last 2 years of getting diagnosed lol

  2. it affects me in joint and decrease my factor VIII … and aquire hemoflobia… i am good now but still having medicine (MMF . HCQS) i remember when i have to eat omnacortail also 😂😂 which made me fat

  3. Love your insight. Here's a article on the causes and organs involved in lupus

  4. 2:24 "ivaders" attack lol. thank you guys this really made things easy , wish university can follow up such teaching techniques.

  5. maybe lupus refers to the marks that go over wolves' noses? Kinda similar looking to the reddening on the nose symptom?

  6. Yes Lupus in Latin means Wolf ~ this name was started because the Malar Rash or also known as the Butterfly rash across the face, looks like a wolf has bitten your face and hence the name Lupus. So far there are 13 genetic markers for SLE ~ found on one of the Chromosomes and those being 1/ 2/ 4/ 6/ 8/ 10/ two on 11, 12/ 13/ two on 20 and another one found on the X chromosome. Great video and tells exactly what Lupus is all about. Thanks

  7. Osmosis can explain a disease more quickly and better than anything. Such an aid in research papers and in nursing school studies! Thanks osmosis!

  8. My God, this guy's a genius. Thank God for people who did their homework in school, took their studies seriously, had supportive parents and family and the means to go to medical school. He rattled off his medical jargon and terminology like a total pro. Great explanation of a very, very complex disease.


    As we all know SLE is an autoimmune disease. We all know wolf is known for eating its own kids.
    Where's the confusion about the origin of this word then?

  10. Why would you take a man as an example if women are much more affected. Makes no sense to me.
    Why wouldn't you have a clear concept and talk twice about symptoms. It is better to learn if you don't skip these and come back to them later but just have a clear layout and red threat… People are watching the videos several times you know. It is just distracting.

  11. Thank  you so  much  … The best  SLE  video I  have  watched   so  far  .  Perfect  gift  for  any  EL [English Learner ]  like  me.May God bless you  &  all  your  works  **   Greetings  from  Korea [South]

  12. Not a lot of people know this, but when a person who has rh negative blood, has a child with someone who has rh positive blood, the offspring has a very high chance of developing lupus. this happens for the same reason why a "rh negative mother who is pregnant with a rh positive fetus, will reject the fetus because her immune system registers the fetus as being not compatable or foreign. in the same way somebody who has a mix of rh positive and rh negative DNA will develop problems because the immune system mistakenly registers it's own cells as being foreign. because their body has a mix of both parents DNA . in short it comes down to cross breeding rh negatives with rh positives. The medical establishment will never share this information because so many of the royal family and the ruling class are rh negative. This is why they only have children with a partner who has the same rh factor. Clearly they have been told of the health risks of mixing the two rh factors. I suspect this is why there is so much secrecy surrounding peoples blood type. Most people don't have a clue what blood type they are. And even if you ask your doctor, they won't tell you, even though it is on the computer screen right in front of them.

  13. I fit nearly all the symptoms for hypothyroidism, and many for lupus. But all testing keeps coming up negative for both, so I'm left wondering, what's wrong with me then?

  14. Thankyou for explaining this where I can understand it. Sort of. I have been diagnosed with Fibromyalgia, UCTD, Osteoarthritis, just to name a few. I believe I also have lupus now but have not yet seen a rheumatologist. After seeing this, I will.

  15. apoptosis does not lead to an inflammatory reaction! in apoptosis the cell is divided into many vesicles with an eat-me signal on the outside of their membrane. the vesicles then get digested by macrophages. this way nothing from the inside of the cell (proteins, dna, etc) gets outside the cells which would trigger an inflammatory reaction.
    what's described in the video is necrosis, which is unprogrammed cell death and in which the cell bursts and cell contents are released and trigger an inflammatory reaction.

  16. And nobody can find the cure in the stem cells of the parents of the person who suffers this illness?

  17. I was diagnosed in ‘98 and I’m 2009 I got a kidney transplant but it only lasted 4 years. I am now doing peritoneal dialysis and going through the Transplant Work Up again to try and get on The List once again and hopefully I will get that amazing gift. I have a gorgeous daughter and 3 amazing and gorgeous grandchildren 💖. This video was spot on. I pray for all of us and everyone that is going through some kind of illness. Stay Strong 💪🏼💜💜💜

  18. Still watching this in 2019. Even though the criteria has changed, the very essence of the disease mechanism is very much briefly explained without missing any important info. Thank you as always, Osmosis!

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