Tuesday, January 24, 2017

erythema nodosum lupus

erythema nodosum lupus

alright, “systemic lupus erythematosus,”k we totally got this. “systemic” is easy, and refers to affecting multiple organs inthe 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...whichwas 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 justlupus, is a disease that’s systemic, and affects a wide variety of organs, but notablyoften 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 lupusis an autoimmune disease, which means that immune cells start attacking the very tissuestheir supposed to protect. with lupus, essentially any tissue or organ can be targeted. and justlike 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 scenarioto show how this plays out. let’s say this guy has susceptibility genes—genes thatmake 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, thinklike sunburn, the cell’s dna can become

so badly damaged, that the cell undergoesprogrammed cell death, or apoptosis, and it dies. this produces all these little apoptoticbodies, 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 genesspecifically have an effect on this person’s immune system such that their immune cellsare more likely to think that these are foreign, or antigens, and since they’re from thenucleus, we call them nuclear antigens, and immune cells try to attack them. not onlythat 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 endup having more nuclear antigens floating around.

this means that b cells might swing by, seethem, and start the production of antibodies against these pieces of nucleus, which arecalled 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-antibodycomplexes. these complexes can get into the blood and then drift away and deposit or stickto 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 causesdamage through the activation of the complement system, which, after a huge cascade of enzymeactivation, leaves cell membranes with channels that let fluid and molecules go in and outall willy nilly, causing the cell to burst

and die, usually though you’d want thisto happen to foreign cell or an infected cell, not healthy cells. when tissues become damagedas 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’tthe only trigger that’s thought to be associated with lupus—other potential triggers thathave been associated with sle include cigarette smoking, viruses, bacteria, use of certainmedications like procainamide, hydralazine, and isoniazid, as well as sex hormones, particularlyestrogen, which might be partly why lupus is more common in women, especially consideringit’s about 10 times more common in women than men during reproductive years, but onlyabout 2 or 3 times more common in childhood

or past the age of 65. okay okay, as a quick recap, the model that’sgenerally thought to be what leads to sle starts with some environmental trigger, whichdamages 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 notso good at clearing these apoptotic bodies and nuclear antigens, so you end up with alot of nuclear antigens floating around. in combination, they probably also have genesthat cause their immune cells to recognize these nuclear antigens as foreign, which initiatesan immune response, creates antinuclear antibodies that bind to antigens and then float aroundand deposit in various tissues, which causes

inflammation. these deposits and inflammation seem to bethe cause of most of the symptoms of lupus, which remember is a type iii hypersensitivityreaction. many patients, though, also develop antibodies targeting other cells like redand white blood cells, and molecules like various phospholipids, which can mark themfor phagocytosis and destruction, leading to additional symptoms. this is considereda type ii hypersensitivity reaction, although it isn’t fully understood why some of theseantibodies 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 difficultbecause it can affect a variety of people of different genders and ages, and there’realso 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 anddamaged. in fact, it’s so unpredictable that a diagnosis is given only when 4 or moreout of eleven diagnostic criteria are met. the first few have to do with the skin andoften happen to sun-exposed areas; the first is a malar rash, meaning a rash over the cheeksthat spares the nasolabial folds, sometimes just called a “butterfly rash” and thisappears after sun exposure. second is a discoid rash, which is chronic rash in sun-exposedareas that are plaque-like or forms a sort

of patchy redness and can scar. finally, ageneral photosensitivity of the skin—essentially a catch-all category for other rashes thathappen to sun-exposed areas—typically only lasting a couple of days. another type of tissue that can be damagedis 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 canalso affect the serosa, which is like the outer membrane of an organ or tissue, so ifit 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 worthnoting that lupus can affect any layer of the heart—meaning in addition to inflammationof the pericardium, they might also have inflammation of the endocardium and myocardium, leadingto endocarditis and myocarditis, of which the former presents as libman-sacks endocarditis,where vegetations form, which are essentially clumps of fibrin, a blood-clotting proteinand immune cells, around the mitral valve. next, if the joints get inflamed, patientsmay also develop arthritis, specifically two or more joints to meet the criteria. if thekidneys are affected, patients might develop renal disorders, like abnormal amounts ofurine protein or diffuse proliferative glomerulonephritis, inflammation of the glomeruli. for reasonsthat aren’t completely understood, some

autoantibodies that target receptors in thebrain have been implicated as well, and this can cause neurologic disorders like seizuresand psychosis. sort of along the same lines, patients can have autoantibodies against componentsof the blood, causing various hematologic disorders, for example they’ll get anemiaif red blood cells are targeted, thrombocytopenia if platelets are targeted, and leukopeniaif white blood cells or immune cells are targeted. that last one is really a mind-bender becauseit means that your immune system is attacking your immune system. alright so the last twohave to do with specific antibodies being found in the blood, the first one being antinuclearantibody, which we already went through. now a large proportion of patients with lupushave these, meaning this test is very sensitive,

but this test isn’t very specific, sincethese are seen in other autoimmune diseases. finally, they can have some other self-directedantibody that isn’t antinuclear antibody, which can be one of three types. it couldbe anti-smith, which is an antibody against small ribonucleoproteins, or it could be anti-dsdnawhich 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-phospholipidwhich is actually against proteins that are bound to the phospholipids, and is less specificfor lupus, meaning that it can pop up in other situations. there are three types of antiphospholipidantibodies - anticardiolipin, which can cause a false-positive test for syphilis since anticardiolipinantibodies are also sometimes involved in

syphilis, the other two are lupus anticoagulantalso known as lupus antibody, and anti-beta2 glycoprotein i. sometimes, because of these,patients with lupus develop an antiphospholipid syndrome, where the antiphospholipid antibodiescause a hypercoagulable state, meaning they’re more prone to developing clots and havingcomplications like deep vein thrombosis, hepatic vein thrombosis, and stroke. these patientsoften end up needing lifelong anticoagulation therapy. so lupus is characterized by periods of flare-upsand periods of remittance, so treatment is often aimed at preventing flares or limitinghow severe they are when they do happen. to help prevent flares, some patients may haveto avoid sunlight exposure with hats and long-sleeved

clothes. to reduce severity of flares, corticosteroidsmay be used to help limit the immune response, and finally, if symptoms are really severe,certain immunosuppressive drugs might be used.

1 comment:

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