erythema nodosum and lupus

with vasculitis, you have “inflammation”,of the “blood vessels”, and even though this can happen in arteries or veins, we’regoing to focus on vasculitis in arteries because it’s way more common. vasculitides are categorizedby the size of the blood vessels they affect, so we have small-vessel, medium-vessel, andlarge-vessel vasculitis. typically vasculitis is due to an autoimmune disease, where theimmune system confuses a part of normal body as a foreign invader, and there are a coupleof ways this might happen. sometimes the body confuses the innermostlayer of the blood vessel, which is the endothelial layer, with a foreign pathogen and directlyattacks it. to be a little more specific, the white blood cells of the immune systemmix up the normal antigens on the endothelial

cells with the antigens of foreign invaderslike bacteria simply because they look similar - this is called molecular mimicry. this autoimmuneconfusion is thought to be the cause several types of medium-vessel and large-vessel vasculitides. other times the immune system attacks healthycells that are near the vascular endothelium, and the endothelial cells are only gettingindirectly damaged. this is the situation in many small-vessel vasculitides, where theimmune system attacks white blood cell enzymes or other non-endothelial cell targets. once the endothelium is damaged either directlyor indirectly, almost all vasculitis diseases progress in a similar way. the damaged endotheliumexposes the underlying collagen and tissue

factor, and these exposed materials increasethe chance of blood coagulation. the blood vessel walls themselves get weaker as theyare damaged, making aneurysms more likely. and finally as the vessel wall heals, it becomesharder and stiffer because fibrin is deposited into the blood vessel walls as part of thehealing process. and actually, that’s vasculitis in a nutshell.the different types of vasculitis for the most part only vary depending on how theyare triggered and where in the body they cause problems. people with vasculitis have generalized symptomscaused by the inflammatory response of the immune system. symptoms like fever, weightloss, fatigue, etc. more specific symptoms

occur usually based off where in body thevasculitis is occurring, and which organ is supplied by that blood vessel. reduced bloodflow caused by vasculitis can cause organ ischemia which can happen in two ways. first,blood cells clump onto the exposed tissue factor and collagen on the inside of bloodvessels forming blood clots that and can restrict blood flow. the second way is caused by thehealing process of the blood vessel. as fibrin is deposited in the vessel wall, the wallsbecome thicker and bulge into the vessel, reducing the diameter of the vessel lumen. alright, now that we have the general ideaof vasculitis covered, let’s take a look at some specific conditions, starting withthe large-vessel vasculitides.

giant cell arteritis is a vasculitis thataffects branches of the carotid arteries. vasculitis in the temporal branch of the carotidartery is the most common location and causes headaches. vasculitis in the ophthalmic arterycan cause visual disturbances, and vasculitis in any of the arteries that supply the jawmuscles can cause pain when someone chews food - called claudication. giant cell arteritisaffects older individuals (typically more than 50 years old) and women more than men,so a grandmother would be in a high-risk group. classically, this type of vasculitis causeslots of inflammation and it results in a really high erythrocyte sedimentation rate (or esrfor short) - sometimes over 100! in giant cell arteritis, a biopsy of the affected arterywill show giant cells embedded in the internal

elastic lamina, which is a thin layer of elastictissue that separates the tunica intima and the tunica media. to be clear, these giantcells are actually not individual cells at all, but rather granulomas - a group of monocytesthat are packed tightly together, and look like one giant cell. now giant cell arteritisis segmental, which means that if you look at the entirety of an affected artery, you’llsee only sections of the artery are actually affected. this means that when biopsies aredone, you have to take a long section of the artery and examine it under a microscope.it also means that, if you don’t see any affected tissue, you can’t for sure ruleout the disease because it’s possible you took an unaffected section of the blood vessel.you can treat people with giant cell artertitis

by giving them corticosteroids, which weakensthe immune response. people whose ophthalmic artery is affected and don’t receive treatmentare at a high risk of blindness, again because poor blood flow to the eyes causes ischemiaand irreversible blindness. alright, so another large-cell vasculitisis called takayasu arteritis, and it’s very similar to giant cell arteritis except fortwo key differences. one is that it usually affects asian women that are under 40 yearsold where giant cell arteritis usually affects people over the age of 60. and two, it affectsthe arteries that branch off from the aortic arch, particularly around the branch points.if the inflammation occurs around aortic branches that serve the upper extremities, it causesa weak or nonexistent pulse. if the inflammation

occurs around the aortic branch that servesthe head, then it causes visual and neurological symptoms. histopathologically it’s quitesimilar to giant cell arteritis because in takayasu arteritis you still see giant cellsand granulomatous inflammation in the internal elastic lamina of the blood vessel. in addition,the erythrocyte sedimentation rate will be elevated, and takayasu arteritis is treatedwith corticosteroids. let’s move onto medium-vessel vasculitisdiseases. these vasculitis diseases typically affect a wide range of muscular arteries thatsupply organs, which gives the conditions a wide range of possible symptoms. the mostcommon type of all vasculitides is kawasaki disease, and we’ve got a separate videoon kawasaki disease, but for now it’s important

to note that it affects the coronary arteries,the muscular arteries serving the heart. next there’s polyarteritis nodosa, whichis thought to occur when the immune cells directly attack the endothelium, confusingit with hepatitis b virus. now, polyarteritis nodosa causes transmural inflammation, whichmeans the entire wall, the tunica intima, media, and adventitia are all affected. thisinflammation causes the vascular wall to die through all three layers of the artery andfibrosis occurs as the vascular wall heals, this process is called fibrinoid necrosis.the fibrosed vessel wall is left weak and prone to aneurysms, so some areas start tobulge out through the weakened walls. so if you step back and look at the artery you seethese fibrotic aneurysms which are hard bulges

down the length of the artery, and they looklike a “string of beads” on angiogram. this pattern is quite unique among the variousvasculitides. organ ischemia in the distribution of affected arteries is the main complication.if the renal arteries are affected, then a person will have hypertension (remember kidneysregulate blood volume). if the mesenteric artery is affected, a person can have mesentericischemia and severe abdominal pain and gastrointestinal bleeding. if the arteries affecting the brainare affected it can cause neurological symptoms, and if arteries supply the skin are affectedthen it can lead to skin lesions. treatment is aimed at reducing the vessel inflammationand generally includes corticosteroids. another medium-vessel vasculitis is buerger’sdisease, named for a nyc pathologist not a

hamburger. it’s other name is thromboangiitisobliterans, which literally translates to clot vessel inflammation blockage, and asthe name suggests this vasculitis is notoriously for causing blood clots in tiny arteries inthe fingers and toes, which leads to ulcers and eventually dead tissue in these digitsand eventual autoamputation. not fun. buerger’s disease typically affects men between theages of 20-40 years and the biggest risk factor for this vasculitis is the use of tobaccoproducts. in fact, the thought is that tobacco might be the trigger for the autoimmune responseagainst blood vessel. stopping the use of tobacco actually slows down (but doesn’tnecessarily stop) the disease and need for amputations in most patients.

alright onto small-vessel vasculitis. small-vesselvasculitis affects small vessels like arterioles, capillaries, and venules. in the diseases,b-cells mistakenly target their antibodies to granules made by a person’s own neutrophils.in a sense, one immune cell attacking another. the antibodies are called “anti-neutrophiliccytoplasmic antibodies” or ancas for short and they are mainly of the igg type. the disease granulomatosis with polyangiitis(gpa) which used to be called wegener’s granulomatosis, is one of these small vesselvasculitides. the b-cells release an autoantibody called cytoplasmic antineutrophil cytoplasmicantibody or c-anca. yep, the name is hilariously redundant - with cytoplasmic included twiceto drive home the point. c-anca targets and

bind to a specific neutrophil granule calledproteinase 3 which is embedded in the membrane of some neutrophils. once c-anca binds tothe neutrophil, it causes the neutrophil to release oxygen free radicals, which enterthe nearby endothelial cells damaging them indirectly and causing vasculitis. on a biopsy,you can see evidence of inflammation and granulomas in the blood vessel wall. gpa affects thenasopharynx, lungs, and kidneys and usually occurs in middle-aged males. people with thedisease can have chronic pain caused by sinusitis or bloody mucus from ulcers within the nose.over time, the nose itself may even cave in or curl, a condition called a saddle nosedeformity. blood vessel inflammation in the lungs and air passages can also make breathingmore difficult causing air passages to constrict,

and ulcers can form causing bloody coughing.in the kidneys, the inflammation restricts blood flow to the glomeruli, causing themto die and leading to decreased urine production and an increase in blood pressure since thekidneys are no longer as efficient at regulating blood volume. gpa is typically treated withcorticosteroids and cyclophosphamide, but relapses in the disease are common, and thatmakes sense. the presence of c-anca is the main cause of the disease, and if it keepsattacking the granules from within neutrophils, there is a good chance the disease will return. another small-vessel vasculitis that is verysimilar to granulomatosis with polyangiitis is microscopic polyangiitis. it’s so similarin fact, that you need to rely on some clues

to help distinguish them. microscopic polyangiitisdoes not affect the blood vessels of the nose/sinuses, only the kidneys and lungs. you also won’tsee the granulomas in the blood vessel walls like you would in granulomatosis with polyangiitis.the third difference is you won’t find c-anca antibodies. instead you’ll find p-anca antibodies(the p stand for perinuclear), which is just a different type of anti-neutrophilic cytoplasmicantibody reacting with the neutrophil granule myeloperoxidase instead of proteinase 3. youtreat microscopic polyangiitis the same way you treat granulomatosis with polyangiitis,corticosteroids and cyclophosphamide, and it’s also common for it to relapse. churg-strauss syndrome is very similar toboth granulomatosis with polyangiitis and

microscopic polyangiitis. it too is causedby p-anca antibodies and it causes similar symptoms such as sinusitis, lung damage, andkidney damage, but it also causes gastrointestinal, skin, nerve, and heart damage like some medium-vesselvasculitis diseases. a lot of the time churg-strauss syndrome ismistaken as allergies and asthma because they all have similar symptoms. that, and likeallergies and asthma, churg-strauss causes a lot of eosinophils to float around in theblood. actually people who have asthma and peripheral eosinophilia are more likely todevelop churg-strauss syndrome because they both have elevated eosinophils. also justlike granulomatosis with polyangiiti, granulomas can form.

next up, henoch-schonlein purpura. now unlikethe other small vessel vasculitis diseases we’ve talked about henoch-schonlein purpura(abbreviated at hsp) doesn’t involve anca antibodies. instead, we find elevated levelsof the iga antibodies floating around in the blood. now iga is an awesome antibody thatis found in our mucosal cells, which are cells that are in some way exposed to the outsideworld, for example cells in our lungs and our gastrointestinal tract. in hsp, the person starts making iga thatis directly targeted at their own endothelial cells because of molecular mimicry. this goesagainst the general trend of small-vessel vasculitides being the result of indirectdamage. symptoms depend on where the iga-mediated

attack on small blood vessels happens. sometypical places is the skin blood vessels around the buttocks and legs, which leads to significantskin discolouration that looks like blood is pooling under the skin surface - calledpurpura. one indication that the disease is henoch-schonlein is that the skin discolorationis palpable, as in you can feel it raise above the normal skin. remember the fibrosis ofthe blood vessel walls hardens and makes it palpable, just like in polyarteritis nodosa.if the iga attacks the blood vessels in the gastrointestinal tract it can cause abdominalpain, and if it attacks the blood vessels in the kidneys, it can lead to hematuria (bloodin the urine) and eventually affect the kidney’s function which is called iga nephropathy.

just like the other small-vessel vasculitisdiseases, henoch-schonlein purpurpa resolves on its own but it can reoccur. generally itis only treated with steroids if the symptoms are severe. and there you go! that’s vasculitis!