Wikipedia:Osmosis/Vasculitis
Vasculitis is inflammation (“itis”) of a blood vessel (“vascul”), and although this can happen in arteries or veins, we’re going to focus on vasculitis in arteries because they are much more common. Vasculitides are categorized by the size of the blood vessels they affect, so we have small-vessel, medium-vessel, and large-vessel vasculitis. Typically vasculitis is due to an autoimmune diseases, where the immune system confuses a part of normal body as a foreign invader, and there are a couple of ways this might happen.
Sometimes the body confuses the innermost layer of the blood vessel, which is the endothelial layer, with a foreign pathogen and directly attacks it. To be more specific, the white blood cells of the immune system mix up the normal antigens on the endothelial cells with the antigens of foreign invaders like bacteria because they look similar - this is called molecular mimicry. This autoimmune confusion is the cause of many medium-vessel and large-vessel vasculitidis.
Other times the immune system attacks healthy cells that are near the vascular endothelium, and the endothelial cells are only getting indirectly damaged. This is the situation in many small-vessel vasculitides, where the immune system attacks white blood cell enzymes or other non-endothelial cell targets. Once the endothelium is damaged either directly or indirectly, almost all vasculitis diseases progress in a similar way. The damaged endothelium exposes the underlying collagen and tissue factor, and these exposed materials increase the chance of blood coagulation. The blood vessel walls themselves get weaker as they are damaged, making aneurysms more likely. And finally as the vessel wall heals, it becomes harder and stiffer because fibrin is deposited into the blood vessel walls.
And actually, that’s vasculitis in a nutshell. The different types of vasculitis for the most part only vary depending on how they are triggered and where in the body they cause problems. People with vasculitis have generalized symptoms caused by the inflammatory response of the immune system. Symptoms like fever, weight loss, fatigue, etc. More specific symptoms occur usually based off where in body the vasculitis is occurring, and which organ is supplied by that blood vessel. Reduced blood flow 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 blood vessels forming blood clots that and can restrict blood flow. The second way is caused by the healing process of the blood vessel. As fibrin is deposited in the vessel wall, the walls become thicker and bulge into the vessel, reducing the diameter of the vessel lumen.
Alright, now that we have the general idea of vasculitis covered, let’s take a look at some specific conditions, starting with the large-vessel vasculitides.
Giant cell arteritis is a vasculitis that affects branches of the carotid arteries. Vasculitis in the temporal branch of the carotid artery is the most common location and causes headaches. Vasculitis in the ophthalmic artery can cause visual disturbances, and vasculitis in any of the arteries that supply the jaw muscles can cause pain when someone chews food - called claudication. Giant cell arteritis affects older individuals (>50 years) and women more than men, so a grandmother would be in a high-risk group. Classically, this type of vasculitis causes lots of inflammation and it results in a really high erythrocyte sedimentation rate (or ESR for short) - sometimes over 100! In giant cell arteritis, a biopsy of the affected artery will show giant cells embedded in the internal elastic lamina, which is a thin layer of elastic tissue that separates the tunica intima and the tunica media. To be clear, these giant cells are actually not individual cells at all, but rather granulomas - a group of monocytes that are packed tightly together, and look like one giant cell. Now giant cell arteritis is segmental, which means that if you look at the entirety of an affected artery, you’ll see only sections of the artery are actually affected. This means that when biopsies are done, 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 rule out 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 weakens the immune response. People whose ophthalmic artery is affected and don’t receive treatment are at a high risk of blindness, again because poor blood flow to the eyes causes ischemia and irreversible blindness.
Alright, so another large-cell vasculitis is called Takayasu Arteritis, and it’s very similar to giant cell arteritis except for two key differences. One is that it usually affects asian women that are under 40 years old where giant cell arteritis usually affects people over the age of 60. And two, it affects the 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 causes a weak or nonexistent pulse. If the inflammation occurs around the aortic branch that serves the head, then it causes visual and neurological symptoms. Histopathologically it’s quite similar to Giant cell arteritis because in Takayasu Arteritis you still see giant cells and granulomatous inflammation in the internal elastic lamina of the blood vessel. In addition, the erythrocyte sedimentation rate will be elevated, and Takayasu arteritis is treated with corticosteroids. Let’s move onto medium-vessel vasculitis diseases. These vasculitis diseases typically affect a wide range of muscular arteries that supply organs, which gives the conditions a wide range of possible symptoms. The most common type of all vasculitides is Kawasaki disease, and we’ve got a separate video on 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, which is thought to occur when the immune cells directly attack the endothelium, confusing it with hepatitis B virus. Now, polyarteritis nodosa causes transmural inflammation, which means the entire wall, the tunica intima, media, and adventitia are all affected. This inflammation causes the vascular wall to die through all three layers of the artery and fibrosis 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 to bulge out through the weakened walls. So if you step back and look at the artery you see these fibrotic aneurysms which are hard bulges down the length of the artery, and they look like a “string of beads” on angiogram. This pattern is quite unique among the various vasculitides. 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 kidneys regulate blood volume). If the mesenteric artery is affected, a person can have mesenteric ischemia and severe abdominal pain and gastrointestinal bleeding. If the arteries affecting the brain are affected it can cause neurological symptoms, and if arteries supply the skin are affected then it can lead to skin lesions. Treatment is aimed at reducing the vessel inflammation and generally includes corticosteroids. Another medium-vessel vasculitis is Buerger’s disease, named for a NYC pathologist not a hamburger. It’s other name is thromboangiitis obliterans, which literally translates to clot vessel inflammation blockage, and as the name suggests this vasculitis is notoriously for causing blood clots in tiny arteries in the fingers and toes, which leads to ulcers and eventually dead tissue in these digits and eventual autoamputation. Not fun. Buerger’s disease typically affects men between the ages of 20-40 years and the biggest risk factor for this vasculitis is the use of tobacco products. In fact, the thought is that tobacco might be the trigger for the autoimmune response against blood vessel. Stopping the use of tobacco actually slows down (but doesn’t necessarily stop) the disease and need for amputations in most patients.
Alright onto small-vessel vasculitis. Small-vessel vasculitis 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-neutrophilic cytoplasmic 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 vessel vasculitides. The B-cells release an autoantibody called cytoplasmic antineutrophil cytoplasmic antibody or c-ANCA. Yep, the name is hilariously redundant - with cytoplasmic included twice to drive home the point. c-ANCA targets and bind to a specific neutrophil granule called proteinase 3 which is embedded in the membrane of some neutrophils. Once c-ANCA binds to the neutrophil, it causes the neutrophil to release oxygen free radicals, which enter the 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 the nasopharynx, lungs, and kidneys and usually occurs in middle-aged males. People with the disease 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 nose deformity. Blood vessel inflammation in the lungs and air passages can also make breathing more 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 them to die and leading to decreased urine production and an increase in blood pressure since the kidneys are no longer as efficient at regulating blood volume. GPA is typically treated with corticosteroids and cyclophosphamide, but relapses in the disease are common, and that makes sense. The presence of c-ANCA is the main cause of the disease, and if it keeps attacking the granules from within neutrophils, there is a good chance the disease will return. Another small-vessel vasculitis that is very similar to granulomatosis with polyangiitis is microscopic polyangiitis. It’s so similar in fact, that you need to rely on some clues to help distinguish them. Microscopic polyangiitis does not affect the blood vessels of the nose/sinuses, only the kidneys and lungs. You also won’t see 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 cytoplasmic antibody reacting with the neutrophil granule myeloperoxidase instead of proteinase 3. You treat 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 to both granulomatosis with polyangiitis and microscopic polyangiitis. It too is caused by p-ANCA antibodies and it causes similar symptoms such as sinusitis, lung damage, and kidney damage, but it also causes gastrointestinal, skin, nerve, and heart damage like some medium-vessel vasculitis diseases. A lot of the time Churg-Strauss syndrome is mistaken as allergies and asthma because they all have similar symptoms. That, and like allergies and asthma, Churg-Strauss causes a lot of eosinophils to float around in the blood. Actually people who have asthma and peripheral eosinophilia are more likely to develop Churg-Strauss syndrome because they both have elevated eosinophils. Also just like granulomatosis with polyangiiti, granulomas can form. Next up, Henoch-Schonlein purpura. Now unlike the other small vessel vasculitis diseases we’ve talked about Henoch-Schonlein purpura (abbreviated at HSP) doesn’t involve ANCA antibodies. Instead, we find elevated levels of the IgA antibodies floating around in the blood. Now IgA is an awesome antibody that is found in our mucosal cells, which are cells that are in some way exposed to the outside world, for example cells in our lungs and our gastrointestinal tract. In HSP, the person starts making IgA that is directly targeted at their own endothelial cells because of molecular mimicry. This goes against the general trend of small-vessel vasculitides being the result of indirect damage. Symptoms depend on where the IgA-mediated attack on small blood vessels happens. Some typical places is the skin blood vessels around the buttocks and legs, which leads to significant skin discolouration that looks like blood is pooling under the skin surface - called purpura. One indication that the disease is Henoch-Schonlein is that the skin discoloration is palpable, as in you can feel it raise above the normal skin. Remember the fibrosis of the 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 abdominal pain, and if it attacks the blood vessels in the kidneys, it can lead to hematuria (blood in the urine) and eventually affect the kidney’s function which is called IgA nephropathy. Just like the other small-vessel vasculitis diseases, Henoch-Schonlein purpurpa resolves on its own but it can reoccur. Generally it is only treated with steroids if the symptoms are severe. And there you go! That’s vasculitis!