Vasculitis | Clinical Medicine

[Music] H what's up Ninja nerds in this video today we're going to be talking about vasculitis inflammation of the blood vessels this is a really interesting lecture there's going to be a lot to talk about here so when we talk about vasculitis let's first discuss the pathophysiology and the best way to do this is to cover the three types of vasculitis the first one is large vessel vasculitis is actually not too hard to understand it's primarily going to affect the aorta and the main aortic branches so if you look here we'll see that they're going

to have inflammation of the aorta inflammation of the branches such as the subclavian and even the catds now this inflamation is going to narrow the blood vessels increase the risk of thrombosis and sometimes the inflammation can even cause anisms to form and we'll talk about that now when we talk about the reason why these large vessels are inflamed often times we don't have a great reason the concept that we believe to be Associated this from potentially biopsies is that this is a cell mediated inflammation so the concept behind this is that let's say that a

patient has lots of monocytes and nutrifil and lymphocytes and what's the what these guys are doing is there's infiltrating into the actual blood vessel wall and inducing injury now you probably bring about the question why in the heck are these monocytes nutrifil and lymphocytes going into into the blood vessel to injure it let's say that a patient's been exposed to an infection of some sort so a virus when they become exposed to that virus they produce an immune response to that virus what if a protein on that virus resembles a protein on the vessel that

is called molecular mimicry and the immune system will kind of attack that protein similarly how they would to a virus the problem is is that when you injure your blood vessel you end up with a bunch of complications one is now your endothelial cells that are supposed to have a natural anti-thrombotic function via releasing things like pgi2 which is prostacyclin and nitric oxide these are supposed to prevent platelets from sticking to the blood vessel wall if you can't make these because you've injured the blood vessel guess what happens the platelets will stick to the injured

blood vessel wall and form a platelet plug these platelet plugs will now narrow the Lumen of of this actual injured blood vessel and now ox that's supposed to be running through this vessel is going to be a decrease in its delivery to the tissues now as a response to that the tissue can become es schic and over time if not corrected can lead to necrosis that's one complication of vessel inflammation or injury a second one is fibrosis so as you have repeated injury to the blood vessel fibr blast will come down here in the lay

down this yellow tissue here called fibrous tissue and this fibrous tissue now will start to narrow the Lumen here of this actual vessel and now the diameter is decreased and the amount of oxygen we can deliver via this blood vessel is decreased and this is going to lead to ischemia that this artery is going to be supplying the last complication is when you have weakness of your blood vessel wall due to constant inflammation the metalloprotein aces are going to start breaking down the elastic lamina and you're going to end up with these like little bubbles

off of the blood vessel and these are called aneurysms the complications that can occur with aneurysms is that if they rupture this can lead to bleeding and that is a pretty concerning thing because this can lead to end organ damage so this is an overarching theme here that in all of these large vessels this whole mechanism could be occurring and it's usually due to these cells kind of interpreting The Vessel as being similar to some type of Prior exposure and that's the theory behind it now when we talk about these let's say that the actual

inflammation is occurring primarily of the kateed and some of its branches that come off near the face if it is we often times will associate this with what's called giant cell arteritis sometimes often referred to as temporal arteritis another one is let's say that the inflammation that's occurring within the vessel is primarily staying within the aorta and the arch and then just off the initial points here like the subclavian and maybe the initial part of the katees if that's the case we're talking about another type of large vessel vasculitis called takayasu so we can differentiate

these two two types of large vessel vasculitis based upon the more predominant arteries and branches that they're going to be affecting even though the mechanism of inflammation may be relatively the same median vessel vasculitis is going to be affecting arteries that run through an organ in other words what would this artery be called going into the kidney it's called the renal artery these would be the mesenteric arteries because they're going to be going to supplying parts of the small and large intestine now if there's inflammation these blood vessels again you're going to cause esema via

thrombosis or stenosis of the actual blood vessels going to these organs and even potentially anisms can form and you can cause bleeding now when we talk about these the mechanism is exactly the same as what we talked about for large vessel vasculitis there's some type of cell mediated process this could be due to a virus or an exposure of some sort that causes our immune system to go haywire and attack those proteins on the vessel that may resemble an exposure that we had at some point now when this happens again the same thing occurs is

that these vessels Arenal mesenteric and so many more can have thrombosis of them which can lead to esema to these organs stenosis which can lead to esia to these organs and aneurysms that can bleed leading to bleeding that can occur along these areas now with that being said the way that we differentiate the two different types of medium vessel vasculitis is if it involves so many different systemic arteries and it only spares one organ and that is the pulmonary system if that is the case we often times refer to this as polyarteritis NOOA all right

if it confines itself primarily to the coronary arteries and not much else we kind of refer to that as Kawasaki's disease so these are going to be again your medium vessel vasculitis which has a similarity in the mechanism but differences in the arteries that are oftentimes most significantly inflamed now the last type of vasculitis is small vessel vasculitis now small vessel vasculitis is interesting because this is going to affect our microvascular if you guys remember this from your anatomy and physiology this is your arterial that can become inflamed this is going to be what we

refer to is your capillary bed here that can also become inflamed and then lastly you have your postc capillary venil these all can become inflamed and again within multiple different organs or tissues when these become inflamed that is what we refer to as our small vessel vasculitis now the mechanism the pathophysiological concept is different it's no longer cell mediated as it was for large and medium it's now in two distinct areas one is it could be Anka mediated or Anka Associated what is this Anka this is anti-neutrophilic cytoplasmic antibodies and there's two types one is

your C anas which are the cytoplasmic anti-neutrophilic cytoplasmic antibodies relatively redundant they're attacking kind of a specific Protein that's present on nutrifil and this one here is very interesting it's called proteinas 3 and whenever the caanka is attached to that they trigger these neutrophils to kind of become agitated and they start releasing reactive oxy species and protases and uh nuclear U extracellular traps that kind of bind up and propagate more inflammation in the area the other one is called panas and these are your kind of your perinuclear anti-neutrophilic cytoplasmic antibodies and these are going to

be kind of going after a protein called mpo myop peroxidase and so if it's going after the myop peroxidase enzyme it's the p anas and if it's going after the proteinas 3 it's the C anas either way what happens is when these anas are formed again they're formed because maybe you exposed to some type of environmental agent of sorts the protein on that environmental agent resembles the proteins on the nutrifil they buy into them and Trigger these nutrifil to induce vessel injury when those vessels become injured you increase the risk of you got it thrombosis

stenosis and aneurism formation within these particular areas of your microvascular now there is a couple different concepts here because the causes are very very dependent upon the organs that they affect and the anchor that's causing this the first one is called granulomatosis with polyangitis also referred to as Wagers now this one is primarily mediated by C Anka whereas eosinophilic granulomatosis with polyangitis also known as chur Strauss syndrome is going to be Panka mediated and microscopic polyangitis is also Panka mediated so all of these are mediated via this Anka antibodies that trigger the same mechanism as

the cell mediated does in large and medium vessel the last one is immune complex deposition this can also injure these smaller vessels here and this is going to be via these different antibodies that are binding and precipitating with one another and then depositing into an actual vessel wall in a particular organ or tissue which precipitates inflammation these immune complexes can be IGA complexes and let's say that you have a bunch of IgA antibodies that bind together and they precipitate and then what basically what they do is they go and bind into a tissue maybe it's

a glomeruli that they bind onto too when they bind to the Glide they can utilize the complement system and our macras who will come in and precipitate lots of inflammation right the big thing to remember here is is diagnostically important is IGA antibodies don't usually precipitate a heavy amount of compliment protein utilization especially C4 compliment proteins there's less of that one why am I mentioning that because there's another type of vasculitis which utilizes heavy amount ounts of IGG and IGM antibodies that complex and bind with one another deposit into the tissue and utilize a heavy

amount of C4 complement proteins which precipitates massive inflammation either way the concept I need you to understand is when these immune complexes bind into the actual vessel wall of the tissue it will cause these little maroon guys here which are your compliment proteins to become activated which will precipitate a lot of inflammation it can do that by pulling in macroasia to enhance opsonization it can release c3a c5a a bunch of different inflammatory molecules or Chemin that attract in more white blood cells either way this is going to precipitate pretty massive injury vessel damage that's going

to lead to you guessed it thrombosis stenosis and increased risk of aneurysm all right my friends so now we move on to the next one which is immune complex deposition this is when you have a bunch of different antibodies maybe they're IG antibodies that utilize compliment proteins cuz you know whenever antibodies bind on to a particular protein they can have compliment proteins come and stick onto it lead to Mac formation or they can cause macras to come by enhancing opsonization or they can release chemokines so the whole concept is that IG antibodies when they utilize

compliment system and propagates inflammation especially of the tissue that it's depositing which is a blood vessel in IG vasculitis you see lots of IgA complexes but here's the big thing diagnostically they don't use a lot of the C4 complement protein use more of the C3 for the other one which is your cryoglobulinemic vasculitis they use lots of IGG and IGM antibodies that will precipitate bind with one another and deposit into the tissues and utilize complement proteins but they use a heavy amount of C4 complement proteins so when you check the C4 levels in between these

two it's going to be very low in cryoglobulinemic and normal in IGA vasculitis all right either way when these compliment proteins are activated these little anti bodies bind onto the actual vessel Wall cause these compliment proteins to stick to it form Mac formations which will damage the actual cell and then cause lots of immune system cells to become enhanced into that area and cause more damage we're going to damage these vessels and this is all propagated again IGA complexes IG vasculitis IGG and IGM with heavy C4 protein utilization cryog globul mimic vasculitis either way guess

what the same result is if you damage the vessel thrombosis stenosis and increased risk of aneurism formation Within These small capillaries and in a particular organ or tissue we've now talked about the pathophysiology of large medium and small vessel vasculitis what about the complications going through of large medium and small vessel vasculitis pertaining to the particular disease so the first one was giant cell arteritis if you guys remember this one is going to particularly hit a very specific artery and whenever these immune system cells cells infiltrate the branches of the karate it tends to hit

this artery first The Superficial tempor artery when you cause this to become inflamed you narrow the Lumen and reduce blood flow to the tissue here especially to the skin and the muscles and this can cause a headache especially near this temporal area and tenderness of the skin over this particular area it also can inflame this little Branch right here called the Opthalmic artery which can narrow the blood flow going to the actual retina which can lead to amoros fugax which is a temporary blindness but then over time it can lead to complete and permanent vision

loss this is the most feared complication of giant cell arteritis and the last one is it affects the maxillary artery this goes to a lot of the muscles of mastication and so you can develop what's called jaw claudication which is a lot of pain soreness tenderness of the actual muscles like the masser the Bator Etc during the chewing action and so these are things to think about if you see this on the clinical exam in a with giant solitis this is what you really need to be thinking about all right another high yield fact for

giant solitis which goes along with the epidemiology is this is most common in females particularly greater than 50 years of age and there is one disorder that if you see this in the vignette will often times cue you up to think about giant solitis it's a patient who comes in presenting with proximal hip and shoulder joint pain tenderness and stiffness within the morning this is called polymyalgia aromatica and that's often times very common and very heavily associated with giant cell arteritis all right we now move to the other large vessel vasculitis which is tasus now

remember think about the artery it involves and follow the flow of that I told you the kateed branch was refer the giant cell well for takayasu if you remember it was like the aorta it was the subclavian and the cored and the proximal parts of them so if I hit particularly a lot of inflammation hitting that aorta especially to the aortic Arch if I inflame the aortic Arch and I narrow this one really prominent complication is if you inflame a vessel wall you increase the risk of tearing through the intima and creating a a dissection

or weakening the vessel and causing it to balloon causing an aneurysm so aortic aneurysms and dissections are relatively common in patients with tasus but really high guil for tasus is when it hits the subclavian and narrows this you're reducing the blood flow to the upper extremities and so often times in these patients if you narrow their subclavian they'll have very decreased pulses bilaterally sometimes we call this a pulseless disease on top of that they may have unequal blood pressures potentially between both arms but the blood pressures in their upper extremities may be significantly lower than

the blood pressure in their lower extremities and so having unequal blood pressure and pulses in the extremities particularly upper in comparison to lower is pretty consistent with takayasu lastly is if you hit these kids if you get the KDs and you narrow these you're narrowing the blood flow up to the brain this can definitely lead to transient launch of Consciousness which is called Syncopy but often times if you osculate over this area you may hear some turbulence of blood flow like a karate brewey so these are potential things to think about with takayasu here's a

really high yield fact though to differentiate takayasu from giant cell because takayasu can potentially extend out to the CED they may get some similar presentation at Giant cell but you will never see takayasu and a patient greater than 50 they're almost always less than 50 years of age female usually have Asian descent all right so that's a good comparison between these two let's now move to medium vessel for medium vessel vasculitis the big one the heavy hitter the mac daddy of this one is is polyarteritis nidza and it's within the name this son of a

gun does almost every artery possible except for those going to the lungs and so when you think about this one of the big ones that it likes to hit is the vessels that supply the nerves the peripheral nerves and so there's a disease that's called monitis multilex so let's say here we have this vessel it's called the Vasa nervorum and the Vasa nervorum becomes inflamed and it gets narrowed and it doesn't Supply oxygen to these nerves well then the nerves start to become less functional and become es schic because of that you're going to get

damage to these nerves and this often times here's the key thing happens to two or more of these peripheral nerves that what happens is you get what's called monitis Multiplex I like to also say it's multiple mon neuropathies meaning for example let's say I injure here because of Vasa nervorum narrowing I injure the radial nerve I'm going to get wrist drop if I injure over here the lateral foror cutaneous nerve I'm going to get lack of sensation over this kind of particular area here and if I hit down here towards the pronal nerve I may

get foot drop so you're seeing a patient who has multiple mononeuropathies and that's usually pretty ke another one is it loves the the the renal system so it loves to hit this by causing a lot of narrowing of the actual Lumen of the renal artery kind of like a renal artery stenosis almost and if you reduce the profusion going into the actual kidney the juxa glaro cells will sense that and they'll pump up renin production renin will lead to Angiotensin formation and aldosterone formation and this combined effect of angiotensin 2 causing basal constriction aerone re

absorbing sodium and water you end up with an increase in BP often times these patients have not very good controlled blood pressure hypertension the other thing is if you have chronic repeated uh pore renal profusion guess what makes up your kidneys your nephrons and you got 1.2 million of those in each kidney these things will start dying off if they're not getting enough oxygen because of poor profusion if that happens you can start to develop kidney injury especially chronic kidney disease so these are really really common features we see in poly aritis and the DOA

especially if you see the monitis multiplex they also love to hit the skin especially the kind of vessels in the dermis and cause the blood to extravasate here and cause things like lavito reticularis which is this Lacy appearance as well as peric lesions that are palpable that appear on the skin again big thing for both of these is they do not blanch it also hits the GI and this is a really really important one I think for Diagnostic purposes when you hit the mesenteric vessels by causing this inflammation it can cause like this beaded appearance

like it does here in the renal vessels but what happens is you get so much beating and stenosis and thrombosis that you reduce perfusion to the small bowel that this can cause abdominal pain via mesenteric esmia and also sometimes if the mesenteric esmia is relatively acute your lactate levels might be elevated right but here's another big thing these little aneurysms that form these little like beaded aneurysms can rupture into the L of the git and can precipitate GI bleeds so this is important to be able to realize that they have these kind of like little

micro aneurysm or rosary bead appearances on the splank vessels as well as the renal vessels which is diagnostically helpful now here's one last thing to take away with polyarteritis NOOA a big high fact is that 10% of cases are associated with hepatitis B virus infection that used to be higher used to be 30% but now with the oncoming of vaccines this is now reduced but if you have a patient who has polyarteritis and DOA and the question comes up what should you test for to reduce the risk of recurrence it's going to be Hepatitis B

virus serology all right all right Kawasaki's disease this is a medium vessel vasculitis that actually affects child our children I should say the arteries that are most commonly affected the coronary arteries now what happens here is that this inflammation occurs and causes these coronary artery andms to occur the problem with these anisms is when they form they can increase the risk of a clot forming here causing thrombosis which can reduce blood flow and lead to nmi or these things can rupture which can actually cause a patient to develop sudden cardiac death so sudden cardiac death

via some type of terrible ventricular rhythmia or mild cardial infarction causing sudden cardiac death these are two big things that you have to be concerned about with Kawasakis now you never want to find Kawasakis via this involvement so how do I find it and make sure I monitor for these potential complications and make sure I try to prevent this since this has a higher mortality rate in these children well look for what's called crash and burn this is indicative of the common manifest ations for this so C is for conjunctivitis R is for a rash

A is for adenopathy which is your lymph adenopathy s is the strawberry tongue H is for hand and feet EMA and Emma and burn is they have a fever for greater than five days these features often times should ceue you up to think about Kawasakis and you should then look for this in a patient who is of one to five years of age all right we now move into small vessel vasculitis now what are the big complications that we need to be considerate of in small vessel vasculitis the first one is going to be granulomatosis

with polyangitis now granulosis of polyangitis can affect a lot of different organs but it's important to remember one big difference that helps you to separate and remember GPA from egpa and MPA so how do I do that the first one is it loves to involve the vessels of the naso farance or the upper respiratory tract so you'll often times see that they have lots of sea anas and these sea anas will kind of cause those neutr to lead to a lot of reactive otion species and proteases that cause inflammation of these vessels in the sinuses

and in the ears and so often times these patients will present with chronic sinusitis maybe even otitis media and on top of that it can cause such inflammation of the nasal septum that it can perforate and kind of in indent and cause something called a saddle nose deformity if you see this definitely be thinking about GPA now the other thing that happens with GPA is it loves to hit the lungs it likes to hit the bronchial blood vessels and cause bleeding which can present with diffuse alviar Hemorrhage which can cause massive pulmonary infiltrates bilaterally and

can cause ARs and it can even cause hemoptisis it can also cause inflammation to occur within the interstitial spaces here and cause interstitial lung disease and it can cause here's the biggest thing when a patient has um infiltrates on their chest x-ray and sometimes these patients with GPA have fevers and a lot of other symptoms that are concerning for pneumonia they'll often times get antibiotics they'll get a repeat chest xray and they'll still have that and so the the common theme to look for on the exam is a patient with recurrent pneumonia who's been treated

with antibiotics it's not necessarily pneumonia it's just they have multiple infiltrates and they keep getting treated with antibiotics and it's not getting any better the other thing is it loves to hit the kidneys so hemoptisis and hematuria it likes to cause anas to cause inflammation of the Glarus which leads to loss of the glamar filtration barrier and then they lose protein and blood and so you'll see hemu in the form of red blood cell cast which we'll talk about in glar nefritis you also going to lose lots of protein which is going to be in

the form of protein Uria and the other thing that can happen in this particular patient is they can cause massive injury here which can lead to loss of proper GFR and clearance of creatinine and so these patients can to have an increase in their creatinine their bu indicating an acute kidney injury so rapid rise in their creatinine in over a couple days that is a big thing to think about here so hematuria hemoptisis via the diffuse alveolar Hemorrhage think about that especially if they have sinus involvement and lastly they like the skin and it's going

to cause extravasation of blood into the skin tissue which can lead to palpable perpa the big thing that you're going to notice as a recurrent theme Here is that these three systems consistently become involved in GPA egpa and MPA they differ really only in minute things let's talk about that egpa is eosinophilic granos oitis so here's the big thing these P anas which is the big thing that they're triggering they like to cause these kind of again changes in neutrophils which lead to injury to the vessels supplying the nerves what's this going to lead to

Vasa nerve warm narrowing two or more nerve damage and monitis Multiplex this is a big thing to think about we see it in this one and we also see it in polyus NOOA but here's the heavy hitter here's the high yield stuff these also tend to increase the production of IG antibodies and increase the development of eosinophils in the airway which can precipitate allergic asthma via intense Broncos spasm so in patients who come in and have monitis Multiplex allergic asthma eosinophilia and elevated IG levels plus what did we just talk about guys pulmonary renal and

skin involvement think about egpa so this is going to be the same thing that you saw in GPA they only differ in this particular area as well as panas here C anas for GPA okay now we move on to MPA now MPA is even easier you want to know why because if we look here guess what this one has elevated P anas similar to egpa okay cool what helps to differentiate it from egpa and GPA well no sinus involvement oh that's that's GPA is the only one with the sinus involvement the upper respiratory tract involvement

okay there's no allergic asthma involvement or eosinophilia or IG antibodies that are elevated okay it's unlikely egpa and there's no granulomas if you took a biopsy which we'll talk about later that means really the only big thing for NPA is they have pulmonary renal and skin involvement so they all can have diffuse Alvar Hemorrhage via hemoptisis they can have infiltrates that require repeated antibiotics and they don't get better interstitial lung disease Glon nefritis and palpable perpa they differ only by small little minute things Now we move on to the other type of small vessel vasculitis

which is your immune complexes we have IGA IGA vasculitis is the most common childhood vasculitis very important to remember usually a kid has been exposed to a some type of upper respiratory tract infection usually it's a group a streptococus bacteria or a viral infection what happens is this triggers the immune system to generate antibodies against the group a strep or the virus but guess what these things unfortunately do they find proteins in our blood vessels that look similar to this protein on these bacteria viruses and they attack it where they love to attack the git

especially near the ilium inflaming these vessels inflaming the ilium can increase the risk of causing this lead point where parts of the ilium slide right into the seeum increasing the risk of inception and a small bowel obstruction here and so you want to look for patients who have intense abdominal pain in IGA vasculitis guess what else it loves to hit the renal vessels the GL Mari it can cause inflammation of the glus if it inflames the Glarus what's it going to do it's going to cause hematuria protein Ura it doesn't necessarily cause as much of

an acute kidney injury but it is possible it also loves to affect what else the skin it loves to affect the skin and cause extravasation of blood into the actual skin tissue causing palpable perpa especially often times we see this over the actual legs and the buttocks and the joints it loves to cause inflammation of the blood vessels near the sinovial joints and causes inflammation of those joints causing joint pain so often times there is a Triad that we will see as a similarity between uh IG vasculitis and cryoglobulinemic which is Glon nefritis palpable perpa

and joint pain they differ really only between mesenteric and GI bleed and the epidemiology that differentiates them as well that then takes us into the cryoglobulinemic vasculitis and this one what we know is that this is most common there is three types type one type two type three type two and type three often times cause vasculitis type one causes hyperviscosity syndrome we won't go too much into that what I want you to remember which is pertinent for your bores is that cryoglobulinemic vasculitis is heavily associated with hepatitis C virus infections so they're exposed to some

type of infection their body generates these antibodies against this hepatitis C virus such as IGM and IGG and these IGM tend to be rheumatoid factors positive so if you check a rheumatoid factor for cryoglobulinemic patients they're often times positive either way they generate these antibodies and these antibodies will precipitate in complex together at temperatures less than 37° that's what we call cryoglobulin proteins that precipitate in complex at low temperatures less than 37° once they do that they go and deposit into the blood vessels of the affected organs right we'll talk about those before we do

that I want to briefly payom to the types so type one we see where there's primarily increased monoclonal IGM antibodies we can see this in patients with multiple Myoma and Walden's macroglobulinemia type two we see that they have what's called monoclonal IGM antibodies and polyclonal IGG antibodies this is the most common one that is associated with hepatitis C and type three is you have polyclonal IGG and IGM antibodies that are complexing and this is most commonly associated with autoimmune disease es the big thing to remember hepatitis C virus is associated IGM and IG antibodies are

the primary antibodies that are precipitating the vasculitis and it occurs often times at lower temperatures now the artery and organ that's involved is the exactly the same as IGA vasculitis it's the renal so they can precipitate glarin nefritis the skin so they can precipitate palpable perpa and the joint involvement so they can precipitate joint pain this is the big thing but look for Hepatitis C virus Virus Infection as the potential trigger here my friends we've talked a lot about vasculitis and differentiating them based upon pathophysiology now if we're presented with a patient who comes in

and says hey I'm having some fever some fatigue I'm having some joint pain some anorexia and maybe they're having other organ specific symptoms and you have a suspicion for vasculitis you have to have a very strong degree of Suspicion the best thing to do is is if they have some systemic and organ specific symptoms get an ESR and a CR P all right so now if we had obtained an ESR and a CRP and it comes back that it's really elevated and they also have that fever the fatigue the anorexia the weight loss that's definitely

suggesting systemic inflammation right so here's where a history and physical examination becomes extremely crucial to nail down a diagnosis of vasculitis if I have constitutional symptoms elevated ESR CRP and I have organ specific symptoms what in the heck does that even mean for example I have a patient who's greater than 50 they're coming in with a temporal headache and tenderness they're having jaw claudication and maybe even some vision changes that's their organ specific symptoms plus constitutional elevated srcp I'm very suspicious of GCA how do I really nail down the diagnosis I could honestly make a

clinical one and give them steroids and see if they get better but if we really need to we can do a temporal artery biopsy and look for giant cells with a lot of granulomatous inflammation that would be diagnostic of GCA all right if I do a good history and I see that the patient's less than 50 they have unequal or weak blood pressure and pulses in the upper extremities and compared to the lower extremities and I noticed they have CED brues maybe a history of Syncopy I'm suspecting takosu but I'm not going to go cutting

into the kateed cutting into their subclavian cutting into the aorta what am I going to do I'm going to look for um Imaging evidence that suggest narrowing inflammation stenosis of those vessels that's when I would go to a CTA or MRA look at this you can see here some of the branches of the atic are very very inflamed and very narrow that's a pretty indicative one a look here on the sagittal view you can see here there's a lot of narrowing of the actual aorta and a lot of thickening and inflammation of the vessel wall

those would be very very suggestive and almost pretty much diagnostic for a patient having takayasu if we go the other route to now Pootis if I have a patient who has Hepatitis B virus infection 10% of cases they have monitis Multiplex they have hypertension they have CKD they have levito reticular are pepic lesions they have mesenteric esia right or GI bleeding I suspect polyarteritis and Doza how do I look for the primary problem I told you the renal vessels mesenteric vessels tend to bead and look like little Ander isms and so if you get a

visceral angiogram it'll show these particular vessels look here here's a mesenteric involvement you see all these like little beaded appearances these are all the aneurysms that's diagnostic if I get it in the renal vessels boom diagnostic I have then made a pretty good diagnostic suspicion of ptis and Doza this would be enough if the patient has skin involvement though and nerve involvement it would go a long way at this point to say I'm going to do a skin or nerve biopsy and if I do that I will find fibron oid necrosis of that tissue that

would be completely diagnostic of polyarteritis no DOA but often times you don't have to if you have that visceral angiogram that makes the diagnosis if I have perer lesions pulmonary infiltrates in other words a patient with the infiltrates on their chest x-ray not getting better with antibiotics or glome nefritis I should be concerned about an ankov vasculitis whereas if I have peric lesions I have arthralgia or joint pain and glarin nefritis I should think about the Triad present for immune complex vasculitis how do I differentiate these two well if I really wanted to I should

just get labs for all of these I should get an Anka level an IGA level a cryoglobulin level and a C4 level now here's why if I get the anas I'll tell if it's Sanka or Panka if it's C Anka it's GPA if it's Panka it's egpa or MPA and I have to look at their clinical features if it comes back IGA levels are elevated it's IGA vasculitis and if the cryoglobulins come back positive and the C4 levels remember I told you the difference between the two if C4 is low that suggests cryog globul anemic

vasculitis this often times may be enough but add in your history and physical exam for GPA they're going to have sinus involvement right that's the big difference so nasopen involvement so sinusitis um the deformity The sadon Noose deformity would also be suggested that otitis media that would often times be good enough if you really wanted to you could obtain a biopsy to really add to the utility here if I had a patient with elevated EOS and IG antibodies and Asthma I would think about egpa and if I have a patient who has no naso ferx

no eosinophilia IG or asthma involvement I'm thinking MPA but again I can get a biopsy to really help me out here igov vasculitis look for a recent upper respiratory tract infection in a young child and cryoglobulinemic what's the main infection hepatitis C virus infection so these are cues to think about now if I get a biopsy this would often times nail down some of the differences between these two and these two if I really wanted to so if I got a biopsy from the skin or from the I did a renal biopsy if I did

any of these I would potentially find granulomas in some of these now granuloma is just fibrous tissue lymphocytes and macrophages in the center often times if we see granulomas that are present and they're necrotizing in the center it suggests GPA and egpa right thus the name granulomatosis granulomatosis so that's why we would see it there if it's giant cells which means that all of these macras have kind of coales together and formed a multinucleated giant cell that suggests Giant aritis and toosi arteritis if you don't see any granulomas here then you want to start thinking

about potentially MPA that's another way to differentiate these another way to differentiate these two is that this has granulomas this does not have granulomas and lastly if I did a biopsy for these two I would see IGA deposition heavy on imuno florescence and G vasculitis and then for this one I would see IGG IGM and C4 proteins that would be deposited into the actual vessel wall there this is an easy way of really being able to systematically approach vasculitis in a very very helpful way all right let's now move into treatment all right my friends

let's now talk about the treatment of large vessel vasculitis so we talked about the two types Giant arteritis and takayasu the nice thing is that we treat both of these relatively the same so steroids is going to be the upfront treatment now what are the reasons why we would initiate steroids in these patients often times it's first line in both of these diseases now there is an extra drug that we can add on if the patient is refractory to cortical steroids or we can't wean them off of the steroids because they're still having symptoms that

would be where we would utilize tossil zmab or Methotrexate so this is an interlukin six blocker and this has the ability to shut down a lot of infl inflammation as well so again that would be a potential indication the last thing that we could also consider as a treatment in large vessel vascularities is angioplasty and stenting we really only would utilize this in severe organ es keemia in patients with tasus so if they were having like really bad limb esea I would then say hey we should go in there balloon open that vessel place a

stent so that we can maintain good profusion and then we can go put them on steroids if we need to I think this is a lot right but I think the biggest thing to remember is an algorithmic approach might make it easier for you so let's say that a patient has giant solid aritis they're having vision changes if they are having vision changes right away you have to put them on steroids no matter what if the vision loss is really bad then okay guess what I'm going to do I'm going to start them on IV

methyl pricone I need to get highd do steroids in there and get the inflammation down now so that they don't lose their Vision if there is no vision changes I don't want them to eventually do lose their so I'm going to put them on steroids but it doesn't have to be Ivy and it doesn't have to be these crazy high doses right away that's when I would use something like oral prazone all right so that's the way I would review this now let's say that I use one of those two agents I don't get them

under control or they're refractory they're still having symptoms that's when I would go to tossal zmab or I would go to Methotrexate same thing if I have a patient with takayasu are they having lisia so are they having like severe claudication they're having a discoloration poor de increased pulses they're having pain out of proportion in their extremities on the upper extremities oh they are okay well then I should probably go ahead and balloon and stent open that vessel the subclavian and if they're not put them on some steroids reduce some of the inflammation down with

some oral prazone and then again if they're not able to get off the steroids and they're not getting any better that's when I would go to tossal Lim map or Methotrexate so that's the way that we would approach these large vessel vascularities and thankfully it's the way that we'll approach a lot of our vasculitis now I think the reason why we're doing this should be straightforward it's to reduce inflammation right yes that's 100% the case you want to use things like steroids Methotrexate tsilis AB because you're shutting down all of these inflammatory Pathways which is

inducing vessel injury so yes there'll be less vessel wall inflammation but what's the benefit of this what are you trying to prevent you're trying to reduce thrombosis you're trying to reduce repeated injury leading to stenosis and you're trying to reduce the risk of aneurysm rupture and causing bleeding that is the goal that you're trying to go after all right so let's talk about the treatment of medium vessel vasculitis so now when we talk about these the treatment often times is corticosteroids plus cyclop fosmid now the reason you would give this is in a patient with

polyarteritis NOOA with very bad organ involvement all right this is the first line treatment you want to reduce the risk of acute kidney injury you want to reduce the risk of a patient developing a nasty GI bleed you want to reduce the risk of irreversible nerve injury Etc so in these patients often times you have to go big or go home all right for IVIG plus aspirin you're giving the IVIG to a patient with Kawasakis to reduce the risk of coronary artery aneurysms and aspirin to reduce inflammation but more specifically you're giving it to reduce

the risk of thrombosis within those aneurysms all right so this is first line in Kawasaki's disease now you're probably like okay so I give cortical steroids Plus pomide for p and IVIG Plus aspin for Kawasaki cool is there another way I should look at this I like to say okay there is another way that you could look at this when a patient has poly aritis and Doza ask yourself the question do they have really bad renal involvement do they have really bad GI involvement or neuro involvement if they don't you could probably get away with

steroids only but if they start to develop any renal GI or neural involvement that is not getting any better you then need to go big and go to steroids and cycop fosite to really shut down the inflammation all right here's the big thing though and they're going to try to ask this on the exam if you treat these patients and you don't get rid of their underlying cause or reason why they're developing vasculitis it'll keep coming back in this patient we know a potential reversible cause do they have Hepatitis B virus infection if they do

you need to treat that because it'll reduce the risk of incurrence recurrence what about Kawasakis it's pretty straightforward you give them IVIG and aspirin and then what you do is you look to see are they getting any Improvement in their coronary artery aneurisms are they remaining stable in size so get an echocardiogram to keep checking on those coronary artery aneurysms to make sure they're not getting any bigger now again why are you doing all of these things you're giving all of these agents to reduce inflammation reduce thrombosis stenosis and anism rupture that's the whole goal

right the last thing is small vessel vasculitis with treating these it all comes down to the same concept for these we can use supportive care in certain types often times IGA vasculitis and very mild cryoglobulinemic vasculitis if they just have joint pain they don't have any glarin aritis or anything like that or they only have skin lesions you can avoid going any too crazy so often times in IG vasculitis and very mild cryoglobulinemic vasculitis we can just do supportive care not doing anything else it's when the patient who has cryoglobulinemic vasculitis or a patient has

any Anka vasculitis do you need to go to corticosteroids plus cyclopamine so you're seeing this one for pan guess what LTC is for I'd say moderate to severe cryoglobulinemia and any type of ankov vasculitis all right right the last treatment option for small vessel vasculitis is Plex the only time we would do Plex is if a patient has ankov vasculitis and they're developing diffuse alveolar Hemorrhage and rapidly Progressive glarin aritis the only other time is if we think that we don't know does the patient have ankka vasculitis or what's called anti-gbm disease often known as

good pasture syndrome if I am unsure if the patient has good pasture syndrome or ankov vasculitis that's causing their hemoptisis and glarin arthritis then I need to start them on Plex the whole concept behind Plex which is really cool is you're taking a large catheter and you're removing the blood that has these antibodies or these kind of anas cleaning it out via this kind of like filter and then sending in a substitution fluid back into the patient's bloodstream and basically just removing the constant inflammation via these anti- nutrific cytoplasmic antibodies or anti-gbm antibodies which will

reduce the risk of rapidly Progressive Glam nefritis and diffuse alviar Hemorrhage that's the concept you want to remember now to recap a lot of this if a patient has ankka vasculitis you have to ask the question do they have rpgn rapidly progressing uh acute kidney injury do they have diffuse alviar hemorage so they're in RS or they're having massive hemoptisis or do they have anti-gbm if they don't it's steroids and cyclophosphomide if they do you go to plexus that's the way that you make that decision for cryoglobulinemic you just want to know do they have

GL nefritis because that's the bad one because this can cause acute kidney injury if they do not it's just supportive care if they do then you want to start them on steroids Plus cyclophosphomide or an alternative agent for this one is R toxmap all right last thing this patient has a high association with hepatitis C Virus Infection like there is hbv and poly no DOA ask them or check for hepatitis virus infection if they do treat it because you reduce the risk of recurrence again why are we doing all of these things here to reduce

vessal inflammation and all of these complications all right my friends that covers vasculitis I hope it made sense I hope that you guys enjoyed it I love you I thank you and as always until next time [Music]