VASCULITIS

Vessel inflammation


Vasculitis is an autoimmune inflammation of blood vessels. It’s kind of rare and deeply complicated, but exam writers love it, so get used to it. There are about ten different kinds of vasculitis that you should learn. Since blood vessels are present in every square inch of the body, it’s easy to see why vasculitis can cause a wide variety of symptoms that involve wildly different organ systems. Chronic low grade fevers and fatigue are common as well. Frustratingly, many of these diseases have multiple names. Originally most of these diseases were named after the individuals who discovered them, but modern medicine is trying to move away from eponyms. So yeah, you have to know both. You should break down the vasculitides into three groups, based on the size of the artery that they affect. 


Large vessels include the Aorta and its branches. Inflammation can cause pulselessness (Takayasu’s) or facial symptoms (Temporal arteritis). On histology, granulomas are found in this group.


Medium vessels include the muscular arteries that feed organs. Think about these diseases based on which organs they damage. Vasculitis can cause thrombosis or aneurysm which can cause end organ ischemia. 


Small vessels include arterioles, venules and capillaries. Capillaries are found near the skin, so Petechiae and Purpura are common here, especially “palpable purpura” which just means that the lesions are raised a little bit. Petechiae and purpura are red-or-purple skin lesions that do not blanch when pressed. This also tends to affect the kidneys a lot. There are two subcategories: 



Vasculitis Map

TEMPORAL ARTERITIS (LARGE)

Giant Cell Arteritis


Temporal Arteritis is inflammation along the Maxillary Artery and its branches. 


The gold standard for diagnosing TA is a biopsy of the affected artery. But that can be problematic. The granulomas appear very seldomly along the artery. So you have to take out a reeeeaaaally loooooong chunk of artery if you have any hope of catching the granuloma. And then the pathologist will require several days to evaluate the slides. Since TA with ophthalmic involvement is a medical emergency, a more practical diagnostic tool is required. Enter the ESR (Erythrocyte Sedimentation Rate). The ESR is one of the oldest lab tests there is. And it’s usually too nonspecific to be useful haha. But it’s ok for identifying general states of inflammation in the body. And the ESR will be markedly elevated in TA (well over 50 or 100). So if the patient has a suspicious story, you can order an ESR, and have the results back in an hour or so. If the ESR is really high, presume that this is TA and initiate treatment (steroids). Then the patient needs a biopsy (because they have to be treated with steroids for an entire year).  If the ESR is low, it’s not TA. (Note that the ESR is elevated in pretty much every vasculitis, but it’s emphasized here because headaches are diagnostically challenging).



Bulging temporal artery

TAKAYASU ARTERITIS (LARGE)

Pulselessness disease


Takayasu Arteritis is basically the same disease process as Temporal Arteritis. But instead of carotid artery branches, it affects the branches of the Aortic Arch that feed the brain and arms. You can probably see why this is called “pulseless disease” because when a Subclavian artery is affected, the downstream pulse in that arm will be weak. Involvement of the Carotids can cause strokes. Instead of old women, young adult Asian females and children are affected (pretty easy to remember since the name is Takayasu). Treatment is also steroids. 

Notice how the Aortic branches appear gnarly

A giant cell.

These are seen in the large vessel vasculitides.



THROMBOANGIITIS OBLITERANS (MEDIUM)

Buerger Disease


Buerger Disease is the easiest vasculitis to remember. There will be a young male smoker with necrosis of his fingers and toes. When digits die and fall off, this phenomenon is called auto-amputation. The toes are involved in 100% of cases, and the fingers are involved 50% of the time. Patients often suffer from continuous pain in their feet. There is no cure, but smoking cessation can dramatically improve this disorder. 




KAWASAKI DISEASE (MEDIUM)

Pediatric vasculitis


Kawasaki Disease is high yield. That’s because it can cause heart attacks in children (commonly of East Asian descent). Many of the symptoms are vague, but there are a few tell-tale signs. Here’s a terrifying picture to help illustrate them.




Treat with Aspirin and IVIg. This is the only time you can give Aspirin to a kid (because the risk of Kawasaki’s outweighs the risk of Reye’s Syndrome). This is the most common cause of heart attacks in kids. Kawasaki’s will resolve after a few weeks, at which point you can stop the ASA.







Aspirin!







POLYARTERITIS NODOSA (MEDIUM)

Poly- (many)       -arteritis (vessel inflammation) Nodosa (knobby)


Polyarteritis Nodosa (PAN) causes widespread organ damage, see the diagram below for some examples. It typically affects middle-aged men. Fatal unless treated with steroids and Cyclophosphamide. Most cases are idiopathic, but about one-third of cases seem to be caused by hepatitis B. When the Hep B surface antigen joins to its antibody (HBsAg + HBsAb), an immune complex is formed. That immune complex can deposit in arteries all over the body (type 3 hypersensitivity), which is believed to cause the inflammation typical of PAN. 

PAN involves a particular pattern of vessel lesions, called the string of pearls or rachitic rosary appearance. These are particularly common in the renal vasculature.

Rachitic rosary


SMALL VESSEL VASCULITIS



There are two flavors of small vessel vasculitis. 


ANCA-Mediated - in ANCA vasculitis, the body curiously makes antibodies against neutrophils, specifically against certain granules found inside them. The antibodies are called ANCA (Anti-Neutrophil Cytoplasmic Antibodies). The exact MOA is a little weird. The granules are usually hidden away in the cytoplasm, but during inflammatory states, they sometimes get expressed on the outside of the neutrophils. The ANCAs will bind to them. This somehow causes the neutrophil to degranulate further and kickstart inflammation. Unfortunately, you are expected to memorize the p-ANCA and c-ANCA proteins.

Immune Complex-Mediated - this is a classic type 3 hypersensitivity. When an antibody binds to its antigen, an immune complex is formed. If the antigen is small, then the immune complex will be small enough to float through the blood. But like leaves in a pool filter, the small immune complexes can get wedged into inappropriate places (like capillaries). They eventually are cleaned up by the complement system, which kills the nearby endothelium -- hence the inflammation. Note - Henoch Schönlein Purpura is the most commonly tested variety for Step and Level 1.




ANCA VASCULITIS (SMALL)

Autoimmunity against neutrophils


Wegener’s Granulomatosis has a classic triad of problems in the ENT, lungs and kidneys, usually in middle-aged males. Treat with steroids and cyclophosphamide. c-ANCA is elevated.

Churg-Strauss Syndrome (aka Eosinophilic Granulomatosis with Polyangiitis) is the eosinophilic vasculitis. It causes asthma and sinusitis first. Then there is slow, creeping damage to lots of organs like the skin (palpable purpura), lungs, kidneys and heart. Most patients die of heart disease years later (i.e., tamponade). As the name implies, eosinophils are usually elevated. As are p-ANCA antibodies.


Microscopic Polyangiitis is identical to Wegener’s Granulomatosis, but without ENT problems  and without granulomas. 






IMMUNE COMPLEX VASCULITIS (SMALL)

Type 3 hypersensitivity


Henoch-Schönlein Purpura (aka IgA Vasculitis) is due to IgA immune complex deposition. Common in kids following a URI (because the body makes more IgA for the pharynx, and some ends up in the blood). It causes characteristic palpable purpura on the butt / legs, plus GI pain and bleeding (since IgA is usually found in the gut). IgA complex deposition into the kidneys can result in IgA nephropathy (Berger disease). Treatment is supportive +/- steroids, but most patients recover spontaneously after a few months.

 

Cryoglobulinemia is due to the deposition of immune complexes made of cryoglobulins. Cryoglobulins are proteins that gel at cold temperatures, particularly in areas exposed to cold temperatures (nose, digits, ears). Therefore, cold temperatures can precipitate typical small-vessel vasculitis symptoms (palpable purpura, arthralgias, weakness, neuropathy, glomerulonephritis). There are different types (mixed IgG/IgM, polyclonal, monoclonal). Perhaps the most common cause is Hep C. 


Behçet Syndrome is associated with HLA-B51. Triggered by herpes or parvo, it causes recurrent mouth / genital ulcers, uveitis and erythema nodosum every few weeks. Seen in Turks and Armenians. Pretty low yield.