Vasculitis: Clinical practice

Vasculitides are a group of disorders that cause vasculitis, which is inflammation in the walls of the blood vessels.

Since blood vessels pass through organs - vasculitis damages those organs, and mimics a variety of diseases.

There are usually systemic symptoms like fever, fatigue, joint pain, and weight loss; as well as organ-specific symptoms that may literally involve any organ.

Whenever vasculitis is suspected, there’s inflammation, which is often reflected by an increased ESR, CRP, and increased white blood cell count, and sometimes requires a biopsy of whichever organ or tissue is involved.

The vasculitides are divided into groups based on the size of the arteries that are mainly involved.

There’s large vessel, medium vessel, and small vessel vasculitis which affects small arteries and capillaries.

Starting with large vessel vasculitis, the first condition is Giant cell arteritis, also called temporal arteritis.

This is the most common vasculitis in individuals over the age of 50.

The most frequently affected arteries are the external carotid, ophthalmic, and temporal arteries.

Symptoms include a headache and vision loss, and a worrisome complication is that there’s a high risk for a stroke.

Often, the temporal artery can become tender and rigid.

In addition, individuals can get jaw claudication, which is when there’s temporal artery insufficiency causing ischemia of the masticatory muscles, leading to pain while chewing.

Diagnosis of giant cell arteritis is done with temporal artery biopsy, looking for giant cells in the tissue.

The next large vessel vasculitis is Takayasu arteritis.

This is an extremely rare condition affecting mostly young women, generally younger than 40 years old, with increased incidence in the Asian populations.

Takayasu arteritis primarily affects the aorta and its major branches.

And the inflammation can cause turbulent blood flow which results in vascular bruits on auscultation of any involved artery - the aorta, carotid, renal, or femoral artery.

Usually, there’s also blood pressure asymmetry on the left compared on the right; reduced or absent peripheral pulses, and limb claudication.

Diagnosis is based on CT angiography or magnetic resonance angiography of the involved artery, which shows skip lesions, where there’s stenosis or aneurysms with normal tissue in between.

Moving on to medium vessel vasculitis, first up is polyarteritis nodosa.

Polyarteritis nodosa sometimes pops up in individuals with Hepatitis B or C, likely due to molecular mimicry between hepatitis antigens and proteins within the blood vessel wall.

Polyarteritis nodosa is a multisystem disease that can affect nearly any site in the body.

Often there’s joint and muscle pain. Also the skin may be involved, and that can cause livedo reticularis which is a lace-like purplish discoloration of the skin.

The skin can also have palpable purpura, which are large reddish spots on the skin caused by bleeding underneath the skin, and the purpura can develop into large ulcers that can get infected. Ultimately, these ulcers can lead to gangrene.

Nerve involvement may occur. Some individuals develop what’s called a mononeuritis multiplex, which is a peripheral neuropathy that causes numbness, pain, and burning as well as muscle weakness.

Over time, individuals with polyarteritis nodosa can develop complications like intestinal ischemia and necrosis, kidney failure, and cardiovascular disease like hypertension or myocardial infarction, which can be fatal.

A key diagnostic feature on angiography is the presence of clusters of small aneurysms that look like a string of beads on a rosary - called the rosary sign.

Finally, a biopsy from blood vessels, skin, muscle, or nerve can show a pattern of inflammation consistent with polyarteritis nodosa.

The next medium vessel disease is Kawasaki disease, and it typically affects young children.

Children can develop bilateral bulbar Conjunctival injection; a polymorphous Rash due to sensitivity to sunlight; cervical lymphAdenopathy; oral mucous membrane changes, including injected or fissured lips, injected pharynx, or Strawberry tongue; and peripheral extremity changes, including erythema of palms or soles, edema of Hands or feet, and periungual desquamation.

Diagnosis of Kawasaki is based on the presence of at least four of those features. In addition, they have a fever for at least five days.

You can remember that these children CRASH and burn.

A severe complication of Kawasaki disease is coronary artery aneurysms, which can cause myocardial infarction. So an echocardiogram is done at diagnosis to evaluate for coronary artery involvement.

Finally, there’s small vessel vasculitis which is divided into two groups.

The first group are the anti-neutrophil cytoplasmic antibody or ANCA-associated vasculitides, which include granulomatosis with polyangiitis which is also called Wegener’s disease, eosinophilic granulomatosis with polyangiitis which is also called Churg-Strauss disease, and microscopic polyangiitis.

The second group are the immune complex vasculitides, which include cryoglobulinemic vasculitis, and IgA vasculitis which is also called Henoch-Schönlein purpura.

Granulomatosis with polyangiitis is characterized by granulomatous inflammation within the blood vessels that supply the eyes, ears, nose, larynx, lungs, and kidneys.

Eye involvement occurs when a granuloma is growing behind the eyeball and pushes on it, causing a painful exophthalmos, and even diplopia and optic nerve ischemia.

The small vessels of the eye may also be affected, causing scleritis or uveitis.

Destruction of the internal ear may lead to otitis and ultimately deafness.

A typical finding is the saddle nose deformity, caused by a huge granuloma that destroys the bony structure of the nose, and opens up the paranasal sinuses causing a recurrent sinusitis.

Laryngeal involvement causes a hoarse voice, but can ultimately progress to collapse, causing suffocation.

Many individuals have lung involvement nodules that resemble tumors, so diagnosis typically requires a lung biopsy.

Finally, renal involvement can cause glomerulonephritis, which can cause both hematuria and proteinuria, with or without a rise in serum creatinine, and can progress to kidney failure.

Laboratory tests show an elevated c-ANCA antibody, which targets the enzyme proteinase 3, but the definitive diagnosis requires a biopsy from an affected organ, generally skin, kidney, or lung.

Eosinophilic granulomatosis with polyangiitis also causes granulomatous inflammation, but there’s usually a predominance of eosinophils.

Symptoms are quite similar to granulomatosis with polyangiitis, but these individuals also develop chronic rhinosinusitis, asthma, and blood eosinophilia.

Also, laboratory tests show a prevalence of another type of ANCA called p-ANCA, which is specific for the enzyme myeloperoxidase.

The high levels of eosinophils can cause damage to cardiac muscle, so it’s important to routinely obtain an electrocardiogram and do echocardiography; and if there’s an abnormality, to follow up with a cardiac magnetic resonance study.

The last ANCA-associated vasculitis is microscopic polyangiitis, which basically causes the same signs and symptoms as granulomatosis with polyangiitis, and even causes an elevated c-ANCA.

The key difference is that these individuals don’t have granulomatous inflammation, which can be identified on a biopsy.

Finally there are the immune complex vasculitis.

First, there’s cryoglobulinemic vasculitis, which is caused by precipitation of cryoglobulins, which are serum proteins that precipitate out in cold temperatures.

These proteins form immune complex with complement proteins and deposit in the walls of small capillaries, venules, and arterioles.

The result is palpable purpura, joint and muscle pain, sensory and motor neuropathies, and glomerulonephritis that can evolve into renal failure.

This disorder is most often associated with hepatitis C virus infection, but also hepatitis B virus and HIV as well, so all three of these viral infections should be screened for and treated.

To make the diagnosis, laboratory tests often show low levels of circulating complement factors, due to complement deposition in tissues.

A biopsy of a skin lesion can confirm the diagnosis by showing the precipitated cryoglobulins.

Cryoglobulinemic vasculitis can lead to strokes, myocardial infarction, intestinal ischemia, or severe kidney dysfunction.

Sometimes a renal biopsy is also done to check for renal disease.

In severe cases, individuals may need a plasma exchange procedure, like plasmapheresis, which is where plasma proteins, like cryoglobulins, get removed from the plasma.

Finally, there’s IgA vasculitis, also known as Henoch–Schönlein purpura or HSP, which is the most common vasculitis of childhood.

HSP usually follows an upper respiratory tract infection, and then causes a fever; palpable purpura, typically on buttocks, back and lower limbs; arthritis affecting large joints; abdominal pain; and sometimes affects the kidney.

For diagnosis, there’s typically an increased serum IgA level, and a biopsy will show IgA deposition into an affected organ or tissue.

The good news is that HSP is relatively benign and usually self-limiting.

But, rarely, it can affect adults, and there it’s usually triggered by a medication and can be more severe. In adults, there’s a much higher chance of glomerulonephritis and kidney failure.

Now, the backbone of initial management of most vasculitides is medium to high doses of glucocorticoids. That specifically applies to Giant cell arteritis, Takayasu arteritis, and Polyarteritis nodosa.

Once remission has been attained, the dose of glucocorticoids is usually steadily lowered, to limit the toxicity, and they are eventually discontinued in most cases.

If there’s glucocorticoid-related toxicity, or if the disease is refractory to glucocorticoids, individuals can be given immunosuppressant medications like azathioprine, mycophenolate, methotrexate, tocilizumab, leflunomide, or cyclophosphamide.

Also, individuals with severe disease may get a combination of glucocorticoids and immunosuppressant medications.

For initial treatment of ANCA-associated vasculitis and cryoglobulinemic vasculitis, immunosuppressant medications are given along with the backbone of glucocorticoids.

The use of glucocorticoids in patients with IgA vasculitis is controversial.

So, individuals with joint or abdominal pain often get NSAIDs like naproxen, and only if that fails to manage the pain, are glucocorticoids given.

For Kawasaki disease, the management is different.

Individuals with Kawasaki disease should get a single dose of intravenous immune globulins or IVIG, administered within the first 10 days of illness, before aneurysms typically develop.

IVIG should be administered even beyond this 10-day window in individuals with evidence of persistent vasculitis or systemic inflammation, such as persistent fever and laboratory markers like an elevated ESR and CRP.

In addition, individuals should get aspirin during the acute phase of illness to prevent blood clots from forming.

Aspirin therapy is started at high doses while the fever lasts, and then is continued at a low dose until laboratory markers return to normal, which usually takes about two months, unless there’s coronary artery involvement, in which case aspirin therapy is continued.

Finally, glucocorticoids can sometimes increase the risk of coronary artery aneurysm, so they’re only given as an adjunct to initial treatment in cases that are refractory to other treatment options.

Finally, most forms of vasculitis can relapse, and flares of vasculitis, defined as new or worsening symptoms, can occur many years after the initial presentation. That’s why ongoing monitoring of organ function with labs and imaging is so important.

Summary

Alright, as a quick recap… Large vessel vasculitis - includes Giant cell arteritis, also called temporal arteritis because it tends to affect the temporal artery, and Takayasu arteritis, which shows skip lesions, where there’s stenosis or aneurysms with normal tissue in between.

Medium vessel vasculitis - includes Polyarteritis nodosa, with clusters of small aneurysms that look like a string of beads on a rosary - called the rosary sign, and Kawasaki disease, which causes children to have symptoms summarized in mnemonic CRASH and burn.

Small vessel vasculitides have two groups. One group is the anti-neutrophil cytoplasmic antibody or ANCA-associated vasculitides, which includes Granulomatosis with polyangiitis or Wegener’s disease, and microscopic polyangiitis, both of which cause inflammation within the blood vessels that supply the eyes, ears, nose, larynx, lungs, and kidneys, as well as an elevated c-ANCA antibody.

The group also includes Eosinophilic granulomatosis with polyangiitis or Churg-Strauss disease, which causes chronic rhinosinusitis, asthma, and blood eosinophilia, and causes an elevated p-ANCA.

The other group of small vessel vasculitides is immune complex vasculitis, which includes Cryoglobulinemic vasculitis, which causes precipitation of cryoglobulins, and IgA vasculitis or Henoch-Schönlein purpura, which has an increased serum IgA level, as well as IgA deposition into affected organs or tissues.

Vasculitis causes systemic symptoms like fever, fatigue, joint pain, and weight loss; as well as organ-specific symptoms, and there’s typically an elevated ESR, CRP, and white blood cell count.

The diagnosis typically involves imaging or a biopsy of an involved organ or tissue, and the backbone of initial management is glucocorticoids for Giant cell arteritis, Takayasu arteritis, and Polyarteritis nodosa.

This is followed by maintenance steadily lowering the doses of glucocorticoids to limit the toxicity until achieving drug-free remission.

And since most forms of vasculitis may eventually relapse, ongoing monitoring is generally indicated for many years.

For initial treatment of ANCA-associated vasculitis and cryoglobulinemic vasculitis, immunosuppressant medications are given along with the backbone of glucocorticoids.

For IgA vasculitis, individuals with joint or abdominal pain often get NSAIDs, and only if that fails, are glucocorticoids given.

Finally, individuals with Kawasaki disease should get a single dose of IVIG, as well as aspirin while the fever lasts.