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• What causes vasculitis?
• What is going to happen to me?
• Is vasculitis curable?
• Is vasculitis hereditary?
• Does diet affect vasculitis?
• Will my vasculitis return?
• How should I guard against the occurrence of a disease flare?
• Why do I have to have bloodwork checked frequently?

What causes vasculitis?

The causes of most forms of vasculitis remain unknown. Infections are strongly suspected of playing a role in in forms such as the association of hepatitis B (a virus) and polyarteritis nodosa, and hepatitis C (another virus) and cryoglobulinemic vasculitis. Bacterial infections have been suspected of playing a possible role in granulomatosis with polyangiitis (GPA, formerly known as Wegener’s) which is the reason that some patients with GPA that is limited to the upper respiratory tract are treated only with an antibiotic, Bactrim (trimethoprim/sulfamethoxazole). A general theory that applies to many types of vasculitis is that the disease results from the occurrence of a particular infection in a person whose genes (and other factors) make him/her susceptible to developing vasculitis.

What is going to happen to me?

The course of vasculitis is often difficult to predict. Some types of vasculitis may occur only once and do not return. Other types are prone to recurrences. For all patients with vasculitis, it is essential to be evaluated by physicians who are experienced in the treatment of these diseases. Vasculitis is treatable, and many patients achieve remissions through treatment. It is important to balance the types of medications necessary to control the disease and the risk of side effects that those medicines often bring. A primary aim of several ongoing new studies in vasculitis is to find drugs that help maintain remission.

Is vasculitis curable?

Most forms of vasculitis are treatable if detected early enough, before substantial organ damage has occurred. While often effective, however, the treatments remain imperfect and require improvement. Further research is needed in all forms of vasculitis. Greater knowledge of these diseases will lead to better treatments and, some day, to cures.

Will my children or other family members get it?

Vasculitis is not contagious. One cannot acquire vasculitis from contact with a vasculitis patient. In addition, despite the fact that genes probably play a role in susceptibility to some forms of vasculitis, it is unusual for vasculitis to occur in more than one member of the same family. Thus, vasculitis is not a heritable disorder. All of these points illustrate the fact that the causes of vasculitis are complex. In all likelihood, patients develop vasculitis because of the simultaneous occurrence of multiple risk factors, most of which remain poorly understood.

Does diet affect vasculitis?

This is one of the most commonly-asked questions by patients with vasculitis. All patients want to do whatever is within their power to help treat their disease. Unfortunately, there is presently no evidence that a person’s diet affects susceptibility to vasculitis, or that consuming or avoiding certain foods or beverages affects the course of the disease. In general, we advocate eating a balanced healthy diet rich in protein and vegetables. Avoidance of excessive empty calories, processed foods, and sugars may be very important, particularly in patients on steroids who are at risk for weight gain.

Will my vasculitis return?

After patients achieve remission from their vasculitis, it is logical for them to wonder if their disease will ever return. The answer, which is often difficult to give with certainty, depends in large part on the patient’s specific type of vasculitis. For example, some types of vasculitis, such as Henoch-Schönlein purpura (HSP) or vasculitis caused by a medication, are often self-limited and resolve on their own. Other forms of vasculitis (e.g., Buerger’s disease, a disease strongly associated with cigarette smoking) resolve with institution of the definitive treatment: smoking cessation.

However,  other forms of vasculitis behave less predictably and never come back in some patients but recur frequently in others. Granulomatosis with polyangiitis (GPA), giant cell arteritis (GCA), Takayasu arteritis, microscopic polyangiitis, and many other types of vasculitis fall into the category of diseases that have periods of quiescence and periods of flare. Disease flares in vasculitis can be mild (rash, minor joint pains) or severe (renal failure, skin ulcers). Flares may occur if medications are discontinued or dosage is lowered. Flare may occur in the context of infection. Often the reason for disease flare is unknown.

At the present time, the ability of doctors to predict who will suffer disease flares and who will maintain in long-term remissions (or be cured) needs refinement. Progress in this area will come through research.

How should I guard against the occurrence of a disease flare?

We believe that several points are worth keeping in mind:

First, the symptoms of flares are usually very similar those experienced at the onset of disease. If headaches signaled the beginning of giant cell arteritis, then the recurrence of headaches may indicate a disease flare. If leg ulcers began as painful red lumps on the leg the first time, then the return of painful red lumps may mean that vasculitis is back. Patients must become experts about their own manifestations of vasculitis so that they can recognize them immediately, consult their doctors, and begin appropriate treatment before serious damage occurs.

Second, we believe that patients truly know and understand their own bodies. It is important to discuss new or changing symptoms with your physicians. Together, patients and physicians can determine if new symptoms truly represent a vasculitis flare or if the cause is something equally as likely (medication side effect, infection, or other common medical issues).

Finally, because vasculitis treatments require careful monitoring by doctors, patients should discuss any changes in treatment with their physicians. Increasing or decreasing medications without consulting a physician may lead to trouble.

Why do I have to have bloodwork checked frequently?

Blood tests are helpful to monitor for the return of vasculitis by keeping a watchful eye on important parameters such as kidney function, liver tests, and markers of inflammation (ESR and CRP). Blood tests are also very important to ensure that medications are not causing any side effects such as liver irritation or low blood counts.

How often should my blood be checked?

This depends on the specific medicine or medicines that you take. Patients on cyclophosphamide (Cytoxan) should have their counts checked every week. Patients on most other kinds of medications used to treat vasculitis (Methotrexate, Azathioprine) usually only need to have their blood work checked monthly. If some laboratory tests are abnormal or nearly so, then more frequent monitoring may be required.

What type of tests do we check?

Regardless of the type of vasculitis and the exact type of medication that a patient takes, similar types of tests are monitored. These tests are:

1. a complete blood count;
2. tests of kidney function including a urinalysis; and
3. liver function tests.

The table below outlines the importance behind checking each of these tests.

Type of Test	What should be checked	Why?
Complete Blood Count (“CBC”)	White blood cells (WBC) Platelets Hematocrit	Low WBC count may lead to infections. Low platelets may cause bleeding. Low hematocrit means insufficient oxygen-carrying capacity of the blood.
Kidney Function	Creatinine Blood Urea Nitrogen (BUN)	High creatinine and BUN indicate that the kidneys are not performing their blood-cleansing function properly.
Urinalysis	Protein Level Red Blood Cells	Normal urinalyses have no protein and no blood. The presence of protein and/or blood in the urine may indicate active vasculitis in the kidneys (or damage to the bladder from cyclophosphamide).
Liver Function	Albumin Aspartate aminotransferase(AST) Alanine aminotransferase (ALT)	Often a good indication of overall health. Elevated AST/ALT levels indicate inflammation in the liver (usually caused by medications).

Vasculitis Center Doctors

Collaborators

Vasculitis can involve virtually any organ system within the body. Hence, our Vasculitis Center maintains close collaborative relationships with experts from other specialties. The Vasculitis Center includes collaborators from several medical disciplines who help provide the highest level of care for our patients. They have extensive experience managing vasculitis within their subspecialty and work closely with the Physicians in the Vasculitis Center to provide comprehensive care for our patients:

Otolaryngology (ENT):

Our ENT team includes specialists in inflammatory sinus disease, sensorineural hearing loss, and chronic middle ear disease. We are pleased to also have a Doctor of Audiology, Dr. Dinkes, who specializes in inflammatory process on our team as well.

• Dr. Jean Kim (sinus disease, middle ear manifestations)
• Dr. Alexander Hiller (upper airway disease)
• Dr. Roni Dinkes (audiology)

Neuro-ophthalmology:

• Dr. Andrew Carey

Endocrinology / Osteoporosis:

• Dr. Han Na Kim

• First Description
• Who gets Microscopic Polyangiitis (the “typical” patients)?
• Classic symptoms of Microscopic Polyangiitis
• Forms of vasculitis similar to Microscopic Polyangiitis
• What causes Microscopic Polyangiitis?
• How is Microscopic Polyangiitis diagnosed?
• Treatment and Course of Microscopic Polyangiitis

First Description

The first description of a patient with the illness now known as microscopic polyangiitis (MPA) appeared in the European literature in the 1920s. The concept of this disease as a condition that is separate from polyarteritis nodosa (PAN) and other forms of vasculitis did not begin to take root in medical thinking, however, until the late 1940s. Even today, some confusing terms for MPA (e.g., “microscopic poly arteritis nodosa ” rather than “microscopic poly angiitis ”) persist in the medical literature. Confusion regarding the proper nomenclature of this disease led to references to “microscopic polyarteritis nodosa” and “hypersensitivity vasculitis” for many years. In 1994, The Chapel Hill Consensus Conference recognized MPA as its own entity, distinguishing it in a classification scheme clearly from PAN, granulomatosis with polyangiitis (GPA, formerly Wegener’s), cutaneous leukocytoclastic angiitis (CLA), and other diseases with which MPA has been confused with through the years.

Much of the explanation for the difficulty in separating MPA from other forms of vasculitis has stemmed from the numerous areas of overlap of MPA with other diseases. MPA, PAN, GPA, and CLA  and other disorders all share a variety of features but possess sufficient differences as to justify separate classifications.

Who gets Microscopic Polyangiitis? A typical patient

MPA can affect individuals from all ethnic backgrounds and any age group. In the United States, the typical MPA patient is a middle-aged white male or female, but many exceptions to this exist. The disease may occur in people of all ages, both genders, and all ethnic backgrounds.

Classic symptoms of Microscopic Polyangiitis

Many signs and symptoms are associated with MPA. This disease can affect many of the body’s organ systems including (but not limited to) the kidneys, nervous system (particularly the peripheral nerves, as opposed to the brain or spinal cord), skin, and lungs. In addition, generalized symptoms such as fever and weight loss are very common.

The FIVE most common clinical manifestations of MPA are:

1. Kidney inflammation (~ 80% of patients).
2. Weight loss (> 70%).
3. Skin lesions (> 60%).
4. Nerve damage (60%).
5. Fevers (55%).

Kidney Inflammation

Inflammation in the kidneys, known as glomerulonephritis, causes blood and protein loss through the urine. This process can occur either slowly or very rapidly in the course of the disease. Patients with kidney inflammation may experience fatigue, shortness of breath, and swelling of the legs.

The image below is from a urinalysis of a patient with kidney inflammation. When MPA is active, red blood cells will form a clump or “cast” (bracketed in white) within the tubules of inflamed kidneys. These “casts” pass through the renal system and may be viewed under the microscope in a patient’s urine.

Constitutional Symptoms

Weight loss, fevers, fatigue, and malaise are part of a collection of complaints regarded as “constitutional” symptoms. Constitutional complaints are a common finding in patients with MPA, because the disorder is a systemic disease confining itself generally not to one specific organ system but rather broadly affecting a patient’s “constitution”.

Skin lesions

Skin lesions in MPA, as in other forms of vasculitis that involve the skin, can erupt on various areas of the body. The lesions tend to favor the “dependent” areas of the body, specifically the feet, lower legs and, in bed-ridden patients, the buttocks. The skin findings of cutaneous MPA include purplish bumps and spots pictured below (palpable purpura).

These areas range in size from several millimeters in diameter to coalescent lesions that are even larger. Skin findings in MPA may also include small flesh-colored bumps (papules); small-to-medium sized blisters (vesiculobullous lesions); or as small areas of bleeding under the nails that look like splinters (pictured below), hence the name splinter hemorrhages.

Peripheral nervous system

Damage to peripheral nerves (i.e., nerves to the hands and feet, arms and legs) results from inflammation of the blood vessels that supply the nerves with nutrients. Inflammation in these blood vessels deprives the nerves of their nutrients, leading to nerve infarction (tissue death). Multiple nerve involvement that is characteristic of vasculitis is known as “mononeuritis multiplex”. This condition is frequently associated with wrist or foot drop: the inability to extend the hand “backwards” at the wrist or to flex the foot upward toward the head at the ankle joint. If the condition is caused by nerve deterioration associated with vasculitis, unfortunately, surgery is not a treatment option due to the nerve infarcton (tissue death).

Neurologic symptoms resulting from peripheral nerve damage may also include numbness or tingling in the arm, hand, leg, or foot. Over time, muscle wasting (pictured below) that is secondary to the nerve damage may result from damage caused by vasculitis.

Pictured:

The hand on the left (the patient’s right hand) is normal, displaying normal muscle bulk of the areas between the fingers.  In contrast, the hand on the right (the patient’s left) shows wasting of the muscle in the web space between the thumb and first finger, leading to a hollowed-out, bowl-like appearance of that area.  The consequence of this muscle wasting is that the patient is unable to grasp objects between his thumb and fingers (i.e., has a weak pinch) and his hand grip is weak.

Lungs

Lung involvement can be a dramatic and life-threatening manifestation of MPA. When lung disease takes the form alveolar hemorrhage – bleeding from the small capillaries that are in contact with the lungs’ microscopic air sacs – the condition may quickly pose a threat to the patient’s respiratory status (and therefore to the patient’s life). Alveolar hemorrhage (pictured below), which is frequently heralded by the coughing up of blood, occurs in approximately 12% of patients with MPA .

Another common lung manifestation of MPA is the development of non-specific inflammatory infiltrates, identifiable on chext x-rays or computed tomography (CT scans) of the lung.

Eyes, Muscles, and Joints

Organs that also merit mention in discussions of MPA include the eyes, muscles, and joints. Intermittent irritation of the eye (resembling “pinkeye”) that is caused by either conjunctivitis or episcleritis may be an early disease manifestation or a sign of a disease flare. Occasionally other types of inflammation (e.g., uveitis) are also observed in MPA. Muscle or joint pains (known to clinicians as “myalgias” or “arthralgias”, respectively) are common complaints in MPA, generally accompanying the types of constitutional symptoms mentioned above. Arthritis (inflammation of the joints accompanied by swelling) can also be observed in MPA. Joint complaints in MPA and related forms of vasculitis tend to migrate from one joint to another – one day involving the left ankle, the next day the right wrist, the third day a shoulder, for example.

Forms of vasculitis similar to Microscopic Polyangiitis

The similarities and differences between MPA, GPA, and PAN are highlighted in the table below.

	MPA	GPA	PAN
BLOOD VESSEL SIZE	Small to Medium	Small to Medium	Medium
BLOOD VESSEL TYPE	Arterioles to venules, And sometimes Arteries and veins	Arterioles to venules, And sometimes Arteries and veins	Muscular Arteries
GRANULOMATOUS INFLAMMATION	NO	YES	NO
LUNG SYMPTOMS	YES1	YES1	NO
GLOMERULONEPHRITIS	YES	YES	NO
RENAL HYPERTENSION	NO	NO	YES
MONONEURITIS MULTIPLEX	COMMON	OCCASIONAL	COMMON
SKIN LESIONS	YES2	YES2	YES2
GI SYMPTOMS	NO	NO	YES3
EYE SYMPTOMS	YES4	YES4	NO
ANCA-POSITIVITY	75%	65-90%	NO
CONSTITUTIONALSYMPTOMS	YES5	YES5	YES5
NECROTIZING TISSUE	YES	YES	YES
MICROANEURYSMS	RARELY	RARELY	TYPICAL

¹ Pulmonary capillaritis in MPA and nodules or cavitary lesions in WG

²MPA can have small blood vessel skin lesions as mentioned above, similar to GPA or medium blood vessel lesions similar to PAN (livedo reticularis, nodules, ulcers, and digital gangrene)

³Stomach pain after meals

⁴MPA eye complications are typically milder than those of GPA, but serious

ocular problems including necrotizing scleritis can occur

⁵Constitutional symptoms include weight loss, fevers, joint and muscle aches, and malaise.

What Causes Microscopic Polyangiitis?

The cause of MPA is not known. However, enough is known about a few types of vasculitides that allow us to describe in general terms how MPA affects the body. MPA is clearly a disorder that is mediated by the immune system; the precise events leading to the immune system dysfunction (hyperactivity), however, remain unclear. Many elements of the immune system are involved in this process: neutrophils, macrophages, T and B lymphocytes, antibodies, and many, many others.

Because MPA is often associated with anti-neutrophil cytoplasmic antibodies (ANCA), antibodies directed against certain constituents of white blood cells (WBCs), the disease is often termed an “ANCA-associated vasculitis”, or AAV. ANCA, discovered in 1982, act against certain specific (and naturally occurring) enzymes in the body residing within the neutrophils and the macrophages, all of which are members of the WBC family. The result of the interactions of ANCA with their target proteins is an increase in the destruction of WBCs at the sites of disease and the release of white blood cell enzymes within blood vessel walls, causing the damage to blood vessels. In MPA, the ANCA are directed generally against to specific proteins: myeloperoxidase (MPO) and proteinase 3 (PR3).

How is Microscopic Polyangiitis diagnosed?

Blood is taken to detect any ANCA levels, if MPA is suspected. In addition, an erythrocyte sedimentation rate (ESR or “sed rate”) and C-reactive protein (CRP) are usually ordered. Both of these tests are elevated in many different types of inflammation and are not specific to MPA or any particular disease. The ESR and CRP, known as “acute phase reactants”, are often sensitive indicators of the presence of active disease. In and of themselves, however, elevations in acute phase reactants are not sufficient to justify additional treatment.

A carefully analyzed urine specimen should be obtained at the initial visit (and every follow-up visit!) to maintain vigilance for either the development or the progression of kidney involvement.

A computed tomography (CT) scan of the chest may also be performed to detect the presence of lung involvement. A tissue biopsy may be needed to make the diagnosis of MPA, and is taken from an organ that seems to be involved at the time. Sometimes an electromyography/nerve conduction (EMG/NCV) study may need to be done to identify a site for biopsy or to detect findings consistent with a mononeuritis multiplex (see classic symptoms section above). Tissues that might be biopsied are kidney, skin, nerve, muscle, and lung.

Pictured: a biopsy of the gastrocnemius muscle, performed in a 69 year–old man with microscopic polyangiitis. A blood vessel within the muscle shows an intense inflammatory infiltrate with destruction of the blood vessel wall, confirming the diagnosis of vasculitis.

Treatment and Course of Microscopic Polyangiitis

A steroid (usually prednisone) in combination with a cyclophosphamide (CYC) or rituximab is typically the first combination of medications to be prescribed.  After control of the disease – usually around 4 – 6 months of treatment maintenance therapy will be used to keep the disease in remission. This will vary between patients. Prednisone may be discontinued after approximately 6 months.

There are many different types of vasculitis, some with different causes than others.

Certain forms of vasculitis that can be due to infection where the microbe directly invades the vessel wall. Syphilis is one example of vasculitis that can be caused by infection in the blood vessel. Treating the infection is the main goal in managing this sort of vasculitis, which is not an autoimmune disease, but rather an infection.

Other infections can provoke the immune system into causing damage in blood vessels. Here, the infection is the trigger, but the immune system is the cause of the vascular damage. Viral hepatitis (B and C) are examples of this sort: some patients with Hepatitis B may develop polyarteritis nodosa, while some patients with Hepatitis C may develop cryoglobulinemic vasculitis.

Other types of vasculitis may be due to an ‘allergic‘-type reaction to medications. For example, certain blood pressure medications (hydralazine) or thyroid medications (propylthiouracil) can trigger ANCA associated vasculitis in some patients. Cocaine is an illicit drug that is linked to vasculitis and vascular damage.

However, the causes of most vasculitides are currently unknown. While we can identify some risk factors (such as older age in giant cell arteritis), we do not know the specific causes of these diseases. These forms of vasculitis of unknown cause are considered autoimmune diseases.

Under normal circumstances, our immune system serves to defend us from infection and other threats, such as cancers. In autoimmune diseases, the immune system generates a response not against a foreign threat, but against normal “self” tissues. This abnormal immune response against “self” tissues can result in a wide array of autoimmune diseases, including relatively common diseases (such as psoriasis or thyroid disease) as well as rare conditions (such as vasculitis).

In most cases, autoimmune diseases are believed to be due to an abnormal immune response that is generated in a susceptible person, and eventually leads to a cycle of ongoing inflammation in otherwise normal tissues where no infection or other identifiable threat is present. Some interaction between the immune system and the environment is thought necessary for this to occur, and a person’s genetic background likely places some individuals at higher risk than others.

A better understanding of the specific causes of these diseases would lead to improved means of diagnosing, treating, and even preventing these conditions. Uncovering the causes of vasculitis is a major goal of vasculitis research.

While we may not know the specific causes of the vasculitidies, we do have a basic understanding of the way that the immune system causes organ damage in these conditions. In all forms of vasculitis, activation of the immune system leads to the deposition of inflammatory cells and proteins in the walls of blood vessels. As this inflammation in blood vessels continues, the vessels become damaged and no longer serve their normal function of delivering blood to the organs that they supply. Consequently, the tissues downstream of these inflamed vessels are starved of oxygen and nutrients needed for normal function. At a basic level, this is a process similar to what occurs in a heart attack or a stroke – but instead of the cholesterol plaque that blocks a coronary artery in a heart attack, the immune system is responsible for blockage of blood vessels in vasculitis.

All information contained within the Johns Hopkins Vasculitis Center website is intended for educational purposes only. Visitors are encouraged to consult other sources and confirm the information contained within this site. Consumers should never disregard medical advice or delay in seeking it because of something they may have read on this website.