Johns Hopkins Vasculitis Center

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Diagnosing Vasculitis

How do we diagnose Vasculitis?

Patients with vasculitis learn that making the diagnosis is sometimes quite difficult. Many endure numerous doctors’ visits, tests, and hospitalizations before the pieces of the puzzle are assembled. The diagnosis of vasculitis usually requires a biopsy of an involved organ (skin, kidney, lung, nerve, temporal artery). This allows us to ‘see’ the vasculitis by looking under a microscope to see the inflammatory immune cells in the wall of the blood vessel. Although, making a diagnosis of vasculitis can be quite involved, this is very important for two main reasons:

# ONE:  Vasculitis has many MIMICKERS (other diseases that have similar features but require different treatments). It is important to rule out other causes of vascular inflammation, other than a primary autoimmune condition as the management could be different.

# TWO:  The treatments for vasculitis itself involve substantial risk. No physician should prescribe such treatment without making every effort to secure a firm diagnosis.

Blood tests, X–rays, and other studies may suggest the diagnosis of vasculitis, but often the only way to clinch the diagnosis is to biopsy  involved tissue, examine the tissue under the microscope in consultation with a pathologist (ideally one experienced at examining biopsies in vasculitis), and find the pathologic hallmarks of the disease.

If a patient’s symptoms, physical examination, and diagnostic testing suggest involvement of a particular organ, one of the procedures below may be used to confirm (or exclude) the diagnosis of vasculitis:

1. Skin Biopsy: One of the least invasive ways of making the diagnosis. A minor procedure performed under local anesthesia. The wound is closed with 1–2 stitches that are removed 7–10 days later.

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An abnormal skin biopsy showing leukocytoclastic vasculitis. The white oval shapes are subcutaneous fat cells beneath the dermis.

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An example of an inadequate skin biopsy.

The correct diagnosis of PAN (polyarteritis nodosa) was not confirmed by this biopsy because the biopsy was not deep enough. The biopsy specimen contains only the epidermis and superficial dermis. PAN classically affects medium–sized arteries located in the deep dermis.

In contrast to the biopsy above, the skin biopsy below was deep enough to include the deep dermis as well as some subcutaneous fat.

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The white, oval–shaped areas are fat lobules. Just superficial to the subcutaneous fat, within the deep dermis, an inflamed medium–sized vessel is evident.

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A closer view of the vessel is provided in the next figure which provides a high power view of the vasculitic artery lying at the junction of the dermis and subcutaneous fat.

2. Kidney Biopsy: A kidney biopsy will be performed if there is evidence of kidney involvement by vasculitis (red blood cells or protein in the urine, for example). This procedure is done under local anesthesia while the kidney is visualized by ultrasound. Because of the small but significant risk of bleeding after this procedure, patients are usually monitored in the hospital for 24 hours after the biopsy.

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This biopsy shows a “crescent” in a glomerulus, a feature of glomerulonephritis which can be seen in ANCA-associated vasculitis (GPA or MPA).

3. Sural Nerve Biopsy: The sural nerve is a sensory nerve over the lateral aspect of the foot. Under local anesthesia in an operating room, a surgeon removes a small piece of the nerve, usually along with a piece of the adjacent muscle (the gastrocnemius). Because the sural nerve does not innervate muscles (remember: it is a sensory nerve, not a motor nerve), the patient does not lose any strength on the side of the foot and lower leg. There maybe, however, some residual numbness on the side of the foot. Patients generally tolerate this numbness well (if the vasculitis has involved the nerve severely enough, some patients already have numbness in that region).

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Below is the surgical site of a sural nerve and gastrocnemius muscle biopsy one week after the procedure: a few sutures and a thin, well–healing scar.

4. Temporal Artery Biopsy: Performed to diagnose Giant Cell Arteritis, also known as Temporal Arteritis, because the temporal artery is often involved. The temporal artery courses up the temples, just in front of the ears. The biopsy, done under local anesthesia, is performed by making a small incision just above the hairline (sometimes shaving a small area of hair is required). The procedure is extremely well–tolerated by patients. Within several weeks, there is usually little or no sign that a biopsy was done. Complications of temporal artery biopsies are extremely rare. Sometimes, to increase the diagnostic yield, both temporal arteries (i.e., the ones on each side of the head) are biopsied.

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5. Lung Biopsy : Often the best way to make a diagnosis of vasculitis that involves the lungs, such as granulomatosis with polyangiitis (GPA). A lung biopsy may be performed in one of two ways: 1) open lung biopsy, a sizable surgical procedure; or 2) thoracoscopic lung biopsy, a less invasive but still significant procedure. Even a thoracoscopic biopsy usually requires at least 48 hours in the hospital and the temporary placement of a chest tube to permit the lung to re–expand.

6. Brain Biopsy: Often necessary to confirm the diagnosis of Central Nervous System (CNS) Vasculitis. This is usually performed on the non–dominant side of the patient’s brain (that is, if the patient is right–handed — and therefore “left–brained” — the biopsy is performed on the right side of the brain). Biopsy of the brain’s covering, the meninges, is usually performed at the same time.

7. Angiogram / angiography: Angiography is helpful in the diagnosis of Polyarteritis Nodosa (PAN). Similar to a heart catheterization,  after inserting a catheter into a large artery in the leg and advancing the catheter into the aorta, radiographic dye is injected into blood vessels supplying the gastrointestinal tract. In the proper clinical setting, the detection of aneurysms (small outpouchings of blood vessel walls) is diagnostic of PAN. This gives an accurate picture of the luminal (inside) anatomy of blood vessels.

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8. Central nervous system angiogram Frequently part of the “work–up” of CNS vasculitis. The procedure is identical to an abdominal angiogram, except the catheter is advanced all the way up to the large vessels supplying the head and neck (for example, the carotid arteries). On angiography, CNS vasculitis is characterized by “beading” (dilated areas alternating with narrowing of the blood vessels). A strikingly abnormal angiogram may eliminate the need for a brain biopsy.

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The angiogram pictured shows prominent dilations of arteries visible at several sites in the intra–cerebral region.

9. Other Useful Tests: There are many other tests that are helpful in the diagnosis of vasculitis, or in evaluating the activity of the disease:

Erythrocyte sedimentation rate (ESR):  Also known as the “sed rate”, for short. This is an old but useful test first employed by the ancient Greeks as a test for pregnancy. It is important to note that there are several influences on the ESR such as anemia and hypergammaglobulinemia which may have nothing to do with an inflammatory state.

C–reactive protein (CRP): CRP is a protein produced by the liver in response to inflammation within the body.

Urinalysis: Many forms of vasculitis affect the kidneys. A simple way of determining whether or not the kidneys are involved is to perform a urinalysis. By performing checks for several indicators of inflammation in a patient’s urine, the physician may determine if inflammation is present within the kidneys. These indicators include:

  • Protein (“proteinuria”)
  • Red blood cells (“hematuria”)
  • Clumps of red blood cells (“casts”)

Pictured below is a urine specimen from a patient with Wegener’s granulomatosis and glomerulonephritis (inflammation in the kidneys).

This is a view of the specimen examined under the microscope, showing cylindrical “casts” comprised of red blood cells. This finding strongly indicates vasculitis in the kidney.

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From another Wegener’s granulomatosis patient’s urinalysis, “blebs” (identified by white arrows) protrude from the surface of the red blood cells that have been damaged in transit through the kidney.

Because inflamed kidneys leak blood, red blood cells — dismorphic as these are — appear in the urine.

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CT Scan (a CAT scan, or computed tomography) — A type of radiology test that permits a non-invasive, cross–sectional view of a patient’s anatomy. On the illustration below (a chest CT scan from a patient with GPA), the view is up (looking toward the patient’s head, from his or her feet). The heart is the white, rounded object in the upper center of the picture. The black regions are the patient’s lungs. The large spot in the left lung (corresponding to the patient’s right lung) is a nodule caused by GPA. Other smaller nodules are also evident.

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MRI / MRA: MRI is another imaging modality that can be useful for diagnosing and following systemic vasculitis; particularly large vessel vasculitis. MRI allows for visualization of the vessel wall. In vasculitis, the vessel wall may be thickened or edematous.

ANCA tests — ANCA is an abbreviation (acronym) for anti–neutrophil cytoplasmic antibodies. These antibodies are found in the blood of patients with several different types of vasculitis, including Wegener’s Granulomatosis, Microscopic Polyangiitis, and the Churg–Strauss Syndrome. ANCAs and their association with vasculitis were recognized in the mid–1980s, and their use has become increasingly widespread since the 1990s. ANCAs are detected by a simple blood test. These antibodies are directed against the cytoplasm (the non–nucleus part) of white blood cells. Their precise role in the disease process remains uncertain but is a topic of considerable research interest. ANCAs come in two primary forms: 1) the C–ANCA [C stands for cytoplasmic] and, 2) the P–ANCA [P stands for perinuclear]. C–ANCAs have a particularly strong connection to Wegener’s Granulomatosis (up to 80% of patients – and possibly more of those with active disease – have these antibodies). When C–ANCAs are present in the blood of a patient with symptoms or signs suggesting Wegener’s, the likelihood of the diagnosis increases considerably. Because of the long list of other conditions that are sometimes associated with ANCAs, however, in most cases it is still VERY IMPORTANT to biopsy an organ involved by vasculitis to verify the diagnosis.

 

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.

Meet Our Team

Vasculitis Center Doctors

Duvuru Geetha, MD

Professor of Clinical Medicine

Dr. Geetha is a Professor of Medicine in the Division of Nephrology. A graduate of Madras Medical College, India, she completed Internal Medicine training in U.K. She did her Internal Medicine Residency at York, PA and Nephrology fellowship at Johns Hopkins Bayview Medical Center. She has been on Hopkins faculty since 1998. She is a member of Royal College of Physicians (U.K.), American Society of Nephrology, American Society of Transplantation and a consultant for the vasculitis foundation. She is a member of the Miller Coulson Academy of Clinical Excellence at Hopkins. Her clinical interests include renal disease in vasculitis patients with a focus on ANCA associated vasculitis and Henoch-Schonlein Purpura. She does clinical and translational research in vasculitis with a focus on ANCA associated vasculitis and renal disease.

Brendan Antiochos, MD

Assistant Professor of Medicine

Dr. Antiochos is a graduate of Dartmouth College and Dartmouth Medical School. He completed internal medicine residency at Oregon Health & Science University, then rheumatology fellowship at Johns Hopkins, before joining the faculty here in 2014. Dr. Antiochos assumed the role of Director for the vasculitis center in 2022. In addition to seeing patients in the vasculitis center, Dr. Antiochos performs laboratory-based research on autoimmune diseases. His laboratory work focuses on activation of the innate immune system and the discovery of novel autoantibodies.

Philip Seo, MD

Associate Professor of Medicine

A graduate of Harvard College and the College of Physicians and Surgeons at Columbia University, Dr. Seo completed his Internal Medicine training as a member of the Osler Medical Service at the Johns Hopkins Hospital. Since then, he has worked at Johns Hopkins in several capacities, including as a hospitalist at Johns Hopkins Bayview Medical Center, and as an Assistant Chief of Service of the Department of Medicine at the Johns Hopkins Hospital, before joining the Division of Rheumatology. His research interests are the assessment and treatment of ANCA-associated vasculitides, including Churg Strauss Syndrome, Wegener’s Granulomatosis, and Microscopic Polyangiitis.

David B. Hellmann, MD

Aliki Perroti Professor of Medicine

Dr. Hellmann is the Chairman of the Department of Medicine and Vice Dean at The Johns Hopkins Bayview Medical Center, and the Aliki Perroti Professor of Medicine. A graduate of Yale University and Johns Hopkins Medical School, Dr. Hellmann received his Internal Medicine training on the Osler Service at Hopkins, and trained in Rheumatology at the University of California, San Francisco. He has been on the Johns Hopkins faculty since 1986.

Desh Nepal, MD

Assistant Professor of Medicine

Michael Cammarata, MD

Assistant Professor of Medicine

Dr. Cammarata is a graduate of The College of William & Mary. He attended Eastern Virginia Medical School and completed his residency in Internal Medicine at the University of California San Francisco. He returned to the east coast for rheumatology fellowship at Johns Hopkins, joining faculty in 2024. He is RhMSUS certified in musculoskeletal ultrasound, and also practices general medicine as a hospitalist at Johns Hopkins Hospital. 

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

Takayasu’s Arteritis

First Description

The first case of Takayasu’s arteritis was described in 1908 by Dr. Mikito Takayasu at the Annual Meeting of the Japan Ophthalmology Society. Dr. Takayasu described a peculiar “wreathlike” appearance of blood vessels in the back of the eye (retina). Two Japanese colleagues at the same meeting reported similar eye findings in patients whose wrist pulses were absent. It is now known that the blood vessel malformations that occur in the retina are a response (new blood vessel growth) to arterial narrowings in the neck, and that the absence of pulses noted in some patients occur because of narrowings of blood vessels to the arms. The eye findings described by Dr. Takayasu are rarely seen in patients from North America.

Pictured below is a close–up view of an angiogram of the left vertebral and subclavian arteries in a patient with Takayasu’s arteritis. Note the narrowing and irregularities that occur at several sites, and the “corkscrew” configuration of one vessel segment near the junction of the two arteries. These changes, caused by inflammation in the blood vessel wall, sometimes cause complete blockage of the artery.

Takayasu’s arteritis is occasionally called “pulseless disease”, because of the difficulty in detecting peripheral pulses that sometimes occurs as a result of the vascular narrowings.

Who gets Takayasu’s Arteritis?

The “typical” patient with Takayasu’s arteritis is a woman under the age of 40. There is a 9:1 female predominance in this disease. Although the disease has a worldwide distribution, it appears to occur more often in Asian women.

Takayasu’s arteritis is a rare disease. The best estimates of the disease frequency suggest that 2 or 3 cases occur each year per million people in a population.

Classic Symptoms of Takayasu’s Arteritis

Takayasu’s arteritis is a chronic inflammatory condition that affects the largest blood vessel in the body (the aorta) and its branches. Thus, the complications of Takayasu’s arise directly or indirectly from damage to these blood vessels. The vasculitides are classified according to the size of blood vessel involved. Takayasu’s is the classic “large vessel” vasculitis.

Pictured below is a normal aortic arch on the left, with narrow, smooth blood vessels. On the right is an example of an abnormal aortic arch in a patient with Takayasu’s, with obvious dilation of the ascending aorta on the left side of the picture.

Clinicians divide Takayasu’s arteritis into two phases: 1) a systemic phase; and 2) an occlusive phase. Although these two phases are not always distinct (i.e., patients may have features of both phases at the same time), this division is a useful way of thinking about the disease.

In the systemic phase, patients have symptoms and signs of an active inflammatory illness. These may include “constitutional symptoms” (fever, fatigue, weight loss), arthritis, and non-specific aches and pains. There may be tenderness overlying affected arteries. Most patients have elevations of the erythrocyte sedimentation rate during the systemic phase.

The systemic phase is succeeded by the occlusive phase, during which patients begin to develop symptoms caused by the narrowing of affected arteries. These may include pain in the limbs that occurs during repetitive activities (“claudication”), such as pain in the arm that occurs while using a handsaw or pain in the calves brought on by walking. The symptoms also include dizziness upon standing up, headaches, and visual problems. During the occlusive phase, affected blood vessels may be narrowed to such an extent that the normal arterial pulsations (“pulses”) in the neck, elbow, wrist, or lower extremities cannot be felt. Using a stethoscope, one may also hear “bruits” (pronounced ‘brew eez’), a harsh, “whooshing” sounds made by the flow of blood through abnormally narrowed vessels. High blood pressure is common, but blood pressures taken in the arms may be read as falsely low if there is a narrowing of an artery high up in the arm. With some patients, it is not possible to get accurate blood pressure readings in the arms. Using an ophthalmoscope, a physician may observe characteristic malformations of blood vessels that occur in advanced cases of Takayasu’s arteritis.

Although the lung involvement in Takayasu’s is frequently overshadowed by involvement of systemic large blood vessels, the pulmonary arteries may also be affected in this disorder. Pictured below is a pulmonary angiogram demonstrating beading and cut–off lesions of the right pulmonary arteries, and a large aneurysm of the left pulmonary artery.

What Causes Takayasu’s Arteritis?

The cause of Takayasu’s arteritis is not known. Some evidence suggests that an infection of some kind — viral, bacterial, or other — occurring in a person with other predisposing factors (such as the correct genes), may lead to this disease. This is an attractive hypothesis, but definitive evidence for it is lacking.

How is Takayasu’s Arteritis Diagnosed?

Making the diagnosis of Takayasu’s arteritis can be extremely difficult. Unfortunately it is very common for the disease to smoulder in the walls of large blood vessels for years, causing only non-specific symptoms associated with the systemic phase of the illness (or no symptoms), until a major complication results. These major complications may include dilation of the aorta with “stretching” of the aortic valve in the heart; critically reduced blood flow to an arm or leg; a stroke caused by high blood pressure in vessels of the brain, and many others.

Once the diagnosis is suspected, it is usually confirmed by a radiographic procedure such as an angiogram or a magnetic resonance imaging study demonstrating significant large artery disease consistent with Takayasu’s. In some cases in which blood vessel damage is so severe as to necessitate surgery to repair the aortic valve, the aorta, or some other large blood vessel, physicians are able to make unequivocal diagnoses by looking at tissue from the involved blood vessels under the microscope. Takayasu’s arteritis is pathologically indistinguishable from giant cell arteritis. In both, destruction of the blood vessel wall and giant cells are frequently present.

Pictured below is an example of large artery involvement in Takayasu’s arteritis. Magnetic resonance imaging study of the aorta and large blood vessels of the upper extremities, showing a large aneurysm of the ascending aorta, blockage of the right axillary artery (note the interruption of blood flow near the shoulder on the left of the figure), and many narrowings of the left subclavian artery (on the right of the figure).

Treatment and Course of Takayasu’s Arteritis

The great majority of patients with Takayasu’s arteritis respond to prednisone. The usual starting dose is approximately 1 milligram per kilogram of body weight per day (for most people, this is approximately 60 milligrams a day). Because of the significant side–effects of long-term high–dose prednisone use, the starting dose is tapered over several weeks to a dose that the physician feels is tolerable for the patient.

For long–term treatment in addition to prednisone (as “steroid sparing agents”), methotrexate, azathioprine, and even cyclophosphamide are sometimes used. There have been few studies of the use of these medications in this disease.

What’s New in Takayasu’s Arteritis?

One of the biggest problems confronting Takayasu’s patients and the physicians who care for them is determining how active the disease is. This can be an exceptionally challenging problem. The erythrocyte sedimentation rate (ESR) probably remains the most reliable marker of disease activity, but even this test is not helpful in a sizeable number of patients who have active arterial inflammation but normal ESRs. Because the treatments for Takayasu’s arteritis may be associated with substantial side–effects, we need more accurate means of gauging disease activity.

To this end, a study conducted by the International Network for the Study of Systemic Vasculitides (“INSSYS”) may be helpful. Investigators from INSSYS, which includes more than 300 physicians, scientists, and other experts in vasculitis from more than 50 different medical centers across the world, have been conducting a “Surrogate Markers Study” for the past several years. In this study, the investigators examine blood specimens from patients with vasculitis for the purpose of identifying proteins and other molecules whose presence indicates ongoing inflammation. Improved understanding of these diseases at a molecular level may permit more rational use of treatments in the future.

In medical terms, by David Hellmann, M.D.

A discussion of Takayasu’s Arteritis written in medical terms by David Hellmannn, M.D. (F.A.C.P.), The Johns Hopkins Vasculitis Center, for the Rheumatology Section of the Medical Knowledge Self-Assessment Program published and copyrighted by the American College of Physicians (Edition 11, 1998). The American College of Physicians has given us permission to make this information available to patients contacting our Website.

Takayasu’s arteritis is a granulomatous vasculitis chiefly of young women that involves the aorta and its major branches. Patients can present initially with obscure systemic symptoms such as fever of unknown origin or more commonly with symptoms and signs of large vessel vasculitis such as hypertension from renal artery stenosis, aortic regurgitation from aortitis, or stroke from carotid artery occlusion. Bruits and diminished or absent pulses are the most reliable signs. Anemia and elevated ESR accompany active disease. Diagnosis is confirmed by angiography showing stenosis and dilation of the aorta, its branches, or both. Thickening of the aortic wall detectable by MRI or ultrasonography can precede angiographic changes. Prednisone is effective for the systemic symptoms and can thwart progression of the vasculitis. Methotrexate may be an effective corticosteroid-sparing agent. Angioplasty alleviates renal artery stenosis about half the time. When needed, vascular bypass procedures and aortic valve replacement usually work well if deferred until the disease is inactive. Estimating disease activity is difficult but is based on systemic symptoms, anemia, ESR, progression of lesions, and pathology (when available).

Supplemental Immunoglobulin (IVIG/SCIG)

What is IVIG/SCIG?

Intravenous immunoglobulin (IVIG) is a therapy consisting of pooled antibodies (immunoglobulin) obtained from healthy donors that is given as an infusion by vein. This same therapy can also be given as a subcutaneous injection (SCIG) rather than an intravenous one.

How does it work?

IVIG and SCIG are often used to treat patients with immunodeficiency syndromes, which are genetic or acquired conditions that lead to low immunoglobulin levels. For these patients, IVIG/SCIG provide the protective effect of antibodies that they otherwise lack.

In treating vasculitis, we sometimes encounter the need for IVIG/SCIG due to the use of Rituximab – a drug that targets B cells. In some patients, the long-term use of rituximab may lead to an acquired deficiency of immunoglobulins. By combining IVIG/SCIG with rituximab, we are able to continue to provide patients with the immunosuppressive benefit of rituximab, while compensating for the increased risk of infection by giving IVIG/SCIG.

How is IVIG/SCIG given?

IVIG is often given as a home infusion. SCIG is given as a subcutaneous injection. These treatments are generally given once per month.

Side effects:

These treatments carry a risk of blood clot, renal injury, and headaches. IVIG constitutes a large fluid challenge, and therefore may not be appropriate for patients with heart or kidney failure.

Polyarteritis Nodosa

First Description

The first description of this disease dates back to 1866 when Kussmaul and Maier identified a condition that consisted of “focal, inflammatory, arterial nodules”. They termed this disorder “periarteritis nodosa” because of the inflammation they observed around the blood vessel wall. The name was changed to polyarteritis nodosa (PAN) to underscore the fact that inflammation throughout the entire arterial wall – not just around the wall – is a major disease feature. Polyarteritis nodosa is sometimes termed “systemic necrotizing vasculitis”, but this term is non-specific as other forms of vasculitis also have systemic and necrotizing features.

Who gets Polyarteritis Nodosa (the “typical” patient)?

Most cases of PAN occur in the 4th or 5th decade, although it can occur at any age. Men are twice as likely to be affected than women. A minority of patients with PAN have an active hepatitis B infection. In the rest of the cases, the cause(s) is presently unknown, and the disease is said to be “idiopathic” in nature.

Classic symptoms and signs of Polyarteritis Nodosa

PAN is a multisystem disease that may present with fever, sweats, weight loss, and severe muscle and joint aches/pains. PAN may develop in a subacute fashion, over several weeks or months. Patients may have nonspecific complaints such as fever, malaise, weight loss, anorexia, and abdominal pain. The disease can affect nearly any site in the body, but it has a predisposition for organs such as the skin, kidney, nerves, and gastrointestinal tract. Many patients with PAN have high blood pressure and elevated erythrocyte sedimentation rates (ESR). The presentation of PAN may also include skin abnormalities (rash, ulcers) and peripheral neuropathy (pain, the sensations of burning, tingling, or numbness, or weakness in a hand or foot). However, the disease has a predilection for certain organs and tissues; these are described below.

Nerve

  • Peripheral neuropathies are very common (50 to 70%). This includes tingling, numbness and/or pain in the hands, arms, feet, and legs.
  • Central nervous system (CNS) lesions may occur 2 to 3 years after the onset of PAN and may lead to cognitive dysfunction, decreased alertness, seizures and neurologic deficits.

Skin

  • Skin abnormalities are very common in PAN and may include purpura, livedo reticularis, ulcers, nodules or gangrene.
  • Skin involvement occurs most often on the legs and is very painful.

Kidney

  • Renal artery vasculitis may lead to protein in the urine, impaired kidney function, and hypertension.
  • Small percentage of patients go on to require dialysis.

Gastrointestinal Tract

  • Abdominal pain, gastrointestinal bleeding (occasionally is mistaken for inflammatory bowel disease)
  • Hemorrhage, bowel infarction, and perforation are rare, but very serious

Heart

  • Clinical involvement of the heart does not usually cause symptoms.
  • However, some patients develop myocardial infarctions (heart attacks) or congestive heart failure.

Eye

  • Scleritis or inflammation in the sclera (white part of the eye)

Genitals

  • Testicular infarction

What causes Polyarteritis Nodosa?

Hepatitis B causes a minority of cases of PAN. With the availability of hepatitis B vaccine now, cases of PAN caused by hepatitis B are now rare in the developed world. It is possible that other infections contribute to other cases of PAN, but links between other infections and this disease remain conjectural at the present time.

How is Polyarteritis Nodosa Diagnosed?

Routine laboratory tests may provide important clues to PAN, but there is no single blood test that is diagnostic of this disease. Most patients with PAN have elevated ESRs. Proteinuria (protein in the urine) is common among those with kidney involvement.

If there is skin or muscle/nerve involvement, a skin or muscle/nerve biopsy can be extremely helpful in coming to a definite diagnosis of PAN. Nerve conduction studies are a non-invasive way of identifying nerves that are involved by the inflammation. (These nerves can then be biopsied to confirm the diagnosis). The diagnosis is confirmed by a biopsy showing pathologic changes in medium-sized arteries. The biopsy site may vary. Most biopsies are taken from skin, symptomatic nerve, or muscle. An angiogram of the abdominal blood vessels may also be very helpful in diagnosing PAN. Aneurysms most often affect the arteries leading to the kidneys, liver or gastrointestinal tract.

The American College of Rheumatology (ACR) has established criteria that should be fulfilled if a patient is to be included in a research study of PAN. The criteria are designed to differentiate PAN from other forms of vasculitis. Not all patients have all criterion. Some, in fact, may have only 2 or 3 criteria, yet their physicians are still comfortable classifying their disease as PAN. A committee of ACR physicians selected 10 disease features (criteria) as being those that best distinguish PAN from other vasculitides. In order to be classified as a PAN patient – for the purpose of research studies – a patient should have at least 3 of the 10 ACR criteria.

The American College of Rheumatology 1990 criteria for the classification of Polyarteritis Nodosa

  1. Weight loss of > 4 kg since beginning of illness
  2. Livedo reticularis
  3. Testicular pain or tenderness
  4. Myalgias, weakness, or leg tenderness
  5. Mononeuropathy or polyneuropathy
  6. Development of hypertension
  7. Elevated BUN or creatinine unrelated to dehydration or obstruction
  8. Presence of hepatitis B surface antigen or antibody in serum
  9. Arteriogram demonstrating aneurysms or occlusions of the visceral arteries
  10. Biopsy of small or medium-sized artery containing granulocytes

Treatment and Course of Polyarteritis Nodosa

Treatment of PAN has improved dramatically in the past couple of decades. Before the availability of effective therapy, untreated PAN was usually fatal within weeks to months. Most deaths occurred as a result of kidney failure, heart or gastrointestinal complications. However, effective treatment is now available for PAN. After diagnosis, patients are treated with high doses of corticosteroids. Other immunosuppressive drugs are also added for patients who are especially ill. In most cases of PAN now, if diagnosed early enough the disease can be controlled, and often cured.

In medical terms, by David Hellmann, M.D.

A discussion of Polyarteritis Nodosa written in medical terms by David Hellmann, M.D. (F.A.C.P.), for the Rheumatology Section of the Medical Knowledge Self–Assessment Program published and copyrighted by the American College of Physicians (Edition 11, 1998). The American College of Physicians has given us permission to make this information available to patients contacting our Website.

Polyarteritis nodosa is a small– and medium–sized arteritis affecting multiple organs, especially the skin, peripheral nerve, gut, kidney, and heart. The age of onset ranges from childhood to late adulthood but averages 40 years. Polyarteritis nodosa has been associated with active hepatitis B, hepatitis C, or both; therefore, the disease is more common in injection drug users.

Polyarteritis nodosa is probably mediated by deposition of immune complexes. Evidence includes the observation that patients with polyarteritis nodosa associated with hepatitis B or hepatitis C have immune complexes consisting of immunoglobulin and viral antigens circulating in the blood and deposited in inflamed vessels. Moreover, antiviral therapy can remit the vasculitis in some of these patients.

The onset is gradual over weeks to months, and the initial symptoms are often nonspecific. The earliest clues that the patient has vasculitis come usually from the skin (where vasculitis may appear as palpable purpura, livedo reticularis, digital gangrene, or tender nodules), or the peripheral nervous system (where infarction of one mixed motor and sensory nerve after another results in mononeuritis multiplex, one of the most specific clues that a patient has vasculitis). Renal involvement eventually develops in most and is accompanied by hypertension in half of patients, whereas Granulomatosis with Polyangiitis
rarely elevates the blood pressure. Polyarteritis nodosa also commonly involves the gut (abdominal angina, hemorrhage, perforation), heart (myocarditis, myocardial infarction), or eye (scleritis). Rupture of renal or mesenteric micoaneurysms can simulate an acute abdomen.

Confirming the diagnosis requires either biopsy specimen showing small– or medium–sized arteries, or mesenteric arteriography showing microaneurysms or alternating areas of stenosis and dilation. Biopsy of a symptomatic nerve or a symptomatic muscle is 65% sensitive, whereas biopsy of an asymptomatic site is less than 30% sensitive. Because mesenteric angiography is 60% sensitive, it should be done when there is not a symptomatic site to biopsy. Renal biopsy should be avoided unless angiography rules out microaneurysms susceptible to rupture.

Without treatment, almost all affected patients die within 2 to 5 years. Treatment with prednisone (starting at 1 mg/kg daily) and cyclophosphamide (2 mg/kg daily) appeared to revolutionize the outcome of polyarteritis nodosa by achieving 70% 10–year survivals and established this combination of agents as the standard therapy. However, newer studies suggest that prednisone alone may achieve the same high survival as prednisone and cyclophosphamide, although flares were less frequent in patients taking cyclophosphamide. Other studies indicate that the traditional therapy with prednisone and cyclophosphamide should be abandoned in patients with polyarteritis nodosa associated with hepatitis B. Patients treated with the traditional combination respond, but almost all survivors become chronic carriers of hepatitis B and may die later of cirrhosis or variceal bleeding. The newly propsed regimen consists of 2 weeks of prednisone to control the vasculitis, followed by plasmapheresis to remove immune complexes, and accompanied by antiviral therapy with lamivudine to rid the patient of the hepatitis B infection. The long–term value of anti–viral therapy for polyarteritis nodosa associated with hepatitis C is not established.

Prednisone

Prednisone is a corticosteroid with potent anti-inflammatory effects. Corticosteroids are a cornerstone of treating most types of vasculitis, and are often used in combination with other immunosuppressive medications. Prednisone works very quickly, and is therefore used (often at high doses) at the time of initial diagnosis to bring vasculitis under control. Then, prednisone is gradually reduced (“tapered”) while another immunosuppressive drug is started for long term treatment. Over time, the “steroid-sparing” immunosuppressive drug is used to control vasculitis, and prednisone is eventually stopped.

Side Effects

Corticosteroids cause a long list of side effects, making it dangerous to use these drugs at significant doses for long term treatment. The side effects of prednisone are related to: 1) the amount of steroid a patient takes in his/her daily dose, and 2) the length of time the patient remains on the medication. We emphasize that not all side effects occur in all patients.

Despite the numerous potential side effects of corticosteroids listed below, their introduction into patient care more than 50 years ago revolutionized the treatment of many diseases, including vasculitis. When used properly, these drugs save lives and avert threats to the function of important organs.

Common Side Effects of Steroids:

Increased Susceptibility to Infections

Patients are at increased risk for many types of infections, from minor fungal infections in the mouth (“thrush”, caused by Candida) to life–threatening infections such as Pneumocystis carinii pneumonia. The higher the steroid dose and the longer the duration of therapy, the greater the risk of infection. The risk is also increased when patients receive combinations of immunosuppressive medications, such as cyclophosphamide (cytoxan) and prednisone. The risk of some infections can be greatly reduced by taking specific types of antibiotics prophylactically (such as Bactrim).

Pictured below is woman under treatment with prednisone and methotrexate for vasculitis and a concurrent neurologic condition (myasthenia gravis) developed painful vesicles in her mouth. The vesicles were confirmed by culture to be caused by reactivation of a Herpes simplex infection, and responded to treatment with acyclovir.

Weight Gain

Weight gain is usually the most dreaded side–effects of steroids, incurred to some degree by nearly all patients who take them. The amount of weight gain varies from individual to individual. In addition to causing weight gain, prednisone leads to a redistribution of body fat to places that are undesirable, particularly the face, back of the neck, and abdomen. Pictured below is an example of redistribution of body fat to the back of the neck. Accumulation of fat in this area is sometimes referred to as a “buffalo hump”.

Another example of this “redistribution” is pictured below. Supraclavical “fat pads” are collections of fat at the base of the neck, just above the collarbones, which are common in patients on steroids. They sometimes cause concern among patients if mistaken for lymph nodes or other causes for worry, but will gradually subside as the prednisone dose is tapered to below 10 milligrams/day.

In addition to this redistribution of fat, many patients undergo loss of muscle strength (muscle atrophy) while taking steroids. Regular physical exercise is key to avoiding this type of deconditioning that often occurs with prednisone treatment.

Glucose Intolerance

High blood sugar, or steroid–induced diabetes. Patients who are “pre-diabetic” can develop diabetes and the need for insulin while taking steroids. This usually resolves when the steroids are decreased or discontinued, but can be worsened by weight gain.

Hypertension

High blood pressure. This usually improves as the corticosteroid dose is reduced.

Bone Thinning (Osteoporosis)

Prednisone may cause thinning of the bones even in people who are not usually at high risk for osteoporosis (for example: males, young people). In people susceptible to osteoporosis, prednisone may accelerate the process of bone loss. Fortunately, in the past few years, excellent treatments and preventive measures have become available for osteoporosis. All patients on prednisone for prolonged periods are candidates for these medicines. Patients should be aware of their daily intake of calcium and Vitamin D while on steroids. Bone density measurement is commonly done using DEXA scans.

Avascular Necrosis of Bone

For reasons that are not known, high dose prednisone (for example, greater than 20 milligrams a day) predisposes some patients to joint damage, most often of the hips. In avascular necrosis (or osteonecrosis, meaning “bone death”) of the hip, the part of the leg bone that inserts into the pelvis dies, resulting in pain with weight–bearing and some loss of joint function. Many patients with avascular necrosis require joint replacements.

Easy Bruising

Prednisone also causes “thin skin”. Patients on moderate to high doses of prednisone often notice that they bruise easily, even with only slight trauma. Pictured below is a patient with giant cell arteritis who suffered a skin laceration after she struck her leg against a chair.

Abdominal Striae

Abdominal striae (“stripes”), as pictured below, frequently occur in patients who take high doses of steroids for long periods of time.

Hirsutism

Hirsutism is excessive growth of body hair. Patients vary in the degree to which this side effect of steroids occurs. Although some patients experience minimal hirsutism, the patient depicted below developed this side effect after taking 10 milligrams of prednisone for a few months.

Acne

High dose prednisone predisposes some patients to acne, especially facial acne, as pictured below. The facial acne developed after several weeks of high steroid doses.

Mood Swings/Insomnia

Many patients find it difficult to fall asleep when taking high doses of steroids. Many also find that they are more irritable or anxious than usual. Steroids sometimes even induce depression or psychosis, which usually improves when the drug is decreased or discontinued.

Cataracts

Long–term steroid use may lead to cataract development in the eyes, which frequently require surgical removal.