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

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.

Rheumatoid Vasculitis

First Description

Rheumatoid Vasculitis (RV) is an unusual complication of longstanding, severe rheumatoid arthritis. The active vasculitis associated with rheumatoid disease occurs in about 1% of this patient population.

RV is a manifestation of “extra-articular” (beyond the joint)rheumatoid arthritis and involves the small and medium-sized arteries in the body. In many of its disease features, RV resembles polyarteritis nodosa.

Other common extra-articular manifestations of rheumatoid arthritis, such as inflammation in the sac surrounding the heart (pericarditis), inflammation in the lining of the lungs (pleuritis), and interstitial lung disease (resulting in fibrosis or scarring of the lungs).

Who gets Rheumatoid Vasculitis? A typical patient

RV can affect a person from any ethnic background, either gender, and from any age group. However, more often than not, the typical patient has long-standing rheumatoid arthritis with severe joint deformities from the underlying arthritis. Although the arthritis has usually led to significant joint damage, at the onset of RV the joint disease is paradoxically quiet.

Figure: Patient with joint damage from rheumatoid arthritis. Note the bulbous swelling of some knuckles and lateral (ulnar) deviation of the fingers.

Classic symptoms of Rheumatoid Vasculitis

RV has many potential signs and symptoms. The manifestations of RV can involve many of the body’s different organ systems, including but not limited to the skin, peripheral nervous system (nerves to the hands and feet) , arteries of the fingers and toes causing digital ischemia, and eyes with scleritis. Scleritis (inflammation of the white part of the eye) commonly occurs in the setting of RV. This ocular complication requires urgent treatment with immunosuppressive medications.

Figure: Digital ischemia – this image shows a blood flow deficiency in the tip of the finger caused by an obstruction of the digital artery.

Figure: Scleritis – Inflammation of the sclera (the white of the eye) causing redness, light sensitivity and pain.

In addition, generalized symptoms such as fever and weight loss are common.

As is true with other forms of vasculitis that involve the skin, cutaneous lesions can erupt on various areas of the body in RV, with a predilection for the lower extremities. Typical findings include ulcers concentrated near the ankles.

Figure: Cutaneous ulcer – an open skin sore caused by an obstruction of the small blood vessels in the superficial ulcers or obstruction of medium vessels in a deeper ulcer.

Small nail fold infarcts (small spots around fingernail) can

occur in rheumatoid arthritis

but these do not necessarily signify the presence of systemic vasculitis and do not necessitate a change in rheumatoid arthritis treatment.

Nerve damage can cause foot or wrist drop, known in medical terminology as “mononeuritis multiplex”. The images below show a patient with a right wrist drop and a patient with right foot drop. This condition, which may be significantly disabling, is often preceded by a change in sensation in the same area (numbness, tingling, burning, or pain). These abnormal sensations can progress to muscle weakness, focal paralysis, and eventually to muscle wasting. Recovery from this condition, caused by nerve infarction, can take months. In some cases, recoveries from mononeuritis multiplex are incomplete.

Figures of drop wrist and drop foot (courtesy of the University of North Carolina)

(Video of drop foot viewable on our Microscopic Polyangiitis page under classic symptoms.)

Laboratory Tests

Most laboratory findings in RV – for example, elevations in the erythrocyte sedimentation rate or C-reactive protein – are non-specific, and reflect the presence of a generalized inflammatory state. Hypocomplementemia, anti-nuclear antibodies (ANA), and atypical anti-neutrophil cytoplasmic antibodies (ANCA) are common. Rheumatoid factor levels are usually extremely elevated. However, there is no definitive laboratory test for RV short of a tissue biopsy. The diagnosis must usually be made using a combination of history, physical examination, pertinent laboratory investigations, specialized testing (e.g., nerve conduction studies), and sometimes a tissue biopsy.

Because the treatment implications for RV are major, any diagnostic uncertainty must be met with definitive approaches to establishing the diagnosis. This usually involves biopsy of an involved organ. Deep skin biopsies (full-thickness biopsies that include some subcutaneous fat) taken from the edge of ulcers are very useful in detecting medium-vessel vasculitis. Nerve conduction studies help identify involved nerves for biopsy. Muscle biopsies (e.g., of the gastrocnemius muscle) should be performed at the same time as nerve biopsies, to increase the chance of finding changes characteristic of vasculitis. Imaging studies have no consistent role in the evaluation of RV, although sometimes angiography of the gastrointestinal tract is useful.

What Causes Rheumatoid Vasculitis?

The cause of RV is unknown, but given the prominence of immune components and the pathologic changes in involved blood vessels, an auto-immune process is suggested.

How is Rheumatoid Vasculitis diagnosed?

Most laboratory findings in RV – for example, elevations in the erythrocyte sedimentation rate or C-reactive protein are non-specific, and reflect the presence of a generalized inflammatory state. Hypocomplementemia, anti-nuclear antibodies (ANAs), and atypical anti-neutrophil cytoplasmic antibodies (atypical ANCAs) are common. Rheumatoid factor levels are extremely elevated, as a rule. However, there is no definitive laboratory test for RV short of a tissue biopsy. The diagnosis must usually be made by the combination of history, physical examination, pertinent lab work, other specialized testing (e.g., nerve conduction studies), and sometimes even a tissue biopsy is required.

The diagnosis of RV should be considered in any rheumatoid arthritis patient who develops new constitutional symptoms, skin ulcerations, decreased blood flow to the fingers or toes, symptoms of a sensory or motor nerve dysfunction (numbness, tingling, focal weakness); or any inflammation of the lining around the heart or lungs (pericarditis or pleurisy/pleuritis).

Patients with a history of joint-destructive rheumatoid arthritis are at an increased risk for infection. Therefore, when a rheumatoid arthritis patient presents with a new onset of non-specific systemic complaints an infection must first be eliminated. Patients with rheumatoid arthritis typically have immune systems that are disordered from previous immunosuppression and underlying disease (e.g., joint damage). This patient population, therefore, is at higher risk of infection.

The differential diagnosis of RV includes:

  • Cholesterol embolization syndromes, in which a piece of cholesterol breaks off of a plaque, may cause digital ischemia (blood flow obstruction to a finger or toe), and a host of other symptoms that mimic vasculitis.
  • Diabetes mellitus is another major cause of mononeuritis multiplex, but multiple mononeuropathies occurring over a short period of time are unusual in diabetes.
  • Many clinical features of RV mimic those of polyarteritis nodosa, cryoglobulinemia, and other forms of necrotizing vasculitis. Therefore they too should be considered in this setting.

Because the treatment implications for RV are major, any diagnostic uncertainty must be met with a definitive approach to establishing the diagnosis. As alluded to earlier, this usually involves the biopsy of an involved organ. Deep skin biopsies (full-thickness biopsies that include some subcutaneous fat) taken from the edge of ulcers are very useful in detecting medium-vessel vasculitis. Nerve conduction studies help identify involved nerves for biopsy. Muscle biopsies (e.g., of the gastrocnemius muscle) should be performed at the same time as nerve biopsies, to increase the chance of finding changes characteristic of vasculitis. Imaging studies have no consistent role in the evaluation of RV, although sometimes angiography of the gastrointestinal tract is useful.

Normally, the cells of the blood vessel wall would be fewer in number (less thick) and the lumen (larger red area) would be larger. The arrow points (Figure 6, left) to an inflamed blood vessel found on a muscle biopsy. The globular pink areas are muscle fibers.

Treatment and Course of Rheumatoid Vasculitis

Therapy should reflect the severity of organ involvement. Prednisone or other steroid therapies are often the first line of treatment. Optimizing treatment of the underlying rheumatoid arthritis is also essential, therefore medications such as methotrexate or tumor necrosis factor inhibitors may be employed. In the setting of impending damage to major organs such as the eyes, a peripheral nerve, the gastrointestinal tract, or of a severe skin ulceration, cyclophosphamide is usually warranted.

What’s New in Rheumatoid Vasculitis?

Compared to other forms of vasculitis, there has been relatively little research in recent years on the specific entity of RV. The lack of similarity in available reports on RV and discrepancies in case definitions have created challenge to building standard approaches to the diagnosis and treatment of this condition. There is some evidence that the incidence of RV has decreased over the past several decades, perhaps because of better treatment of the underlying rheumatoid arthritis.

Glossary of Vasculitis Terms

A

Active disease: Disease state characterized by active, ongoing inflammation due to vasculitis. In this state, vasculitis causes damage to organs. Treatment is initiated to induce disease remission.

Alkylating agents: A group of drugs originally used to treat cancer, now used (in lower doses) to treat some forms of severe vasculitis.

ANCA: Anti-neutrophil cytoplasmic antibodies. The abbreviation is pronounced just like the last name of the singer, Paul Anka. These antibodies are found in patients with some forms of vasculitis, particularly granulomatosis with polyangiitis, microscopic polyangiitis, and the Churg-Strauss syndrome.

Anemia: A low hematocrit (roughly corresponding to a low red blood cell count).

Anesthesic: Means literally “without feeling”. A drug administered for medical or surgical purposes, that induces partial or total loss of sensation. An anesthesic may be topical, local, regional, or general, depending on the method of administration and area of the body affected.

Aneurysms: Weakening of a blood vessel wall by inflammation. Sometimes leads to rupture of the vessel.

Angiogram: An X-ray representation of blood vessels made after the injection of a radio-opaque dye. Used to visualize the inner layer of blood vessels and to determine the location and degree of narrowing or dilation.

Antibodies: A Y-shaped protein on the surface of B cells that is secreted into the blood in response to a challenge to the immune system, such as a bacterium, virus, parasite, or transplanted organ. Antibodies neutralize foreign proteins by binding specifically to them. Antibodies are also known as immunoglobulins.

Aphthous ulcers: Ulcerations on the mucous membranes of the mouth or genitals, often caused by an infection or trauma. Aphthous ulcers also occur in Behcet’s disease and connective tissue diseases such as Lupus.

Arthralgias: Aches or pains in joints, without obvious swelling, warmth, or redness.

Arthritis: Inflammation of a joint, usually accompanied by pain, swelling, and stiffness, and resulting from infection, trauma, degenerative changes, metabolic disturbances, or other causes. Arthritis occurs in various forms, such as the arthritis associated with infections, osteoarthritis, or rheumatoid arthritis. Many forms of vasculitis can also be associated with arthritis.

Aseptic: Using sterile techniques or methods to protect against infection by microbes.

Asymmetrical: Having no balance or symmetry. Different on the left side of the body as compared to the right. “Asymmetric weakness of the left lower extremity” means that the left leg is weak but the right is not.

Autoimmune: Relating to an immune response by the body against one of its own tissues; for example, its own cells, molecules, or organs. Autoimmune diseases often involve the formation of antibodies directed against specific body tissues, such as parts of the kidney or blood vessel walls.

B

Beading: The appearance of a blood vessel as of a string of beads, with alternating areas of narrowing and dilation.

Biopsy: Removal of a piece of a tissue or organ through either surgery or sampling with a needle to determine the existence or cause of a disease.

C

Capillaries: The smallest blood vessel in the body. Capillaries connect arterioles (small arteries) with venules (small veins). Capillaries form an intricate network throughout the body for the interchange of various substances, such as oxygen and carbon dioxide, between blood and tissue cells.

Casts: A cluster of cells or proteins formed in the kidney and excreted in the urine. Red blood cell casts usually indicate the presence of active vasculitis within the kidney. Kidney vasculitis is also known as glomerulonephritis.

CAT Scan (CT scan): A Computerized Axial Tomography scan is an x-ray tube that rotates in a circle around the patient, making many pictures as it rotates. The multiple x-ray pictures are reconstructed by a computer in cross-sectional images, permitting doctors to examine “slices” through different organs.

Catheterization: The insertion of a small plastic tube into a blood vessel, for the purpose of infusing fluid or radio-opaque dye (as in angiography), or for the purpose of sampling blood.

Cavity: A hollow area within the body.

Chlorambucil: A medication used to depress lymphocytic production and maturation. The brand name for this medication is Leukeran.

Claudication: A symptom caused by lack of blood flow to the muscles caused by narrowing of the arteries. The symptom of claudication usually occurs in the calf or in an arm, and is an aching pain that resolves with rest.

Conjunctivitis: Inflammation of the most superficial layer of the eye, characterized by redness and often accompanied by a discharge. Conjunctivitis can be caused by certain infections, but is also associated with some types of vasculitis.

Constitutional: Symptoms Symptoms that relate to the entire body as a whole, rather than to an individual organ. Constitutional symptoms include fatigue, malaise, and weight loss.

Crescent: A shape resembling the curved shape of the moon in its first or last quarters. With regard to vasculitis, a crescent is a pathological finding in the kidney that is observed under the microscope. Crescents are caused by damage to glomeruli, the individual blood-filtering units within the kidney.

Cutaneous: Relating to, existing on, or affecting the skin.

Cyclophospamide: An alkylating agent used in combination with corticosteroids (such as prednisone) to treat serve cases of vasculitis.

Cystoscopy: The inspection of the interior of the bladder using a lighted tubular endoscope, inserted through the urethra. The major reason for performing cystoscopy in patients with vasculitis is to screen for bladder injury caused by cyclophosphamide.

Cytoplasmic: The protoplasm outside the nucleus of a cell.

D

Dermis: The layer of the skin located below the epidermis, containing nerve endings, sweat and sebaceous glands, and blood and lymph vessels. Small and medium-vessel forms of vasculitis affect the dermis and sometimes the layer just below the dermis; the subcutaneous fat.

Dialysis: A pathological deficiency in the oxygen-carrying component of the blood, measured in unit volume concentrations of hemoglobin, red blood cell volume, or red blood cell number.

E

Eosinophils: A type of white blood cell containing cytoplasmic granules that are stained easily by eosin or other acid dyes.

Epidermis: The protective outer layer of the skin.

ESR: Erythrocyte Sedimentation Rate is the rate at which red blood cells settle out in a tube of blood under standardized conditions; a high rate usually indicates the presence of inflammation.

Etiology: The cause or origin of a disease.

G

Gangrene: Death and decay of body tissue, often occurring in a limb, caused by insufficient blood supply and usually following injury or disease.

Glomerulonephritis: Inflammation in the kidney, characterized often by decreased production of urine and by the presence of blood and protein in the urine.

Glomerulus: A tuft of capillaries within the kidney that filters blood in order to form urine. Normally, each kidney has approximately 1 million glomeruli.

H

Hematuria: The presence of blood in the urine.

Hyperpigmented: An excess of pigment (color) in a tissue. For example, in some patients, parts of the skin affected by vasculitis become hyperpigmented after the vasculitis has resolved.

I

IgA: Immunoglobulin A. A specific subcategory of antibodies (which all individuals have). For reasons that are not understood, IgA deposits within the blood vessels of the skin, joints, kidney, and GI tract in Henoch-Schonlein purpura, leading to vasculitis.

Incident/incidence: The number of new cases of a disease in a population over a period of time. Physicians often refer to the “annual incidence” of a given disease; that is, the number of new cases occurring each year.

Infarction: Localized necrosis resulting from obstruction of the blood supply. Myocardial infarction is another name for a heart attack.

Infection: Invasion by and multiplication of pathogenic microorganisms in part of the body, or in the body’s bloodstream.

Infiltrates: A collection of inflammatory cells within a body tissue; for example, in the lung. Pulmonary infiltrates are visible on chest x-rays in pneumonia and in some forms of vasculitis.

Inflammation: A localized protective response of the body tissues to injury, irritation, or infection; characterized by pain, swelling, redness, and heat. Vasculitis is inflammation within the blood vessels.

Intravenous: A drug, nutrient solution, or other substance administered into a vein.

Invasive: Relating to a medical procedure in which a part of the body is entered, as by puncture or incision. Invasive procedures such as tissue biopsies or angiograms are sometimes necessary to diagnose vasculitis.

Ischemia: A decrease in the blood supply to an organ, tissue, or body part caused by constriction or obstruction of the blood vessels.

L

Lesion: A wound or injury. A localized pathological change in a bodily organ or tissue. An infected or diseased patch of skin.

Localized: Restricted or limited to a specific body part or region: localized pain and numbness.

Lupus: A systemic disease that results from an autoimmune mechanism. Individuals with lupus produce antibodies to their own body tissues. The resultant inflammation can cause kidney damage, arthritis, pericarditis, and, sometimes, vasculitis.

M

Meninges: The three membranes that cover the brain and spinal cord. The three layers are called the arachnoid (the “spider-like” innermost layer), the pia mater (the middle layer), and the dura mater (the “tough mother” outermost layer).

Mesenteric: Relating to folds of the peritoneum (the abdominal cavity) that connect the intestines to the abdominal wall, especially such a fold that envelops the small intestine.

Mimicker: A disease process that imitates or simulates another. For example, the lung lesions of granulomatosis with polyangiitis may be mimickers of tuberculosis.

MRI Magnetic Resonance Imaging: Another fancy x-ray, similar to a CT scan. MRI scans also provide cross-sectional images of body organs. Because MRI technology involves the use of a large magnet, people with pacemakers, metallic aneurysm clips, and other metallic inserts are not eligible to have these studies.

Myeloperoxidase Abbreviated MPO: An enzyme found in many tissues and cells throughout the body. For reasons that are unknown, many patients with granulomatosis with polyangiitis and microscopic polyangiitis make antibodies to this protein.

N

Nasal septum: A thin wall dividing the nasal cavity into two halves.

Neuropathy: A disease or abnormality of peripheral nerves, the nerves that mediate sensation and movement in the arms, legs, and other body parts.

O

Occlusion: An obstruction or a closure of a blood vessel.

Opportunistic infections: A pathological deficiency in the oxygen-carrying component of the blood, measured in unit volume concentrations of hemoglobin, red blood cell volume, or red blood cell number.

Otitis media: Inflammation of the middle ear (the space just behind the eardrum). This may occur because of an infection or as a result of some forms of vasculitis, such as granulomatosis with polyangiitis.

P

Palpable: Perceptible to touch; capable of being palpated.

Pathologist: A physician who examines tissue biopsies for the purpose of determining the precise cause of disease.

Perforation: A hole in an organ, such as the gastrointestinal tract.

Perinuclear: Of or pertaining to a nucleus; situated around a nucleus. In some forms of vasculitis (e.g., microscopic polyangiitis), anti-neutrophil cytoplasmic antibodies (ANCA) cause perinuclear staining on immunofluorescence tests.

Pneumonia: An acute or chronic disease marked by inflammation of the lungs and caused by viruses, bacteria, or other microorganisms. Forms of vasculitis that involve the lung are often misdiagnosed as pneumonia. Pneumonia is also a type of opportunistic infection that may occur in vasculitis patients under treatment.

Prevalence: The total number of cases of a disease present within a given population at a particular time. The prevalence of giant cell arteritis in the United States, for example is estimated to be 160,000.

Proteinuria: The presence of excessive amounts of protein in the urine. Proteinuria is usually caused by damage to the kidneys.

Purpura: A condition characterized by small amounts of bleeding into the skin and mucous membranes that result in the appearance of purplish spots or patches.

R

Raynaud’s phenomenon: Spasm of the arteries to the fingers and/or toes, resulting in blanching or pain.

Remission: When vasculitis has been treated to the point that there are no signs or symptoms of ongoing active inflammation. In this state, patient may experience symptoms related to damage from prior disease activity, but no active inflammation is present.

Retinal: The innermost layer of the eye. Serves as the eye’s camera, transmitting images to the brain via the optic nerve.

Rheumatologist: A physician who specializes in the diagnosis and treatment of diseases in which the immune system has gone awry, leading to inflammation in a variety of organs.

S

Sclera: The white part of the eye. “Scleritis” is a type of inflammation that occurs in the sclera in some forms of vasculitis.

Stenosis: A constriction or narrowing of a blood vessel.

Steroid-sparing drug: An immunosuppressive drug that has the benefits of prednisone but does not cause as many side effects.

Subcutaneous: Underneath the skin. Some medications, for example, are injected under the skin.

Systemic: Relating to a system or relating to, or affecting the entire body or an entire organism.

T

Teratogenic potential: The risk of causing birth defects. Some medications are said to have “teratogenic potential”.

Thrombosis: A blood clot.

U

Urinalysis: Laboratory analysis of urine, used to aid in the diagnosis of disease or to detect the presence of a specific substance. In vasculitis, the urinalysis is used to detect protein, blood, or clumps of blood cells in the urine. All of these findings may suggest kidney inflammation.

Uveitis: Inflammation within either the anterior (front) or posterior (back) part of the eye.

V

Vasculitis: What this website is all about!

Behcet’s Disease

First Description

In the 1930’s, a Turkish dermatologist, Hulusi Behcet, noted the triad of aphthous oral ulcers, genital lesions, and recurrent eye inflammation, and became the first physician to describe the disease in modern times. Another name for Behcet’s Disease is Behcet’s syndrome.

Who gets Behcet’s Disease (the “typical” patient)?

Behcet’s disease is most common along the “Old Silk Route,” which spans the region from Japan and China in the Far East to the Mediterranean Sea, including countries such as Turkey and Iran. Although the disease is rare in the United States, sporadic cases do occur in patients who would not appear to be at risk because of their ethnic backgrounds (e.g., in Caucasians or African–Americans). The disease is not rare in regions along the Old Silk Route, but the disease’s epidemiology is not well understood. In Japan, Behcet’s disease ranks as a leading cause of blindness. Below is a magnetic resonance image (MRI) study of a Behcet’s patient demonstrating central nervous system involvement (white matter changes in the pons).

Classic symptoms and signs of Behcet’s Disease

Behcet’s disease is virtually unparalleled among the vasculitides in its ability to involve blood vessels of nearly all sizes and types, ranging from small arteries to large ones, and involving veins too. Because of the diversity of blood vessels it affects, manifestations of Behcet’s may occur at many sites throughout the body. However, the disease has a predilection for certain organs and tissues; these are described below.

Eye

  • Behcet’s may cause either anterior uveitis (inflammation in the front of the eye) or posterior uveitis (inflammation in the back of the eye), and sometimes causes both at the same time.
  • Anterior uveitis results in pain, blurry vision, light sensitivity, tearing, or redness of the eye.
  • Posterior uveitis may be more dangerous and vision–threatening because it often causes fewer symptoms while damaging a crucial part of the eye — the retina.

(top of section)

Mouth

  • Painful sores in the mouth called “aphthous ulcers”(pictured below). These are very similar in appearance to ulcers that frequently occur in the general population, usually as a result of minor trauma. In Behcet’s, however, the lesions are more numerous, more frequent, and often larger and more painful. Aphthous ulcers can be found on the lips, tongue, and inside of the cheek. Aphthous ulcers may occur singly or in clusters, but occur in virtually all patients with Behcet’s.

Skin

  • Pustular skin lesions that resemble acne, but can occur nearly anywhere on the body. This rash is sometimes called “folliculitis”.
  • Skin lesions called erythema nodosum: red, tender nodules that usually occur on the legs and ankles but also appear sometimes on the face, neck, or arms. Unlike erythema nodosum associated with other diseases (which heal without scars), the lesions of Behcet’s disease frequently ulcerate.

Lungs

  • Aneurysms (outpouchings of blood vessel walls, caused by inflammation) of arteries in the lung, rupture of which may lead to massive lung hemorrhage.

Joints

  • Arthritis or “arthralgias” (pain in the joints not accompanied by joint swelling).

Brain

  • Central nervous system involvement is one of the most dangerous manifestations of Behcet’s. The disease tends to involve the “white matter” portion of the brain and brainstem, and may lead to headaches, confusion, strokes, personality changes, and (rarely) dementia. Behcet’s may also involve the protective layers around the brain (the meninges), leading to meningitis. Because the meningitis of Behcet’s disease is not associated with any known infection, it is often referred to as “aseptic” meningitis.

Genitals

  • Male — painful genital lesions that form on the scrotum, similar to oral lesions, but deeper.
  • Female — painful genital ulcers that develop on the vulva.

Gastrointestinal

  • Ulcerations may occur anywhere in the gastrointestinal tract from the mouth to the anus. The terminal ileum and cecum are common sites. Involvement of the GI tract by Behcet’s may be difficult to distinguish from inflammatory bowel disease (such as Crohn’s disease).

Blood Vessels

  • Clots can occur in veins in any site, most often including veins in the lower extremity (superficial or deep venous thrombosis).
  • Inflammation in arteries can occur as well, such as the pulmonary or abdominal arteries, sometimes causing obstruction of the vessel (thrombosis).

What causes Behcet’s Disease?

Behcet’s is one of the few forms of vasculitis in which there is a known genetic predisposition. The presence of the gene HLA–B51 is a risk factor for this disease. However, it must be emphasized that presence of the gene in and of itself is not enough to cause Behcet’s: many people possess the gene, but relatively few develop Behcet’s. Despite the predisposition to Behcet’s conferred by HLA–B51, familial cases are not the rule, constituting only about 5% of cases. Thus, it is believed that other factors (perhaps more than one) play a role. Possibilities include infections and other environmental exposures.

How is Behcet’s Disease Diagnosed?

There is not one specific test to diagnose Behcet’s. Rather the diagnosis is based on the occurrence of symptoms and signs that are compatible with the disease. The presence of certain features that are particularly characteristic (e.g., oral or genital ulcerations), elimination of other possible causes of the patient’s symptoms, and if possible, proof of vasculitis by biopsy of an involved organ would together support a diagnosis of Behcet’s.

A positive pathergy test can be supportive of the diagnosis of Behcet’s but is not diagnostic by itself of the condition. A pathergy test is a simple test in which the forearm is pricked with a small, sterile needle. Occurrence of a small red bump or pustule at the site of needle insertion constitutes a positive test. Please note, that although a positive pathergy test is helpful in the diagnosis of Behcet’s, only a minority of Behcet’s patients demonstrate the pathergy phenomenon (i.e., have positive tests). Patients from the Mediterranean region are more likely to demonstrate pathergy. In addition, other conditions can occasionally result in positive pathergy tests, so the test is not 100% specific.

Pictured below is an example of the pathergy test; 1) taken at the time when the patient was “stuck” with the sterile needle; 2) shows the area immediately after the stick; 3) & 4) show the area one day and two days after the needle stick, respectively.

Treatment and Course of Behcet’s Disease

For disease that is confined to mucocutaneous regions (mouth, genitals, and skin), topical steroids and non–immunosuppressive medications such as colchicine or dapsone may be effective. Apremilast (Otezla) is now FDA-approved for treatment of oral ulcers in Behcet’s. Moderate doses of systemic corticosteroids are also frequently required for disease exacerbations. Some patients require chronic, low doses of prednisone or conventional immunosuppressives such as (azathioprine) to keep the disease under control.

In the event of serious end–organ involvement such as eye or central nervous system disease, both high doses of prednisone and some other form of immunosuppressive treatment are usually necessary. Immunosuppressive agents used in the treatment of Behcet’s include azathioprine, cyclosporine, cyclophosphamide, and TNF-alpha inhibitors (infliximab, adalimumuab). Cyclophosphamide is generally used in life-threatening disease, such as central nervous system involvement. Blood clots can be another manifestation of Behcet’s, and in some scenarios blood thinners may be used in treatment.