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• First Description
• Who gets Buerger’s Disease (the “typical” patients)?
• Classic symptoms of Buerger’s Disease
• What causes Buerger’s Disease?
• How is Buerger’s Disease diagnosed?
• Treatment and Course of Buerger’s Disease

First Description

This disease was first reported by Buerger in 1908, who described a disease in which the characteristic pathologic findings — acute inflammation and thrombosis (clotting) of arteries and veins — affected the hands and feet. Another name for Buerger’s Disease is thromboangiitis obliterans.

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

The classic Buerger’s Disease patient is a young male (e.g., 20–40 years old) who is a heavy cigarette smoker. More recently, however, a higher percentage of women and people over the age of 50 have been recognized to have this disease. Buerger’s disease is most common in the Orient, Southeast Asia, India and the Middle East, but appears to be rare among African–Americans.

Classic symptoms and signs of Buerger’s Disease

The initial symptoms of Buerger’s Disease often include claudication (pain induced by insufficient blood flow during exercise) in the feet and/or hands, or pain in these areas at rest. The pain typically begins in the extremities but may radiate to other (more central) parts of the body. Other signs and symptoms of this disease may include numbness and/or tingling in the limbs and Raynaud’s phenomenon (a condition in which the distal extremities — fingers, toes, hands, feet — turn white upon exposure to cold). Skin ulcerations and gangrene (pictured below) of the digits (fingers and toes) are common in Buerger’s disease. Pain may be very intense in the affected regions.

An angiogram demonstrating lack of blood flow to vessels of the hand (figure below). This decreased blood flow (“ischemia”) led to ulcers of the fingers and severe pain.

An abnormal result from an angiogram of the hand (figure below).

Despite the severity of ischemia (lack of blood flow) to the distal extremities that occurs in Buerger’s, the disease does not involve other organs, unlike many other forms of vasculitis. Even as ulcers and gangrene develop in the digits, organs such as the lung, kidneys, brain, and gastrointestinal (GI) tract remain unaffected. The reasons for the confinement to the extremities and sparing of other organs are not known.

What Causes Buerger’s Disease?

The association of Buerger’s Disease with tobacco use, particularly cigarette smoking, cannot be overemphasized. Most patients with Buerger’s are heavy smokers, but some cases occur in patients who smoke “moderately”; others have been reported in users of smokeless tobacco. It has been postulated that Buerger’s Disease is an “autoimmune” reaction (one in which the body’s immune system attacks the body’s own tissues) triggered by some constituent of tobacco.

Pictured below, are a patient’s fingertips that have developed gangrene. This is a very painful condition which sometimes requires amputation of the affected area.

How is Buerger’s diagnosed?

Buerger’s disease can be mimicked by a wide variety of other diseases that cause diminished blood flow to the extremities. These other disorders must be ruled out with an aggressive evaluation, because their treatments differ substantially from that of Buerger’s Disease (for Buerger’s, there is only one treatment known to be effective: complete smoking cessation — see below).

Diseases with which Buerger’s Disease may be confused include atherosclerosis (build–up of cholesterol plaques in the arteries), endocarditis (an infection of the lining of the heart), other types of vasculitis, severe Raynaud’s phenomenon associated with connective tissue disorders (e.g., lupus or scleroderma), clotting disorders of the blood, and others.

It should be noted that other substances, such as marijuana, have also been associated with a vasculitis similar to Buerger’s or polyarteritis nodosa that should be considered in the differential diagnosis.

Angiograms of the upper and lower extremities can be helpful in making the diagnosis of Buerger’s disease. In the proper clinical setting, certain angiographic findings are diagnostic of Buerger’s. These findings include a “corkscrew” appearance of arteries that result from vascular damage, particularly the arteries in the region of the wrists and ankles. Angiograms may also show occlusions (blockages) or stenoses (narrowings) in multiple areas of both the arms and legs.

Pictured below on the left is a normal angiogram. On the right, is an abnormal angiogram of an arm demonstrating the classic “corkscrew” appearance of arteries to the hand. The changes are particularly apparent in the blood vessels in the lower right hand portion of the picture (the ulnar artery distribution).

In order to rule out other forms of vasculitis (by excluding involvement of vascular regions atypical for Buerger’s), it is sometimes necessary to perform angiograms of other body regions (e.g., a mesenteric angiogram).

Skin biopsies of affected extremities are rarely performed because of the frequent concern that a biopsy site near an area poorly perfused with blood will not heal well.

Treatment and Course of Buerger’s

It is essential that patients with Buerger’s disease stop smoking immediately and completely. This is the only treatment known to be effective in Buerger’s disease. Patients who continue to smoke are generally the ones who require amputation of fingers and toes.

Despite the clear presence of inflammation in this disorder, anti-inflammatory agents such as steroids have not been shown to be beneficial. Similarly, strategies of anticoagulation (thinning of the blood with aspirin or other agents to prevent clots) have not proven effective. The only way to prevent the progression of the disease is to abstain from all tobacco products.

contributed by Brenda Shilling

I have always known that chronic and life-threatening diseases can have a devastating effect on people’s lives. I’ve seen it happen to friends’ families and heard of it happening to friends of friends. But until 2002, the realities of such challenges were quite remote to me, as I had never felt a loved one struggle with a serious condition.

Linda Gray and her twin sister, Brenda Shilling.

In the spring of 2002, my identical twin, Linda, was diagnosed with neuropsychiatry lupus and central nervous system vasculitis. It was a scary time for all of us, particularly for Linda and her family. Like many lupus patients, Linda had been ill often and had many problems in the years leading up to her diagnosis. We were extremely thankful that The Johns Hopkins Vasculitis Center quickly identified what was wrong and started Linda on a treatment program.

In the months that followed, I watched my sister experience a multitude of emotions, including devastation over her diagnosis, fear for her future, and relief that she had finally found help. Although I know that not all lupus patients fare well, I learned that the treatment of lupus has come a long way over the years and I prayed that Linda would benefit from these advances. Her treatment was extremely challenging. However, during the hard realities of chemotherapy and steroids on Linda’s body, her spirit was amazing.

Despite knowing that family is extremely important during times like this and that frequent calls, letters, and visits to Linda were supportive, I slowly began to feel helpless. This was an unexpected emotion. I wanted to do more. I needed to do more. My sister was going through the most difficult time of her life, and I had do something more.

One morning in the late spring of 2003 I considered coordinating a bicycle ride to raise funds for The Johns Hopkins Vasculitis Center. Our sister, Liz, thought it was wonderful idea and wanted to help. We were driven by love for our sister and that was all the motivation we needed!

Linda Gray and her sister, Liz Adams.

We decided on a 50-mile ride – short enough to manage but long enough to sound good! We then mailed over 200 letters to friends and family asking for a financial gift to The Johns Hopkins Vasculitis Center in honor of our sister and others with her disease. We also distributed the letter to social and religious groups in which we are involved. Four of our friends asked if they could join us on the bike ride in a generous gesture of support. We even had t-shirts made!

Participants in Linda’s Loop:

Left to Right: (Front Row, kneeling) Georgann Pattillo, Jan Rowe, Bill Schilling ; (Middle Row) Kevin Adams, Linda Moore, Liz Adams, Sue Schilling, Brenda Schilling, Betty Lamey, Patrick Pattillo, Leroy Lamey ; (Back Row) Chandler Burroughs, Steven Rowe, and Bill Schilling, Sr.

The night before the ride, we finished packing up drinks, snacks, and lunches and then headed home to get some sleep. Liz told me that she didn’t sleep a wink that night – neither did I! We were too excited.

The day finally arrived and everything went so well. It was such a wonderful day that I simply didn’t want it to end! Our family and friends came out to cheer us along. It felt great to have them there. But wow! The miles were more difficult than I expected. Although three riders finished far ahead, the remaining three of us dragged ourselves over the finish line some time later. We were quite the motley crew!

Hot, sweaty, hungry, but happy!

Response to our effort was overwhelming. My husband Bill teases that this was the only time I actually picked up the mail! Liz and I were moved by all the contributions. Some were from people who don’t know Linda but had read about the ride in the local paper. When we started planning we weren’t sure how much money we could raise. It was wonderful to have received just over $8,600 in contributions to vasculitis research!

Linda told me how much love she felt because of what we did for The Johns Hopkins Vasculitis Center. What more could I have asked of myself? We wanted to show Linda how proud we were of all she accomplished during her difficult treatment. We also wanted to say thank you to The Johns Hopkins Vasculitis Center for the wonderful work they do in caring for their patients everyday.

Hopefully we accomplished both.

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.

The term “vasculitis” refers to a group of inflammatory diseases that cause inflammation centered in the wall of blood vessels. This vascular inflammation ultimately leads to damage and dysfunction of the organs that contain the affected vessels. The symptoms of vasculitis depend on the particular blood vessels (and organs) that are involved by the inflammatory process.

As a group, the vasculitis syndromes have the ability to affect nearly every organ in the body. Yet different forms of vasculitis tend to involve blood vessels in specific locations throughout the body. For example, Giant Cell Arteritis typically involves the medium– to large–sized blood vessels supplying the head and neck, but rarely involves the blood vessels of the kidneys. In contrast, Granulomatosis with Polyangiitis (GPA) frequently involves the kidneys, very often the lungs, and almost always the upper respiratory tract, but rarely blood vessels to the brain.

Different types of vasculitis have characteristic (localized) patterns of blood vessel involvement.  However, vasculitis is often a systemic illness. Thus, patients with vasculitis generally feel sick. They often have fevers, weight loss, fatigue, a rapid pulse, and diffuse aches and pains that are difficult to pinpoint. It has been said that vasculitis is a “hurting disease”, because it is so commonly associated with pain of one type or another: pain from a nerve infarction, pain from insufficient blood to the gastrointestinal tract, pain from skin ulcers. In some cases, however, identifying the source and underlying cause of the pain is extremely challenging. Because vasculitis can involve virtually every organ system in the body, it often masquerades as other diseases, and may be a challenging diagnosis to make.

What organ systems may be affected?

It is important to note that not every organ system will be affected in every patient. The pattern of organ involvement (and symptoms) is unique to the individual, as well as the type of vasculitis (category).

Skin

A variety of rashes, the most classic of which is “palpable purpura” –purplish–red spots, usually found on the legs. These spots can usually be felt by the examiner’s fingertips, hence the descriptor “palpable”.

Joints

Symptoms range from full–blown arthritis to aches in the joints without obvious swelling (arthralgias).

Lungs

Cough (particularly coughing up blood), shortness of breath, a pneumonia–like appearance to a patient’s chest X–ray, lung “infiltrates”, and the development of cavities in the lungs are among the manifestations that may occur in forms of vasculitis with lung involvement.

Kidneys

In contrast to many other organs, inflammation in the kidneys does not hurt or cause other symptoms a patient would notice until renal damage is quite advanced. Instead, evidence of vasculitis involving the kidneys is made by obtaining lab tests, and in many cases a kidney biopsy. Glomerulonephritis is the most common type of kidney damage encountered in vasculitis. This syndrome can cause abnormal lab findings in the urine, including the presence of red blood cells (usually invisible to the naked eye), clumps of red blood cells (known as “casts”, also invisible to the naked eye), and abnormal levels of protein in the urine. If renal involvement is not recognized, renal failure can develop, sometimes leading to the need for dialysis or kidney transplant.

Blood

Vasculitis can cause abnormal findings on blood counts. Anemia (low hematocrit or red blood cell count) is a typical finding in patients with active vasculitis. A slightly elevated white blood cell count may also occur. These findings are very non-specific, meaning that they can occur in many other situations and diseases. Elevated inflammatory markers (erythrocyte sedimentation rate and C-reactive protein) are also frequently identified in patients with active vasculitis.

Sinus, Nose & Ears

The sinuses, nose and ears are common sites of involvement by ANCA-associated vasculitis, including GPA, EGPA and MPA. Symptoms can include chronic sinus congestion and “infections” that persist for longer than they should and require repeated courses of antibiotics; bleeding from the nose; perforations (holes) in the nasal septum; hearing loss; inflammatory fluid in the ears requiring drainage; inflammation in the cartilage of the ears or nose.

Eyes

Brain

Nerve

Peripheral nerves are a relatively common site of vasculitis involvement. Damage to the peripheral nerves can cause shooting pains in the arms and legs, numbness, and asymmetrical weakness (i.e., weakness that involves one side of the body more than the other).

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.

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.

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

The name literally means “cold antibody in the blood”, which refers to the chemical properties of the antibodies that cause this disease: cryoglobulins are antibodies that precipitate under cold conditions. Drug use is a prime risk factor for cryoglobulinemia because more than 90% of cases of cryoglobulinemic vasculitis are associated with hepatitis C infections. Hepatitis C is acquired by injection drug use (needle–sharing), tainted blood products, and (probably rarely), sexual transmission. Treatment of the underlying hepatitis may be an effective therapy for this type of vasculitis.

Pictured below is the hand from the same patient at different times. The image on the left is normal and the one on the right shows the patient in the midst of a flare of cryoglobuinemic vasculitis.

Pictured below is an electron micrograph of a kidney biopsy specimen from a patient with cryoglobulinemia.

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

A discussion of Cryoglobulinemia written in medical terms by David Hellmann, M.D. (F.A.C.P.), Co-Director of 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.

Cryoglobulins are immunoglobulins that precipitate in the cold and disolve on rewarming. Three types of cryoglobulins are distinguished based on whether the cryoglboulin is monoclonal and has rheumatoid factor activity. Knowing the type usually allows the physician to predict the clinical features; alternatively knowing the clinical features allows one to deduce the type of cryoglobulin. Type I is a monoclonal antibody that does not have rheumatoid factor activity. Most commonly, type I is associated with lymphoma, Waldenström’s macroglobulinemia, and multiple myeloma. Because type I cryoglobulins do not easily activate complement, patients with type I are asymptomatic until the level of cryoglobulinemia is sufficiently high to cause hyperviscosity syndrome. Both types II and III are rheumatoid factors — antibodies that bind to the Fc fragment of IgG. Therefore, both types are called mixed cryoglobulins. In type II, the rheumatoid factor is monoclonal, whereas in type III it is polyclonal. Type II is associated with lymphoproliferative diseases, and both types can occur in patients with rheumatic diseases and chronic infections. Cryoglobulinemia is said to be essential when there is no identifiable underlying disease. Type II and III cryoglobulinemia frequently presents as vasculitis, most commonly with recurrentlower extremity purpura, glomerulonephritis, and peripheral neuropathy.

It is now evident that most patients diagnosed with type II or type III mixed essential cryoglobulinemia have the disease as an immune response to chronic hepatitis C infection. The role of hepatitis C virus is suggested by finding that the cryoglobulins in these patients are enriched with anti–hepatitis C antibody and hepatitis C RNA. Moreover, antviral therapy can remit the disease in some patients.

Treatment depends on the type of cryoglobulin, underlying disease, and severity of symptoms. Cryoglobulinemia with severe hyperviscosity syndrome requires plasmapheresis and chemotherapy of the underlying malignancy. Some patients with cryoglobulinemia suffer from mild, recurrent crops of lower extremity purpura that require no specific therapy. More extensive vasculitis associated with autoimmune diseases or essential cryoglobulinemia may respond to prednisone, cyclophosphamide, or both. The most effective treatment for cryoglobulinemia associated with hepatitis C has not yet been determined. Brief use of prednisone followed by 6 months of interferon alfa has produced clinical and liver function test improvement, but relapse of liver disease and vasculitis often occurs when interferon alfa is stopped.

• Fast Facts
• First Description
• Who gets Henoch-Schönlein Purpura (the “typical” patients)?
• What causes Henoch-Schönlein Purpura?
• How is Henoch-Schönlein Purpura diagnosed?
• Treatment and Course of Henoch-Schönlein Purpura
• Living with Henoch-Schönlein Purpura

Fast Facts

• HSP is usually self-limited. Therefore, treatment is not indicated in all cases, and full recovery is the rule.
• HSP is more common in children than adults, but has a tendency to be more severe when it occurs in adults.
• In a small minority of cases, HSP can cause severe kidney or bowel disease.

First Description

Dr. William Heberden, a London physician, described the first cases of Henoch-Schönlein purpura (HSP) in 1801. In describing HSP, Heberden wrote of a 5-year old boy who “…was seized with pains and swellings in various parts…He sometimes had pains in his belly with vomiting…and the urine was tinged with blood. Presently, the skin of his leg was all over full of bloody points” (purpura). The young boy suffered all four disease hallmarks of HSP: arthritis, gastrointestinal involvement, kidney inflammation, and purpura. Johann Schönlein (1837) and Edouard Henoch (1874) reported additional cases decades after Heberden. They recognized that the disorder often followed upper respiratory tract infections and was not always self-limited, sometimes progressing to serious kidney involvement.

Who gets Henoch-Schönlein Purpura (the “typical” patient)?

Usually, HSP affects a child shortly after an upper respiratory infection has resolved.

HSP is the most common form of vasculitis in children, with an annual incidence on the order of 140 cases/million persons. The mean age of patients with HSP is 5.9 years.

What causes Henoch-Schönlein Purpura?

In two-thirds of the cases, the disease follows an upper respiratory tract infection, with onset an average of ten days after the start of respiratory symptoms. Despite this association, no single microorganism or environmental exposure has been confirmed as an important cause of HSP.

How is Henoch-Schönlein Purpura Diagnosed?

Purpura not due to a low platelet count, caused by inflammation in blood vessels of the skin, is the hallmark of HSP. The tetrad of purpura, arthritis, kidney inflammation, and abdominal pain is often observed. However, all four elements of this tetrad are not required for diagnosis. The microscopic hallmark of HSP is the deposition of IgA (an antibody found in blood, saliva, tears, etc.) in the walls of involved blood vessels.

More than 90% of cases occur in children. The disease usually resolves within a few weeks. However, adult cases are sometimes more difficult. Skin manifestations are more variable in adults, and sometimes symptoms in adults endure longer [Figure 1, 2].

Figure 1. Pustular lesions. These can occur in HSP, but they are more common with the adult form of HSP.

Figure 2. Vesiculobullous lesions These are also more common with the adult form of HSP.

Adults are more prone to permanent kidney damage. However, patients can take some comfort in knowing that fewer than 5% of patients with HSP develop progressive renal insufficiency.

HSP can be mimicked by other forms of systemic vasculitis that are more often life-threatening. Granulomatosis with polyangiitis and microscopic polyangiitis can also present with purpura, arthritis, and renal inflammation. These disorders both have the potential for serious involvement of other organs (for example, the lungs, eyes, and peripheral nerves) and carry more dire renal prognoses. Therefore, it is very important to distinguish the difference by performing a careful evaluation including bloodwork, urinalysis, chest imaging, and possibly biopsies. HSP may be misdiagnosed as another form of vasculitis – most commonly hypersensitivity vasculitis – because of the frequent failure to perform direct immunofluorescence (DIF) testing on skin biopsy and the consequent failure to detect IgA.

Treatment and Course of Henoch-Schönlein Purpura

NSAIDs may alleviate arthralgias but can aggravate gastrointestinal symptoms, and should be avoided in any patient with renal disease. Dapsone (100 mg/day) may be effective in cases of HSP, perhaps through disrupting the abnormal immune response. Although steroids have not been evaluated rigorously in HSP, they appear to ease joint and gastrointestinal symptoms, in many (but not all) patients. Steroids, however, do not appear to improve the rash; although usually, over weeks to months, the recurrent bouts of purpura usually resolve on their own.

Living With HSP

Supportive care may involve a short course of prednisone or an NSAID, such as naprosyn or ibuprofen, if the kidneys are not involved. Keeping the legs elevated may help prevent purpura during flares of active disease. Additionally, many patients’ purpura will recur after they start to feel better and become more active, inherently increasing their exposures to very minor trauma (e.g. jogging, leg shaving, increasing gravity exposures). Often, the recurring purpura is less prevalent [Figure 3], and additional HSP symptoms are often absent. In many fewer cases, primarily in adults, HSP can progress from hematuria (blood in the urine) to renal insufficiency (decreased kidney function). HSP patients who experience this symptom should be followed more closely, with regular testing of their urine for blood and protein. Recurrences, found in 33% of patients, usually develop within the first few months after resolution of the first bout.

Figure 3. Palpable purpura . Occurring in a more diffuse pattern.

Figure 4. Palpable purpura . Here they are occurring in a very dense pattern with coalescing lesions.

Figure 5. Swelling around the hand and wrist . Although arthralgias are more common in HSP, arthritis can occur as well as periarticular swelling, such as the tenosynovitis shown here.

Figure 6. Swelling around the ankle and foot .

Figure 7. Palpable purpura can appear in many different patterns . This picture shows a denser distribution with a sharp demarcation caused by what is known as Koebner’s Phenomenon (Minor trauma, such as the elastic band in one’s sock, can cause such a pattern). In this case, the “trauma” was caused by the patient’s shaving of her legs, leading to the eruption of purpura in the area of skin where the razor had passed. Sufficient pressure, such as this, causes the rupture of inflamed blood vessels.

Figure 8. CT of abdomen showing bowel edema . This image is of a distended large bowel. The characteristic dips between haustra (bowel sections) are less pronounced because of the swelling / inflammation seen in HSP.

Figure 9. Formally known as DIF (Direct Immunofluorescence) testing. This picture shows immunofluorescence testing of a skin biopsy, IgA positive. Palpable purpura should be biopsied, and two fresh samples should always be sent for testing (an adequate biopsy should be large enough to divide; one for H&E (hematoxylin and eosin) staining, and one for DIF testing.

Figure 10. Arm rash . It is more common to have a purpuric outbreak on the lower extremities. However, an outbreak can occur on the abdomen, chest, or as in the case with this woman, on the upper extremities. Note the hive-like lesions that appear larger than the papules. The rash may also be itchy.

Figure 11. Colonoscopy of HSP-affected bowel . This image shows what the lining of the bowel could look like when it is inflamed and swollen, as in HSP. Looks painful…it is.