GENERAL

I have vasculitis, are my children at risk?

We do not know that there is any increased risk for vasculitis in your children. Increased risk for family members would suggest that there is either an inherited factor that is responsible for developing vasculitis, or that there is a common exposure that causes disease. To date, there is nothing to suggest that either of these factors causes vasculitis. Testing to try to identify vasculitis in anyone, whether a family member of a patient or not, should be driven by specific symptoms or medical problems.

How can I find a doctor?

The first step to find a specialist with expertise in vasculitis treatment is to ask your primary physician. Many patients with vasculitis are cared for by rheumatologists. The American College of Rheumatology has a tool on its website to help locate a rheumatologist by geographic site and many local chapters of the Arthritis Foundation maintain lists of local rheumatologists. For physicians with expertise in vasculitis care, the Vasculitis Foundation can also offer suggestions. Some patients with vasculitis affecting specific organs need care from other specialists, such as pulmonologists (lung disease specialists) or nephrologists (kidney specialists).

Should I seek a second opinion?

This is a complicated question and raises issues about trust and confidence in one’s physician. Because of the complexities in diagnosing and treating vasculitis, patients with vasculitis should receive care directed by a physician with expertise in vasculitis. Seeking a second opinion might be considered if there is a problem making a diagnosis, or to help answer questions about therapy, especially if current therapy is not effective or complicated by adverse reactions.

What is the life expectancy of patients with vasculitis?

There is no simple answer. Specific data are not available and it is hard to answer as there are many different types of vasculitis, some of which are mild and others which are more severe. Some forms of vasculitis can affect vital organs and be life-threatening when the disease is active. Vasculitis can also cause damage to organs that can affect overall life expectancy. In addition, use of medications to treat vasculitis that suppress the body’s immune system can increase the risk of infection. It is best to address this with your own physician to take into account your particular type of vasculitis and problems that might have arisen from the disease and its treatment.

What types of laboratory tests should I have?

This question is difficult to address in general terms because there are a lot of individual factors that influence the need for specific laboratory tests. In principle, serial laboratory testing over time has two major goals. First, laboratory testing should screen for disease activity. Second, laboratory testing should look for toxicity of the medications used to control the disease activity.The following battery of tests is usually sufficient for most types of vasculitis; markers of inflammations (erythrocyte sedimentation rate and C-reactive protein), a complete blood count (with differential cell count), a blood chemistry panel (that includes liver function tests and kidney function tests), and a urinalysis with urine microscopy (for forms of vasculitis that frequently involve the kidneys). The frequency of these tests depends on the individual situation (type of disease, organ system involvement, medications used, whether remission has been achieved, and the duration of remission, etc.)In addition to laboratory testing, your doctor may also choose certain imaging studies such as chest x-ray, chest CT (CAT) scan, MR angiograms (MRI), or others, to follow specific disease manifestations in specific forms of vasculitis.

What is the difference between disease activity and disease damage?

Disease activity represents the aspects of your disease that are caused by active inflammation in organs targeted by the vasculitis and response to treatment with steroids and immunosuppressive drugs. Disease damage represents the parts of your disease that do not respond to anti-inflammatory and immunosuppressive therapy. In any particular patient, damage might include problems caused directly by your disease (such as chronic kidney problems or neuropathy causing numbness in the feet), or problems caused by the drugs used to treat vasculitis (such as diabetes or high blood pressure, both of which can be caused by steroid use).

What qualifies as a severe case of vasculitis?

Severity can have many definitions. From an individual patient’s perspective, severity can be viewed impact the vasculitis has on their overall functioning or the functioning of an individual organ system. From the perspective of your treating physician or a researcher involved in vasculitis, severe disease usually is taken to mean involvement with potentially life-threatening or organ-threatening disease. Involvement of the kidneys, brain, eyes, heart and intestines, as well as bleeding into the lung, is typically considered features of “severe” disease.

What are the chances of recovering nerve damage caused by vasculitis?

The earlier that vasculitis is identified and treated the greater the chance of recovery from nerve damage. Unfortunately, many times recovery may only mean a partial recovery that may take many months or years to happen.

Are there other health issues related to vasculitis that I need to be aware of?

Yes, other health issues have to be kept in mind in patients who have vasculitis. Some can be related to vasculitis directly and others can be related to side effects of treatment of vasculitis. Those related to vasculitis directly include things such as stroke, heart attacks, nerve damage causing weakness, lung damage causing shortness of breath and cough and kidney damage that may lead to swelling of the legs and dialysis. Issues related to treatment include such things as osteoporosis, high blood pressure, high cholesterol, infections and development of certain types of cancers.

Should I be on a particular diet?

This is a general question that cannot be answered specifically without knowing the patient’s individual situation. A well-balanced diet following recommendations of the American Heart Association is usually sufficient. In patients with high blood pressure, a low-salt diet maybe necessary. Patients with renal insufficiency will have specific restrictions of protein and potassium intake. Specific dietary recommendations also apply to patients with diabetes, which in turn may be worsened by the use of glucocorticoids. A consultation with a dietitian who can factor in an individual patient’s specific needs is certainly a good option for some patients.

Should I get a flu shot?

Yes, patients with vasculitis should get a flu shot every fall. The treatments taken by most patients with vasculitis make them at higher risk of getting infections like influenza A, which could be severe. Patients should get the regular flu shot, which is a “killed virus” vaccine an unable to cause infection, rather than the nasal spray version, which is a “live attenuated” virus and able to cause infection in people who receive it, a special problem for patients taking immune suppressing treatments. The University of North Carolina – Chapel Hill Kidney Center developed an extensive podcast on immunizations. Click here to listen.

What is steroid myopathy?

Prednisone directly causes atrophy of muscle fibers (myopathy) leading to muscle weakness. This is a very common side effect of chronic (a few months or more) prednisone use but can be either mild or severe. Patients usually notice weakness most in the upper legs. It is not a painful condition directly, but weak muscles and their tendons are more easily strained, which can lead to pain. Muscle weakness that is so severe as to involve the muscles of breathing is rare, but leg weakness can lead to shortness of breath with climbing stairs.

Is asthma a part of EGPA/Churg-Strauss?

Not exactly. Even though asthma is present in almost all patients with Churg Strauss syndrome and corticosteroids represent the cornerstone treatment for both conditions, asthma it is not part of the vasculitis. In Churg Strauss syndrome, asthma is more to be considered as an underlying predisposing condition, and it usually persists even after effective treatment for vasculitis.

What does the word polyangiitis mean (related to the name changes of GPA and EGPA)?

“Poly” indicates that many blood vessels are involved, and “angiitis” is used instead of “arteritis” because granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis affect the smallest vessels in the body (arterioles, capillaries, and venules), all of which are smaller than arteries. In contrast, in polyarteritis nodosa, giant cell arteritis, and Takayasu’s arteritis, only arteries (either a little or much larger than arterioles) are affected.

What is the difference between ANCA and ANA?

Both are blood tests used by doctors to help in the diagnosis of autoimmune disease. Antineutrophil cytoplasmic antibody (ANCA) is a blood test commonly elevated in patients with diseases such granulomatosis with polyangiitis, microscopic polyangiitis, and Churg-Strauss syndrome. Antinuclear antibody (ANA) is a blood test most often elevated in patients with systemic lupus erythematosus (“lupus”), Sjogren’s syndrome, scleroderma, and other types of autoimmune diseases.

What are the chances of recovering lost hearing in a patient with GPA/Wegener's?

Hearing can be transiently decreased in patients with GPA with acute otitis, because of the presence of liquid in the inner ear(s), which will regress under appropriate treatment. However, when the inner ear damage is severe, because of prolonged or multiple recurrences of otitis, and/or when the auditory nerve(s) are involved by inflammation or compression, the hearing loss can be permanent.

When can we expect results on whether rituximab will work for other types of vasculitis?

Studies have been performed that suggest that rituximab works well in cryoglobulinemic vasculitis particularly when associated with hepatitis C infection, and some of these studies are already published. Other types of vasculitis in which rituximab seems likely to work (polyarteritis nodosa, Churg-Strauss) are more difficult to study due to their rarity. It seems unlikely that rituximab would be effective in giant cell arteritis or Takayasu’s arteritis, and therefore it may be a long time before studies are done in these diseases.

What are the anti-GBM antibodies and what do they have to do with my vasculitis?

Anti-GBM antibodies are antibodies directed against glomerular basement membranes. Patients with anti-GBM disease (Goodpasture’s syndrome) will present with involvement of lungs and kidneys, so-called pulmonary-renal syndrome. This can include bleeding in the lungs (hemoptysis) that can lead to respiratory failure and bleeding in the kidney (hematuria) that can lead to rapidly progressive loss of kidney function. Goodpasture’s syndrome has to be considered in patients who are thought to have ANCA-related vasculitides (granulomatosis with polyangiitis and microscopic polyangiitis) as those diseases can also present with pulmonary-renal syndrome. Measuring anti-GBM antibodies and ANCA in these patients will usually help distinguish the two conditions although there are rare cases of patients with both ANCA and anti-GBM antibodies.

Diagnosis

How is progressive multifocal leukoencephalopathy (PML) diagnosed? Should I worry?

PML is a brain infection that is caused by the JC virus. Exposure to this virus is common, but it generally causes problems only in patients who have been treated with aggressive immunosuppressive therapy, such as chemotherapy for cancer. PML has also been reported in patients receiving drugs to treat rheumatic or autoimmune diseases, such as lupus and rheumatoid arthritis, although this is extraordinarily rare. PML is diagnosed by brain autopsy or by looking for evidence of the JC virus in cerebrospinal fluid (CSF) obtained by lumbar puncture (spinal tap), using a technique called polymerase chain reaction. Because neither brain biopsy or CSF examination is perfect, it is generally recommended that such tests are performed only when the suspicion of PML is very high.

What is the difference between Takayasu's and Giant cell arteritis?

The key difference between Takayasu’s arteritis (TA) and giant cell arteritis (GCA) is the age of the patients affected by the disorders. Takayasu’s arteritis affects younger patients, generally less than 40 years of age, while giant cell arteritis affects older patients, generally over 50 years of age. Both Takayasu’s arteritis and giant cell arteritis affect large arteries, but the typical initial manifestations of the two diseases are also usually different. Patients with giant cell arteritis typically present with headaches affecting the temples, scalp tenderness, jaw pain and fatigue with chewing, shoulder or hip pain and stiffness, and/or sudden changes in vision (temporary or permanent blindness or partial vision loss). Patients with Takayasu’s arteritis usually do not have these symptoms but may have arm or leg pain with use, or chest pain, or be found to have no pulse in an arm or leg. However, many clinical findings may be similar between the two diseases, including the presence of constitutional symptoms (fatigue, fevers, chills, malaise, weight loss), muscle and joint pains, stroke-like symptoms, diminished or absent pulses, asymmetric blood pressures, and narrowed or blocked primary branches of the aorta found on imaging studies. Giant cell arteritis is usually diagnosed by a temporal artery biopsy, whereas Takayasu’s arteritis is not, since the temporal artery is not classically affected in TA. Diagnosis of Takayasu’s arteritis is usually made by imaging studies of arteries such as angiography.

What is the difference between systemic PAN and cutaneous PAN?

Polyarteritis nodosa (PAN) is a vasculitis affecting medium-sized blood vessels. In patients with “cutaneous polyarteritis nodosa”, the findings of the disease are localized to the skin (purpura or subcutaneous nodules), but also sometimes the peripheral nerve(s) of the same limb (causing weakness and/or numbness). Patients with systemic polyarteritis nodosa have involvement of other organs, including the gastrointestinal tract, heart and/or kidneys. The systemic form is therefore usually most severe and requires stronger treatment.

Can you still be diagnosed with GPA/Wegener's if the ANCA is negative?

Yes. Although ANCA is elevated in a majority of patients with granulomatosis with polyangiitis (Wegener’s), it is not detectable in all patients and is not necessary to make the diagnosis.

Treatments

Can you become resistant to prednisone after many treatments?

This is not thought to occur as a general rule. Need for an increased dose of prednisone is thought to indicate that the level of inflammation is higher.Do patients taking prednisone need to be on treatment for osteoporosis?Long-term treatment with prednisone, even at relatively low doses, is associated with bone loss and is considered a risk factor for bone fractures even with a normal bone density test. All patients treated with prednisone should be on supplemental calcium (1000-1200 mg daily) and vitamin D (800 IU daily) therapy unless contraindicated. The decision regarding therapy with other medications can be made after a more detailed individual risk profiling for fracture.

How long does prednisone stay in your system?

The drug is “out of your system” within a day, but the side effects that have accumulated over time (weight gain, diabetes, round face, easy bruising, muscle weakness, osteoporosis) can take a long time to reverse, and some may not revere (stretch marks, cataracts). Risk of infection probably goes down quickly after stopping prednisone, but the exact timing is not known.

Please discuss reasonable precautions to take to prevent infections when immunosuppressed.

Patients immunosuppressed due to treatment for vasculitis do not need to take extraordinary precautions to avoid infection, the way patients with severe AIDS or recent bone-marrow transplants do. Participation in employment and recreational activities are strongly encouraged. It is probably wise to avoid under-cooked meat and a few very specific activities: travel to a country with a high rate of tuberculosis, extensive rehab of an old house, cleaning a central air-conditioning system, exploration of caves inhabited by bats, extensive exposure to soil in the southwest US or Ohio river valley.

What are the long-term side effects of cyclophosphamide use?

The long-term side effects of cyclophosphamide (Cytoxan) are damage to the bladder and the bone marrow. Bladder cancer is a well-known risk and continues to arise at least 10-15 years after the drug was given. Periodic urinalysis is considered a good screen, such that a normal urinalysis is very reassuring; however, any blood seen on urinalysis that cannot be confidently attributed to the kidney should be followed by cystoscopy to visualize the bladder and rule out cancer. Damage to the bone marrow can result in chronically low white blood cell counts (with risk of infection), red blood cell counts (anemia, with fatigue), and platelet counts (risk of bleeding), and patients are also at increased risk of lymphoma and leukemia. All of that being said, the risk of all of these long-term side effects is related to the total dose, and most of the patients who have had such problems took Cytoxan for much longer than 6 months.

Does Cytoxan usage increase possibility of infection? What should a patient look for? CBC? WBC? RBC?

Yes. The risk of infection is higher when the WBC count is low, but patients with normal WBC counts are still at increased risk, and not everyone with a low WBC count (less than 3-4) gets infections. Usually the dose of Cytoxan is reduced when the WBC count falls below 4, but the strategy can vary for individual patients.

How long can a patient stay on Methotrexate? Many patients with rheumatoid arthritis have stayed on this drug for 20 years or more. It used to be recommended that every patient who reached a certain lifetime dose of methotrexate receive a liver biopsy, but that is no longer recommended by rheumatology organizations as long as blood tests related to liver function remain normal. Some dermatology organizations remain concerned about liver damage in this setting, particularly in patients with psoriasis.

How long can a patient stay on Methotrexate?

Many patients with rheumatoid arthritis have stayed on this drug for 20 years or more. It used to be recommended that every patient who reached a certain lifetime dose of methotrexate receive a liver biopsy, but that is no longer recommended by rheumatology organizations as long as blood tests related to liver function remain normal. Some dermatology organizations remain concerned about liver damage in this setting, particularly in patients with psoriasis.

What is the role for intravenous immunogloblin in treating vasculitis?

Intravenous immunologlobulin (IVIG) is not often used to treat vasculitis. IVIG is the purified antibody-containing part of the blood proteins obtained from blood donations. IVIG is most often used in treating vasculitis when a patient with active vasculitis also has an infection. Unlike most other treatments used in treating vasculitis, IVIG does not suppress the immune system, and hence does not make it more difficult to get over infections. IVIG may also be used when other standard treatments for vasculitis have failed or have not been tolerated well. IVIG is usually given in monthly courses for 3-6 months; treating physicians usually decide on a case-by-case basis how many days of IVIG to give.

Medrol vs prednisone? Indications? Contraindications?

Prednisone needs to be modified in the liver in order to be active, but methylprednisolone (Medrol) and prednisolone do not. Theoretically, some people, whether due to liver disease or a deficiency in the liver enzyme, may not convert prednisone to its active metabolite efficiently and would do better on a directly active drug. In practice, this is thought to be quite rare. A switch from prednisone to Medrol may be indicated in some patients who are expected to respond to prednisone but don’t, but only if the patient has remarkably few side effects also.

Mepolizumab: What is the toxicity of this drug? Side effects? Effects on pregnancy? What is the drug indicated for now?

This drug is still considered investigational and is not generally available. It has been studied in small numbers of patients with Churg-Strauss syndrome and hypereosinophilic syndromes, and although it has appeared safe in these studies, the numbers of patients are too small to draw any conclusions about safety and side effects.

IL-5 – What diseases have high levels of IL-5? How are the treated? Do you know when trials of IL-5 will take place? Will CSS patients be eligible to participate?

Mepolizumab is an IL-5-blocking antibody and there is enthusiasm for studying it in Churg-Strauss. Trials have been proposed, but I do not whether and when they will start.

Are there any alternative therapies for vasculitis?

There is no clear data on alternative therapies for vasculitis. Since we do not know the immunologic effects of medications such as over-the-counter supplements, they may be associated with unwanted effects related to stimulation of the immune system.

Can a saddle nose deformity be repaired?

Yes, a saddle nose deformity can be repaired as long as the underlying vasculitis is not active. This would require consultation with a surgeon – oftentimes an ear nose and throat (ENT) specialist who could discuss this option with you.

Mepolizumab: What is the toxicity of this drug? Side effects? Effects on pregnancy? What is the drug indicated for now?

This drug is still considered investigational and is not generally available. It has been studied in small numbers of patients with Churg-Strauss syndrome and hypereosinophilic syndromes, and although it has appeared safe in these studies, the numbers of patients are too small to draw any conclusions about safety and side effects.

For people with autoimmune disorders/vasculitis, will IVIG have a detrimental effect similar to the disease?

In theory, vasculitis caused by immune complexes (cryoglobulinemia, polyarteritis nodosa, Henoch-Schonlein purpura, and vasculitis associated with rheumatoid arthritis, lupus, or Sjogren’s syndrome) could get either better or worse with IVIG. Worsening of cryoglobulinemic vasculitis after IVIG (or rituximab, for the same reason) has been reported.

Relapses and Remission

What is remission?

“Remission” is a term used to indicate that there is no longer any detectable inflammatory disease activity. The use of the term “remission” implies that the disease may not be cured, and that relapses are possible in the future. Once a state of remission has been achieved the intensity of immunosuppressive therapy is usually reduced. This means that the dose of prednisone is reduced and that the first-line remission-induction agent (such as cyclophosphamide) is replaced by better-tolerated, milder forms of immunosuppression that are used more long-term to keep the patient in remission (such as methotrexate, azathioprine, or mycophenolate mofetil).“Remission” does not necessarily mean that the patient is feeling perfectly well. This is because symptoms may be caused by either active inflammation associated with vasculitis, or by organ damage resulting from active disease or by side effects of medications used to put the patient in remission. “Remission” also does not mean that all serological markers of a specific form of vasculitis (such as ANCA or ESR) have completely disappeared or normalized.The concept of “remission” is often expanded through use of the terms “partial remission”, “complete remission”, or “sustained remission”. Partial remission means that the disease has improved but that there is still some detectable inflammatory activity in at least some of the organs afflicted by the disease before treatment was started. Complete remission means that there is no more inflammatory activity detectable in any of the affected organs.Sustained remission implies that the state of complete remission has been maintained for at least six months. A patient can be in remission on medication or off all immunosuppressive medications. The ideal state, of course, is to have experienced a sustained complete remission lasting long enough to allow for discontinuation of all immunosuppressive therapy and maintaining that state long-term without suffering a relapse.

What triggers disease relapses (flares)?

The triggers for disease relapses are unknown. While many questions have appropriately been raised about factors such as infection and stress, no definitive association between these or other possible triggers have been found to be linked with disease relapses.

If I have a relapse after achieving remission is it likely that I will have further relapses?

Not necessarily. The pattern of relapses that people will experience is very individual. Some people may experience no relapses after their vasculitis enters remission. Some people may have one relapse early on and no more, some may have multiple relapses but then have no more, and some people may have their first relapse many years after they are first diagnosed. Because of this, it is difficult to view people with relapses as having any predictable pattern for the future. It is important that people who relapse should not feel discouraged that they are always destined to relapse in the future as this may not be the case. Ongoing monitoring by careful evaluation of new symptoms, regular physician visits, laboratory tests, and possibly imaging studies, all play important roles in the follow-up of patients with vasculitis, regardless of the number and type of relapses an individual has had.

What are the chances that my newly diagnosed vasculitis will relapse?

The term “relapse” is used to indicate disease related inflammation that has the potential to cause organ injury and requires treatment. Determination of a relapse is based upon the finding of disease-related inflammation. The evidence for this comes from review of symptoms, physical examination, laboratory tests, and sometimes imaging studies. Relapses must be differentiated from damage, infection, medication side effects, or other problems that can cause similar symptoms or laboratory abnormalities. Relapse manifestations and frequency vary for each form of vasculitis and have been determined based on studies published in the medical literature.

Do increases in the sedimentation rate or C-reactive protein predict relapse of vasculitis?

Increases in the sedimentation rate and/or C-reactive protein do not predict disease relapses. The sedimentation rate, more formally termed the erythrocyte sedimentation rate, also known as the “ESR” or “sed rate,” and the C-reactive protein (or “CRP”) are non-specific markers of inflammation. They are usually, but not always, elevated at the time of vasculitis relapse, but not necessarily before the relapse. Since they are non-specific markers, they can be elevated in any condition associated with inflammation ranging from any type of infection to surgical procedures. The sedimentation rate can also be high in patients with renal insufficiency or anemia. Decisions about treatment should not be made based on the sedimentation rate and C-reactive protein alone.

In ANCA-associated vasculitis (EGPA, GPA and MPA), do increases in the ANCA predict disease relapse?

A general and over-simplified answer is: no. This answer is based on the statistical analysis of large groups of patients followed prospectively in clinical trials. The results from these studies have led to the general opinion held by vasculitis experts that treatment decisions should not be made based on changes in ANCA levels alone.There are some patients, however, for whom ANCA levels track the disease activity very well. In these patients, ANCA increases do predict relapses. To know how ANCA levels relate to disease activity in individual patients, their ANCA levels need to be monitored over time.It should also be noted that there are different ways of measuring ANCA levels. To follow serial ANCA levels, they need to be measured by the same method to be able to make comparisons.

How do I predict relapse in EGPA/Churg-Strauss syndrome?

It can be hard to determine relapses in EGPA/Churg Strauss syndrome. A return of sinus symptoms and asthma is very common, but these but may not represent active vasculitis. These symptoms may require treatment with prednisone and are commonly the rate-limiting features in being able to reduce the prednisone dose in EGPA/Churg Strauss syndrome.Relapses of vasculitis in EGPA/Churg Strauss are less common and have been reported in ranges from 10-30%.

In EGPA/Churg-Strauss syndrome do increases in the eosinophil count predict relapse?

We do not have very good data to tell us what the most reliable markers of disease activity or predictors of relapse in EGPA/Churg Strauss syndrome are. Eosinophils are one of the subtypes of white blood cells and the level of eosinophils can be measured in the blood.In addition to a careful clinical evaluation, the eosinophil count and other markers of inflammation such as the erythrocyte sedimentation rate (ESR, sed rate) and C-reactive protein (CRP) are usually followed in patients with EGPA/Churg Strauss syndrome. In patients with EGPA/Churg Strauss syndrome who have positive ANCA assays, we also monitor the ANCA level (MPO-ANCA). Some patients with EGPA/Churg Strauss syndrome have elevated IgE levels at the beginning of their disease. In these patients, IgE levels can be useful in follow-up to help predict relapse.Disease activity is absent in most patients with CSS when eosinophil levels are low. Prednisone suppresses eosinophil counts quickly and effectively. Therefore, eosinophil counts may drop faster than disease activity disappears. On the other hand, when disease activity recurs, this is usually associated with – or preceded by – increases in eosinophil counts. If increasing eosinophil counts are not addressed by changes in therapy, worsening disease activity often follows.

How can I be in remission if my creatinine is still elevated?

Measuring the creatinine level in the blood provides an indicator of how well your kidneys are working. Higher creatinine levels mean worse kidney function. When you have a form of vasculitis affecting the kidneys, small filtering parts of your kidneys (glomeruli) are gradually being injured by your disease. The purpose of treatment, in general, is to stop this injury, but treatment doesn’t restore the kidneys to their previous, healthy state. Thus, even after the vasculitis in the kidney has been quieted, the creatinine may remain elevated.For many patients, a stable creatinine level is an excellent indicator that the treatment is working, and that your kidneys are not being subjected to further injury by your disease.