You will find series of articles regarding the various ailments under the Vasculitis umbrella.
Behcet’s disease is a type of vasculitis characterized by mouth sores, genital sores, inflammation inside of the eye, skin problems, and arthritis (swelling of the joints).The disease usually affects more men than women. The disease appears to be more severe in young, male, and Middle Eastern or Far Eastern patients.
The most striking feature is the presence of painful ulcers (sores). Oral (mouth) ulceration that happens more than three times in one year is considered to be diagnostic for Behcet’s disease. Genital ulceration and skin lesions occur in 75% or more of patients. Brain (neurologic) disease occurs in less than one-fifth of patients. Inflammation inside the eye occurs in 25-75 % of patients. Both the small and large blood vessels (the vascular system) can be affected. People who have vascular involvement are at an increased risk of venous thrombosis (a blood clot in a vein). The vessels of the central nervous system (brain and spinal cord) or the heart may also be affected by Behcet’s disease.
The underlying cause of Behcet’s disease is unknown. There may be environmental or viral factors that make a person’s immune system act differently, due to a genetic predisposition. Investigators are researching these and other possible causes.
There are no specific laboratory tests in Behcet’s disease and therefore the diagnosis is made on the basis of the clinical findings.
The available data on treatment of Behcet’s disease were systematically reviewed and published in 2000. Ten trials involving 679 patients were included. Some of the classic treatments for Behcet’s syndrome appeared to be less effective than previously thought. These included colchicine, cyclophosphamide, and glucocorticoids for eye involvement, azapropazone and colchicine for arthritis, and acyclovir, colchicine, and topical interferon for mouth ulcers. Protective effects were noted with cyclosporine and azathioprine for eye disease and benzathine-penicillin for arthritis.
Several other agents such as Interferon alfa, thalidomide, methotrexate, mycophenolate mofetil, anti-tumor necrosis factor-alpha (TNF) therapy, and infliximab have been used in small studies.
Side effects of treatments for Behcet’s disease include suppression of the bone marrow and the immune system leading to a greater chance of getting infections.
Corticosteroids are associated with increased risk of diabetes and bone mineral loss depending on the total period of treatment as well as the specific characteristics of the patient (gender, age). The use of Cyclosporine may cause hypertension (high blood pressure) and glucose intolerance. Cyclosporine is also considered to be damaging to the kidney, so close monitoring of the kidneys is needed.
Prognosis: Most people with Behcet’s disease can lead productive lives and control symptoms with proper medication, rest, and exercise. When treatment is effective, flares usually become less frequent. Many patients eventually enter a period of remission (a disappearance of symptoms). Sometimes, treatment does not relieve symptoms, and gradually more serious symptoms such as eye disease may occur. Serious symptoms may appear months or years after the first signs of Behcet’s disease occur.
Buerger’s Disease is vasculitis causing insufficient blood flow to the hands and feet, producing numbness, tingling and ultimately skin and gangrene. The classic Buerger’s patient is a male, between the ages of 20 and 40, although there is a higher percentage of women and people over the age of 50 being diagnosed. Buerger’s disease is most common in the Orient, Southeast Asia, India and the Middle East, but appears to be rare among African–Americans.
Diagnosis: Angiograms of the extremities is helpful in making the diagnosis. Skin biopsies are not recommended due to the concern that the biopsy site will not heal.
Treatment: Buerger’s disease is associated with smoking and tobacco products. Patients must stop smoking immediately. Abstinence from these products is the only way to treat this disease. Although anti-inflammatory agents (steroids) have proven beneficial in other vasculitides, they are not beneficial in treating Buerger’s.
Central Nervous System
Isolated central nervous system vasculitis also known as primary angiitis of the central nervous system (CNS), is a condition where the body’s immune system attacks arteries of the brain, causing inflammation (swelling).
The cause of CNS is unknown. Researchers believe that some sort of event, like an infection, may trigger an inappropriate immune response directed mistakenly to the small and medium sized arteries of the brain.
Among the reported cases of CNS, there are more males who are diagnosed with the disease, and although most get the disease in their 40s or 50s, children as young as 3 and adults as old as 78 have been diagnosed with CNS.The most common symptoms of CNS are: confusion, headache, personality changes, and muscle weakness/paralysis similar to what happens when someone suffers a stroke. Other symptoms include seizures, bleeding in the head, coma, and vision loss. Symptoms usually occur over the course of several months, but can also occur very quickly.
Nonspecific laboratory abnormalities have been noted among patients with CNS. The diagnosis of CNS can be done in different ways. The principal form of diagnosis remains angiography (x-rays of arteries), but magnetic resonance imaging (MRI) and CT scanning have also been utilized. None of these alone can be diagnostic of CNS. A common concern is that angiography in a patient with possible cerebral vessel inflammation is unsafe, and may result in complications. However a study of 125 cerebral angiograms, found no greater risk of complications in patients with proven CNS vasculitis than in those with normal angiograms. A lumbar puncture may also be performed to look for abnormalities in the cerebrospinal fluid.
The symptoms, signs, or findings among patients with CNS may “mimic” a number of disorders including other primary CNS vasculitides, systemic vasculitis, CNS infections or drug-induced disorders by methamphetamine, cocaine, “crack”, and ephedrine abuse.
Early reports of patients with cerebral vasculitis suggested a less optimistic prognosis but more recent experience with immunosuppressive therapy has resulted in encouraging outcomes.
If the diagnosis of CNS is confirmed by biopsy, treatment with high doses of glucocorticoids (steroids) is warranted. Cytotoxic agents such as cyclophosphamide (Cytoxan) can be added depending on the clinical severity of the vasculitis.
Side-effects of high-dose glucocorticoids should be anticipated such as glucose intolerance or frank diabetes mellitus (condition of abnormal glucose levels in blood). Use of calcium supplements, vitamin D, hormone replacement therapy, and bisphosphonates can be taken to help protect the body from bone mineral loss. Antibiotics can also be taken to help prevent infection due to the use of immunosuppressants.
Churg Strauss Syndrome
Churg Strauss Syndrome (CSS), also called allergic granulomatosis and angiitis, is a disorder characterized by allergic rhinitis (inflammation of the nose), asthma, and an increase in certain blood cells known as eosinophils, which infiltrate and inflame different organ systems. The organs most commonly involved are the lungs, peripheral nerves, sinuses, and the skin, although any organ system can be affected including the cardiovascular (heart), gastrointestinal (stomach), kidneys and the central nervous system.
Both men and women are equally diagnosed with CSS. The mean age at diagnosis is 50 years, but the systemic vasculitic phase is frequently apparent in patients who are in their late 30s. It is uncommon in people older than 65 years, and in children.
The disease is most likely due to an autoimmune process, which is a disorder of the immune system.
The clinical manifestations of CSS usually has three stages.
- The first phase is called the “allergic” phase and is characterized by characterized by allergic inflammation of the nose, the sinuses, the skin and the lungs. People are often diagnosed with late onset asthma during this phase. Others may have childhood onset asthma and allergies that suddenly worsen later in life.
- The second phase is called the “hypereosinophilic” phase, which means that there are too many eosinophils (a type of white blood cell) in the blood and in certain organs. This phase is characterized by eosinophilic inflammation of the lungs, esophagus, stomach or intestines.
- The third phase is the “systemic vasculitis” phase. During this phase there is inflammation and damage of blood vessels. Blood vessels can be damaged in different parts of the body, leading to organ damage from restricted blood flow. During this phase people may suffer from fever, weight loss, and lack of energy.
Asthma is the main feature of CSS (occurring in more than 95 % of patients) and usually precedes the vasculitic phase by approximately 8 to 10 years. It is frequently chronic and of sufficient severity to require long-term corticosteroid therapy.
Allergic rhinitis and skin involvement with rashes and nodules are also common. Manifestations of cardiac involvement in CSS include pericarditis, a condition characterized by inflammation of the external part of the heart, heart failure and myocardial infarction (heart attack). Dysfunction of the peripheral nerves, usually called mononeuritis multiplex, is seen in up to 75 % of patients with CSS.
Kidney involvement may be more common than is generally reported. A gastroenteritis (inflammation of the gastrointestinal duct) characterized by abdominal pain, diarrhea, bleeding, may precede or coincide with the vasculitic phase of CSS.
There are no specific laboratory tests for CSS. Eosinophilia, the increased percent of eosinophils, a type of white blood cells, above the normal range in blood counts is the most characteristic finding.
Antineutrophil cytoplasmic antibodies (ANCA) are found in several systemic vasculitides including CSS, and 38 to 59 % of CSS patients are ANCA positive. Some are also ANA positive.
Other tests for inflammatory markers such as sedimentation rate (ESR) or c-reactive protein (CRP) are often high during active disease.
The diagnosis of CSS is suggested by the clinical findings, imaging studies and then confirmed by lung biopsy or biopsy of affected tissues.
Treatment: Most patients with CSS respond favorably to corticosteroid therapy. Many patients with CSS do relapse over time, and may require indefinite steroid therapy. If a patient has difficulty being maintained on low dose steroids alone, it is usually preferable to add another immunosuppressive drug to the regime to allow the steroids to be tapered to as low a dose as possible. Additional treatment options include inhaled steroids, cyclophosphamide (cytoxan), azathioprine (imuran) , and high-dose intravenous immune globulin (IVIG) have been used in patients with severe disease or disease that is unresponsive to corticosteroids. Such patients have been improved with a regimen of corticosteroids and interferon-alpha. Plasma exchange occasionally has been used in conjunction with other therapies.
All the immunosuppressive drugs include the possibility of development of infections since the immune system is weakened. In addition, adverse effects of corticosteroids may include glucose intolerance or frank diabetes mellitus (condition of abnormal glucose levels in blood). Patients should be aware and watchful in order to report symptoms suggestive of diabetes or infection. Use of glucocorticoids may also predispose to, or worsen, preexisting osteoporosis, a disorder of the bone density. This is a particular concern especially for post-menopausal women and older men. Use of calcium supplements, vitamin D, hormone replacement therapy and/or bisphosphonates can help protect against bone mineral loss.
Cryoglobulinemia is the presence of abnormal proteins that are occasionally found in the blood of people with some forms of autoimmune diseases, multiple myeloma, leukemia, and certain forms of pneumonia. The proteins cause the blood to gel at low temperatures causing tissue necrosis.
Causes: Type 1 cryoglobulinemia is often associated with lymphoma. Type 2 cryoglobulinemia is often associated with hepatitis C infection. Drug usage is a prime risk factor for patients with cryoglobulinemia. Hepatitis C is acquired by injection drug use (needle–sharing), tainted blood products, and (probably rarely), sexual transmission.
Symptoms may include a rash on the lower limbs, arthritis, nerve damage and tissue necrosis of affected areas.
Treating the hepatitis may be an effective therapy for this type of vasculitis.
Giant Cell Arteritis (Temporal Arteritis)
Giant Cell (temporal) Arteritis (GCA) is a vasculitis of large and medium size vessels. It may be generalized but vessel inflammation most frequently involves vessels in the scalp and head, especially the arteries over the temples. The disease is called temporal arteritis because the temporal arteries, which course along the sides of the head just in front of the ears (to the temples) often become inflamed. Women, Caucasians, and individuals over 50 years of age are most commonly affected by GCA.
The onset of the symptoms in GCA tends to be gradual and includes low grade fever, fatigue, weakness and weight loss. A new headache, mild or severe, occurs in at least two-thirds of patients with the pain tending to be located over the sides of the head in front of the ears but may be frontal or other located. Nearly one-half of patients suffer from pain in the jaw after chewing (called jaw claudication). Impaired vision is often an early manifestation of the disease.
Permanent partial or complete loss of vision in one or both eyes has been observed in 15-20 % of patients. It is rare for patients to become completely blind in both eyes.
Polymyalgia rheumatica (PMR), which is characterized by pain in the shoulders and hips, is closely linked to GCA, occurring in about 40-50 % of patients.
A laboratory abnormality seen in most patients with GCA is a very high erythrocyte sedimentation rate (ESR). The ESR measures how fast a patient’s red blood cells settle when placed in a small tube. Anemia or low red blood cell count and microscopic hematuria (blood in the urine) may be found but renal (kidney) impairment is unlikely to be due to GCA. Other tests are occasionally abnormal with non specific meaning.
Temporal artery biopsy is suggested in all cases of suspected GCA. Even though the diagnosis may appear “classic” a temporal artery biopsy is still recommended. The biopsy is of low risk, causes very little pain, and often leaves little or no scar. After the use of a topical numbing medication (the same one used by a dentist), the doctor can remove a small part of the temporal artery from under the scalp in order to examine it under the microscope.
Other ways to diagnose GCA include: ultrasonography, angiographic examination, computerized topographic scanning and magnetic resonance angiography, high resolution magnetic resonance imaging and position emission tomography (PET).
Glucocorticoid treatment should be instituted once the diagnosis of GCA is established. Glucocorticoids have inhibitory effects on a broad range of specific immune responses. Their effectiveness in GCA is well established by years of use. Daily dosing is more effective than alternate day dosing. This response usually occurs within two to four weeks after the institution of therapy. The diagnosis should be reevaluated in patients who are resistant to adequate steroid therapy. Steroid withdrawal can begin once clinical remission has been induced. Relapses are seen more frequently in the first year or two of the disease.
Adverse effects of corticosteroids are glucose intolerance or frank diabetes mellitus (condition of abnormal glucose levels in blood) and infections. Patients should be aware and watchful so as to report symptoms suggestive of diabetes or infection. Use of glucocorticoids may also predispose to, or worsen preexisting, osteoporosis (abnormal bone density condition) especially in postmenopausal women and older men. Use of calcium supplements, vitamin D, hormone replacement therapy and/or bisphosphonates are can be helpful in preventing bone mineral loss.
Relapses often necessitate increased dosage or prolonged steroid treatment. Some researchers have suggested that the addition of methotrexate may be steroid-sparing while others have not demonstrated any benefit. However the routine addition of methotrexate to glucocorticoid therapy for GCA is not recommended. The efficacy of other cytotoxic drugs, dapsone, antimalarials, etanercept, and penicillamine has not been studied adequately although they have been reported to be helpful in some case reports.
The finding of an increased risk of visual loss in patients with GCA and thrombocytosis (increase of the number of platelets in the blood), has led some to suggest the addition of drugs like aspirin for patients with high platelet counts, but there is not a lot of data to prove that this may reduce brain/skull problems.
Henoch-Schönlein PurpuraHenoch-Schönlein purpura (HSP) is a systemic vasculitis that causes the blood vessels in the skin to become inflamed, causing red spots. When the blood vessels in the skin get inflamed, they can bleed, causing a rash that is called purpura. This rash is typically seen on the lower legs or arms. The specific skin lesion is characterized by the tissue deposition of an immune system product, called IgA immunoglobulin, which is also found in kidneys of patients with a renal disease, called IgA nephropathy.
HSP occurs more often in children than in adults, and many cases follow an upper respiratory tract infection (infection in your sinuses and /or lungs). Half of affected children are under age five, although kidney involvement is more likely to be severe in older children. Compared to children, adults had more severe and frequent kidney involvement.
Symptoms occur over a period of days to several weeks: skin rash, joint aches and pains, usually in knees and ankles, occasional swelling, abdominal pain and renal disease manifesting mostly as hematuria (blood in your urine), proteinuria (abnormal excretion of proteins in urine), edema (swelling) or alteration in the volume of urine. The hematuria may be noticed as red or tea-colored or cola-colored urine or the amount may be so small that it can only be seen under a microscope. The brain or the lung may also be involved in HSP.
Gastrointestinal symptoms are present in the majority of patients including abdominal pain that is frequently associated with vomiting. The pain typically develops within eight days of the appearance of the rash. Bleeding of the gastrointestinal duct presenting with black or bright red color in stools is seen in these patients. Although rare, more serious complications may develop like intussusception, a situation in which one portion of the bowel slides into the next creating an obstruction in the bowel, leading to swelling, inflammation, and decreased blood flow to the intestines involved or inflammation of other organs leading to pancreatitis, cholecystitis, and entero nephrotic pathy.
Renal (kidney) involvement is common, occurring in 30-70 % of patients. Kidney disease is usually noted after the onset of systemic symptoms. More marked findings may also occur including nephrotic syndrome, a situation characterized by abnormal excretion of proteins and lipids in urine, swelling (edema), low level of albumin in blood and hyperlipidemia. High blood pressure (hypertension) and acute kidney failure may also be seen. Worsening of the kidney symptoms and biopsy-confirmed worsening of the kidney lesions may be observed in patients with repeated attacks of rash or hematuria (blood in the urine).
Even though the symptoms of HSP make it easier to diagnose in children, confirmation of the diagnosis of HSP requires evidence of tissue deposition in the skin or kidney of IgA immunoglobulin. Renal biopsy is another method to establish the diagnosis, but is reserved for patients in whom the diagnosis is uncertain or in whom there is evidence of more severe renal involvement.
The overall outcome is good in most patients. All of the manifestations of active HSP usually resolve spontaneously, although recurrent episodes of skin rash and hematuria may be seen. Among those with kidney involvement, only a minority have persistent disease. The kidney prognosis is excellent in most patients. However some patients will have persistent protein in their urine, high blood pressure, and renal insufficiency. It is estimated that HSP accounts for approximately 3% of cases of end-stage kidney disease in children. Poor renal prognosis is more common among those with the nephrotic syndrome, renal insufficiency, and more advanced findings on biopsy.
Recurrences are common, occurring in approximately one-third of patients.
Since complete recovery occurs in 94% of children and 89 % of adults, respectively, most patients receive no specific therapy. There is suggestive evidence that corticosteroids enhance the rate of resolution of the arthritis and abdominal pain, although they do not appear to prevent recurrent disease.
However, specific treatment is recommended in patients with marked proteinuria (protein in the urine) and/or impaired kidney function during the acute episode. A kidney biopsy can be performed to reveal the severity of the lesions which appears to be the best indicator of prognosis. Advanced disease, usually defined as crescentic nephritis, is treated with a regimen consisting of pulse intravenous methylprednisolone followed by oral prednisone.
Other regimens that have been evaluated in children with kidney disease include corticosteroids and azathioprine and multidrug regimens such as corticosteroids, cyclophosphamide, and dipyridamole, or corticosteroids, cyclophosphamide, heparin/warfarin, and dipyridamole. However, since spontaneous recovery is often observed in these patients, it remains unknown whether these regimens are superior to no or less aggressive therapy.
Plasmapheresis has also been used in a number of patients with severe disease although its efficacy is uncertain. Intravenous immune globulin has been tried in a small number of patients with heavy proteinuria and a progressive decline in kidney function.
Kidney transplantation can be performed in those patients who progress to end-stage kidney disease, although recurrent disease can occur. This appears to be more likely in patients with aggressive initial disease who progressed to end-stage kidney disease in less than three years after the onset of HSP. Therefore it is recommended the transplantation to be delayed for 12-24 months after the disappearance of the rash. Some observations suggest that the risk of recurrent disease also may be higher in living-related donors.
Hypersensitivity VasculitisHypersensitivity vasculitis (HV) is often used to describe different types of vasculitis related to drug reactions, skin disorders or allergic vasculitis; however this is not always the correct use of the term.
Given the wide range of symptoms, the varying definitions and frequent incorrect use of the term, the American College of Rheumatology made a list of criteria for the classification of HV. Three or more of these criteria are needed to determine that a patient with some form of vasculitis is defined as specifically having HV. The criteria are:
- older than 16 years of age
- use of a drug before the development of symptoms
- skin rash
- biopsy of the skin rash that shows neutrophils, a type of white blood cells, around a small vessel
It should be noted that having three of these criteria does not always distinguish HV from other forms of vasculitis, particularly when the only or first symptom of vasculitis is a skin rash.
The presence of skin vasculitis, usually red spots, is the main symptom in hypersensitivity vasculitis. A biopsy of these skin spots reveals inflammation of the small blood vessels, called a leukocytoclastic vasculitis.
HV may be caused by a specific drug or occur in association with an infection, but it may also be idiopathic, meaning there is no known cause. Although drugs are the most common cause, drug-induced vasculitis is a poorly defined disorder.
There are no symptoms or tests that prove HV results directly from a particular drug. The drugs that are most frequently listed as being associated with the development of HV include: penicillin, cephalosporin, sulfonamide, some medicines used to control blood pressure (loop and thiazide-type diuretics), phenytoin and allopurinol. Infections that may be associated with HV include hepatitis B or C virus, chronic infection with bacteria and HIV virus (provide links?).
Symptoms: The major symptoms of HV, in addition to a skin rash, are joint pains and increasing size of lymph nodes. Lymph nodes are located in several places, but particularly along the neck, and supply special cells to the bloodstream that help remove bacteria from the body. In most patients, symptoms begin 7 to 10 days after the exposure to the drug or infection, but can be as short as two to seven days in some people.
Organ involvement in addition to the skin rash is very rare, but can be severe. Kidney inflammation and even more rarely liver, lung, heart and brain injury have occurred in patients with hypersensitivity vasculitis. The kidney inflammation is usually mild.
Symptoms of kidney involvement may not be noticed by the patient, but can be evaluated by a doctor by looking at a urine sample for small amounts of blood and protein. Kidney failure is not common, but can occur particularly with heavy or prolonged exposure to the suspected drug or infection. Kidney failure can be ‘acute’, meaning there is a fast loss of kidney function, but supportive treatment with dialysis (mechanical cleansing of the blood) can be done for a few days or weeks and kidney function returns. In some cases, ‘chronic’ kidney failure occurs, meaning that there is an ongoing need for dialysis because the kidneys do not recover their normal function.
Treatment: If a drug may have caused the HV, then discontinuation of that specific drug usually leads to the disappearance of symptoms within a few days or weeks. If an infection may have caused the hypersensitivity, then treatment of the infection usually results in the disappearance of symptoms.
In some patients, especially those with ongoing infections such as hepatitis B or C, there may be ongoing or ‘chronic’ symptoms of HV. Drugs used to manage the skin rash and joint pains associated with HV might include corticosteroids and/or nonsteroidal anti-inflammatory drugs.
In patients with more severe or ongoing skin rashes that are not due to infection, drugs such as colchicine, antihistamines, and dapsone (or a combination of these drugs) may be helpful to control symptoms. Patients with disease in organs beyond the skin should be referred to a specialty doctor such as a nephrologist if the kidneys are involved.
Kawasaki DiseaseKawasaki Disease is a rare vasculitis, which strikes children. In the U.S. over 4,200 children are diagnosed with it each year. 80% of patients are under the age of five. Patients usually begin with a fever that lasts at least five days, despite fever medications.
Symptoms may include red eyes without discharge, red swollen lips; rash; swollen and red hands and feet; and swollen lymph nodes. The disorder affects the mucus membranes, lymph nodes, walls of the blood vessels, and the heart. The most important aspect of the disease is the heart’s involvement. The disease can cause inflammation of blood vessels in the coronary arteries, which can lead to aneurysms. Kawasaki disease is the leading cause of acquired heart disease in children.
Cause: There is no known cause of the disease.
Symptoms: Kawasaki disease often begins with a high and persistent fever greater than 102°F, often as high as 104°F. A persistent fever lasting at least five days is considered a hallmark sign. The fever may persist steadily for up to two weeks and is not very responsive to normal doses of acetaminophen or ibuprofen.
Diagnosis is usually based on evaluation of classic symptoms. Possible diagnostic tests may include a complete blood count (CBC), Erythrocyte Sedimentation Rate (ESR), electrocardiogram, echocardiogram, chest x-ray and urinalysis.
Immediate treatment is critical to avoid permanent damage to the coronary arteries and heart. Standard treatment includes high doses of Intravenous Gamma Globulin. The patient’s condition often greatly improves within 24 hours of treatment.
With early recognition and treatment within 10 days of onset, full recovery can be expected. Although extremely rare, some patients die from complications of coronary blood vessel inflammation. Patients who have had Kawasaki disease should follow up with a cardiologist on a regular basis.
For more information: Kawasaki Disease Foundation
Microscopic PolyangiitisMicroscopic polyangiitis (MPA) is an inflammation of the medium and small vessel walls that can affect different parts of the body including (but not limited to) the kidneys, lungs, sinuses, nerves and skin.Over 90% of those with MPA have the disease in their kidney and it is indistinguishable from the kidney disease that patients with classic Wegener’s granulomatosis (WG) often have. The main difference between MPA and WG is that MPA does not have a particular type of inflammation –granulomatous inflammation. Similarly, MPA shares some overlap with PAN and other vasculitudes. Thus in 1994, characteristics of MPA were defined at the Chapel Hill Consensus Conference.
While MPA is often viewed as a disease striking mainly middle-aged white people, in reality, it may occur in people of all ages and ethnicity.
The presenting symptoms include fever, joint and muscle pain, weakness, lack of energy and weight loss. Kidney symptoms in MPA may be “silent” in that the patient may notice little change initially even though damage is occurring. A urinalysis may pick up abnormal microscopic blood and protein. In some instances, a patient may have some symptoms of kidney disease such as less urine output or swelling. The kidney damage is called glomerulonephritis (an inflammation of the glomerulous, the part of the kidney that filters urine). Lung symptoms like shortness of breath, coughing up blood and/or chest pain are experienced in approximately half of the patients. MPA is the most common cause of the pulmonary-renal syndrome, which is the combination of inflammation in both the lung and the kidney.
In MPA the symptoms of the upper airway (sinuses and ears) can occur, but are less common than kidney or lung symptoms. The eyes and nervous system can also be affected by the disease. A skin rash, usually purplish bumps and spots on the extremities, is sometimes seen. Additionally, the stomach and intestinal track can also be affected by the disease, resulting in pain or an alteration of the color of stool into black or bright red as a result of bleeding.
Over 80% of patients with MPA will test positive for ANCA.
The diagnosis of MPA often is established with the biopsy of an affected organ often either the skin or kidney. A biopsy may reveal diseased tissue specific to this disease.
The treatment and prognosis of MPA are essentially the same as for WG. Treatment has several stages.
The first phase is the induction therapy. The goal of this therapy is to get the inflammation reduced and controlled. This phase of therapy usually lasts a minimum of three to six months. During this phase, the immunosuppressive therapy is usually a combination of corticosteroids (prednisone) and either daily oral or monthly intravenous cyclophosphamide (Cytoxan). For patients with mild disease, methotrexate may be used. Prednisone alone is usually not considered for induction therapy as the remission rate is much lower. In severe cases, plasmapheresis may be used. .
The second phase of therapy is maintenance therapy. Once the inflammation and disease activity is under control, the patient will continue with therapy for 12-18 months (or longer) to lessen the chance of relapse. The agents used during this phase are generally less toxic and may include agents such as mycophenolate mofetil (Cellcept), Rituximab, azathioprine (Imuran), methotrexate, cyclosporine and etanercept.
Finally, the patient will need to be monitored on a regular basis to insure that the disease does not relapse or to catch it at the earliest stages of a relapse. MPA patients are prone to relapse (estimates vary from 30-50%).
The treatments needed to control MPA have significant side affects and toxicities. It is important for the patient to remember that MPA is a serious disease and that without treatment, it is often fatal.
Treatment –associated toxicity: Cyclophosphamide treatment is associated with hair loss or thinning. Both men and women may have their fertility affected which may or may not return to normal after stopping treatment. Furthermore, cyclophosphamide (Cytoxan) is known to irritate the bladder or cause bladder cancer. Although not common, myelodysplasia (a bone marrow disorder) and lymphoma may also occur.
Long term use of corticosteroid use can include cataracts, diabetes, osteoporosis, fractures, aseptic necrosis of the bone (a condition where poor blood supply leads to bone death) and inflammation of the stomach.
Pneumonia and other infections are serious complications of any immunosuppressive therapy.
Prophylaxis: Given the toxicities of cyclophosphamide (Cytoxan), prophylactic therapy is usually provided with specific drugs to help prevent things like pneumonia, permanent loss of menstrual cycles and bladder cancer. Prophylactic treatments may also be given to help with the toxicities of prolonged steroid use such as mouth infections, stomach pain and bone loss.
The course of MPA is variable among patients depending on several factors. Some patients may have long intervals between flares. For others, flares will be more difficult to control. Furthermore, some people with MPA will have the disease mildly with little change to their lifestyle (although they will always need to be monitored by their physicians), others will suffer permanent damage such as kidney failure or lung scarring. Therefore, the natural history of the disease is diverse among patients.
PolyarteritisPolyarteritis nodosa (PAN) is a vasculitis disease, which affects the small and medium-sized arteries. PAN commonly affects the skin, heart, kidneys and central nervous system.
Cause: There is no known cause of PAN.
Symptoms include fever, fatigue, weakness, loss of appetite, and weight loss. Muscle and joint aches are common. The skin may show rashes, swelling, ulcers, and lumps.
Other symptoms include abdominal pain and gastrointestinal bleeding (occasionally is mistaken for inflammatory bowel disease). Nerve involvement may cause sensory changes with numbness, pain, burning, and weakness. Central nervous system involvement may cause strokes or seizures. Kidney involvement can produce varying degrees of renal failure. Involvement of the arteries of the heart may cause a heart attack, heart failure, and inflammation of the sack around the heart (pericarditis).
There is no specific test to diagnosis PAN. Diagnosis is based upon physical examination, lab tests and biopsy of affected area. Most patients with PAN have elevated ESRs. Proteinuria (protein in the urine) is common among patients with kidney involvement.
The American College of Rheumatology 1990 criteria for the classification of Polyarteritis Nodosa
- Weight loss of > 4 kg since beginning of illness
- Livedo reticularis
- Testicular pain or tenderness
- Myalgias, weakness, or leg tenderness
- Mononeuropathy or polyneuropathy
- Development of hypertension
- Elevated BUN or creatinine unrelated to dehydration or obstruction
- Presence of hepatitis B surface antigen or antibody in serum
- Arteriogram demonstrating aneurysms or occlusions of the visceral arteries
- Biopsy of small or medium-sized artery containing granulocytes
Treatment will vary based on patient symptoms, disease activity, organ involvement and lab test results.
Treatment of PAN has improved dramatically in the past couple of decades. Before the availability of effective therapy, untreated PAN was usually fatal within weeks to months. Most deaths occurred as a result of kidney failure, heart or gastrointestinal complications. However, effective treatment is now available for PAN. After diagnosis, patients are treated with high doses of corticosteroids. Other immunosuppressive drugs are also added for patients who are especially ill. In most cases of PAN now, if diagnosed early enough the disease can be controlled, and often cured.
The newly proposed regimen for patients with PAN associated with hepatitis B, consists of 2 weeks of prednisone to control the vasculitis, followed by plasmapheresis to remove immune complexes, and accompanied by antiviral therapy with lamivudine to rid the patient of the hepatitis B infection. The long–term value of anti–viral therapy for polyarteritis nodosa associated with hepatitis C is not established.
Polymyalgia rheumaticaPolymyalgia rheumatica (PMR) is a condition that is frequently linked to giant cell arteritis (GCA) (link). PMR occurs in about 50 % of patients who have GCA, while approximately 15% of patients with PMR develop GCA. There may be a common genetic component between the two disorders. PMR is almost exclusively a disease that affects older adults and is rarely diagnosed in people under the age of 50 years.
Symptoms: Symptoms of PMR almost always include aching and morning stiffness in the shoulders, hips, neck and mid-body. These symptoms usually affect both sides of the body the same, but can be stronger on one side than the other. Having difficulty with pain, stiffness and movement of the shoulders and hips can result in trouble with things such as getting dressed. Some patients also complain of general tiredness, weakness, weight loss (without trying to lose weight), and a low fever (a high spiking fever is rare).
Inflammation in the bones and joints cause the discomfort and stiffness (difficulty in moving) found among patients with PMR. Some patients develop swelling or fluid retention (edema) of the hands, wrists, ankles, and top of the feet. The edema usually occurs with other signs of PMR but can be the only symptom experienced.
Decreased ability to fully move the shoulders, neck and hips is frequent. Muscle strength is usually normal and the tenderness found about the shoulders is more likely due to inflammation in the shoulder bones. However, muscle weakness may become a problem over time because of the lack of use due to pain and stiffness.
The characteristic laboratory finding in both PMR and GCA is an elevation in the erythrocyte sedimentation rate. This rate measures how fast a patient’s red blood cells settle when placed in a small tube.
Routine x-rays (radiographs) of joints with the disease rarely reveal any abnormalities, while magnetic resonance imaging (MRI) examinations can confirm the presence of inflammation. Ultrasounds and Positron emission tomography (PET scanning) have also been used to confirm the PMR inflammation.
Since there is no specific test for PMR, a checklist that requires a certain group of symptoms and laboratory characteristics is used by doctors to make the diagnosis.
There is considerable overlap between PMR and GCA but patients with “pure” PMR lack the symptoms of GCA. Thus, a biopsy of the temporal artery, which is diagnostic for GCA, is not necessary in patients with PMR unless there are symptoms suggestive of GCA.
Treatment: The beneficial effect of corticosteroids (predinsone) in patients with PMR has been established by a combination of clinical experience and several research studies. Initial treatment most often starts with a dose of prednisone between 7.5 and 20 mg/day. Patients usually respond quickly but the dose is increased if the symptoms are not well controlled within one week. In some patients a single daily dose of prednisone does not provide relief from evening or night-time pain or stiffness while a divided dose (2 times a day, usually 12 hours apart) may be more helpful in reducing symptoms. The effective steroid dose is maintained for 2-4 weeks after the symptoms have resolved. The dose is then gradually lowered and stopped, with careful monitoring for return of symptoms.
Return of symptoms (relapse) occurs in as many as 25-50% of patients. Relapse is more likely to occur if the steroid dose is decreased too fast. If symptoms return, restarting or increasing the dose of corticosteroids is appropriate.
Side effects with corticosteroids: The risk of diabetes (abnormal glucose blood levels) and risk of fractures (small cracks) in the bones of the back, hip and neck are increased, especially with frequent use of this therapy. In patients who require corticosteroid treatment for more than six months, an assessment of bone density is suggested to test for osteoporosis (loss of bone thickness). To help protect bones from fractures and osteoporosis, calcium and vitamin D are often taken regularly, and sometimes drugs such as bisphosphonates are given.
In patients who have side-effects from or a long history of taking corticosteroids, the use of methotrexate may allow the corticosteroid dose to be eliminated or lowered, however this has only been suggested by some, but not all, studies. Anti-inflammatory drugs such as ibuprofen can also be used to decrease painful symptoms, especially when symptoms are only mild, and may also help avoid use of corticosteroid treatment
Effort must be focused at control of symptoms with a minimum of drug-induced side effects. In most patients, symptoms of PMR will eventually end (over a period of months to years) and corticosteroid therapy can be discontinued.
Rheumatoid VasculitisRheumatoid vasculitis (RV) refers to patients with rheumatoid arthritis, a chronic disease with painful inflammation of the joints, who also develop inflammatory disease in small and medium-sized blood vessels. RV most commonly occurs in the skin as venulitis or capillaritis, meaning the very smallest blood vessels are affected by inflammation from the disease. RV occurs in approximately 2 to 5 % of patients who have rheumatoid arthritis.
The reason why RV develops in some patients with rheumatoid arthritis and not others is not clear. Genetic factors may be involved. Viral infections and drug reactions have been suggested as causes of RV, but there is little research to support this. Some research suggests that long time use of drugs such as corticosteroids, gold compounds, penicillamine and azathioprine that are used to treat rheumatoid arthritis can cause the development of RV. However, this may not be true and difficult to determine because more use of these drugs is probably because of more severe or long standing rheumatoid arthritis, both of which may also be associated with the development of RV.
RV typically occurs in patients who have had rheumatoid arthritis for a long time. In one study, for example, the average time between the diagnosis of rheumatoid arthritis and the onset of RV symptoms was 13.6 years. Patients with rheumatoid arthritis seem more likely to develop RV when they have high rheumatoid factor levels (a specific laboratory finding for rheumatoid arthritis) and disease of at least one year’s duration. Males with rheumatoid arthritis are more likely (2 to 4 times more likely) than females with rheumatoid arthritis to develop RV.
The manifestations of RV can involve many of the body’s organs, including the skin, nerves to the hands and feet, blood vessels of the fingers and toes, and the eyes. Skin vasculitis is the most common manifestation of RV, occurring in as many as 90% of patients. Inflammation of the small blood vessels in the skin results in the development of red spots on the skin. When the eyes are involved, there is usually inflammation of the white part of the eye (scleritis).
The heart can also be affected by the disease, which can cause inflammation of the external part of the heart (pericarditis) and abnormal heart rate (arrhythmia). These symptoms put these patients at a higher risk for having a heart attack (myocardial infarction).
Patients with rheumatoid arthritis should see a physician if they develop new or worsened symptoms such as weight loss, fever, and lack of energy, any new symptoms beyond the usual joint symptoms. A blood test for specific antibodies that are directed against the inner layer of blood vessels (endothelial cells) are present in approximately 75% of patients with RV compared to only 15to 20% of those with rheumatoid arthritis alone. Therefore, this blood test may be checked regularly in patients with any of these new or worsened symptoms.
Diagnosis: Many of the drugs used to treat RV have a number of side effects; therefore it is important to be sure of the diagnosis before treatment is started (see treatment section below). The diagnosis of RV almost always requires a biopsy of tissue affected by the disease; an inflamed nerve or a kidney if there are clinical signs of kidney involvement, for example.
In rare cases RV may affect large blood vessels. If this happens or your doctor thinks it may have happened, then ‘pictures’ will be taken so that the vessels can be evaluated. Some of these pictures require that you drink something called ‘contrast’ material. This material shows up on the picture and helps to show different parts of the inside of your body. This test is called contrast angiography and is especially useful to help determine the location and appearance of large vessels that may be affected by the disease.
Biopsy-proven RV, even if only in one organ, requires aggressive therapy. The limited data specifically related to RV suggest that most such patients should be treated with the same or similar drugs that are used in other primary systemic vasculitides such as combination therapy with cytotoxic drugs (usually cyclophosphamide) and corticosteroids. Cyclophosphamide given through the veins (intravenous) once a month has been used with success, although daily oral therapy with the same drug may also be effective. A variety of different types of corticosteroid treatment have been used.
Patients with aggressive RV disease are usually begun on pulse methylprednisolone (corticosteroids given through the veins once a day for several days) followed by daily oral prednisone. Other drugs have been explored in patients with RV. Some patients have done well with azathioprine and corticosteroids. However azathioprine may be better used to maintain a remission after initial cyclophosphamide therapy helps to control the disease and its symptoms. Methotrexate and tumor necrosis factor (TNF), also known as infliximab, have also been used. However, some patients have developed RV while on these drugs for the treatment of rheumatoid arthritis. Since RV most often occurs when there is very active rheumatoid arthritis, aggressive treatment usually helps to control symptoms of both rheumatoid arthritis and vasculitis.
Supportive care is also very important. Smoking has been associated with an increased
risk for rheumatoid arthritis and for RV. Therefore smoking cessation is essential in any rheumatoid arthritis patient, especially those with RV. Good skin care may also prevent infectious complications of skin rashes in RV.
Limited data are available concerning the outcome of patients with RV, although they usually have worse and more ongoing symptoms than those with rheumatoid arthritis who do not have RV.
Takayasu’s ArteritisTakayasu’s Arteritis (TA) is an inflammation of large blood vessels, that is more common in women than in men. 80% to 90% of cases occur in women. People who get this form of vasculitis are usually between the ages of 10 and 40 years when the disease starts. Rarely, however, even children and young infants develop TA. The disease affects people around the world, but is most common in Asians, especially in Japan.
TA primarily affects the aorta, the major blood vessel that carries blood from the heart to supply oxygen to the body. Inflammation from the disease may be localized to one small part of the aorta, or may involve the entire length of the vessel. As the disease progresses, other major blood vessels may also become inflamed. The abdominal aorta, the part of the aorta that runs through the middle of the body and supplies blood to the stomach, intestines, and kidneys is involved in about 50% of patients. The inflammatory process causes the walls of the aorta to become thick, which makes it difficult for blood to flow easily. This may cause a wide variety of symptoms, depending upon which organs have their blood flow affected.
The cause of TA, and the reason that it develops in some people is not understood. Several studies suggest that genetic factors are involved. Nonetheless, the risk that more than one person in a family will develop TA is very small.
Symptoms: Symptoms that are common when TA first develops include lack of energy, weight loss, weakness and low-grade fever. Symptoms that affect the blood vessels take time to develop. As the disease progresses the arms and legs may become cool. Later, claudication or pain with use may develop. Other symptoms include joint pain, muscle weakness and pain, and skin lesions. If the vessels supplying blood to the heart or lungs become affected, people may develop chest pain, a myocardial infarction (heart attack). Anemia (low blood count) is present in most patients and results in a general feeling of weakness and fatigue.
Involvement of the major blood vessel that carries blood to the head and brain (the carotid artery) causes decreased blood flow that can lead to dizziness, fainting, headaches,seizures and difficulties thinking and remembering. Difficulty with seeing may also develop. Stomach pain, diarrhea, or ulcers can result from inflammation in the blood vessels supplying the stomach or intestines.
Diagnosis: Because the symptoms of TA may be so variable, the most importants step in diagnosis is considering the possibility of vasculitis. Physical examination often demonstrates decreased pulses in the arms or legs, and abdominal turbulence (bruits) in the neck or abdomen. Laboratory studies confirm the presence of inflammation. The next step is for doctors to visualize what is happening to the aorta and other blood vessels. Several different imaging methods are available. Radiography (x-ray) of the chest may be used to look for changes in the aorta. Other types of pictures show the actual flow of blood within the vessels, and require drinking or injecting something called contrast material. This material travels with the blood and helps to outline location and appearance of vessels affected by the disease. Such procedures include angiography, computed tomographic (CT) or magnetic imaging resonance (MR) imaging scans of the chest, abdomen, head and neck, or other areas. Positron emission tomography (PET scanning) can also be used to take pictures of the aorta and other large vessels. More than one of these types of tests and pictures may be needed in order to diagnose and manage TA optimally.
Treatment: Medications used to treat TA include drugs that decrease inflammation or weaken the part of the immune system causing inflammation in the blood vessels. The main drug used to treat TA is corticosteroids, also known as glucocorticoids. Treatment with this medicine usually stops this disease from getting worse by reducing the inflammation associated with the disease. However, use of this medicine, especially for long periods of time, can cause many adverse reactions or side affects.
Approximately one-half of all patients with TA have disease that is ongoing and does not get completely better with the use of corticosteroids. When this is the case, other drugs such as methotrexate, cyclophosphamide, and azathioprine may reduce the inflammation and be helpful in controlling symptoms of the disease. A new drug that may be helpful for patients with TA who do not get better with the treatments listed above is called an anti-tumor necrosis factor alpha (anti-TNF) agent. More information about the role of this type drug in treating TA is needed, a large study is planned.
Several types of medical procedures may be used to help repair damaged blood vessels and to restore blood flow if major damage from the disease occurs. Angioplasty is a medical procedure in which a balloon is used to open narrowed or blocked blood vessels. A by-pass graft, in which blood is surgically redirected around a clogged or damaged vessel may also be done.
Prognosis: TA is a chronic disease. The degree of new disease involvement over time can be quite different between patients, and the inflammation may never completely go away. In some patients the disease eventually burns out and symptoms and inflammation do not ever return. Despite this, most people with TA may be treated effectively, and new and better medications continue to improve their prognosis.
Granulomatosis with polyangiitis (Wegener’s) (GPA)GPA is an uncommon disease that affects about 1 in 20,000 to 1 in 30,000 people. Symptoms are due to inflammation that can affect many tissues in the body, including blood vessels (vasculitis). It is also considered a disease of abnormal immune function.
There is no known cause of GPA; but it is not contagious, and there is no evidence it is hereditary. It is systemic, meaning it affects the body as a whole. It affects the upper (sinuses and nose), and lower (lungs), respiratory system and frequently involves the kidneys, lungs, eyes, ears, throat, skin and other body organs. For reasons not clear, blood vessels in those areas may become inflamed and clusters of certain cells (granulomas) may occur.
GPA is an uncommon disease, which can occur at any age. It most often occurs in the 4th and 5th decade of life. Patients are divided equally between males and females. It appears that Caucasians are far more commonly affected than other racial groups.
Symptoms: Onset of GPA may be indolent, slow moving with few symptoms, or have a rapid and severe onset. About 90% of patients have symptoms of a cold or runny nose or sinusitis that fail to respond to the usual therapeutic measures and last considerably longer than the usual upper respiratory tract infection. Other symptoms include nasal membrane ulcerations and crusting, saddle-nose deformity, inflammation of the ear with hearing problems, inflammation of the eye with sight problems, cough (with or without the presence of blood), pleuritis, (inflammation of the lining of the lung), rash and/or skin sores, fever, lack of energy, weakness, fatigue, loss of appetite, weight loss, arthritic joint pain, night sweats, and blood in urine which may or may not be indicated by a change in urine color.
Be aware that not all GPA patients experience all symptoms. Different patients experience different symptoms, and the severity of the disease is also different for each GPA patient. If any of the above symptoms persist, consider a possible diagnosis of GPA and arrange to have a complete evaluation, including health history, physical exam, laboratory studies, including a urinalysis and an ANCA test.
Diagnosis is established by clinical and laboratory findings such as the ANCA blood test, other blood and urine tests, x-rays, and tissue biopsy, if needed.
Treatment: The treatment of GPA can be divided into two stages: first, the induction of disease remission, and secondly, the maintenance of disease remission. Medication usually consists of cytotoxic agents (a form of chemotherapy), using relatively low doses of Cytoxan, and/or methotrexate and/or azathioprine (Imuran), and glucocorticoids (prednisone).
Treatment will vary based on patient symptoms, disease activity, organ involvement and lab test results. Patients with kidney involvement and more severe GPA are commonly prescribed Cytoxan and prednisone as initial treatment. Ideally, the use of Cytoxan will be limited to a three to six month period and then replaced, based on kidney function, by methotrexate or azathioprine.
Those with milder forms of GPA are commonly prescribed methotrexate and prednisone. These medications will be reduced over time, and even eliminated, if the patient remains in a stable remission. GPA patients may also be prescribed calcium supplements, vitamin D and other medications to prevent osteoporosis from extended prednisone use.
Many patients will also be prescribed the antibiotic Bactrim to help prevent secondary lung infections with a dangerous “bug” called Pneumocystis carinii pneumonia (PCP). In addition, there is some evidence that Bactrim, used cautiously, can have the beneficial effects of reducing relapses and upper airway infections.
Remission: There is no cure for GPA, but early diagnosis and proper treatment will be effective and the disease can be brought into remission with complete absence of all signs of disease.
Long-term remission can be induced and maintained with medications, close management and regular lab tests to help monitor the disease. Treatment can produce symptom-free intervals of 5 to 20 years or more. Some patients will achieve a drug-free remission. However, relapses are common but can be caught at their earliest and most treatable stage, for most patients, by paying attention to patient symptoms and lab tests. GPA patients in remission must not hesitate to see a doctor if any GPA symptoms return or if they are not feeling well.