Wegener's granulomatosis is an uncommon disorder characterized by inflammation of blood vessels (vasculitis) that results in damage to various organ systems of the body, most often the respiratory tract and kidneys. Symptoms may include ulcerations of the mucous membranes in the nose with secondary bacterial infection, a persistent runny nose, sinus pain, and chronic middle ear infection (otitis media) potentially resulting in hearing loss. In some cases, kidney abnormalities may progress to kidney failure, a serious complication. If the lungs are affected, a cough, expectoration of blood (hemoptysis), and inflammation of the thin membrane lining the outside of the lungs and the inside of the lung may be present. The exact cause of Wegener's granulomatosis is not known.
The specific symptoms associated with Wegener’s granulomatosis vary greatly from case to case. In most cases, the disorder affects the respiratory tract and the kidneys. The severity of specific symptoms also varies greatly from case to case. Onset of Wegener’s granulomatosis may be gradual or rapid (acute).
Initial symptoms usually occur in the upper respiratory tract and appear similar to those associated with a severe common cold, including a persistent runny nose (rhinorrhea), sinus pain, bloody nasal discharge, ulcerations of the mucous membranes in the nose with secondary bacterial infection, and inflammation of the sinuses (paranasal sinusitis). Affected individuals may also develop middle ear inflammation (otitis media), which may eventually result in hearing loss. In some cases, affected individuals will develop a hole or tear in the wall (septum) dividing the nostrils, resulting in the collapse of the bridge of the nose, a condition called saddle nose.
In some cases, initial symptoms of Wegener’s granulomatosis may include fever, a general feeling of ill health (malaise), weakness and fatigue, joint paint (arthralgia), loss of appetite, and weight loss.
Individuals with Wegener’s granulomatosis often develop symptoms affecting the lungs (pulmonary). These symptoms include a persistent cough, episodes of coughing up of blood (hemoptysis), difficulty breathing (dyspnea), chest pain, and inflammation of the thin membrane lining the outside of the lungs and the inside of the lung (pleuritis). In some cases, affected individuals experience narrowing of the windpipe (trachea), a condition known as subglottic stenosis.
Approximately 75 percent of individuals with Wegener’s granulomatosis eventually develop kidney (renal) disease. However, in many cases no symptoms are apparent (asymptomatic). Affected individuals may develop high blood pressure (hypertension), and/or inflammation of the cluster of blood vessels and nerve fibers of the kidney (glomerulo), a condition known as glomerulonephritis. Without treatment, life-threatening kidney (renal) failure may occur.
Most individuals with Wegener’s granulomatosis experience symptoms affecting the muscles and skeleton (musculoskeletal), including pain in various joints (polyarthralgia), swelling of joints, inflammation of the joints (arthritis), inflammation of muscles (myositis), and muscle pain (myalgia).
More than half of individuals with Wegener’s granulomatosis experience eye (ocular) abnormalities, including inflammation of the delicate membrane that lines the eyes (conjunctivitis), inflammation of the white, outer-covering (sclera) of the eyeball (scleritis), and inflammation of the membrane covering the sclera (episcleritis). Affected individuals may also develop an abnormal mass or sore behind the eye (orbital mass lesion). Eye abnormalities may result in eye pain, redness, bulging eyeballs (proptosis), double vision (diplopia), and vision loss.
Approximately half of individuals with Wegener’s granulomatosis develop skin abnormalities including small bumps just below the surface of the skin (subcutaneous nodules), small raised areas (papules), skin ulcers, bleeding (hemorrhage) within skin layers, causing the appearance of small purplish spots on the skin (petechiae), and/or areas of purple discoloration caused by bleeding vessels near the surface of the skin (purpura). Skin lesions may or may not be painful.
Some affected individuals may have painfully cold fingers and toes caused by widening (dilation) or narrowing (constriction) of small vessels in response to cold (Raynaud’s phenomenon). Affected individuals may experience lack of blood flow to the fingers and toes (digital ischemia).
Individuals with Wegener’s granulomatosis may also develop neurological abnormalities including inflammation and degeneration of nerve fibers outside of the brain and spinal cord (peripheral neuropathy), injury to several different nerves simultaneously (mononeuritis multiplex), and inflammation of cranial nerves (cranial neuritis).
In some cases, affected individuals may experience abnormalities of the heart (cardiac) including inflammation of the membranous sac that surrounds the heart (pericarditis), disease of the heart muscle (cardiomyopathy), and inflammation of the arteries that supply blood to the heart muscles (coronary arteritis).
The exact cause of Wegener’s granulomatosis is unknown. Although the disorder resembles an infectious process, no viral, bacterial or other causative agent has been isolated.
Because of the characteristic histologic tissue changes, an immune reaction has been suggested as a possible basis for the disorder. Many researchers consider Wegener’s granulomatosis an autoimmune disorder. Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms begin to attack healthy tissue for unknown reasons.
The symptoms of Wegener’s granulomatosis occur because of inflammation of the blood vessels (vasculitis) that results in reduced blood flow to, and loss of tissue in, various organ systems of the body. The disorder is marked by the clumping or massing (aggregation) of inflammatory cells (granulomas) within various organ tissues and blood vessels (granulomatosis).
Wegener’s granulomatosis is a rare disorder that affects males and females in equal numbers. In most cases, onset is after fourth or fifth decade; however, it can occur at any age. Approximately 15 percent of cases occur in individuals under 19 years of age.
According to one estimate, the frequency of Wegener’s granulomatosis is one in 30,000 to 50,000 individuals in the United States. However, because cases of Wegener’s granulomatosis often go unrecognized, the disorder is under-diagnosed making it difficult to determine its true frequency in the general population. Wegener’s granulomatosis predominately affects Caucasians.
A diagnosis of Wegener's granulomatosis is made based upon a thorough clinical evaluation, a detailed patient history, identification of classic symptoms, and a variety of specialized tests. In many cases, surgical removal (biopsy) and microscopic examination of small samples of tissue from an affected organ (e.g., lung, kidneys) may reveal characteristic vasculitis or granulomas.
In addition to biopsy, blood tests may be performed to rule out other disorders. A blood test may also reveal the presence of a specific type of antibody known as antineutrophil cytoplasmic antibody (ANCA). Because the test is positive in the majority of individuals with Wegener's granulomatosis, the ANCA blood test may help support a suspected diagnosis of the disorder. However, in some affected individuals, the test is negative and, therefore, should not be used in place of a biopsy.
X-ray tests are also helpful in supporting a suspected diagnosis of Wegener's granulomatosis. X-rays of the lungs or sinuses may reveal characteristic findings associated with the disorder (e.g., thickening of the lining of the sinus).
Individuals with Wegener's granulomatosis are treated with a combination of corticosteroid drugs that reduce inflammation such as prednisone and cytotoxic drugs that impede the abnormal growth (proliferation) of cells. Cyclophosphamide (Cytoxan) is the most common cytotoxic drug used to treat Wegener's granulomatosis. Other drugs that have been used to treat individuals with Wegener's granulomatosis include methotrexate, azathioprine, and chlorambucil.
Duration of therapy depends on an affected individual's response. White blood cell (leukocyte) counts are closely monitored. Dosages are reduced gradually to prevent severe deficiency of white blood cells. Attempts should be made to discontinue therapy if symptoms of the disorder have been absent for one year. The possibility of kidney disease relapse is carefully monitored when reducing (tapering) medication dosage or discontinuing the drug. Long-term, complete remissions are often achieved with drug therapy, even with advanced disease.
Individuals with Wegener's granulomatosis may experience a recurrence (relapse) of the disorder after remission. In some cases, relapses of Wegener's granulomatosis may be triggered by an infection.
Kidney transplantation has been successful for kidney failure resulting from Wegener's granulomatosis. Antibiotics have been used to treat secondary bacterial infections sometimes associated with Wegener's granulomatosis.
Research at the National Institute of Allergy and Infectious Diseases (NIAID) on regulation of the immune function has benefited individuals with such inflammatory vascular diseases as Wegener's granulomatosis, lymphatoid granulomatosis and polyarteritis nodosa. Before the introduction of treatment regimens developed at the NIAID, the majority of those with Wegener's granulomatosis died within one year after the onset of the disorder. Today, ninety-three percent of those treated with cyclophosphamide and prednisone show complete remission.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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Research physicians at the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH), have studied Wegener’s granulomatosis and possible treatments for many years.
NIH has awarded a $6.25 million, five-year grant to establish a multicenter research network known as the Vasculitis Clinical Research Consortium (VCRC). This consortium will foster and facilitate clinical investigation of Wegener’s granulomatosis and related diseases.
The VCRC will consist of four major U.S. vasculitis centers: Boston University School of Medicine, Massachusetts; the Cleveland Clinic, Ohio; Johns Hopkins Vasculitis Center, Baltimore; and Mayo Clinic College of Medicine, Rochester. Additional information about the VCRC can be found at www.rarediseasesnetwork.org/vcrc.
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