You are here: Home / Rare Disease Information / Rare Disease Database

Search Rare Diseases

Enter a disease name or synonym to search NORD's database of reports.

0-9 - A - B - C - D - E - F - G - H - I - J - K - L - M - N - O - P - Q - R - S - T - U - V - W - X - Y - Z

Wegener's Granulomatosis

Synonyms of Wegener's Granulomatosis

  • Midline granulomatosis
  • Necrotizing Respiratory Granulomatosis
  • Pathergic Granulomatosis

Disorder Subdivisions

  • No subdivisions found.

General Discussion

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.

Symptoms

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).

Causes

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).

Affected Populations

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.

Related Disorders

Symptoms of the following disorders can be similar to those of Wegener's granulomatosis. Comparisons may be useful for a differential diagnosis:

Systemic lupus erythematosus is a chronic, inflammatory autoimmune disorder affecting the connective tissue. In autoimmune disorders, the body's own immune system attacks healthy cells and tissues causing inflammation and malfunction of various organ systems. In lupus the organ systems most often involved include the skin, kidneys, blood and joints. Many different symptoms are associated with lupus, and most affected individuals do not experience all of the symptoms. In some cases, lupus may be a mild disorder affecting only a few organ systems. In other cases, it may result in serious complications. Lupus can be differentiated from Wegener's granulomatosis by the presence of antinuclear antibodies and lupus cells in the serum. Additionally, the serum complement level is depressed. (For more information on this disorder, choose "Lupus" as your search term in the Rare Disease Database.)

Goodpasture syndrome is a rare autoimmune disorder characterized by inflammation of the filtering structures (glomeruli) of the kidneys (glomerulonephritis) and excessive bleeding into the lungs (pulmonary hemorrhaging). Autoimmune syndromes occur when the body's natural defenses (antibodies) against invading or "foreign" organisms begin to attack the body's own tissue, often for unknown reasons. Symptoms of Goodpasture syndrome include recurrent episodes of coughing up of blood (hemoptysis), difficulty breathing (dyspnea), fatigue, chest pain, and/or abnormally low levels of circulating red blood cells (anemia). In many cases, Goodpasture syndrome may result in an inability of the kidneys to process waste products from the blood and excrete them in the urine (acute renal failure). In some cases of Goodpasture syndrome, affected individuals have had an upper respiratory tract infection before the development of the disorder. The exact cause of Goodpasture syndrome is not known. (For more information on this disorder, choose "Goodpasture" as your search term in the Rare Disease Database.)

Polyarteritis nodosa, a rare multisystem disorder that usually becomes apparent between the ages of 40 to 50 years, is characterized by widespread inflammation, weakening, and degeneration of small- and medium-sized arteries. Blood vessels in any organ or organ system may be affected, including arteries supplying the kidneys, heart, intestine, nervous system, and/or skeletal muscles. Damage to affected arteries may result in abnormally increased blood pressure (hypertension), "ballooning" (aneurysm) of an arterial wall, the formation of blood clots (thrombosis), obstruction of blood supply to certain tissues, and/or tissue damage and loss (necrosis) in certain affected areas. In many cases, affected individuals experience weight loss, fever, a general feeling of ill health (malaise), fatigue, weakness, headache, muscle aches (myalgias), and/or abdominal pain. Additional symptoms and findings are often present and depend upon which areas of the body are affected. Although the exact cause of polyarteritis nodosa is not known, many researchers suspect that the disorder is due to disturbances of the body's immune system. (For more information on this disorder, choose "polyarteritis nodosa" as your search term in the Rare Disease Database.)

Lymphatoid granulomatosis is a rare, progressive, disease of the lymph nodes and blood vessels characterized by infiltration and destruction of the veins and arteries by nodular lesions created by accumulations of various cells. These lesions can affect various parts of the body, especially the lungs. However, the condition may start by affecting the small arteries and eventually the lungs, skin, kidneys and nervous system. Affected individuals may have a cough with or without blood, fever, weight loss, diarrhea, joint (arthralgias) and muscle (myalgias) pain, shortness of breath (dyspnea), chest pain and a generalized feeling of discomfort (malaise). If the skin is involved, flat and red lesions (macules), nodules and sometimes ulcerations can appear. Lymphomatoid granulomatosis may lead to breathing difficulties and eventually failure of the respiratory system. (For more information on this disorder, choose "lymphatoid granulomatosis" as your search term in the Rare Disease Database.)

Churg-Strauss syndrome is a rare disorder that may affect multiple organ systems, especially the lungs. The disorder is characterized by the formation and accumulation of an unusually large number of antibodies, abnormal clustering of certain white blood cells (eosinophilia), inflammation of blood vessels (vasculitis), and the development of inflammatory nodular lesions (granulomatosis). Many individuals with Churg-Strauss syndrome have a history of allergy. In addition, asthma and other associated lung (pulmonary) abnormalities (i.e., pulmonary infiltrates) often precede the development of the generalized (systemic) symptoms and findings seen in Churg-Strauss syndrome by one or more years. Nonspecific findings associated with Churg-Strauss syndrome typically include flu-like symptoms, such as fever, a general feeling of weakness and fatigue (malaise), loss of appetite (anorexia), weight loss, and muscle pain (myalgia). Additional symptoms and findings may be variable, depending upon the specific organ systems involved. Without appropriate treatment, serious organ damage and potentially life-threatening complications may result. Although the exact cause of Churg-Strauss syndrome is unknown, many researchers indicate that abnormal immunologic and autoimmune factors play an important role. (For more information on this disorder, choose "Churg Strauss" as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
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).

Treatment
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.

Investigational Therapies

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:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

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.

Organizations related to Wegener's Granulomatosis

References

TEXTBOOKS
Fauci AS, et al., eds. Harrison's Principles of Internal Medicine, 14th Ed. New York, NY: McGraw-Hill, Inc; 1998:1914-17.

Bennett JC, Plum F., eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:1495-98.

Hasleton PS. Spencer's Pathology of the Lung. McGraw Hill,
New York, 1996.

Farrelly C, Foster DR. Atypical Presentation of Wegener's Granulomatosis.
Br J Radiol. 1980;53:721-722.

MacGregor MBB, Sandler G. Wegener's Granulomatosis:
A Clinical and Radiological Survey. Br J Radiol 1964;37:430-439.

JOURNAL ARTICLES
Stone JH, et al., Etanercept with conventional treatment in Wegener's granulomatosis: a six-month open-label trial to evaluate safety. Arthritis Rheum. 2001;44:1149-54.

Yang C, et al., Bony abnormalities of the paranasal sinuses in patients with Wegener's granulomatosis. Am J Rhinol. 2001;15:121-5.

Aasarod K, et al., Renal histopathology and clinical course in 94 patients with Wegener's granulomatosis. Nephrol Dial Transplant. 2001;16:953-60.

Boudewyns A, et al., Wegener's granulomatosis triggered by infection? Acta Otorhinolaryngol Belg. 2001;55:57-63.

Langford CA, et al., Wegener Granulomatosis. Am J Med Sci. 2001;321:76-82.

Toyoshima M, et al., Wegener's granulomatosis responding to antituberculous drugs. Chest. 2001;119:643-5.

Wegener's granulomatosis in children and young adults. A case study of ten patients. Pediatr Nephrol. 2000;14:208-13.

Savige J, et al., International consensus statement of testing and reporting of antineutrophil cytoplasmic antibodies (ANCA). Am J Clin Pathol. 1999;111:507-13.

Stegeman CA, et al., Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. N Engl J Med. 1996;335:16-20.

DeRemee RA, et al., Empericism and Wegener's granulomatosis. N Engl J Med. 1996;335:54-5.

Weir A, et al., Co-trimoxazole in Wegener's granulomatosis. N Engl J Med. 1996;335:1769-70.

van Putten JW, et al., Association between Wegener's granulomatosis and Staphylococcus aureus infection? Eur Respir J. 1996;9:1955-7.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2007/07/23 00:00:00 GMT+0

0-9 - A - B - C - D - E - F - G - H - I - J - K - L - M - N - O - P - Q - R - S - T - U - V - W - X - Y - Z

NORD's Rare Disease Information Database is copyrighted and may not be published without the written consent of NORD.

 
Copyright ©2014 NORD - National Organization for Rare Disorders, Inc. All rights reserved.
The following trademarks/registered service marks are owned by NORD: NORD, National Organization for Rare Disorders, the NORD logo, RareConnect. .