$Unique_ID{BRK03786} $Pretitle{} $Title{Granulomatosis, Wegener's} $Subject{Granulomatosis Wegener's Necrotizing Respiratory Granulomatosis Pathergic Granulomatosis} $Volume{} $Log{} Copyright (C) 1986, 1988, 1989 National Organization for Rare Disorders, Inc. 270: Granulomatosis, Wegener's ** IMPORTANT ** It is possible the main title of the article (Wegener's Granulomatosis) is not the name you expected. Please check the SYNONYMS listing to find the alternate names and disorder subdivisions covered by this article. Synonyms Necrotizing Respiratory Granulomatosis Pathergic Granulomatosis General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Wegener's Granulomatosis is an uncommon collagen vascular disorder that begins as a localized inflammation of the upper and lower respiratory tract mucosa, and usually progresses into generalized inflammation of the blood vessels (vasculitis) and kidney (glomerulonephritis). Symptoms Onset of Wegener's Granulomatosis may be gradual or acute. Initial symptoms usually occur in the upper respiratory tract and appear as a severe common cold, paranasal sinusitis, ulcerations of the mucous membranes in the nose with secondary bacterial infection, middle ear infection (otitis media) with hearing loss, cough, expectoration of blood (hemoptysis), and pleuritis. The nasal mucous membrane appears red with a raised granular appearance, and it may bleed easily. Other initial symptoms may include fever, malaise, loss of appetite, weight loss, and migratory disease of the joints (polyarthropathy). Skin lesions and eye problems such as obstruction and bulging of the tear duct may be present. Inflammation of the ear cartilage (chondritis), myocardial infarction caused by the inflammation of the blood vessels (vasculitis), aseptic meningitis and non-healing granuloma of the central nervous system may also occur. After a few weeks or months, a disseminated vascular phase characteristically develops. Necrotizing inflammatory skin, lung and kidney lesions (glomerulitis) may progress, causing hypertension and kidney failure (uremia). Kidney disease is the hallmark of this disorder in the generalized phase. Urinalysis shows protein (proteinuria), blood (hematuria), and red blood cell casts in the urine. Functional kidney impairment is inevitable without immediate appropriate therapy. Occasionally, the disease is limited to the lungs. The levels of the complex series of enzymatic proteins in the blood serum (serum complement) are normal or elevated. The sedimentation rate of red blood cells (erythrocyte sedimentation rate or ESR) is elevated. An increase in white blood cells (leukocytosis) is present. Antinuclear antibodies and lupus erythematosus cells are not found in patients with Wegener's Granulomatosis. Causes The exact cause of Wegener Granulomatosis is unknown. Though the disorder resembles an infectious process, no viral, bacterial or other causative agent has been isolated. Because of the characteristic histologic tissue changes, an allergic reaction has been suggested as a possible basis for the disorder. Affected Population Wegener's Granulomatosis can occur at any age. It affects males about twice as often as females. Related Disorders Polyarteritis is a disorder characterized by inflammation and necrosis of medium-sized muscular arteries, with secondary lack of oxygen in the tissues supplied by the affected vessels. Differential diagnosis of Polyarteritis is ruled out by biopsy of the skin lesions and pathologic examination of the vascular lesions. The presence of cells that are easily stained with eosin (eosinophilia), is not a feature of Wegener's Granulomatosis, but it is often found in polyarteritis. Nasal and pulmonary granulomatous inflammation are absent in polyarteritis. The vascular renal phase of Subacute Bacterial Endocarditis (SBE) can be differentiated from Wegener's Granulomatosis by characteristic blood cultures and changing heart murmurs. Systemic Lupus Erythematosus can be differentiated from Wegener's Granulomatosis by the presence of antinuclear antibodies and Lupus Erythematosus 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.) Glomerulonephritis is a disorder characterized by diffuse inflammatory changes in the kidney glomeruli, by the abrupt appearance of protein and blood in the urine, and, by red blood cell casts. In Midline Malignant Reticulosis vascular granulomatous inflammation is absent. Therapies: Standard The complete syndrome of Wegener's Granulomatosis can progress rapidly to kidney failure once the diffuse vascular phase begins. Persons with the limited form of the disorder have only nasal and pulmonary lesions with little or no systemic involvement. Pulmonary symptoms may improve or worsen spontaneously. Early diagnosis and treatment are important in view of the potential success of drugs that have a toxic effect on certain cells (cytotoxic drugs). The prognosis for this disease has been improved in recent years by treatment with immunosuppressive cytotoxic agents. Cyclophosphamide is the drug of choice, but azathioprine and chlorambucil are also useful. Duration of therapy depends on the patient'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 tapering medication dosage or discontinuing the drug. Long-term, complete remissions are often achieved with drug therapy, even with advanced disease. Kidney transplantation has been successful for kidney failure resulting from Wegener's Granulomatosis. Corticosteroids can be used intermittently for non-renal symptoms in conjunction with the above drugs. Research at the National Institute of Allergy and Infectious Diseases (NIAID) on regulation of the immune function has benefited patients 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. Therapies: Investigational The National Institute of Allergy and Infectious Diseases (NIAID) is conducting a study on a treatment for Wegener's Granulomatosis. Patients who wish to participate in the clinical trials must be at least 14 years of age and had a recent onset of the illness. For further information, physicians can contact Dr. Gary S. Hoffman or Dr. Randi Y. Levitt at NIH/National Institute of Allergy and Infectious Diseases, Bldg. 10, Rm. 11813, 9000 Rockville Pike, Bethesda, MD 20892 or phone (301) 496-1124. Travel expenses are usually covered by the NIH and all treatment is free. This disease entry is based upon medical information available through September 1989. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Wegener's Granulomatosis, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Wegener's Granulomatosis Support Group, National Chapter P.O. Box 1518 Platte City, MO 64079 (816) 431-2096 or (816) 431-5469 Wegener's Foundation 9000 Rockville Pike Bldg. 31A, Rm. B1W30 Bethesda, MD 20892 NIH/National Heart, Lung and Blood Institute (NHLBI) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-4236 The National Kidney Foundation 30 East 33rd St. New York, NY 10016 (212) 689-2210 or (800) 622-9010 American Lung Association 1740 Broadway New York, NY 10019 (212) 315-8700 References The Merck Manual of Diagnosis of Therapy: Berkow et al., eds.: Merck Sharp & Dohme (1982).