F11 tuşu siteyi tam sayfa görmenizi sağlar.  2. kez basılarak normal konumuna döner

Wegener's granulomatosis is vasculitis that often begins with inflammation of the lining of the nose, sinuses, throat, or lungs and may progress to inflammation of blood vessels throughout the body (generalized vasculitis) with potentially fatal kidney failure.

Wegener's granulomatosis can occur at any age and is twice as common in men as in women. Its cause is unknown. It resembles an infection, but no infecting organism has been found. Wegener's granulomatosis is thought to be caused by an allergic response to a trigger that has not yet been identified. The result is a potent, inappropriate immune reaction that damages many tissues in the body.

The disorder produces inflammation of blood vessels (vasculitis) and an unusual type of inflammatory tissue called a granuloma, which ultimately destroys normal tissue.

Symptoms

The disorder may begin suddenly or gradually. The first symptoms usually affect the upper respiratory tract—the nose, sinuses, ears, and windpipe (trachea)—and may include severe nosebleeds, sinusitis, middle ear infections (otitis media), coughing, coughing up of blood, and shortness of breath. The lining of the nose may become red and rough, bleeding easily. A fever, a generally sick feeling (malaise), loss of appetite, joint aches and swelling, and inflammation of the eye or ear may develop. The disease may affect arteries to the heart, causing chest pain or a heart attack, or it may affect the brain or spinal cord, producing symptoms that resemble those of several neurologic diseases.

The disorder may progress to a generalized (disseminated) phase, with inflammation of blood vessels throughout the body. As a result, sores appear on the skin and spread extensively; they can severely scar the skin. Kidney damage, common at this stage of Wegener's granulomatosis, ranges from mild impairment to life-threatening kidney failure. Severe kidney disease causes high blood pressure and symptoms resulting from the buildup of wastes in the blood (uremia). Anemia is common and can be severe.

In some cases, only the nasal passages, sinuses, and upper airways are affected for many years; this less severe disorder is called limited Wegener's granulomatosis. However, progression to the more serious disorder is possible.

Diagnosis

Wegener's granulomatosis must be diagnosed and treated early to prevent complications, including kidney disease, lung disease, heart attacks, and brain damage.

A doctor usually recognizes the distinctive pattern of symptoms. Although blood test results cannot specifically identify Wegener's granulomatosis, they can strongly support the diagnosis. A blood test can detect antineutrophil cytoplasmic antibodies in the blood, which strongly suggest this disease. If the nose, throat, or skin is not affected, diagnosis can be difficult because the symptoms and x-rays can resemble those of several lung diseases.

A chest x-ray may show cavities or dense areas in the lungs that look like cancer. Doctors can make a definite diagnosis only by examining a small piece of tissue under a microscope (a biopsy); the tissue sample may be taken from an affected area, such as the nasal passages, airways, or lungs. Skin and kidney biopsies may be less helpful.

Treatment

Corticosteroids may be used alone to treat the early symptoms of Wegener's granulomatosis. However, most people also need another immunosuppressive drug, such as cyclophosphamideSome Trade Names
CYTOXAN
.

The generalized form of Wegener's granulomatosis is treated with immunosuppressive drugs, such as cyclophosphamideSome Trade Names
CYTOXAN
and azathioprineSome Trade Names
IMURAN
, which control the disease by reducing the body's inappropriate immune reaction. Such use significantly improves the prognosis because, without treatment, this form of the disorder is fatal. Treatment is usually continued for at least a year after the symptoms disappear. Corticosteroids, given at the same time to suppress inflammation, can usually be tapered off and discontinued.

For people who are receiving immunosuppressive drugs, a doctor treats any suspected infection as early as possible because of the body's decreased ability to fight infections. Pneumonia is particularly common when the lungs are damaged. An antibiotic may be used to prevent infections in people who have been taking immunosuppressive drugs for years.

Also known as:
Klinger's syndrome
Klinger-Wegener syndrome
Wegener's disease
Wegener's syndrome
Wegener-Churg-Klinger syndrome
Wegener-Klinger syndrome

Synonyms:
Arteritis-pulmonary-nephropathy syndrome, classical granulomatosis, glomerulonephritis syndrome, granuloma-arteritis, granulomas-arteritis-glomerulonephritis syndrome, granulomata-arteritis-glomerulonephritis syndrome, granuloma gangraenescens, granulomatosis pathergic syndrome, malignant granulomatous angiitis, necrotizing granulomatosis, necrotizing respiratory granulomatosis, rhinogenic polyarteritis.

Buy The Book Print This Topic Email This Topic Pronunciations arteritis azathioprine corticosteroid cyclophosphamide granuloma myalgia neurologic otitis media pneumonia trachea vasculitis Wegener’s granulomatosis Wegener's granulomatosis is vasculitis that often begins with inflammation of the lining of the nose, sinuses, throat, or lungs and may progress to inflammation of blood vessels throughout the body (generalized vasculitis) with potentially fatal kidney failure. Wegener's granulomatosis can occur at any age and is twice as common in men as in women. Its cause is unknown. It resembles an infection, but no infecting organism has been found. Wegener's granulomatosis is thought to be caused by an allergic response to a trigger that has not yet been identified. The result is a potent, inappropriate immune reaction that damages many tissues in the body. The disorder produces inflammation of blood vessels (vasculitis) and an unusual type of inflammatory tissue called a granuloma, which ultimately destroys normal tissue. Symptoms The disorder may begin suddenly or gradually. The first symptoms usually affect the upper respiratory tract—the nose, sinuses, ears, and windpipe (trachea)—and may include severe nosebleeds, sinusitis, middle ear infections (otitis media), coughing, coughing up of blood, and shortness of breath. The lining of the nose may become red and rough, bleeding easily. A fever, a generally sick feeling (malaise), loss of appetite, joint aches and swelling, and inflammation of the eye or ear may develop. The disease may affect arteries to the heart, causing chest pain or a heart attack, or it may affect the brain or spinal cord, producing symptoms that resemble those of several neurologic diseases. The disorder may progress to a generalized (disseminated) phase, with inflammation of blood vessels throughout the body. As a result, sores appear on the skin and spread extensively; they can severely scar the skin. Kidney damage, common at this stage of Wegener's granulomatosis, ranges from mild impairment to life-threatening kidney failure. Severe kidney disease causes high blood pressure and symptoms resulting from the buildup of wastes in the blood (uremia). Anemia is common and can be severe. In some cases, only the nasal passages, sinuses, and upper airways are affected for many years; this less severe disorder is called limited Wegener's granulomatosis. However, progression to the more serious disorder is possible. Diagnosis Wegener's granulomatosis must be diagnosed and treated early to prevent complications, including kidney disease, lung disease, heart attacks, and brain damage. A doctor usually recognizes the distinctive pattern of symptoms. Although blood test results cannot specifically identify Wegener's granulomatosis, they can strongly support the diagnosis. A blood test can detect antineutrophil cytoplasmic antibodies in the blood, which strongly suggest this disease. If the nose, throat, or skin is not affected, diagnosis can be difficult because the symptoms and x-rays can resemble those of several lung diseases. A chest x-ray may show cavities or dense areas in the lungs that look like cancer. Doctors can make a definite diagnosis only by examining a small piece of tissue under a microscope (a biopsy); the tissue sample may be taken from an affected area, such as the nasal passages, airways, or lungs. Skin and kidney biopsies may be less helpful. Treatment Corticosteroids may be used alone to treat the early symptoms of Wegener's granulomatosis. However, most people also need another immunosuppressive drug, such as cyclophosphamideSome Trade Names CYTOXAN . The generalized form of Wegener's granulomatosis is treated with immunosuppressive drugs, such as cyclophosphamideSome Trade Names CYTOXAN and azathioprineSome Trade Names IMURAN , which control the disease by reducing the body's inappropriate immune reaction. Such use significantly improves the prognosis because, without treatment, this form of the disorder is fatal. Treatment is usually continued for at least a year after the symptoms disappear. Corticosteroids, given at the same time to suppress inflammation, can usually be tapered off and discontinued. For people who are receiving immunosuppressive drugs, a doctor treats any suspected infection as early as possible because of the body's decreased ability to fight infections. Pneumonia is particularly common when the lungs are damaged. An antibiotic may be used to prevent infections in people who have been taking immunosuppressive drugs for years. Associated persons:
Jacob Churg

Heinz Karl Ernst Klinger

Friedrich Wegener


Description:
An uncommon disorder characterized by necrotizing vasculitis, granulomatous lesions of the entire respiratory tract, and glomerulonephritis. The lesions closely resemble those in polyarteritis nodosa. The symptoms are weakness, malaise, progressive weight loss, purulent rhinitis, sinusitis, polyarthralgia, ulcerations of the nasal septum, signs of severe progressive renal disease, and fever. The disease commonly occurs in mid-adult life. Either sex may be affected. If it is not treated early, death occurs in a matter of months, most often from kidney damage.

The condition was first described by Peter McBride (1854-1946) in 1897. The pathological-anatomical picture was described by Heinz Karl Ernst Klinger (born 1907), a German medical student, in 1931. Detailed description by Friedrich Wegener in 1936 and 1939.

Introduction

Wegener's granulomatosis is an uncommon disease defined by inflammation of the blood vessels (vasculitis), kidneys (glomerulonephritis) and the upper and lower respiratory tract (sinuses, nose, trachea, and lungs). A characteristic feature of the inflammation in Wegener's granulomatosis is the presence of discrete groups of inflammatory cells called granulomas. Wegener's granulomatosis most commonly affects individuals in the 4^th or 5^th decade of life. The disease can, however, affect people at any age (age range: 5-91 years), with approximately 15% of cases beginning before 20 years of age. Wegener's granulomatosis strikes both men and women. It is most common in Caucasians (97%) and is rare in African Americans (2%).

History

In 1931, Heinz Klinger of the University of Berlin first reported two patients who died of inflammation of blood vessels (vasculitis) scattered throughout the body. Five years later, Friederic Wegener, a German pathologist from Breslau described three patients with necrotizing (a description of the microscopic appearance of dying tissue) granulomas involving both upper and lower respiratory tract. He was the first one to recognize this disorder as a distinct form of vasculitis. Other names used for Wegener's granulomatosis are Wegener's arteritis, Wegener's disease, or midline granulomatosis.

Course of Disease

Although Wegener's granulomatosis may involve other body systems, the classic features are vasculitis, glomerulonephritis and granulomas of the upper and lower respiratory tract. Ninety to 95% of patients have lung or sinus disease and involvement of the respiratory tract (sinuses, nose, trachea, and lungs) is the first sign of the disease in 90% of patients. Symptoms may include cough, sinus pain, coughing up blood (hemoptysis), chest discomfort, and pain on breathing. A common sign of the disease is an almost constant "runny nose" (rhinorrhea) or other cold symptoms that are not responsive to cold medicines. Rarely, a perforation (hole) may develop in the cartilage of the nose, which may lead to collapse or flattening of the nasal bridge (called a saddle-nose deformity). Eighty-five percent of patients with Wegener's granulomatosis suffer from kidney disease. Glomerulonephritis causes blood (hematuria) and increased protein (proteinuria) in the urine which may change its color. Almost 50% of patients with Wegener's granulomatosis develop skin lesions that appear as small red or purple raised areas (rash), ulcers (sores) or bumps (nodules). Inadequate blood flow can lead to extreme cold sensitivity in the fingers and toes (Raynaud's phenomenon).

In some patients, the initial symptoms of Wegener's granulomatosis may include fever, fatigue, ill-feeling (malaise), loss of appetite (anorexia), weight loss, joint pain, and night sweats. Not all Wegener's patients experience all symptoms and the severity of the disease is different with each patient.

Eye symptoms may be the first manifestation in 16% of patients with Wegener's granulomatosis, while overall approximately half of patients will eventually develop eye involvement. A common eye problem in Wegener's granulomatosis is tearing due to closure of the passage between the eye and nose (nasolacrimal duct obstruction). Inflammation in the eye socket (orbit) can cause loss of vision, pain behind the eyes, double vision, bulging or protrusion of the eyes, or orbital bone erosion. Orbital involvement has been reported in 45-70% of patients. The cornea and sclera compose the outer wall of the eye and vision loss in patients with Wegener's granulomatosis may result from inflammation affecting the cornea (peripheral ulcerative keratitis) or sclera (scleritis). Other less common eye findings in Wegener's granulomatosis include uveitis, retinal vasculitis, optic neuropathy, restricted movement of the eye muscles and conjunctival scarring. Proptosis (a prominent or bulging eye) in the setting of upper and lower respiratory disease is highly suggestive of Wegener's.

Diagnosis and Testing

The diagnosis of Wegener's granulomatosis requires evidence of inflammation affecting the blood vessels, kidneys or respiratory tract. Because of its variable presentation, there is often a delay in the diagnosis of 1-2 years. Wegener's granulomatosis must be distinguished from other causes of vasculitis. A positive biopsy of an involved organ (for example sinus, kidney or lung) confirms the diagnosis of Wegner's granulomatosis. Lung tissue provides the highest likelihood of making the diagnosis, however, biopsy may not be practical in all patients because of the associated risks.

Laboratory tests can be helpful in making the diagnosis of Wegner's granulomatosis. The presence of anti-neutrophil cytoplasmic antibodies in a classic or cytoplasmic pattern (c-ANCA) is highly specific (90%) and sensitive (50% to 100%, depending on disease extent) for Wegener's granulomatosis. Urinalysis is often used as a screening test and to assess kidney function. A chest X-ray is important since the lungs are frequently involved. Definitive diagnosis requires a biopsy.

Treatment

The goal of therapy in patients with Wegener's granulomatosis is control of the inflammation in the affected part of the body. In most cases, treatment consists of a combination of corticosteroids (for example, prednisone) and another immunosuppressant medication such as cyclophosphamide, methotrexate or azathioprine. Using a regimen of high dose prednisone along with cyclophosphamide, more than 90% of patients improve and 75% achieve long-term remissions. Unfortunately, 50% of these patients subsequently relapse. Recurrences of Wegener's are usually responsive to the same treatment that induced remission, but sometimes additional medications are required.

Cause of Condition

The cause of Wegener's granulomatosis is unknown. Although the exact mechanism of the disease is unclear, the high occurrence of respiratory tract involvement suggests affected patients may have an abnormal immune response to inhaled substances.

Prognosis

Until the 1970's, Wegener's granulomatosis was nearly always fatal. Untreated, the prognosis is very poor, with a mean survival of only 5 months. With appropriate treatment, the outlook for patients with Wegener's granulomatosis is generally good. Treatment with prednisone and cyclophosphamide leads to improvement in 90% of patients, though even with treatment, up to 13% of patients may die.

Research and Future Outlook

Since the 1970's, physicians at National Institute of Health have been testing novel therapies for Wegener's granulomatosis. Use of the combination of steroids with cyclophosphamide for treatment was recommended based on this work. Despite the success of these medicines, all have potentially serious side effects and cannot be tolerated by everybody.

Significant advances in understanding Wegener's disease have occurred recently. In the next few years scientific breakthroughs may lead to the design of more specific ways to treat patients with this disease.

The National Institute of Allergy and Infectious Diseases (NIAID) is currently conducting several studies to investigate new treatments for Wegner's granulomatosis. Although there are specific inclusion criteria, these studies are open to patients with definitive diagnosis of Wegener's granulomatosis and those with active disease. The following studies are currently available:

1.         Daclizumab to Treat Wegener's Granulomatosis

2.         Etanercept for Wegener's Granulomatosis

3.         Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases

4.         Analysis of Bronchial Tissue and Fluid in Patients with Wegener's Granulomatosis

5.         Comparison of Treatments to Maintain Disease Remission in Patients with Wegener's Granulomatosis and Related Vasculitis Syndromes

Further information about these studies may be found at http://www.niaid.nih.gov/dir/labs/lir/sneller.htm

[ Ana Sayfa ] [ Üst ]

Sorularınızı Dr.Emir@varis.org adresine yönlendiriniz.
Copyright © 2005 Damar Cerrahisi
Son yenileme: 09/04/08