Wegener's granulomatosis


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Wegener's Granulomatosis

 

Definition

Wegener's granulomatosis is a very rare disease that affects many different organs and systems of the body. It mainly attacks the respiratory system (sinuses, nose, windpipe, and the lungs) and the kidneys. One of the main features of the disease is an inflammation of the blood vessels (vasculitis). The inflammation narrows the blood vessels and reduces the blood flow to the affected organs. This destroys tissues and damages vital organs.

Description

Wegener's granulomatosis (WG) is not a contagious disease, and there is no evidence to suggest that it is hereditary either. It is a very rare disease, affecting only 1 in every 30,000-50,000 people. About 500 new cases are diagnosed each year. The disease can occur at any age, however, it mostly affects individuals in their 30s and 40s. It affects males and females equally. Ninety seven percent of all patients are Caucasian, 2% are Black and 1% are of another race.

Causes and symptoms

No viral, bacterial, or other causative agent has yet been identified for WG. It is thought to be an autoimmune disease, meaning that the body's immune system attacks "itself," that is, the body's own tissues.
Whenever there is an infection in the body, proteins called antibodies, which are capable of attacking the infectious agent, are formed in the blood. In WG, the antibodies that are formed are directed against the white blood cells of the immune system. They are therefore called "auto-antibodies" (antibodies against one's own body cells). These auto-antibodies bind to the blood cells and forms clumps known as immune complexes. The complexes accumulate in the tissues and the blood vessels, leading to a tumor-like (granulomatous) inflammation of the blood vessels. This slows down the blood flow to the different organs and tissues, causing damage and resulting in the many symptoms of WG.
The symptoms of WG, and the severity of the symptoms, vary from patient to patient. One of the most common features is a chronic runny nose and other cold-like symptoms that do not respond to standard treatment. The cold symptoms gradually worsen and could lead to sinusitis (inflammation of the sinuses), middle ear infection (otitis media), cough, coughing of blood, and inflammation of the lung (pleuritis and pneumonia). Other symptoms include fever, fatigue, loss of appetite, weight loss, joint pain, night sweats, change in urine color, and weakness.
Kidney (renal) disease is the most serious development of WG. Patients who do not have renal disease are said to have "Limited Wegener's."

Diagnosis

Early diagnosis is critical for the most effective treatment of the disease. However, there are no specific laboratory tests for WG. Blood tests are used to rule out other causes of the symptoms and to determine which organs are affected. The blood tests often show anemia (low red cell count) and high white blood cell counts. If the kidneys are involved, red blood cells are seen in the urine when viewed under a microscope. Also, blood tests aimed at measuring kidney function may show abnormalities.
Chest x rays are used to determine if the lungs are involved. Computed tomography scans (CT scans) of sinuses and lungs, and kidney biopsy, are also important tools used in diagnosing WG.
A specific type of antibody called anti-neutrophil cytoplasmic antibody (ANCA) is seen in the blood of about 90% of the patients with WG. The ANCA are a group of antibodies directed against the individual's own white blood cells (namely, the neutrophils). These anti-neutrophil cytoplasmic antibodies are also found in other inflammatory conditions and diseases (such as HIV infection). Though the ANCA test is useful, it cannot be used by itself to make a diagnosis of WG. However, the amount of ANCA in the blood can be measured and correlates well with the progression of the disease. When there is a relapse or a flare-up, the ANCA levels go up. Levels decrease when the disease is controlled by appropriate treatment.
Since there are no definitive laboratory tests for WG, and the initial symptoms of the disease are not very specific, it takes five-15 months, on an average, to make a diagnosis of WG.

Treatment

Cyclophosphamide (Cytoxan) which is an anticancer drug, and corticosteroids, such as prednisone, are used to treat WG. These are powerful drugs that suppress the immune system. However, they are also very toxic and can have serious side effects. The patient has to be watched carefully by the doctors and the dosage of the drugs has to be adjusted, if needed.
Since the patient's immune system is suppressed while on these drugs, he or she is at an increased risk for contracting infections. Vaccinations for flu and pneumonia are recommended.

Prognosis

In the past, approximately 80% of the patients with untreated WG died within a year of contracting the disease and 90% died within two years. Today, however, the prognosis has been dramatically improved. With appropriate treatment, patients can survive for much longer periods and lead relatively normal lives.
Approximately 50% of the patients with WG will have a relapse of the disease. This generally happens within two years of stopping the medication, but can occur at any point either during treatment or after stopping treatment. Therefore, it is extremely important that patients continue to see their doctors regularly even after stopping the medications.

Prevention

At present, there are no preventive measures known for Wegener's granulomatosis.

Key terms

Auto-antibodies — An antibody that is produced in, and reacts with, an antigen in the same person or animal.
Autoimmune disease — Any disease which causes tissue injury due to an immunological reaction of antibodies against the patient's own tissues.
Granulomatous — Resembling a tumor made of granular material.
Immune complexes — Clusters or aggregates of antigen and antibody bound together.
Vasculitis — Inflammation of the walls of the blood vessels.

Resources

Organizations

National Organization for Rare Disorders. P.O. Box 8923, New Fairfield, CT 06812-8923. (800) 999-6673. http://www.rarediseases.org.
Wegener's Foundation, Inc. 3705 South George Mason Drive, Suite 1813 South, Falls Church, VA 22041. (703) 931-5852.
Wegener's Granulomatosis Support Group, Inc. P.O. Box 28660, Kansas City, MO 64188-8660. (800) 277-9474. http://www.wgsg.org/wgsg.

granulomatosis

 [gran″u-lo″mah-to´sis]
any condition involving the formation of multiple granulomas.
allergic granulomatosis churg-strauss syndrome.
eosinophilic granulomatosis Langerhans cell histiocytosis.
Langerhans cell granulomatosis Langerhans cell histiocytosis.
lymphomatoid granulomatosis a multisystem disease involving predominantly the lungs, skin, central nervous system, and kidneys, caused by invasion and destruction of vessels by atypical lymphoreticular cells. Many affected patients develop frank lymphoma. It usually affects males, and the most frequent presenting symptoms are cough, shortness of breath, and chest pain. Extrapulmonary manifestations are common, with skin lesions being present in many cases.
granulomatosis sidero´tica a condition in which brownish nodules are seen in the enlarged spleen.
Wegener's granulomatosis a multisystem disease chiefly affecting males, characterized by necrotizing granulomatous vasculitis involving the upper and lower respiratory tracts, glomerulonephritis, and variable degrees of systemic, small vessel vasculitis, which is generally considered to represent an aberrant hypersensitivity reaction to an unknown antigen.

Wegener's granulomatosis

[wā′gənərz]
Etymology: Friedrich Wegener, German pathologist, 1907-1990; L, granulum, little grain; Gk, oma, tumor, osis, condition
an uncommon disease occurring mainly in the fifth decade and characterized by granulomatosis vasculitis of the upper and lower respiratory tract, necrotizing glomerulonephritis, and varying degrees of small-vessel vasculitis. Symptoms may include sinus pain; bloody, purulent nasal discharge; saddle-nose deformity; chest discomfort and cough; weakness; anorexia; weight loss; and skin lesions. Renal involvement is seen in 80% of cases. Use of cytotoxic drugs, especially cyclophosphamide, has produced long-term remissions in many patients. The cause of the disease is unknown.
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Wegener's granulomatosis

Wegener's granulomatosis

Midline granulomatosis, Wegener syndrome Internal medicine A rare condition characterized by small vessel
vasculitis and by granulomatous inflammation of the respiratory tract, formation of ANCA and necrotizing vasculitis of small-to-medium-sized
vessels–eg, capillaries, arteries, arterioles, and venules, which is often accompanied by necrotizing glomerulonephritis ; ♂:♀ ratio 2:1, middle aged population, hemoptysis, fever, rash, prostration, arthritis, neuropathy, splenomegaly, progressive glomerulonephritis ending in terminal renal failure Etiology Possibly hypersensitivity or autoimmunity Diagnosis Renal biopsy determines extent of renal involvement; open lung Bx of a solid or cavitating lesion DiffDx polyarteritis, vascular renal phase of SBE, rapidly or slowly progressive glomerulonephritis, SLE, and lethal midline granuloma–ie, lymphoma Clinical–early Sx anorexia, weight loss, fatigue, malaise, persistent FUO, night sweats, migratory polyarthritis, granulomatous skin lesions, proptosis, ocular manifestations with nasolacrimal duct obstruction, episcleritis, chondritis of ear, acute MI from vasculitis, aseptic meningitis and nonhealing granulomas of CNS may occur; upper respiratory tract complaints–ulcers, pneumonia, granulomas of oral cavity and periorbital regions, skin lesions; eye problems–eg, conjunctivitis; renal disease may be asymptomic, necrotizing hemorrhagic rhinorrhea, paranasal sinusitis, nasal ulcerations–with 2º bacterial infection, serous or purulent otitis media with hearing loss, cough, hemoptysis, pleuritis, and progressive dyspnea–later requiring O2; Pts usually present with a granuloma of nose that simulates chronic sinusitis; nasal mucosa is red, raised, granular, friable, bleeds easily, and may perforate; eventually, a disseminated vascular phase may develop and is associated with necrotizing inflammatory skin lesions, pulmonary lesions with cavitation, diffuse leukocytoclastic vasculitis, focal glomerulitis that may progress to generalized crescentic glomerulonephritis with HTN and uremia Lab Anemia may be profound; normal/ ↑ complement, ↑ ESR, leukocytosis, ↑ antineutrophilic cytoplasmic antibodies Urinalysis Proteinuria, hematuria, RBC casts Management side effects Cyclophosphamide–leukopenia, ergo infections; hemorrhagic cystitis; gonadal dysfunction; and some hair loss, reversible on discontinuing the drug Management Corticosteroids–eg, prednisone, MTX JAMA 1995; 273:1288gr, azathioprine, cyclophosphamide induces remission in 75%; long-term prophylactic T-S may be effective for upper respiratory tract lesions; kidney transplant if renal failure Prognosis Dramatically improved by immunosuppressants; ↑ solid tumors post high-dose cyclophosphamide; complete WG usually progresses rapidly to renal failure once diffuse vascular phase begins; Pts with the limited form of the disease may have nasal and pulmonary lesions, with little or no systemic involvement. See Small vessel vasculitis, Systemic vasculitis.

Wegener's granulomatosis

A form of AUTOIMMUNE small blood vessel disease in which local masses of cells, blood capillaries and fibrous tissue (granulation tissue) form in the nose, the kidneys, the lungs and the heart. These masses cause local damage and become gangrenous. Symptoms include nose-bleeds, blood in the urine (haematuria) and chest pain. The condition may progress to kidney failure. Treatment is with cyclophosphamide. (F. Wegener, German pathologist, b. 1907).

scleritis 

Inflammation of the sclera, which in its severe necrotizing or in the posterior type may cause sight-threatening complications such as keratitis, uveitis, angle-closure glaucoma or optic neuropathy. It affects females more commonly than males in the fourth to sixth decades of life. Like episcleritis it has a tendency to recur. It is characterized by pain, which can be severe, redness, tearing and some patients may develop nodules (nodular scleritis). It is often associated with a systemic disease (e.g. rheumatoid arthritis, Wegener's granulomatosis, polyarteritis nodosa, lupus erythematosus, ankylosing spondylitis, syphilis, herpes zoster). It can involve part of the sclera, e.g. anterior scleritis (which is the most common, and it is classified as diffuse non-necrotizing or nodular non-necrotizing) or posterior scleritis. Treatment includes topical and systemic steroids and immunosuppressive drugs for very severe cases. See acute stromal keratitis; Brown's superior oblique tendon sheath syndrome.
necrotizing scleritis The most severe form of scleritis, much less common than the other types. About half the patients have one of the following diseases: rheumatoid arthritis, Wegener's granulomatosis, polyarteritis nodosa, systemic lupus erythematosus, or herpes zoster. It is characterized by pain, and white, avascular areas next to damaged areas through which one can see the brown colour of the underlying uveal tissue, and to congested areas of the sclera. In most cases visual acuity is decreased. The necrosis gradually spreads around the globe. Treatment typically consists of topical steroids, immunosuppressive agents and occasionally surgery to repair scleral or corneal perforation. See keratolysis; scleromalacia.
scleritis necroticans See scleromalacia.
posterior scleritis Inflammation of the sclera involving the posterior segment of the eye. The condition is often associated with a systemic disease (e.g. rheumatoid arthritis). It is characterized by pain and reduced visual acuity. The severity of the visual impairment depends on the involved tissue and its location. Signs include eyelid oedema, proptosis, limitation of ocular movements and, if anterior scleritis is present, redness. The ocular fundus may present disc swelling, choroidal folds, macular oedema and serous retinal detachment. Treatment consists mainly of systemic steroids and immunosuppressive agents. See choroidal folds.

granulomatosis

the formation of multiple granulomas.

lymphomatoid granulomatosis
a lymphohistiocytic proliferative disorder in dogs, usually involving viscera but occasionally including skin lesions.
Wegener's granulomatosis
a mononuclear granulomatous disease characterized by granulomatous inflammation and necrotizing vasculitis.
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