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| '''For patient information click [[{{PAGENAME}} (patient information)|here]]'''
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| {{DiseaseDisorder infobox |
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| Name = Wegener's granulomatosis |
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| Image = Wegner's-granulomatosis-001.jpg|
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| Caption = |
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| ICD10 = {{ICD10|M|31|3|m|30}} |
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| ICD9 = {{ICD9|446.4}} |
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| ICDO = |
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| OMIM = |
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| DiseasesDB = 14057 |
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| MedlinePlus = 000135 |
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| eMedicineSubj = |
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| eMedicineTopic = |
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| MeshID = D014890 |
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| }}
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| {{Wegener's granulomatosis}} | | {{Wegener's granulomatosis}} |
| {{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}
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| ===Click [[The Heart in Wegener's Granulomatosis|here]] for The heart in Wegener's granulomatosis===
| | '''For patient information click [[Wegener's granulomatosis (patient information)|here]]''' |
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| | '''Click [[The Heart in Wegener's Granulomatosis|here]] for The heart in Wegener's granulomatosis''' |
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| | {{CMG}}{{APM}}{{AE}}{{ADS}}{{KW}}{{CZ}} |
| ==[[Wegener's granulomatosis overview|Overview]]== | | ==[[Wegener's granulomatosis overview|Overview]]== |
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| ==[[Wegener's granulomatosis historical perspective|Historical Perspective]]== | | ==[[Wegener's granulomatosis historical perspective|Historical Perspective]]== |
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| | ==[[Granulomatosis with polyangiitis classification|Classification]]== |
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| ==[[Wegener's granulomatosis pathophysiology|Pathophysiology]]== | | ==[[Wegener's granulomatosis pathophysiology|Pathophysiology]]== |
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| ==[[Wegener's granulomatosis epidemiology and demographics|Epidemiology]]==
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| ==[[Wegener's granulomatosis risk ractors|Risk Factors]]==
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| ==[[Wegener's granulomatosis screening|Screening]]==
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| ==[[Wegener's granulomatosis causes|Causes]]== | | ==[[Wegener's granulomatosis causes|Causes]]== |
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| ==[[Wegener's granulomatosis differential diagnosis|Differential diagnosis]]== | | ==[[Wegener's granulomatosis differential diagnosis|Differentiating Wegener's granulomatosis from other Diseases]]== |
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| ==[[Wegener's granulomatosis natural history|Natural History, Complications & Prognosis]]== | | ==[[Wegener's granulomatosis epidemiology and demographics|Epidemiology and Demographics]]== |
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| ==Diagnosis== | | ==[[Wegener's granulomatosis risk factors|Risk Factors]]== |
| [[Wegener's granulomatosis history and symptoms|History and Symptoms]] [[Wegener's granulomatosis other imaging findings|Other Imaging Findings]] | |
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| ==Treatment== | | ==[[Wegener's granulomatosis screening|Screening]]== |
| Before steroid treatment became available, mortality within one year was over 90%, with average survival being 5 months. Steroids prolonged average survival to 8 months. The introduction of [[cyclophosphamide]] (CYC) in the 1970s was a major breakthrough.<ref name=Bosch>{{cite journal |author=Bosch X, Guilabert A, Espinosa G, Mirapeix E |title=Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review |journal=JAMA |volume=298 |issue=6 |pages=655–69 |year=2007 |pmid=17684188 |doi=10.1001/jama.298.6.655}}</ref>
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| Initial treatment is generally with [[corticosteroids]] and oral [[cyclophosphamide]] (CYC), 1 mg/kg/day and 2 mg/kg/day, respectively. Occasionally CYC is given in monthly intravenous (IV) doses. Monitoring of the [[white blood cell|white blood count]] is essential during CYC therapy. Once remission is attained (normally 3 to 6 months), treatment is frequently changed to [[azathioprine]] or [[methotrexate]], which are less toxic drugs. Total duration of therapy should be at least one year, or longer in high risk patients. Corticosteroids are tapered to a low maintenance dose, 5-10 mg/day. [[Plasmapheresis]] may be beneficial in severe disease or [[pulmonary hemorrhage]]. Experience with other treatment agents is very limited.<ref name=Seo/>.
| | ==[[Wegener's granulomatosis natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| A [[systematic review]] of 84 trials examined the evidence for various treatments in Wegener's granulomatosis. Many trials include data on pooled groups of patients with Wegener's and microscopic polyangiitis. In this review, cases are divided between localized disease, non-organ threatening, generalized organ-threatening disease and severe renal vasculitis and immediately life-threatening disease.<ref name=Bosch/>
| | == Diagnosis == |
| * In localized disease, treatment with the antibiotic [[co-trimoxazole]] is recommended, with steroids in case of treatment failure.<ref name="pmid8637536">{{cite journal |author=Stegeman CA, Tervaert JW, de Jong PE, Kallenberg CG |title=Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch Co-Trimoxazole Wegener Study Group |journal=N. Engl. J. Med. |volume=335 |issue=1 |pages=16–20 |year=1996 |pmid=8637536 |doi= |url=http://content.nejm.org/cgi/content/abstract/335/1/16}}</ref>
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| * In generalized non-organ threatening disease, remission can be induced with [[methotrexate]] and steroids, where the steroid dose is reduced after a remission has been achieved and methotrexate used as maintenance.
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| * In case of organ-threatening disease, pulsed [[intravenous]] cyclophosphamide with steroids is recommended. Once remission has been achieved, [[azathioprine]] and steroids can be used to maintain remission.
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| * In severe renal vasculitis, the same regimen is used but with the addition of plasma exchange.
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| * In [[pulmonary hemorrhage]], high doses of cyclophosphamide with pulsed [[methylprednisolone]] may be used, or alternatively CYC, steroids, and plasma exchange.
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| In severe disease not responsive to previously mentioned treatment, the review is positive about [[mycophenolate mofetil]], 15-deoxyspergualin, [[anti-thymocyte globulin]], [[rituximab]] and [[infliximab]]; data was less favourable for [[intravenous immunoglobulin]] (IVIG) and [[etanercept]].<ref name=Bosch/>
| | [[Wegener's granulomatosis diagnostic criteria|Diagnostic Criteria]] | [[Wegener's granulomatosis history and symptoms| History and Symptoms]] | [[Wegener's granulomatosis physical examination | Physical Examination]] | [[Wegener's granulomatosis laboratory findings| Laboratory Findings]] | [[Wegener's granulomatosis chest x ray|Chest X Ray]] | [[Wegener's granulomatosis CT|CT]] | [[Wegener's granulomatosis other diagnostic studies|Other Diagnostic Studies]] |
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| In some patients with severe subglottic stenosis, [[tracheotomy]] is required to maintain an airway.
| | ==Treatment== |
| | | [[Wegener's granulomatosis medical therapy|Medical Therapy]] | [[Wegener's granulomatosis surgery|Surgery]] | [[Wegener's granulomatosis primary prevention|Primary Prevention]] | [[Wegener's granulomatosis secondary prevention|Secondary Prevention]] | [[Wegener's granulomatosis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Wegener's granulomatosis future or investigational therapies|Future or Investigational Therapies]] |
| With the appropriate treatment, the outlook is good for people with Wegener's granulomatosis. In a study of 158 patients who were treated with prednisone and cyclophosphamide at the National Institutes of Health (NIH), 91 percent of them markedly improved. After 6 months to 24 years of follow-up, 80 percent of the patients survived.
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| In most cases, treatment consists of a combination of a glucocorticoid (a steroid) and a cytotoxic medicine. Although these medicines are helpful in treating Wegener's granulomatosis, people and their doctors should be aware that they potentially have serious side effects. In many instances these can be minimized or prevented by careful monitoring by both the doctor and patient.
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| Approximately half of people with Wegener's granulomatosis may experience a return of their disease. This occurs most frequently within 2 years of stopping medicine but can occur at any point both during treatment or after stopping treatment. Thus, it is extremely important that people continue to see their doctors regularly, both while they are on these medicines, as well as after the medicines have been stopped.
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| ===Prednisone=== | |
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| Prednisone is the most common glucocorticoid that doctors use. Prednisone is similar to cortisol, the natural glucocorticoid hormone produced by the body. It is chemically different from the anabolic steroids that have been used by athletes and is given in doses much higher than the body normally produces. Doctors usually give prednisone as a single morning dose to try to imitate how the body normally secretes cortisol.
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| When the person's illness improves, the prednisone dose is gradually decreased and converted to an every other day dosing schedule, usually over a period of 3 to 4 months. With further improvement in the disease, prednisone is gradually decreased and discontinued completely after approximately 6 to 12 months.
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| When prednisone is taken by mouth, the body stops making its own natural cortisol. As the prednisone dose is gradually reduced, the body will resume making cortisol again. It is extremely important that prednisone never be stopped suddenly because the body requires prednisone (or cortisol) to function and may not be able to immediately make what it needs.
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| Prednisone can affect the body's ability to fight off infection. People taking this medicine should report immediately any symptoms of infection and specifically, any fever to their doctors. Prednisone can also cause weight gain, cataracts, brittle bones, diabetes, and changes in mood and personality.
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| ===Cyclophosphamide===
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| Cyclophosphamide (Cytoxan) is the most commonly used cytotoxic drug used to treat Wegener's granulomatosis. People take cyclophosphamide once a day by mouth and must take the drug all at once in the morning followed by drinking a large amount of liquid. Although the first dose of cyclophosphamide is based on the person's weight and kidney function, the doctor may adjust the dosage based on blood counts, which are monitored closely to be sure that the white blood cell count is maintained at a safe level.
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| In the original regimen, cyclophosphamide was continued for a full year beyond that point at which the disease was in remission. The dose of cyclophosphamide was then decreased gradually and eventually stopped. In more recent treatment approaches, however, cyclophosphamide is given until remission and then switched to another medicine such as methotrexate or azathioprine (discussed below).
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| Cyclophosphamide is a powerful medicine that keeps the immune system from working normally. Doctors must monitor their patients carefully and perform blood tests frequently. Cyclophosphamide can cause an increased risk of infection, bone marrow suppression (lowering of blood counts), sterility, hemorrhagic cystitis (bleeding from the bladder), bladder cancer, as well as other serious side effects.
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| ===Methotrexate===
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| Methotrexate has been studied at NIH for the treatment of Wegener's granulomatosis since 1990. In people with active, but not immediately life threatening, Wegener's granulomatosis, methotrexate has been used in combination with prednisone to bring about remission. It also is used to maintain remission after a person has initially received cyclophosphamide. Methotrexate is usually given for 1 to 2 years, after which time if people stay in remission, it is decreased and stopped.
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| Methotrexate is given once a week usually by mouth, but occasionally as an injection under the skin or in the muscle. People taking methotrexate need to have regular blood work to monitor their response and to watch for side effects.
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| The side effects of methotrexate include infection, lowering of the blood counts, nausea, soreness and ulceration of the mouth lining, irritation of the lungs (pneumonitis), and inflammation and scarring of the liver. People taking methotrexate cannot drink alcoholic beverages. Methotrexate cannot be given to people who have poor kidney function or who have underlying liver disease such as hepatitis.
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| ===Azathioprine===
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| Azathioprine (also called Imuran) is used primarily to maintain remission in people who have initially been treated and gone into remission with cyclophosphamide. It is taken once a day by mouth. Similar to methotrexate, it is usually given for 1 to 2 years after which time the dosage is lowered until it is stopped.
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| The side effects of azathioprine include infection, lowering of the blood counts, and rarely an allergic type reaction. In people who receive azathioprine to prevent rejection of a transplanted organ, there has been a suggestion of an increased risk of blood cancers (leukemia and lymphoma) but it is not clear whether this risk exists in other situations. People with poor kidney function or liver disease can take azathioprine.
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| ===Other medicines===
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| During the course of treating Wegener's granulomatosis, doctors often give their patients other medicines to prevent medicine-related side effects. These include
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| * Trimethoprim/sulfamethoxazole (also called bactrim or septra) is given three times a week to prevent Pneumocystis carinii infection (a lung infection)
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| * A medicine regimen is often given to prevent prednisone-related bone loss (osteoporosis)
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| * Folic acid or folinic acid (also called leucovorin) are often given to people taking methotrexate
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| ===Follow-up===
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| General well-being and laboratory organ markers are checked on a regular basis to ascertain the patient has remained in remission.
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| ==Prognosis==
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| 25 to 40% of patients suffer from flare-ups, but a majority responds well to treatment. Anatomical problems ([[sinusitis]], tracheal stenosis) may require surgery in a small proportion. Relapses can be long and troublesome.
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| Long-term complications are very common (86%): mainly [[chronic renal failure]], hearing loss and [[deafness]].<ref name=Seo/>
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| ==References==
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| {{Reflist|2}}
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| ==External links==
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| * [http://www.rheumatology.org/publications/classification/wegener.asp?aud=mem Classification criteria] by the American College of Rheumatology
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| * [http://vasculitisfoundation.org Vasculitis Foundation] Formerly the Wegener's Granulomatosis Association
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| * [http://www.weareb.org/WG/ Wegener's Granulomatosis Info]
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| * [http://wegenersnet.org WegenersNet] A Wegener's Granulomatosis Community Portal
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| {{Diseases of the musculoskeletal system and connective tissue}}
| | ==Case Studies== |
| {{Symptoms and signs}}
| | [[Wegener's granulomatosis case study one|Case #1]] |
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| [[fr:Granulomatose de Wegener]] | | [[fr:Granulomatose de Wegener]] |
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| [[Category:Pulmonology]] | | [[Category:Pulmonology]] |
| [[Category:Autoimmune diseases]] | | [[Category:Autoimmune diseases]] |
| [[Category:Signs and symptoms]]
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