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'{{redirect|Goodpasture}} {{Infobox medical condition | Name = Goodpasture syndrome | Image = Crescentic glomerulonephritis - high mag.jpg | Caption = [[Micrograph]] of a [[crescentic glomerulonephritis]] that was shown to be antiglomerular basement membrane disease, [[PAS stain]]| DiseasesDB = 5363 | ICD10 = {{ICD10|M|31|0|m|30}} ([[ILDS]] M31.010) | ICD9 = {{ICD9|446.21}} | ICDO = | OMIM = 233450 | MedlinePlus = 000142 | eMedicineSubj = med | eMedicineTopic = 923 | eMedicine_mult = {{eMedicine2|ped|888}} | MeshID = D019867 | }} '''Goodpasture syndrome''' (GPS; also known as '''Goodpasture’s disease''', '''antiglomerular basement antibody disease''', or '''anti-GBM disease''') is a [[rare disease|rare]] [[autoimmune disease]] in which antibodies attack the [[basement membrane]] in lungs and kidneys, leading to bleeding from the lungs and [[kidney failure]]. It is thought to attack the alpha-3 subunit of [[type IV collagen]], which has therefore been referred to as Goodpasture's antigen.<ref>http://ghr.nlm.nih.gov/gene/COL4A3</ref> Goodpasture syndrome may quickly result in permanent lung and kidney damage, often leading to death. It is treated with immunosuppressant drugs such as [[corticosteroid]]s and [[cyclophosphamide]], and with [[plasmapheresis]], in which the antibodies are removed from the blood. The disease was first described by an American pathologist [[Ernest Goodpasture]] of [[Vanderbilt University]], in 1919 and was later named in his honor.<ref>{{cite journal | author=Goodpasture EW | title=The significance of certain pulmonary lesions in relation to the etiology of influenza | journal=Am J Med Sci | year=1919 | volume=158 | pages=863–870 | doi=10.1097/00000441-191911000-00012 | issue=6}}</ref><ref>{{cite journal |vauthors=Salama AD, Levy JB, Lightstone L, Pusey CD |title=Goodpasture's disease |journal=Lancet |volume=358 |issue=9285 |pages=917–920 |date=September 2001 |pmid=11567730 |doi=10.1016/S0140-6736(01)06077-9}}</ref> ==Signs and symptoms== The anti[[glomerular basement membrane]] (GBM) [[antibodies]] primarily attack the kidneys and lungs, although, generalized symptoms like malaise, weight loss, fatigue, fever, and chills are also common, as are joint aches and pains.<ref name = PMSR>{{cite web|title=Goodpasture Syndrome Clinical Presentation|work=Medscape Reference|publisher=WebMD|date=21 May 2013|accessdate=14 March 2014|url=http://emedicine.medscape.com/article/240556-clinical#showall|editor=Batuman, C|author1=Kathuria, P |author2=Sanghera, P |author3=Stevenson, FT |author4=Sharma, S |author5=Lederer, E |author6=Lohr, JW |author7=Talavera, F |author8=Verrelli, M }}</ref> 60 to 80% of those with the condition experience both lung and kidney involvement; 20-40% have kidney involvement alone, and less than 10% have lung involvement alone.<ref name = PMSR/> Lung symptoms usually antedate kidney symptoms and usually include: [[hemoptysis|coughing up blood]], chest pain (in less than 50% of cases overall), cough, and [[dyspnoea|shortness of breath]].<ref name = MM>{{cite web|title=Goodpasture Syndrome: Diffuse Alveolar Hemorrhage and Pulmonary-Renal Syndrome|work=Merck Manual Professional|date=November 2013|accessdate=14 March 2014|url=http://www.merckmanuals.com/professional/pulmonary_disorders/diffuse_alveolar_hemorrhage_and_pulmonary-renal_syndrome/goodpasture_syndrome.html|author=Schwarz, MI}}</ref> Kidney symptoms usually include [[hematuria|blood in the urine]], [[proteinuria|protein in the urine]], [[edema|unexplained swelling of limbs or face]], [[uremia|high amounts of urea in the blood]], and [[hypertension|high blood pressure]].<ref name = PMSR/> ==Cause== Its precise cause is unknown, but an insult to the blood vessels taking blood from and to the lungs is believed to be required to allow the anti-GBM antibodies to come into contact with the [[alveoli]].<ref name = MSR>{{cite web|title=Goodpasture Syndrome|work=Medscape Reference|publisher=WebMD|date=21 May 2013|accessdate=14 March 2014|url=http://emedicine.medscape.com/article/240556-overview#showall|editor=Batuman, C|author1=Kathuria, P |author2=Sanghera, P |author3=Stevenson, FT |author4=Sharma, S |author5=Lederer, E |author6=Lohr, JW |author7=Talavera, F |author8=Verrelli, M }}</ref> Examples of such an insult include:<ref name = MSR/> {{colbegin|2}} * Exposure to organic solvents (e.g. [[chloroform]]) or hydrocarbons * Exposure to [[tobacco]] smoke * Certain gene mutations (''[[HLA-DR15]]'') * Infection, such as [[influenza A]] * Cocaine inhalation * Metal dust inhalation * [[Bacteraemia]] * [[Sepsis]] * High-oxygen environments * Treatment with antilymphocytic treatment (especially [[monoclonal antibodies]]) {{colend}} ==Pathophysiology== GPS causes the abnormal production of anti-GBM antibodies, by the [[plasma cells]] of the blood.<ref name = MSR/> The anti-GBM antibodies attack the alveoli and [[glomeruli]] basement membranes.<ref name = MSR/> These antibodies bind their reactive [[epitopes]] to the basement membranes and activate the complement cascade, leading to the death of tagged cells.<ref name = MSR/> [[T cells]] are also implicated.<ref name = MSR/> It is generally considered a type II hypersensitivity reaction.<ref name = MSR/> ==Diagnosis== The diagnosis of GPS is often difficult, as numerous other diseases can cause the various manifestations of the condition and the condition itself is rare.<ref name = WMSR>{{cite web|title=Goodpasture Syndrome Workup|work=Medscape Reference|publisher=WebMD|date=21 May 2013|accessdate=14 March 2014|url=http://emedicine.medscape.com/article/240556-workup#showall|editor=Batuman, C|author1=Kathuria, P |author2=Sanghera, P |author3=Stevenson, FT |author4=Sharma, S |author5=Lederer, E |author6=Lohr, JW |author7=Talavera, F |author8=Verrelli, M }}</ref> The most accurate means of achieving the diagnosis is testing the affected tissues by means of a [[biopsy]], especially the kidney, as it is the best-studied organ for obtaining a sample for the presence of anti-GBM antibodies.<ref name = WMSR/> On top of the anti-GBM antibodies implicated in the disease, about one in three of those affected also has [[c-ANCA|cytoplasmic antineutrophilic antibodies]] in their bloodstream, which often predates the anti-GBM antibodies by about a few months or even years.<ref name = WMSR/> The later the disease is diagnosed, the worse the outcome is for the affected person.<ref name = MSR/> ==Treatment== The major mainstay of treatment for GPS is [[plasmapheresis]], a procedure in which the affected person's blood is sent through a [[centrifuge]] and the various components separated based on weight.<ref name = TMSR/> The [[Blood plasma|plasma]], clear liquid part of the blood, contains the anti-GBM antibodies that attacks the affected person's lungs and kidneys and is filtered out.<ref name = TMSR/> The other parts of the blood, that is, the [[red blood cells]], [[white blood cells]], and [[platelets]], are recycled and given intravenously as a replacement fluid.<ref name = TMSR>{{cite web|title=Goodpasture Syndrome Treatment & Management|work=Medscape Reference|publisher=WebMD|date=21 May 2013|accessdate=14 March 2014|url=http://emedicine.medscape.com/article/240556-treatment#showall|editor=Batuman, C|author1=Kathuria, P |author2=Sanghera, P |author3=Stevenson, FT |author4=Sharma, S |author5=Lederer, E |author6=Lohr, JW |author7=Talavera, F |author8=Verrelli, M }}</ref> Most individuals affected by the disease also need to be treated with [[immunosuppressant]] drugs, especially [[cyclophosphamide]], [[prednisone]], and [[rituximab]], to prevent the formation of new anti-GBM antibodies so as to prevent further damage to the kidneys and lungs.<ref name = TMSR/> Other, less toxic immunosuppressants such as [[azathioprine]] may be used to maintain remission.<ref name = TMSR/> ==Prognosis== With treatment the five-year survival rate is >80% and fewer than 30% of affected individuals require long-term dialysis.<ref name = MSR/> A study performed in [[Australia]] and [[New Zealand]] demonstrated that in patients requiring renal replacement therapy (including dialysis) the median survival time is 5.93 years.<ref name = MSR/> Without treatment, virtually every affected person will end up dying from either advanced kidney failure or lung hemorrhages.<ref name = MSR/> ==Epidemiology== GPS is rare, affecting about 0.5-1.8 per million people per year in Europe and Asia.<ref name = MSR/> It is also unusual among [[autoimmune disease]]s in that it is more common in males than in females and is also less common in blacks than whites, but more common in the [[Māori people]] of New Zealand.<ref name = MSR/> The peak age ranges for the onset of the disease are 20-30 and 60–70 years.<ref name = MSR/> ==See also== * [[HLA-DR#DR2]] * [[Pulmonary-renal syndrome]] ==References== {{reflist|2}} ==External links== *[http://www.antibodypatterns.com/gbm.php GBM antibodies: immunofluorescence image] {{Systemic vasculitis}} {{Autoimmune diseases}} {{Collagen disease}} {{Urologic disease}} [[Category:Autoimmune diseases]] [[Category:Kidney diseases]] [[Category:Rare diseases]] [[Category:Systemic connective tissue disorders]]'