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Goodpasture Syndrome

Goodpasture's Syndrome

Goodpasture syndrome is a rare autoimmune disease characterized by diffuse pulmonary hemorrhage and acute or rapidly progressive glomerulonephritis.


Presentation

Up to 80% of individuals with Goodpasture syndrome exhibit both respiratory and renal symptoms. Acute presentation of symptoms occurs more frequently than chronic symptoms. An individual may initially complain of loss of appetite, fatigue and weakness. Renal involvement is accompanied by blood in urine, difficulty while urination, nausea, pallor and edema of extremities. Pulmonary involvement includes dry cough with shortness of breath and coughing out blood [26].

Rapidly Progressive Glomerulonephritis
  • From Wikidata Jump to navigation Jump to search hypersensitivity reaction type II disease that is characterized by glomerulonephritis located in kidney and hemorrhaging located in lung anti-glomerular basement membrane disease Rapidly progressive glomerulonephritis[wikidata.org]
  • Abstract Goodpasture (GP) syndrome is a form of anti-glomerular basement membrane (GBM) disease, in which autoantibodies bind to alpha3(IV) collagen in GBM causing rapidly progressive glomerulonephritis and pulmonary hemorrhage.[ncbi.nlm.nih.gov]
  • Plasmapheresis is the most important part of the therapies for Goodpasture's syndrome and anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis which are causes of rapidly progressive glomerulonephritis.[ncbi.nlm.nih.gov]
  • Serologic evidence of both p-ANCA and anti-GBM antibodies are becoming more frequently recognized in the setting of rapidly progressive glomerulonephritis.[ncbi.nlm.nih.gov]
  • The overall and renal outcomes of patients with Goodpasture syndrome (GS), a rare autoimmune disorder characterized by circulating anti-GBM antibodies and rapidly progressive glomerulonephritis and/or pulmonary hemorrhage, have mostly been reported in[ncbi.nlm.nih.gov]
Anemia
  • Abstract In its characteristic form Goodpasture's syndrome is a disease of young white men, who develop fulminating glomerulonephritis, hemorrhagic pneumonitis, and severe anemia.[annals.org]
  • Anemia from pulmonary bleeding is usual. Radiographic examination reveals diffuse bilateral alveolar filling. The diagnosis is made on the basis of renal biopsy.[histopathology-india.net]
  • Diagnostic Tests: Laboratory studies often reveal an anemia that may be related to both anemia of chronic disease and iron deficiency, depending on the severity and chronicity of the pulmonary hemorrhage. Patients may also be hypoxic.[rheumaknowledgy.com]
  • Blood testing often shows anemia. Laboratory tests reveal the characteristic antibodies in the blood. Doctors usually remove a small piece of kidney tissue (biopsy) for analysis.[merckmanuals.com]
Fever
  • The patient has intermittent fever and cough for 45 days and oliguria for 6 days.[ncbi.nlm.nih.gov]
  • Symptoms include the following: Constitutional symptoms (eg, malaise, chills and fever, arthralgias) may precede or develop concurrently with pulmonary or renal manifestations Hemoptysis is the presenting symptom when the disease affects the lungs.[emedicine.medscape.com]
  • Other common symptoms include Dyspnea Cough Fatigue Fever Weight loss Hematuria Up to 40% of patients have gross hematuria, although pulmonary hemorrhage may precede renal manifestations by weeks to years.[merckmanuals.com]
  • University in 1919 and was later named in his honor. [2] [3] Signs and symptoms [ edit ] The anti glomerular basement membrane (GBM) antibodies primarily attack the kidneys and lungs, although, generalized symptoms like malaise, weight loss, fatigue, fever[en.wikipedia.org]
  • The most common symptom of Goodpasture syndrome is Coughing up blood (hemoptysis) Other symptoms of Goodpasture syndrome include Shortness of breath Cough Fever Unplanned weight loss Fatigue Blood in the urine Fatigue and paleness (pallor) may be symptoms[merckmanuals.com]
Leg Edema
  • (edema swelling) Tests to diagnose the syndrome Urinalysis.[quizlet.com]
Intermittent Fever
  • The patient has intermittent fever and cough for 45 days and oliguria for 6 days.[ncbi.nlm.nih.gov]
Cough
  • Pulmonary involvement includes dry cough with shortness of breath and coughing out blood. A physical exam is first conducted assess any signs of respiratory or renal discomfort.[symptoma.com]
  • The patient has intermittent fever and cough for 45 days and oliguria for 6 days.[ncbi.nlm.nih.gov]
  • As the disease advances, the lung symptoms are: Dry cough Coughing up blood Difficulty breathing If the kidneys are affected, symptoms include: Burning sensation during urination Blood in the urine High blood pressure Edema (swollen body parts) Low urine[davita.com]
  • The most common symptom of Goodpasture syndrome is Coughing up blood (hemoptysis) Other symptoms of Goodpasture syndrome include Shortness of breath Cough Fever Unplanned weight loss Fatigue Blood in the urine Fatigue and paleness (pallor) may be symptoms[merckmanuals.com]
  • Other common symptoms include Dyspnea Cough Fatigue Fever Weight loss Hematuria Up to 40% of patients have gross hematuria, although pulmonary hemorrhage may precede renal manifestations by weeks to years.[merckmanuals.com]
Hemoptysis
  • Smoking in young men may trigger anti-GBM disease manifesting with hemoptysis.[ncbi.nlm.nih.gov]
  • Symptoms are dyspnea, cough, fatigue, hemoptysis, and hematuria. Goodpasture syndrome is suspected in patients with hemoptysis or hematuria and is confirmed by the presence of anti-GBM antibodies in the blood or in a renal biopsy specimen.[merckmanuals.com]
  • The patient had known glomerulonephritis and hemoptysis.[learningradiology.com]
  • The level of hemoptysis may vary and, in a small percentage of patients, may be absent.[emedicine.medscape.com]
Dyspnea
  • Other common symptoms include Dyspnea Cough Fatigue Fever Weight loss Hematuria Up to 40% of patients have gross hematuria, although pulmonary hemorrhage may precede renal manifestations by weeks to years.[merckmanuals.com]
  • List ranges from Dyspnea to Glomerulonephritis and more.[ranker.com]
  • Patients may present with cough, dyspnea, hemoptysis and hypoxia. Pulmonary manifestations are usually the cause of presentation although most also have evidence of renal disease.[radiopaedia.org]
Rales
  • […] hemosiderin The alveolar haemorrhage syndrome is an acute condition, which requires diagnosis and rapid and efficient treatment for the multiple clinical manifestations (dysp-noea, coughing up blood, auscultation of bilateral basal crepitant and subcrepitant rales[pneumologia.eu]
Tachypnea
  • […] manifestations include hematuria, edema, high blood pressure and eventually uremia Significant anemia may result from persistent intrapulmonary bleeding Physical Examination Physical examination findings in patients with anti-GBM disease include the following: Tachypnea[emedicine.medscape.com]
Vomiting
  • The symptoms of Goodpasture syndrome may initially include fatigue, nausea, vomiting, and weakness.[niddk.nih.gov]
  • Incidence: 1-2/1,000,000 most commonly occurs in early adulthood Men 8x than women People who smoke people who use hair dyes fatigue, nausea, vomiting, weakness, and pale skin bloody urine, foamy urine, and burning sensation when urinating high blood[quizlet.com]
  • […] have blood or protein in your urine suffer from back pain below your ribs go to the bathroom more often, especially at night have burning or difficulty when urinating have swelling of the hands and feet experience high blood pressure. have nausea and vomiting[kidneyhi.org]
  • Lung symptoms may include: Coughing up blood Dry cough Shortness of breath Kidney and other symptoms include: Bloody urine Burning sensation when urinating Nausea and vomiting Pale skin Swelling (edema) in any area of the body, especially in the legs[nlm.nih.gov]
Hematuria
  • Other common symptoms include Dyspnea Cough Fatigue Fever Weight loss Hematuria Up to 40% of patients have gross hematuria, although pulmonary hemorrhage may precede renal manifestations by weeks to years.[merckmanuals.com]
  • Renal Symptomology Inflammation of the glomerulus initiates the pathogenesis of a nephritic syndrome with symptomology of hematuria, pyuria, secondary hypertension , oliguria, and azotemia (See nephritic syndrome page).[pathwaymedicine.org]
  • Renal Symptomology Inflammation of the glomerulus initiates the pathogenesis of a nephritic syndrome with symptomology of hematuria, pyuria, secondary hypertension, oliguria, and azotemia (See nephritic syndrome page).[pathwaymedicine.org]
  • The anti-GBM antibody titer is indicated when patients have acute renal failure, pulmonary hemorrhage and/or rising serum creatine concentrations with hematuria (Hellmark et al ., 1997).[bio.davidson.edu]

Workup

A physical exam is first conducted assess any signs of respiratory or renal discomfort. Urinalysis reveals abnormal finding such as presence of red blood cells and protein in the urine.

An important diagnostic test to determine evidence of the syndrome is testing the serum for anti-glomerular basement membrane antibodies. A positive antibody test confirms Goodpasture syndrome.

Other tests are used to confirm symptoms such as tests for serum BUN and creatnine levels, chest X-rays, arterial blood gas analysis are carried out. Kidney biopsies are preferred over lung biopsies to assist in diagnosis as signs of crescent formation, glomerular membrane damage, interstitial fibrosis and tubular atrophy can determine extent of renal injury [27] [28].

Pulmonary Infiltrate
  • A 68-year-old Caucasian woman presented to the hospital with nodular pulmonary infiltrates and acute renal failure.[ncbi.nlm.nih.gov]
  • SUPPORTING VENTILATION The breakdown of the permeability of the alveolar basement membrane causes pulmonary infiltrates and hemorrhage, so the patient with Goodpasture's syndrome may need to be intubated and mechanically ventilated to maintain a patent[the-medical-dictionary.com]
  • Pulmonary function tests and bronchoalveolar lavage are not diagnostic but can be used to help confirm diffuse alveolar hemorrhage in patients with glomerulonephritis and pulmonary infiltrates but without hemoptysis.[merckmanuals.com]
  • Pulmonary manifestations include dyspnea, cough, sometimes hemoptysis, pulmonary infiltrates on chest x-ray, and an increased carbon monoxide diffusing capacity (DLCO) due to the presence of hemoglobin in the alveoli.[ispub.com]
HLA-DRw2
  • Individuals carrying alleles HLA-DRW2, HLA-DRB4 and HLA-DRB1 within the Major Histocompatibility Complex (MHC) locus are susceptible to events that trigger autoantibody activation.[symptoma.com]
  • DRw2, DRB1 1501 AND DRB1 1502 If one twin develops the syndrome it invariably manifests in the second twin ANCA and Anti-GBM Disease There is a consistently strong association between the presence of antineutrophil cytoplasmic antibodies (ANCA) and the[news-medical.net]
  • Genetic predisposition with presence of HLA-DRw2. HLA-B7 relates to more severe anti-GBM nephritis and is seen to be more frequent. Exposure to hydrocarbons and organic solvents. Smoking. Exposure to metal dusts.[epainassist.com]

Treatment

Plasmapharesis is carried out to purify the blood and remove anti-GPDM antibodies from the plasma [30].

Steroids may be recommended to reduce renal or pulmonary inflammation [31]. Symptomatic treatment includes blood pressure medication, diuretics etc.

In extreme cases, dialysis and/or renal transplantation may be recommended [32].

Prognosis

The prognosis is good if disease is detected and treated early. Individuals with pulmonary hemorrhage tend to get treated quicker than those with asymptomatic renal injury.

Presence of oliguria or decrease in frequency and amount of urine, greater than 50% crescents on renal biopsy, fibrosis and reliance on dialysis tend to have poorer prognosis [29].

Etiology

Goodpasture syndrome is characterized by the presence of autoantibodies that target the α3, α4 and α5 chain of non collagenous 1 (NC1) domain of type IV collagen found within the glomerular and pulmonary basement membrane layers [6] [7] [8].

Individuals carrying alleles HLA-DRW2, HLA-DRB4 and HLA-DRB1 within the Major Histocompatibility Complex (MHC) locus are susceptible to events that trigger autoantibody activation [9] [10] [11]. The events implicated include inhalation of cigarette smoke, metal dust or drugs such as cocaine, exposure to hydrocarbons and infectious diseases such as influenza A2 that also affect the respiratory system [12] [13] [14] [15] [16].

Epidemiology

Goodpasture syndrome is rare in occurrence with approximately one case reported per two million individuals in Europe3. A study conducted on patients with end stage renal disease (ESRD) in Australia and New Zealand noted that 0.8 percent individuals suffered from Goodpasture syndrome [4].

Demographically, young and elderly adult Caucasian and Asian males have a higher incidence of developing this syndrome5. Younger males show symptoms of lung hemorrhage prior to renal disease while older and elderly males will initially present with renal disease [4] [6].

Sex distribution
Age distribution

Pathophysiology

The basement membrane layer serves as a foundation for epithelial cell organization. It is formed by the polymerization of agrin, laminin and Type IV collagen fibers to various glycoprotein molecules [17]. In the renal glomerulus, the basement membrane is flanked by fenestrated endothelial cells of the glomerular capillary and podocytes. This layer provides mechanical support to the capillary wall, provide a base for receptor ligand interaction and assists in the ultrafiltration process of the kidney [18]. Three novel collagen IV chains α3,α4 and α5 first identified by scientists in 1987, serve as epitopes for binding of autoantibodies.

Researchers hypothesize that in the presence of triggering factors such as cigarette smoke or hydrocarbon exposure in susceptible individuals damage the basement membrane. This results in a conformational change of the collagen IV molecule that then exposes the α3,α4 and α5 epitopes to both CD4+ reactive T cells and B cells [19] [20] [21] [22]. These antibodies are highly specific and have been observed in serum samples of patients suspected of Goodpasture’s disease [23].

Downstream effects that occur after antibody target interaction results in activation of complements, cytokines and proteases interferes with the glomerular filtration process resulting in glomerulonephritis, identified by crescent formation and proteinuria. Continued antibody assault will result in migration of macrophages and neutrophils into the kidney leading to interstitial nephritis and fibrosis in kidney. 2-D electrophoresis and western blot analysis of collagen domains isolated from human alveolar basement membrane also showed a positive reaction to anti-glomerular basement membrane antibodies [23] [24].

The alveolar basement membrane is impervious to anti-glomerular basement membrane antibodies under normal circumstances. However, environmental factors damage the alveolar basement layer especially in susceptible individuals and expose the epitopes to antibody binding [25].

Prevention

There are no guidelines for prevention of Goodpasture syndrome.

Summary

Goodpasture syndrome is an autoimmune condition that affects both the pulmonary and the renal system as evidenced by glomerulonephritis and pulmonary hemorrhage [1].

It is named after Dr. Ernest Goodpasture (1886-1960), an American physician and pathologist. During the influenza pandemic in 1919, he observed that some infected patients suffered acute symptoms of renal failure along with hemoptysis or coughing up blood [2].

Patient Information

Goodpasture syndrome is a rare autoimmune disease. Individuals with acute renal failure and pulmonary hemorrhage should be evaluated for this condition. Presence of anti-glomerular basement membrane antibodies in sera of affected patients is diagnostically relevant.

Plasmapharesis and steroids are usually recommended for treatment. The prognosis is good when diagnosed and treated promptly. However, delay in treatment will lead to complications such as renal failure and death.

References

Article

  1. Goodpasture Syndrome. National Kidney and Urologic Diseases Information, Clearinghouse (NKUDIC) 2012, NIH pub 12-4558.
  2. Goodpasture EW. The Significance of Certain Pulmonary Lesions in Relation to the Etiology of Influenza. 1919, 158 (6): 863-870.
  3. Anti molecular basement membrane disease. Oxford Textbook of Nephrology 1998, 645-666.
  4. Tang W, McDonald SP, Hawley CM, Badve SV, Boudville NC, Brown FG, Clayton PA, Campbell SB, de Zoysa JR, Johnson DW. Anti-glomerular basement membrane antibody disease is an uncommon cause of end-stage renal disease’. Kidney International 2013, 83: 503–510.
  5. Anti-Glomerular Basement Membrane Disease. JASN 1999,10 (11): 2446-2453.
  6. Segelmark M, Butkowski R, Wieslander J. Antigen restriction and IgG subclasses among Anti-GBM autoantibodies. Nephrology Dialysis Transplantation 1990 (5): 991-996.
  7. Butkowski RJ, Langeveld JP, Wieslander J, Hamilton J, Hudson BG. Localization of the Goodpasture epitope to a novel chain of basement membrane collagen. Journal of Biological Chemistry 1987, 262: 7874-7877.
  8. Ries A, Engel J, Lustig A, Kühn K. The Function of the NC1 Domains in Type IV Collagen. Journal of Biological Chemistry 1995, 270: 23790-23794.
  9. Rees AJ, Peters DK, Compston DA, Batchelor JR. Strong association between HLA-DRW2 and antibody-mediated Goodpasture’s syndrome. Lancet 1978, 311(8071):966-968.
  10. Fisher M, Pusey CD, Vaughan RW, Rees AJ. Susceptibility to anti-glomerular basement membrane disease is strongly associated with HLA-DRB1 genes. Kidney International 1997, 51: 222-229.
  11. Phelps RG, Rees AJ. The HLA complex in Goodpasture’s disease: A model for analyzing susceptibility to autoimmunity. Kidney International 1999, 56: 1638-1653.
  12. Sirvent AE, Enríquez R, Andrada E, Amorós F, Gallego JA, González C, Padilla I. Goodpasture's syndrome in a patient using cocaine--a case report and review of the literature’. Clinical Nephrology 2007, 68(3): 182-185.
  13. Stevenson A, Yaqoob M, Mason H, Pai P, Bell GM. Biochemical markers of basement membrane disturbances and occupational exposure to hydrocarbons and mixed solvents. QJM 1995, 88(1):23-28.
  14. Donaghy M, Rees AJ. Cigarette smoking and lung hemorrhage in glomerulonephritis caused by autoantibodies to glomerular basement membrane. Lancet 1983, 322 (8364):1390-1393.
  15. Lechleitner P, Defregger M, Lhotta K, Tötsch M, Fend F. Goodpasture's syndrome. Unusual presentation after exposure to hard metal dust. Chest 1993, 103 (3): 956-957.
  16. Wilson CB, Smith RC. Goodpasture’s syndrome associated with Influenza A2 virus infection. Annals of Internal Medicine 1972, 76(1): 91-94.
  17. Yurchenco PD1, Smirnov S, Mathus T. Analysis of basement membrane self-assembly and cellular interactions with native and recombinant glycoproteins. Methods in cell-matrix adhesion 2002, 69: 111-144.
  18. Suleiman H, Zhang L, Roth R, Heuser JE, Miner JH, Shaw AS, Dani A. Nanoscale architecture of the kidney glomerular basement membrane. eLife 2013, 2: e01149.
  19. Hudson BG. The molecular basis of Goodpasture and Alpert Syndrome: Beacons for the Discovery of the Collagen IV family. J Am Soc Nephrol 2004, 15: 2514-2527.
  20. Hudson BG, Reeders ST, Tryggvason K. Type IV Collagen: Structure, Gene organization and role in human disease. Journal of Biological Chemistry 1993, 258(35): 260133-160136.
  21. Good Pasture disease- New secrets revealed. N Engl J Med 2010; 363: 388-391.
  22. Salama AD, Chaudhry AN, Ryan JJ, Eren E, Levy JB, Pusey CD, Lightstone L, Lechler RI. In Goodpasture's disease, CD4(+) T cells escape thymic deletion and are reactive with the autoantigen alpha3(IV)NC1. J Am Soc Nephrol. 2001, 12(9): 1908-15.
  23. Derry CJ, Pusey CD. Tissue-specific distribution of the Goodpasture antigen demonstrated by 2-D electrophoresis and western blotting. Nephrol Dial Transplant. 1994, 9(4): 355-61.
  24. Kriz W, LeHir M. Pathways to nephron loss starting from glomerular diseases- Insights from animal models. Kidney International 2004, 67:404-419.
  25. Yoshioka K, Iseki T, Okada M, Morimoto Y, Eryu N, Maki S. Identification of Goodpasture antigens in human alveolar basement membrane. Clinical and Experimental Immunology 1988, 74(3): 419-424.
  26. Kelly PT, Haponik EF. Goodpasture Syndrome: Molecular and Clinical Advances. Medicine 1994, 73 (4): 171-185.
  27. Kielstein JT, Helmchen U, Netzer KO, Weber M, Haller H, Floege J. Conversion of Goodpasture’s Syndrome into membraneous glomerulonephritis. Nephrology Dialysis Transplantation 2001, 16: 2082-2085.
  28. Pulmonary-renal syndromes in the intensive care unit. Critical Care Clinics 2002, 18: 881-895.
  29. Levy JB, Turner AN, Rees AJ, Pusey CD. Long-term outcome of anti-glomerular basement membrane antibody disease treated with plasma exchange and immunosuppression. Annals of Internal Medicine 2001, 134 (11): 1033-1042.
  30. Rosenblatt SG, Knight W, Bannayan GA, Wilson CB, Stein JH. Treatment of Goodpasture’s syndrome with plasmapheresis: A case report and review of literature. The American Journal of Medicine 1979, 66(4):689-696.
  31. Johnson JP, Whitman W, Briggs WA, Wilson CB. Plasmapheresis and Immunosuppressive Agents in Antibasement Membrane antibody-induced Goodpasture’s syndrome. The American Journal of Medicine 1978, 64(2): 354-359.
  32. Poddar B, Singhal S, Azim A, Gulati S, Baronia A. Goodpasture’s Syndrome in children. Saudi Journal of Kidney Disease and Transplantation 2010, 21(5): 935-939.

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Last updated: 2019-07-11 21:11