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

  […] 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 with pulmonary hemorrhage Anti-GBM syndrome Glomerulonephritis [wikidata.org]

  Affected individuals present with symptoms of rapidly progressive glomerulonephritis Rapidly Progressive Glomerulonephritis Rapidly progressive glomerulonephritis (RPGN) is a syndrome of severe glomerular disease with progressive loss of kidney function [lecturio.com]

  Only those with rapidly progressive glomerulonephritis should be regarded as examples of Goodpasture’s syndrome. [histopathology-india.net]

  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]

  Circulating antibodies are directed against the collagen of the part of the kidney known as the glomerular basement membrane (GBM), resulting in acute or rapidly progressive glomerulonephritis. [ebi.ac.uk]

• Fatigue

  […] that attack collagen (collagen = protein) in the glomeruli of the kidneys; the presence of circulating antibodies in the blood which attack the basement membrane of the kidney's glomeruli and the lung's alveoli and that is marked initially by coughing, fatigue [quizlet.com]

  an autoimmune disorder of unknown cause that is characterized by the presence of circulating antibodies in the blood which attack the basement membrane of the kidney's glomeruli and the lung's alveoli and that is marked initially by coughing, fatigue [merriam-webster.com]

  Symptoms include cough with bloody sputum, bloody urine, decreased urine output, fatigue (weakness), and weight loss. Hypertension and swelling ( edema ) are also common findings on physical examination. [medicinenet.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]

• Anemia

  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]

  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]

  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]

  Coexisting Diseases and Conditions Hemoptysis, dyspnea, hypertension, arthritis, anemia, acute kidney failure, chronic kidney disease, heart disease, and respiratory failure. Sources Article Sources and Footnotes Goodpasture Syndrome. (n.d.-a). [autoimmuneinstitute.org]

• Fever

  Fever, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. [lecturio.com]

  The patient has intermittent fever and cough for 45 days and oliguria for 6 days. [ncbi.nlm.nih.gov]

  She had fever, cough, severe dyspnea and lately hemoptysis and severe hypoxia with bilateral alveolar opacity in chest imaging, with no response to broad spectrum antibiotic. [caspjim.com]

  She denied chills, fever, sputum production, or previous pulmonary or cardiovascular complaints. She had been treated for a urinary tract infection with antibiotics at 11 years of age. [jamanetwork.com]

  (see Fever, [[Fever]]) Malaise Treatment Plasmapheresis (see Plasmapheresis, [[Plasmapheresis]]) Indications Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]]) Clinical Efficacy Retrospective Review of [mdnxs.com]

• Leg Edema

  […] in the legs (edema = swelling) Tests to diagnose the syndrome Urinalysis. [quizlet.com]

• Cough

  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]

  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]

  Common symptoms of Goodpasture syndrome include Shortness of breath Cough Fever Unplanned weight loss Fatigue Blood in the urine Coughing up blood (hemoptysis) Fatigue and paleness (pallor) may be symptoms of anemia that results from blood loss. [msdmanuals.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]

  respiratory failure or pulmonary hemorrhage Renal: glomerulonephritis Hematuria, proteinuria, RBC casts Symptoms are often rapidly progressive Differential Diagnosis Hemoptysis Infectious Bronchitis Pneumonia Lung abscess Tuberculosis Plague Aspergilloma [wikem.org]

• Dyspnea

  Other common symptoms include Cough Dyspnea Fatigue Fever Hematuria Weight loss Up to 40% of patients have gross hematuria, although pulmonary hemorrhage may precede renal manifestations by weeks to years. [msdmanuals.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]

  Coexisting Diseases and Conditions Hemoptysis, dyspnea, hypertension, arthritis, anemia, acute kidney failure, chronic kidney disease, heart disease, and respiratory failure. Sources Article Sources and Footnotes Goodpasture Syndrome. (n.d.-a). [autoimmuneinstitute.org]

  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]

• Tachypnea

  Tachypnea and basal râles were heard bilaterally. The liver was palpated two fingerbreadths below the right costal margin. Blood pressure was 140/80 mm. Hg and the pulse rate was 80/min. [pubs.rsna.org]

  […] 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]

  Pulmonary hemorrhage can progress rapidly, and patients may develop worsening respiratory distress, hypoxia, and tachypnea during the ED course.10,11 Patients may have systemic symptoms including fevers, chills, malaise, and arthralgias. [emdocs.net]

  […] respiratory failure may occur Renal manifestations are rapidly progressive glomerulonephritis that may lead to azotemia and volume overload Arthralgias Physical examination Physical examination findings in patients with anti-GBM disease include the following: Tachypnea [catatanseorangdoktor.wordpress.com]

• Pulmonary Disorder

  Allergic Disorders Infectious Diseases Injuries; Poisoning Musculoskeletal and Connective Tissue Disorders Neurologic Disorders Nutritional Disorders Pediatrics Psychiatric Disorders Pulmonary Disorders Special Subjects Resources Videos Figures Images [msdmanuals.com]

  Some less common pulmonary disorders, In: Seaton A, Seaton D, Leith AG, editors. Crofton and Douglas's Respiratory Diseases 5th ed. Oxford: Blackwell Science 2000;1330-45. 24. Salam N, Rezki H Fadili W, Hachim K, Ramdani B. Goodpasture's syndrome. [sjkdt.org]

• Nausea

  Common Symptoms Bleeding in the lungs, fatigue, nausea, breathing issues, vomiting, pale skin, burning sensations when urinating, blood in the urine, protein in the urine, coughing, foamy urine, swelling of the legs, and high blood pressure. [autoimmuneinstitute.org]

  If the kidney disease is very severe, patients may notice that they are passing only small amounts of urine and may have nausea and vomiting as well. Treatments include medications and a procedure called plasmapheresis. [my.clevelandclinic.org]

  The symptoms of Goodpasture syndrome may initially include fatigue, nausea, vomiting, and weakness. [niddk.nih.gov]

  Symptoms Early symptoms include general body aches and pains, fatigue, weakness or lethargy, pale skin, nausea, lack of appetite, and shortness of breath. [vasculitisfoundation.org]

• Vomiting

  Common Symptoms Bleeding in the lungs, fatigue, nausea, breathing issues, vomiting, pale skin, burning sensations when urinating, blood in the urine, protein in the urine, coughing, foamy urine, swelling of the legs, and high blood pressure. [autoimmuneinstitute.org]

  If the kidney disease is very severe, patients may notice that they are passing only small amounts of urine and may have nausea and vomiting as well. Treatments include medications and a procedure called plasmapheresis. [my.clevelandclinic.org]

  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]

• Kidney Failure

  Coexisting Diseases and Conditions Hemoptysis, dyspnea, hypertension, arthritis, anemia, acute kidney failure, chronic kidney disease, heart disease, and respiratory failure. Sources Article Sources and Footnotes Goodpasture Syndrome. (n.d.-a). [autoimmuneinstitute.org]

  Dialysis at chronic kidney failure. Kidney transplant at loss of kidney function. A transplant is not done until the level of harmful antibodies drops. 10. Autopsy of consolidated lung from extensive bleeding, which led to asphyxiation. 11. [slideshare.net]

  As a result, people with Goodpasture syndrome can develop kidney failure and bleeding in the lungs, which causes them to cough up blood. In some people, antibodies attack only the kidneys. [ghr.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]

  Other common symptoms include Cough Dyspnea Fatigue Fever Hematuria Weight loss Up to 40% of patients have gross hematuria, although pulmonary hemorrhage may precede renal manifestations by weeks to years. [msdmanuals.com]

  This condition typically causes people to have blood in their urine (hematuria) but no other signs or symptoms of kidney disease. In the past, this condition was often called benign familial hematuria. [ghr.nlm.nih.gov]

  and glomerulonephritis (hematuria) along with circulating anti-glomerular basement membrane (anti-GBM) antibodies [ 1 ]. [jmedicalcasereports.biomedcentral.com]

• Oliguria

  The patient has intermittent fever and cough for 45 days and oliguria for 6 days. [ncbi.nlm.nih.gov]

  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]

  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. [symptoma.com]

  The results are proteinuria, hemauria and oliguria. Immunopathogenesis[edit | edit source] The autoantibodies are mainly of the IgG1 and IgG4 subclasses, but in one third of the cases IgA and IgM autoantibodies are also present. [wikilectures.eu]

• Headache

  Reversible posterior leukoencephalopathy syndrome (RPLS) is characterized by headache, altered consciousness, seizures, and cortical blindness. [ncbi.nlm.nih.gov]

  It involves headache, altered state of consciousness, visual abnormalities (blurred vision, scotoma, cortical blindness) and tonic-clonic seizures. [revistanefrologia.com]

  She had been in excellent health, except for a two-day episode of rhinitis and headache one week before admission. She denied chills, fever, sputum production, or previous pulmonary or cardiovascular complaints. [jamanetwork.com]

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]

  […] by diffuse parenchymal infiltrates and findings suggesting renal disease. [merckmanuals.com]

  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]

• HLA-DRw2

  There is an inherited predisposition to this syndrome (HLA-DRw2 is associated with anti-GBM disease). Incidence The incidence is estimated at approximately 1:100,000 people worldwide. It is most often present in males at the age of 20 years. [accesspediatrics.mhmedical.com]

  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]

  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]

  […] subtypes, especially HLA 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 [news-medical.net]

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].

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].

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].

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].

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].

There are no guidelines for prevention of Goodpasture syndrome.

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].

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.

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