Goodpasture Syndrome (Anti-glomerular Basement Membrane Antibody Disease)


Article Author:
Bradley DeVrieze


Article Editor:
John Hurley


Editors In Chief:
Sisira Reddy
Joseph Nahas
Chokkalingam Siva


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
3/24/2019 9:34:40 PM

Introduction

Goodpasture syndrome refers to an anti-glomerular basement membrane (anti-GBM) disease that involves both the lungs and kidneys, often presenting as pulmonary hemorrhage and glomerulonephritis.  However, some clinicians may use several terms interchangeably, including anti-glomerular basement membrane disease, Goodpasture syndrome, and Goodpasture disease. [1]The latter is the most specific term, and refers to the presence of renal and pulmonary involvement, along with anti-glomerular basement membrane antibodies. The spectrum of disease may present classically or as glomerulonephritis alone.

Etiology

At this point, a triggering stimulus has not been identified for the development of anti-glomerular basement membrane antibodies. However, there are certain human leukocyte antigen (HLA) subtypes that have been implicated in conferring increased genetic susceptibility to Goodpasture syndrome, most notably HLA-DR15.[2]

Epidemiology

Goodpasture syndrome and anti-glomerular basement membrane glomerulonephritis are rare. The incidence is around one case per million.

Pathophysiology

Goodpasture syndrome is due to circulating auto-antibodies directed at the glomerular basement membrane. The resulting crescentic glomerulonephritis is the result of the antigen-antibody complexes that form at the basement membrane.[3] The inflammatory response in that area results in the typical glomerulonephritis clinical picture.

Alveolar basement membrane shares the same collagen target as that of the glomerulus. Despite the presence of circulating antibodies in anti-glomerular basement membrane disease, pulmonary symptoms are not always observed. An inciting lung injury seems to make pulmonary symptoms more likely.

Histopathology

Microscopy will show crescentic glomerulonephritis, and immunofluorescence will show linear deposition of IgG. A kidney biopsy is not only important for diagnosis, but the percentage of crescents identified on biopsy confers renal survival prognosis. Lung tissue is typically not sought due to the invasiveness of the procedure and more difficult immunofixation process for lung tissue.

History and Physical

Patients with anti-glomerular basement membrane antibody syndrome will initially present similarly to other forms of rapidly progressive glomerulonephritis with acute renal failure. There are no symptoms specific to anti-glomerular basement membrane that distinguish it from other diseases causing similar organ dysfunction, and careful and expedient workup must be undertaken for accurate diagnosis. The pulmonary symptoms are typically present at the time of the initial encounter, or shortly after that. Hemoptysis of varying degrees is typical when there is pulmonary involvement, ranging from serious and life-threatening bleeding to more subtle diffuse hemorrhage that is only apparent on more careful evaluation. It is more typical for younger patients affected by the anti-glomerular basement membrane disease to present with simultaneous renal and pulmonary symptoms (Goodpasture syndrome) and to be critically ill on presentation. Patients over 50 years old tend to present with glomerulonephritis alone and follow a less severe course.

Careful physical examination of patients presenting with finding suspicious for the anti-glomerular basement membrane disease should be done, particularly for other signs such as a purpuric rash. This finding may suggest so-called “double-positive” patients who have concurrent ANCA-associated vasculitis (granulomatosis with polyangiitis).

Evaluation

A kidney biopsy is the gold standard for diagnosis but is not required either to begin treatment or to continue treatment if a biopsy is not feasible. When performed, biopsy provides important information regarding the activity and chronicity of renal involvement that may help guide therapy. Serologic testing for ELISA assay for circulating anti-GBM antibodies should be done immediately on suspicion of the disease. Specifically, it is important that the alpha3 NC1 domain area of collagen IV be used as the target in this assay as false positives may be seen in less specific testing.[4] Quantitative titers are followed during treatment phases to guide treatment decisions.

Treatment / Management

Patients presenting with Goodpasture syndrome (both glomerulonephritis and pulmonary hemorrhage) may be critically ill on presentation. Urgent hemodialysis often is needed for standard indications, and intubation for respiratory failure may be necessary. When the diagnosis is being considered, kidney biopsy should be done as soon as the clinical situation allows.

Upon diagnosis, patients should be started on prednisone, cyclophosphamide, and daily plasmapheresis to improve overall mortality in general, and renal survival in particular. If therapy can start before the patient progresses to the point of needing renal replacement therapy, the overall renal prognosis is better. All patients with pulmonary symptoms should be started on combined therapy regardless of their renal status. For patients, without pulmonary symptoms in whom renal recovery is very unlikely (i.e., for those that presented with the urgent need for dialysis within the first 72 hours) the risk of plasmapheresis and immunosuppressive may outweigh the benefits. The choice to withhold treatment in these cases remains controversial as the disease has not been well-studied in controlled trials, and it remains difficult to predict who in this group exactly will respond and recover renal function. Overall return of renal function in this group is approximately 8%, yet many clinicians still opt for a trial of aggressive combined therapy at this time.

Typically, daily plasmapheresis is performed until anti-glomerular basement membrane antibodies are undetectable, with steroid and cyclophosphamide continuing after that for 3 to 6 months until full remission is achieved. This can be gauged by checking repeated titers following plasmapheresis, as well as any time new symptoms develop that could be a harbinger of relapse. Overall, relapse remains rare.

Pearls and Other Issues

Prognosis for this spectrum of diseases is overall good, provided the disease is identified efficiently, and treatment started promptly. Overall survival, and renal recovery track along with the degree of renal impairment on presentation.

Recurrence is rare but possible, and patients typically do well with recurrent episodes. This is most likely due to heightened clinical suspicion. Treatment in recurrent cases is identical to the initial episode.[5]

Patients that do not recover renal function and remain dependent on renal replacement therapy may qualify for renal transplantation. Anti-glomerular basement membrane antibody titers should be negative for at least 6 months before transplantation.[6] These patients rarely experience recurrent disease in the current era following transplant, but it has been reported in the literature.[7] It has been theorized that long-term use of immunosuppressive agents aimed at protecting the graft from rejection simultaneously keeps the autoimmune disease from recurring.[8]

Enhancing Healthcare Team Outcomes

Management of Goodpasture syndrome requires careful coordination of several specialties. Involvement of pulmonary/critical care, nephrology, and rheumatology should be sought depending on the spectrum of clinical findings and severity of the disease. an interprofessional team consisting of nurses, nurse practitioners, physician assistants, and physicians will provide the best results. Transfer to a center capable of providing input from those specialties is advisable. Plasmapheresis, if indicated, should be sought. Initial lab assays should be expedited, and protocols should be put in place for all members of the team are aware of positive test results and can act on them immediately.


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Goodpasture Syndrome (Anti-glomerular Basement Membrane Antibody Disease) - Questions

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What condition typically shows bright linear deposits of immunoglobulin IgG?



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A patient presents with hemoptysis and hematuria. Work-up reveals an autoimmune disorder. Serology reveals antibody towards the glomerular basement membrane. Which of the following is the most likely diagnosis?



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A patient with Goodpasture syndrome will have glomerulonephritis and possibly which other complication?



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A patient has hemoptysis and anti-glomerular basement membrane antibodies. What is the most probable diagnosis?



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A 7-year-old child was brought in for severe hemoptysis. His lab results also reveal alterations in renal function. What is the most likely diagnosis?



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Goodpasture syndrome is classified as what type of hypersensitivity reaction?



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Patients with Goodpasture syndrome have what type of antibody in serum?



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A patient with Goodpasture syndrome will have renal involvement and involvement of which other organ?



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What part of the kidney is involved in Goodpasture syndrome?



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A child was brought in for severe hemoptysis. His lab results show derangement of his renal function. What is the most likely diagnosis?



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A 52-year-old male complains of coughing up about a teaspoon of blood daily for three days. He has a 20-pack-year history but quit five years ago. The chest x-ray shows bilateral diffuse infiltrates mostly in the lower lobes. Hemoglobin is 10.2 g and serum creatinine is 3.8 mg/dL. They had been normal six months ago. Urinalysis is remarkable for red cell casts and 2+ protein. Which autoantibody is most likely to be positive?



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What is the five-year survival rate for Goodpasture syndrome?



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A patient presents with a cough productive of blood. Chest x-ray shows interstitial pneumonia that does not improve with appropriate antibiotics. Laboratories show a negative HIV but a positive antibody to the collagen of the kidney basement membrane. What is the most likely diagnosis?



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A 17-year-old male presents with hemoptysis. Hemoglobin was 10.5 mg/dL. Blood pressure was greater than 130/90 mm Hg for the hospitalization. Urinalysis showed proteinuria and hematuria. What is the most likely diagnosis?



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A 35-year-old female presents with a week history of a few episodes of dyspnea and hemoptysis. She is a nonsmoker without any prior illnesses. She is hypertensive and has 2+/4 pedal edema, hematuria, proteinuria, and RBC casts. What is the most likely diagnosis?



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What antibody is often found in Goodpasture syndrome?



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A 44-year-old man who has not been to a physician in over twenty years presents to the emergency department with a week of progressive weakness and shortness of breath. He decided to seek care because he started to cough up blood. On admission to the emergency department, he is afebrile. His blood pressure is 90/40 mmHg, and his heart rate is 110 beats per minute. His respiratory rate is 35 breaths per minute, and his SpO2 is 85% despite 100% FiO2 via simple face mask. He is intubated by the ER physician and is placed on the mechanical ventilator. Copious amounts of blood have been suctioned from the endotracheal tube. His chest x-ray shows bilateral infiltrates, with the bases worse than the apices. The labs show sodium 135 mEq/L, potassium 7.9 mEq/L, carbon dioxide 13 mEq/L, BUN 90 mg/dL, and creatinine 6.7 mg/dL. A Foley is placed with the return of 50 mL of urine. The urinalysis is significant for red cell casts and 2+ protein. The patient is transferred to the intensive care unit with plans for immediate placement of a temporary dialysis catheter. What is the likelihood that this patient will regain renal function with aggressive therapy including plasmapheresis, cyclophosphamide, and corticosteroid?



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Goodpasture Syndrome (Anti-glomerular Basement Membrane Antibody Disease) - References

References

Identification of the alpha 3 chain of type IV collagen as the common autoantigen in antibasement membrane disease and Goodpasture syndrome., Kalluri R,Wilson CB,Weber M,Gunwar S,Chonko AM,Neilson EG,Hudson BG,, Journal of the American Society of Nephrology : JASN, 1995 Oct     [PubMed]
Anti-glomerular basement membrane antibody disease is an uncommon cause of end-stage renal disease., Tang W,McDonald SP,Hawley CM,Badve SV,Boudville NC,Brown FG,Clayton PA,Campbell SB,de Zoysa JR,Johnson DW,, Kidney international, 2013 Mar     [PubMed]
Goodpasture's disease., Salama AD,Levy JB,Lightstone L,Pusey CD,, Lancet (London, England), 2001 Sep 15     [PubMed]
Recurrent Goodpasture's disease., Levy JB,Lachmann RH,Pusey CD,, American journal of kidney diseases : the official journal of the National Kidney Foundation, 1996 Apr     [PubMed]
The HLA complex in Goodpasture's disease: a model for analyzing susceptibility to autoimmunity., Phelps RG,Rees AJ,, Kidney international, 1999 Nov     [PubMed]
Loss of a renal graft due to recurrence of anti-GBM disease despite rituximab therapy., Sauter M,Schmid H,Anders HJ,Heller F,Weiss M,Sitter T,, Clinical transplantation, 2009 Jan-Feb     [PubMed]
Diagnosis and classification of Goodpasture's disease (anti-GBM)., Hellmark T,Segelmark M,, Journal of autoimmunity, 2014 Feb-Mar     [PubMed]
KDOQI US commentary on the 2012 KDIGO clinical practice guideline for glomerulonephritis., Beck L,Bomback AS,Choi MJ,Holzman LB,Langford C,Mariani LH,Somers MJ,Trachtman H,Waldman M,, American journal of kidney diseases : the official journal of the National Kidney Foundation, 2013 Sep     [PubMed]

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