Goodpasture Syndrome (Anti-glomerular Basement Membrane Antibody Disease)

Article Author:
Bradley DeVrieze
Article Editor:
John Hurley
Updated:
10/27/2018 12:31:36 PM
PubMed Link:
Goodpasture Syndrome (Anti-glomerular Basement Membrane Antibody Disease)

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. 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.

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. 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. 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

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. Transfer to a center capable of providing input from those specialties. Plasmapheresis, if indicated, should be sought. Initial lab assays should be expedited, and protocols should be put in place for immediate notification of positive results.

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.

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. These patients rarely experience recurrent disease in the current era following transplant, but it has been reported in the literature. 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.