Description
Goodpasture syndrome, also known as anti-glomerular basement membrane (anti-GBM) disease, is a rare autoimmune disease characterised by rapidly progressive glomerulonephritis and pulmonary haemorrhage.
Pathogenesis
Goodpasture syndrome is a type II hypersensitivity reaction with the formation of autoantibodies directed against the alpha-3 chain of type IV collagen, which is present in the glomerular and alveolar basement membranes. These autoantibodies bind to the basement membranes, initiating a cascade of inflammatory reactions that ultimately lead to tissue damage and organ dysfunction.
Epidemiology, Risk Factors & Associations
Goodpasture syndrome is rare, with an incidence of approximately 1 in a million per year.
- Bimodal age distribution: Late teens and in the late 50s.
- Men are more commonly affected than women (~M:F 3:1)
Risk factors include:
- Exposure to certain organic solvents and hydrocarbons
- Tobacco smoking
- Infections with influenza A or B.
No known specific associations with other diseases.
Clinical Features
The hallmark clinical features of Goodpasture syndrome are:
- Renal involvement: Presents as rapidly progressive glomerulonephritis (RPGN) with symptoms such as haematuria, proteinuria, hypertension, and renal failure.
- Pulmonary involvement: Manifests as pulmonary haemorrhage leading to cough, dyspnoea, hypoxia, and haemoptysis.
- Systemic symptoms: Fatigue, loss of appetite, nausea, and weight loss may also be present.
Complications
Without treatment, Goodpasture syndrome can lead to severe complications such as end-stage renal disease, respiratory failure, and even death.
Subtypes
Goodpasture syndrome is typically considered a singular entity rather than having specific subtypes. However, variability exists in the extent of organ involvement; some patients may primarily have kidney disease, while others have prominent lung disease.
Pathological Features
Morphology
In both the kidney and lungs, the main morphological change is the thickening and disruption of the basement membrane.
Histopathology
- Biopsy specimens show a pattern of crescentic glomerulonephritis in the kidneys and diffuse alveolar damage in the lungs.
- Immunofluorescence reveals linear deposits of IgG along the glomerular basement membrane.
Biochemistry & Genetics
- The pathogenic autoantibodies are typically of the IgG class.
- There are no specific genetic mutations associated with the development of Goodpasture syndrome, but there appears to be a slight association with certain HLA types, particularly HLA-DR15.
Radiological Features
Chest X-ray
- Normal in early stages.
- Pulmonary haemorrhage – diffuse bilateral alveolar infiltrates, may coalesce.
CT Chest
- Diffuse alveolar haemorrhage – Ground-glass and airspace opacities and consolidations in the lung parenchyma. May progress to crazy paving.
- Hilar lymphadenopathy may be present.
Kidney Ultrasound
- Enlarged and hyperechoic kidneys due to acute inflammation. However, these changes are not specific and are similar to those seen in other forms of rapidly progressive glomerulonephritis.
Grading and Staging
There is no specific grading or staging system for Goodpasture syndrome.
Diagnosis
The diagnosis of Goodpasture syndrome is confirmed by the presence of anti-GBM antibodies in the blood or in kidney biopsy samples.
Differential Diagnosis
- Granulomatosis with polyangiitis (GPA): Characterised by necrotising granulomatous inflammation, usually involving the respiratory tract and kidneys, and presence of c-ANCA/PR3-ANCA. The renal biopsy shows pauci-immune crescentic glomerulonephritis.
- Microscopic polyangiitis (MPA): Similar to GPA, but lacks the granulomatous inflammation. Renal and lung involvement is common, and the patient typically has p-ANCA/MPO-ANCA. Renal biopsy shows pauci-immune crescentic glomerulonephritis.
- Systemic lupus erythematosus (SLE): This is a multisystem autoimmune disease with varied clinical presentations. Renal involvement (lupus nephritis) is common, but lung involvement is less common. The presence of anti-nuclear antibodies (ANA) and anti-double stranded DNA antibodies (anti-dsDNA) is characteristic. Renal biopsy in lupus nephritis shows “full house” immune complex deposition.
- IgA nephropathy (Berger’s disease): This is the most common cause of glomerulonephritis worldwide, typically presenting with hematuria. Lung involvement is extremely rare. The diagnosis is made by renal biopsy showing mesangial IgA deposits.
- Alveolar haemorrhage syndromes (not related to anti-GBM disease): These include conditions like idiopathic pulmonary haemosiderosis, which presents with iron-deficiency anemia, diffuse lung infiltrates, and haemoptysis but without renal involvement. The diagnosis is confirmed by bronchoalveolar lavage showing haemosiderin-laden macrophages.
- Idiopathic rapidly progressive glomerulonephritis (RPGN): This condition presents with rapidly declining renal function and nephritic syndrome. Lung involvement is not typical. Renal biopsy shows crescentic glomerulonephritis.
- Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis: This group of diseases (which includes GPA and MPA as mentioned earlier, and also eosinophilic granulomatosis with polyangiitis), is characterised by small-vessel vasculitis and presence of ANCA, with varying degrees of renal and pulmonary involvement.
- Pulmonary-renal syndrome: This is a group of disorders characterised by diffuse alveolar haemorrhage and glomerulonephritis, which includes Goodpasture syndrome, GPA, MPA, and SLE, among others. The specific differentiating features would depend on the individual diseases in this group.
Management
- Primarily managed by rheumatologists or nephrologists and involves immunosuppressive therapy to reduce the levels of circulating autoantibodies. This usually includes corticosteroids and cyclophosphamide.
- Plasma exchange may be used in severe cases to remove the pathogenic autoantibodies from the circulation.
- End-stage renal disease requires renal replacement therapy such as dialysis or kidney transplantation.