Goodpasture SyndromeDz

Synonyms: Antiglomerular basement membrane antibody disease.

ICD-9 Code: 446.21.
ICD-10: M31.0

Definition: Goodpasture syndrome is an autoimmune disorder characterized by pulmonary hemorrhage and rapidly progressive glomerulonephritis in association with antibodies to alveolar and glomerular basement membrane (GBM).

Etiology: The cause of Goodpasture syndrome is unknown. Most cases are without cause, but some are preceded by respiratory infections (e.g., influenza), toxic lung injury or drug exposure (D-penicillamine). The pathogenesis of Goodpasture’s syndrome is related to anti-GBM antibodies.

Pathology: Immunofluorescent staining of biopsy specimens from the lungs and kidneys of patients with Goodpasture syndrome reveals a characteristic linear pattern of anti-GBM antibody deposition. Crescentic glomerulonephritis is seen in 80% of patients. The specific antigenic epitopes recognized by anti-GBM antibodies were recently shown to be present on the a3 chain of type IV collagen. Type IV collagen is the major component of basement membranes and provides structural support. Although other chains of type IV collagen occur widely throughout the body, the a3 chain has more limited expression. This provides an explanation for why end-organ involvement of Goodpasture syndrome is typically limited to the lungs and kidneys.

Demographics: Goodpasture syndrome is rare and mostly affects white men in their third decade, although all races and ages may be affected.

Cardinal Findings: Approximately 75% of those with Goodpasture syndrome have both pulmonary and renal involvement; the remainder have only rapidly progressive glomerulonephritis. Isolated pulmonary disease is rare. Hemoptysis is the initial complaint in most patients, and alveolar infiltrates may be seen on chest radiographs. Other symptoms include cough and dyspnea. Smoking history may be associated with pulmonary hemorrhage. Renal manifestations generally lag behind pulmonary signs and symptoms.

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. Less than half of patients demonstrate renal insufficiency at initial evaluation, but more than 80% eventually display azotemia or proteinuria. Hematuria is very common. Anti-GBM assays are performed by ELISA in a number of reference laboratories, and anti-GBM is present in >95% of patients with Goodpasture syndrome (see Antiglomerular Basement Membrane (GBM) Antibody).

Imaging: Chest radiographs usually reveal diffuse, extensive alveolar infiltrates.

Differential Diagnosis: Various other pulmonary/renal syndromes, such as SLE, cryoglobulinemia, and several types of vasculitis, must be distinguished.

Keys to Diagnosis: The diagnosis of Goodpasture syndrome may be secured by demonstrating linear antibody staining of the basement membrane of renal or pulmonary biopsy specimens. However, patients are often quite ill during the initial course of the disease, making biopsy more difficult. Tests for serum anti-GBM antibodies are most commonly used to diagnose Goodpasture syndrome because of their widespread availability and high sensitivity and specificity.

Therapy: Goodpasture syndrome used to be associated with a poor prognosis and high associated mortality. Recently, the prognosis has improved, in part because of the availability of diagnostic tests and advances in immunomodulatory interventions, although improvements in the intensive care of critically ill persons have no doubt contributed. Because most patients present in extreme distress (e.g., hemoptysis, hypoxia), large boluses of corticosteroids (e.g., 1 g methyl- prednisolone intravenously for 3–4 days) are commonly used. Plasmapheresis appears to benefit many patients and is also commonly used. Many patients are treated with cytotoxic drugs, such as daily oral cyclophosphamide, in conjunction with plasmapheresis. In contrast to some other pulmonary renal syndromes, such as SLE, production of anti-GBM antibodies is usually self-limited. Thus, these aggressive immunomodulatory therapies may often be stopped when the patient has demonstrated significant clinical improvement.

BIBLIOGRAPHY

Gravelyn TR, Lynch JP. Alveolar hemorrhage syndromes. IM Intern Med Special 1987;8:63–83. Hudson BG, Tryggvason K, Sundaramoorthy M, et al. Alport’s syndrome, Goodpasture’s syndrome, and type IV collagen. N Engl J Med 2003;348:2543–2556. PMID:12815141 

Levy JB, Turner AN, Rees AJ, et al. Long-term outcome of anti-glomerular basement membrane antibody disease treated with plasma exchange and immunosuppression. Ann Intern Med 2001;134:1033–1042. PMID:11388816

Shah MK, Hugghins SY. Characteristics and outcomes of patients with Goodpasture’s syndrome. South Med J 2002;95:1411–1418. PMID:12597309

Hellmark T, Segelmark M. Diagnosis and classification of Goodpasture's disease (anti-GBM).  J Autoimmun. 2014 Feb-Mar;48-49:108-12. PMID: 24456936