Time-limited (2-48 months) autoimmune disease with circulating antiglomerular basement membrane (anti-GBM) antibodies affecting the lungs and the kidneys of unknown cause (viral and streptococcal infections and exposure to hydrocarbon fumes have been suggested as causes). A medical condition reported lethal during the acute phase. Most patients who survive will progress to end-stage renal disease.
Antiglomerular Basement Membrane Disease.
Autoimmune disease, the major antigen target is the carboxyl terminus of the noncollagenous (NC-1) domain of the α3-chain in Type IV (basement membrane) collagen. The antibodies are directed against a 28-kDa monomeric subunit present within the noncollagenous domain. The disease may also occur in the transplanted kidneys of patients with Alport Syndrome. There is an inherited predisposition to this syndrome (HLA-DRw2 is associated with anti-GBM disease).
The incidence is estimated at approximately 1:100,000 people worldwide. It is most often present in males at the age of 20 years. White people are more affected than black people, as are certain ethnic groups (eg, Maoris of New Zealand).A bimodal distribution has been reported (young men presenting with a Pulmonary-Renal Syndrome and elderly women presenting mainly with glomerulitis).
Genetic predisposition depends on genes localized on chromosomes 2 and 6.
The primary cause of the syndrome is the presence of antibodies directed against specific collagen chains, which are present in the glomerular and the pulmonary alveolar capillary basement membrane. Following an initiating event, for example, infection or toxin exposure, an autoimmune response is set in motion, resulting in crescentic glomerulonephritis and progressive deterioration in renal function and leakage of blood from alveolar capillaries into the air spaces.
The presence of bound anti-GBM antibodies in renal glomeruli is diagnostic. The antibodies are usually IgG, but may be IgA or IgM. Circulating anti-GBM antibodies are present in 90% of patients. Radioimmunoassays are more specific and sensitive than anti-GBM analysis. These findings, in addition to the presence of pulmonary hemorrhage, are pathognomonic of Goodpasture Syndrome.
Hemoptysis ranging from blood-streaked sputum to massive hemorrhage is commonly the presenting feature. Patients may complain of dyspnea and cough. Pulmonary hemorrhage may be associated with severe hypoxemia and death. Intubation, assisted ventilation, and hemodialysis are often required in the acute phase. Renal function can range from normal to severe insufficiency, and the deterioration in renal function can occur rapidly. Some proteinuria is common, but Nephrotic Syndrome is rare. Hypertension is an unusual finding. Renal ultrasonography is usually normal. Pulmonary hemorrhage is often responsive to pulse methylprednisolone therapy, whereas renal involvement rarely is. Cyclophosphamide has also been used in the management. Plasmapheresis is frequently useful in ...