Goodpasture’s syndrome

Goodpasture’s syndrome is presence of alveolar hemorrhage and glomerulonephritis along with the presence of anti–glomerular basement membrane (GBM) antibody in serum or diagnosed by immunofluorescent stains of renal or lung tissue (Ehrlich etal, 2004). Anti–glomerular basement membrane antibody disease is the alterenative name for Goodpasture’s syndrome, as it differentiates this from other pulmonary–renal syndromes. As stated by Ehrlich etal (2004)The combination of massive haemoptysis and acute renal failure (Goodpasture’s syndrome) was originally described by Goodpasture in 1918 during an influenza epidemic.

Epidemiology

Goodpastures syndrome is not a common disorder. Very few estimates of the disorder in terms of incidence is not currently known, but what is known is that this disease may account for 1% to 5% of all cases of glomerulonephritis. It has been observed that disease is more common in the white population. Males are more frequently affected, and the reported male is to female ratio varies from 2:1 to 9. The largest number of cases occur in the age group of 20 – 50 years, but the other ages are not immune from the development of this disorder (Kluth . and Rees, 1999, Ehrlich etal, 2004).

Etiology Anti-GBM antibody disease is an autoimmune disorder in which antibodies form against basement membrane, the exact reasons for which are currently unknown. The suspected etiology is viral upper respiratory tract infection (20% to 60% of patients) (Ehrlich etal, 2004). and exposure to hydrocarbon solvent (less than 5% of patients). Smoking has a very strong association (75% to 80% of patients), and this is especially common among patients with pulmonary hemorrhage.

It has been postulated that an event, such as infection or exposure to a toxin, acts as a precipitating factor in genetically predisposed persons (Wikipedia. org). This initial attack damages basement membrane and exposes an antigen that triggers IgG autoantibody production. Genetic predispositions – Anti-GBM antibody has been described in identical twins, siblings, and first cousins. HLA-DR2 is expressed in 88% of patients with anti-GBM disease compared to 25-32% of a control group of blood donors.

Important source – Andy Warhol and Asperger’s Syndrome

Simultaneous expression of HLA-B8 and HLA-DR2 is associated with a worse prognosis because of the tendency to form glomerular crescents. Anti-GBM antibody is strongly associated with HLA-DR15 and HLA-DR4 alleles. HLA-DR7 and HLA-DR1 have strong negative associations; both are highly protective (Valentini, 2006). Basement membrane is heterogeneous in the different organs of the body. The anti-GBM antibody appears to have specificity for an ? 3 domain on type IV collagen. This particular antigen is present in high concentrations in alveolar basement membranes and Glomerular Basement Membrane.

This binding specificity may account for the organ specificity of this disease as in the article by Kluth . and Rees, 1999. Once formed, the circulating autoantibody has direct access to GBM. In contrast, alveolar capillaries lack the large fenestrations of glomeruli. An increase in capillary permeability appears to be necessary for antibodies to gain access to alveolar basement membrane. Alveolar hemorrhage is more common among smokers and episodes of hemoptysis often occur after infection and fluid overload.

Once the anti-GBM antibody is bound to basement membrane, complement binding occurs, and there is an influx of neutrophils and other inflammatory cells (Ehrlich etal, 2004. Kluth . and Rees, 1999). Light microscopic examination of the kidney tissue reveals focal segmental necrotizing glomerulonephritis with epithelial crescents. Lung findings include alveolar red blood cells, hemosiderin-laden macrophages, and type II cell hyperplasia. In both the kidney and lung, immunofluorescent microscopic examination reveals linear deposits of IgG along the basement membrane( Kluth . and Rees, 1999. )

Symptomatology

The most common presenting symptom is hemoptysis (80% to 90% of patients), which can be mild to life threatening. Patients also have dyspnea, a cough, and fatigue. Patients may have fever and chills, chest pain, weight loss, in some patients, gross hematuria. Patient is usually pale from anemia. Lung examination may have normal findings or reveal rales, rhonchi, or decreased breath sounds. Patients with advanced renal disease may have peripheral edema.

Investigations Circulating anti-GBM antibodies found with enzyme-linked immunosorbent assay can be detected among more than 90% of patients. Anemia occurs among 90% of patients and is caused primarily by pulmonary blood loss. Serum iron levels are decreased. The white blood cell count may be elevated. The majority of patients have some degree of azotemia. Urinalysis reveals hematuria or proteinuria among 80% to 100% of patients. Chest x-ray of patients with alveolar hemorrhage show nonspecific patchy or diffuse alveolar infiltrates.

Several days after a bout of alveolar hemorrhage, a reticulonodular pattern may emerge which is from the clearance of hemoglobin by macrophages into lymphatic vessels and the interstitium. ( (Ehrlich etal, 2004. Kluth . and Rees, 1999, Valentini, 2006) A CT chest does not add any clinically relevant information. Pulmonary function testing reveals an elevated diffusion capacity for carbon monoxide consistent with recent alveolar hemorrhage.. Bronchoscopy performed to investigate an undiagnosed infiltrate suggests alveolar hemorrhage if the recovered lavage material is or becomes increasingly bloody during lavage (Valentini, 2006).

Lavage typically reveals hemosiderin-laden macrophages; this is a nonspecific finding that occurs with any type of bleeding in the lung. Arterial blood gas analysis may show low oxygen in the blood due to the reduced oxygen diffusion through alveoli and subsequent hypoxia. Management. The potentially fatal course of the problem requires an early diagnosis and management. The confirmation can be done immunofluorescent staining. The kidney is the preferred biopsy site for obtaining tissue biopsies, due to ease of procedure (Ehrlich etal, 2004).

Without treatment, anti-GBM disease has a very high mortality, sometimes in excess of 90%, and a high incidence of renal failure. A combination of immunosuppression and plasma exchange, allows reduction of pathogenic anti-GBM antibodies and suppression of future antibody production. Prednisone 1 to 2 mg per kilogram per day and cyclophosphamide 2 mg per kilogram per day are recommended. Plasmapheresis should be repeated every 1 to 3 days until circulating anti-GBM antibodies disappear (approximately 2 weeks) (Ehrlich etal, 2004, Valentini, 2006)

The addition of plasmapheresis to immunosuppression is associated with a faster decline in circulating antibody levels and better recovery of renal function. Renal failure with poor chance of recovery occurs among patients who come to medical attention with anuria, a creatinine level greater than 7 mg per deciliter, or more than 50% glomeruli with crescent formation at renal biopsy. Early relapse is not uncommon and has been associated with concurrent infection, fluid overload, resumption of cigarette smoking, and taper of immunosuppression (Ehrlich etal, 2004).