Good pasteur syndrome

AUTOIMMUNE DISEASE

1. GOOD PASTEUR SYNDROME

2. A subtype of pulmonary-renal syndrome, is an autoimmune syndrome of alveolar haemorrhage and glomerulonephritis caused by circulating anti-glomerular basement membrane (anti-GBM) antibodies. Goodpasture syndrome most often develops in genetically susceptible people who smoke cigarettes, but hydrocarbon exposure and viral respiratory infections are additional possible triggers. Symptoms are dyspnoea, cough, fatigue, haemoptysis, and haematuria. Goodpasture syndrome is suspected in patients with haemoptysis or haematuria and is confirmed by the presence of anti-GBM antibodies in the blood or in a renal biopsy specimen. Prognosis is good when treatment is begun before onset of respiratory or renal failure. Treatment includes plasma exchange, corticosteroids, and immunosuppressants, such as cyclophosphamide. Goodpasture syndrome is a rare but serious autoimmune disease that attacks the lungs and kidneys. The disease occurs when the body's immune system mistakenly produces antibodies against collagen in the lungs and kidneys. Collagen is a protein that helps form connective tissue. Goodpasture syndrome initially causes vague symptoms such as fatigue. But it can rapidly involve the lungs and kidneys. It is almost always fatal if it is not quickly diagnosed and treated.

3. PATHOPHYSIOLOGY Goodpasture syndrome is the combination of glomerulonephritis with alveolar haemorrhage and anti-GBM antibodies. Goodpasture syndrome most often manifests as diffuse alveolar haemorrhage and glomerulonephritis together but can occasionally cause glomerulonephritis (10 to 20%) or pulmonary disease (10%) alone. Men are affected more often than women. Anti-GBM antibodies are directed against the non collagenous (NC-1) domain of the alpha3 chain of type IV collagen, which occurs in highest concentration in the basement membranes of renal and pulmonary capillaries. Environmental exposures—cigarette smoking, viral URI, and hydrocarbon solvent inhalation most commonly and pneumonia less commonly—expose alveolar capillary antigens to circulating antibody in genetically susceptible people, most notably those with HLA-DRw15, -DR4, and -DRB1 alleles. Circulating anti-GBM antibodies bind to basement membranes, fix complement, and trigger a cell-mediated inflammatory response, causing glomerulonephritis, pulmonary capillaritis, or both.

4. SYMPTOMS Haemoptysis is the most prominent symptom; however, haemoptysis may not occur in patients with alveolar haemorrhage, and patients may present with only chest x-ray infiltrates or with infiltrates and respiratory distress, respiratory failure, or both. Other common symptoms include Dyspnea Cough Fatigue Fever Weight loss Haematuria

5. DIAGNOSIS Serum anti-GBM antibody tests Sometimes renal biopsy Patients are tested for serum anti-GBM antibodies by indirect immunofluorescence testing or, when available, direct enzyme-linked immunosorbent assay (ELISA) with recombinant or human NC-1 alpha3. Presence of these antibodies confirms the diagnosis. Antineutrophil cytoplasmic antibodies (ANCA) testing is positive (in a peripheral pattern) in only 25% of patients with Goodpasture syndrome. If anti-GBM antibodies are absent and patients have evidence of glomerulonephritis (haematuria, proteinuria, red cell casts detected with urinalysis, renal insufficiency, or a combination of these findings), renal biopsy is indicated to confirm the diagnosis. A rapidly progressive focal segmental necrotizing glomerulonephritis with crescent formation is found in biopsy specimens in patients with Goodpasture syndrome and all other causes of pulmonary-renal syndrome. Immunofluorescence staining of renal or lung tissue classically shows linear IgG deposition along the glomerular or alveolar capillaries. IgG deposition also occurs in the kidneys of patients with diabetes or with fibrillary glomerulonephritis (a rare disorder causing the pulmonary-renal syndrome), but GBM binding of antibodies in these disorders is nonspecific and does not occur in linear patterns.

6. TREATMENT Plasma exchange Corticosteroids and cyclophosphamide Immediate survival in patients with pulmonary haemorrhage and respiratory failure is linked to airway control; endotracheal incubation and mechanical ventilation are recommended for patients with borderline ABGs and impending respiratory failure. Patients with significant renal impairment may require dialysis or kidney transplantation. Treatment is daily or every-other-day plasma exchange for 2 to 3 week using 4-L exchanges to remove anti-GBM antibodies, combined with a corticosteroid to prevent formation of new antibodies. Therapy can be tapered when pulmonary and renal function stop improving. Rituximab could be used in some patients who have severe adverse effects due to cyclophosphamide or refuse cyclophosphamide as treatment, but it has not been studied in patients with Goodpasture syndrome.