What condition presents with pulmonary hemorrhage, renal involvement, and linear glomerular basement membrane deposits, not inherited in an autosomal recessive manner?

Anti-GBM Disease (Goodpasture's Syndrome) is the Condition Described

Anti-GBM disease (Goodpasture's syndrome) is characterized by linear deposits of antibodies along the glomerular basement membrane, pulmonary hemorrhage, and is not inherited in an autosomal recessive manner. 1

Key Diagnostic Features

Anti-GBM disease presents with a distinctive constellation of findings:

• Inheritance pattern: Not autosomal recessive; it is an acquired autoimmune disorder 2
• Demographics: More common in young adults, with bimodal age distribution (20-30 years and 60-70 years) 2
• Immunofluorescence pattern: Linear deposits of IgG along the glomerular basement membrane (pathognomonic finding) 1
• Pulmonary-renal relationship: Pulmonary hemorrhage may precede, occur simultaneously with, or follow renal involvement 1
• Skin manifestations: Vasculitic skin rash is not a typical early feature of anti-GBM disease 1

Pathophysiology

Anti-GBM disease is characterized by:

• Autoantibodies (primarily IgG) directed against the NC1 domain of the α3 chain of type IV collagen in the glomerular and alveolar basement membranes 2, 3
• Type II hypersensitivity reaction with complement activation 4
• Linear deposition of antibodies along the GBM visible on immunofluorescence 1
• In approximately 30% of cases, patients may have dual positivity for both anti-GBM antibodies and ANCA 1

Clinical Presentation

The classic presentation includes:

• Rapidly progressive glomerulonephritis with hematuria, proteinuria, and declining renal function 1
• Pulmonary hemorrhage (occurs in many but not all cases) manifesting as hemoptysis, dyspnea, and cough 2
• Laboratory findings: elevated creatinine, microscopic hematuria with dysmorphic RBCs, moderate proteinuria (1-3 g/day) 1
• Positive anti-GBM antibodies in serum (though rarely can be seronegative) 5

Diagnostic Approach

1. Serologic testing: Anti-GBM antibodies, ANCA (dual positivity in 30% of cases) 1
2. Kidney biopsy: Crescentic glomerulonephritis with linear IgG deposits along the GBM on immunofluorescence 1
3. Chest imaging: To evaluate for pulmonary hemorrhage 1
4. Bronchoscopy: May be performed if pulmonary hemorrhage is suspected 5

Treatment

For patients with anti-GBM disease, especially with pulmonary hemorrhage:

• Immediate therapy: Plasmapheresis, high-dose glucocorticoids, and cyclophosphamide 1
• Plasma exchange: Particularly important in patients with pulmonary hemorrhage and should be initiated promptly 1
• Immunosuppression: Cyclophosphamide and glucocorticoids for induction therapy 4

Prognosis

Prognosis depends on:

• Renal function at presentation (serum creatinine >5.7 mg/dL indicates poor prognosis) 2
• Percentage of crescents on kidney biopsy (>50% crescents indicates poor renal outcome) 2
• Presence of pulmonary hemorrhage (increases mortality risk) 1
• Promptness of diagnosis and treatment initiation 4

Differential Diagnosis

• ANCA-associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis)
• Lupus nephritis
• Infection-related glomerulonephritis
• C3 glomerulopathy

Anti-GBM disease must be distinguished from other causes of pulmonary-renal syndrome, particularly ANCA-associated vasculitis, as treatment approaches may differ 1.