A 26-year-old previously healthy man comes to the office with a 3-week history of shortness of breath, cough, and hemoptysis preceded by an upper respiratory tract infection. He has no fever, night sweats, or weight loss. His blood pressure is 150/85 mm Hg and pulse is 86/min and regular. Physical examination reveals bilateral inspiratory crackles and lower extremity edema. His creatinine is 4.1 mg/dL. Urinalysis shows proteinuria and hematuria with dysmorphic red blood cells. Bilateral pulmonary infiltrates are seen on chest x-ray. He is also found to have an increased carbon monoxide diffusing capacity (DLCO) on pulmonary function testing. Antibodies directed against which of the following is most likely to be associated with this patient's condition?

Question

A 26-year-old previously healthy man comes to the office with a 3-week history of shortness of breath, cough, and hemoptysis preceded by an upper respiratory tract infection.  He has no fever, night sweats, or weight loss.  His blood pressure is 150/85 mm Hg and pulse is 86/min and regular.  Physical examination reveals bilateral inspiratory crackles and lower extremity edema.  His creatinine is 4.1 mg/dL.  Urinalysis shows proteinuria and hematuria with dysmorphic red blood cells.  Bilateral pulmonary infiltrates are seen on chest x-ray.  He is also found to have an increased carbon monoxide diffusing capacity (DLCO) on pulmonary function testing.  Antibodies directed against which of the following is most likely to be associated with this patient's condition?

Quizplus · Accepted Answer

This patient has Goodpasture syndrome, which is caused by autoantibodies against the alpha 3 chain of type IV collagen found in the glomerular basement membrane (GBM) and pulmonary capillary membrane (anti-GBM antibodies). Antibody formation may be triggered by an antecedent viral respiratory infection, although most cases are idiopathic. These antibodies promote inflammatory injury of the glomerular and alveolar basement membranes, resulting in rapidly progressive glomerulonephritis and alveolar hemorrhage, respectively. Rapidly progressive glomerulonephritis results in nephritic syndrome, characterized by hypertension, edema, acute renal failure, hematuria (eg, dysmorphic red cells and red cell casts), and proteinuria. On renal biopsy, light microscopy shows glomerular crescent formation and immunofluorescence shows linear deposition of IgG and C3 on the GBM. Alveolar hemorrhage manifests with shortness of breath and hemoptysis with infiltrates on chest x-ray. Hemoglobin in the alveoli leads to increased alveolar oxygen absorption and high carbon monoxide diffusing capacity (DLCO). (Choice B) Patients with beta-hemolytic streptococci infection of the pharynx or skin can develop glomerular immune complex deposition resulting in poststreptococcal glomerulonephritis and nephritic syndrome; however, this usually occurs in children and pulmonary involvement with alveolar hemorrhage is not characteristic. (Choice C) Anticardiolipin antibodies are characteristic of antiphospholipid antibody syndrome, which typically presents with unprovoked/recurrent arterial and venous thrombosis or recurrent spontaneous abortions. (Choice D) Antibodies to double-stranded DNA (dsDNA) are typically seen in systemic lupus erythematosus (SLE), particularly in individuals with active lupus nephritis. Although this patient has findings of glomerulonephritis, other features of SLE such as constitutional symptoms (eg, fatigue, fever, weight loss), malar rash, arthritis, serositis, and cytopenias are not evident. Pulmonary hemorrhage is also not characteristic of SLE. (Choice E) Anti-topoisomerase I (anti-Scl-70) antibodies are found in patients with systemic sclerosis, which typically presents with diffuse thickening/hardening of the skin, Raynaud phenomenon, and esophageal dysfunction. Acute renal failure and hypertension may occur during scleroderma renal crisis; however, glomerulonephritis is not characteristic. Lung involvement typically leads to pulmonary fibrosis and pulmonary arterial hypertension as opposed to pulmonary hemorrhage. Educational objective: Goodpasture syndrome is caused by autoantibodies against the alpha 3 chain of type IV collagen in glomerular and alveolar basement membranes (anti-GBM antibodies). Patients typically present with rapidly progressive glomerulonephritis (nephritic syndrome) and alveolar hemorrhage (shortness of breath, hemoptysis). __________ References: Specificity of circulating and tissue-bound autoantibodies in Goodpasture syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/8705733) Goodpasture's disease: a report of ten cases and a review of the literature. (http://www.ncbi.nlm.nih.gov/pubmed/23806563)

A 26-Year-Old Previously Healthy Man Comes to the Office with a 3-Week