A 55-year-old man comes to the physician due to myalgias, arthralgias, and weight loss. He has not felt well for 2 years. Over that time, he has experienced 4 episodes of sinusitis that responded poorly to treatment and required prolonged courses of antibiotics for symptom resolution. During the last 6 months, the patient has experienced diffuse aches. He has pain that migrates from his knees to his shoulders and wrists and has also lost 4.5 kg (10 lb). He has no history of hypertension, diabetes mellitus, or chronic kidney disease.
His blood pressure is 138/90 mm Hg. A small amount of crusted blood is present in one nostril. There are no other significant physical findings.
Laboratory results are as follows:

Chest CT reveals two 2-3 cm nodules in the left upper lobe. Serum anti-neutrophil cytoplasmic antibodies are negative.
Which of the following would be the best method to establish the diagnosis?

Question

A 55-year-old man comes to the physician due to myalgias, arthralgias, and weight loss.  He has not felt well for 2 years.  Over that time, he has experienced 4 episodes of sinusitis that responded poorly to treatment and required prolonged courses of antibiotics for symptom resolution.  During the last 6 months, the patient has experienced diffuse aches.  He has pain that migrates from his knees to his shoulders and wrists and has also lost 4.5 kg (10 lb).  He has no history of hypertension, diabetes mellitus, or chronic kidney disease.
His blood pressure is 138/90 mm Hg.  A small amount of crusted blood is present in one nostril.  There are no other significant physical findings.
Laboratory results are as follows:

Chest CT reveals two 2-3 cm nodules in the left upper lobe.  Serum anti-neutrophil cytoplasmic antibodies are negative.
Which of the following would be the best method to establish the diagnosis?

Quizplus · Accepted Answer

This patient most likely has granulomatosis with polyangiitis (GPA), formerly called Wegener's granulomatosis. Prompt diagnosis and institution of therapy may be kidney- and life-sparing. GPA is suspected in patients with >2 of the following: nasal or oral inflammation, abnormal chest radiograph, abnormal urinary sediment, and granulomatous inflammation on biopsy of an artery or perivascular area. Pathogenesis involves anti-neutrophilic cytoplasmic antibodies (ANCA) reacting with 1 of 2 proteins (serine proteinase 3 or myeloperoxidase) on the surface of cytokine-stimulated white blood cells. Although up to 90% of patients with generalized GPA have positive ANCA, negative ANCA does not rule out the diagnosis. Tissue biopsy is typically obtained at the site of active disease (eg, skin, kidney, lung) to make a definitive diagnosis. This patient has evidence of renal disease with active urinary sediment; therefore, kidney biopsy should be obtained and may show pauci-immune segmental necrotizing glomerulonephritis with few or no immune deposits on electron microscopy. Lung biopsy can be obtained in patients with predominant lung disease; however, this often requires open or thoracoscopic biopsy as transbronchial biopsy generally does not yield a sufficient quantity of tissue (Choice B). The diagnostic yield of nasal biopsy is also very low due to the small amount of tissue obtained (Choice D). Therapy should be started in patients with suspected GPA if there is a delay in obtaining tissue biopsy, regardless of the ANCA result. (Choice A) Infective endocarditis can have a similar presentation, especially if it is right-sided given the lung lesions. However, this patient's 6-month history of multiple, refractory sinus infections makes this diagnosis unlikely. (Choice E) Urine eosinophils are seen in acute interstitial nephritis, which is rarely associated with GPA. In addition, this patient has no rash or history of recent exposure to triggering medications. Educational objective: Prompt diagnosis of granulomatosis with polyangiitis can be life- and kidney-sparing. Although positive anti-neutrophilic cytoplasmic antibodies (ANCA) support the diagnosis, both false-positive and false-negative ANCA results do occur. Tissue biopsy is typically obtained at the site of active disease to make a definitive diagnosis (eg, skin, kidney, lung). __________ References: ANCA-negative pauci-immune renal vasculitis: histology and outcome. (http://www.ncbi.nlm.nih.gov/pubmed/15855209) Renal histopathology and clinical course in 94 patients with Wegener's granulomatosis. (http://www.ncbi.nlm.nih.gov/pubmed/11328900)

A 55-Year-Old Man Comes to the Physician Due to Myalgias