musculoskeletal and connective tissue disorders
Granulomatosis with Polyangiitis (GPA)
Diagnosis of GPA
Routine laboratory tests, including urinalysis Tests for antineutrophil cytoplasmic antibodies Chest and sinonasal CT Biopsy for definitive diagnosis Granulomatosis with polyangiitis should be suspected in patients with chronic, unexplained respiratory symptoms and signs (including otitis media in adults), particularly if manifestations in other organ systems, especially the kidneys, also suggest the disorder. Routine laboratory tests are done, but ANCA testing and selective biopsy of involved tissues yield the most specific findings. Biopsy of nasal tissue only rarely provides a definite diagnosis. Routine laboratory tests include erythrocyte sedimentation rate, C-reactive protein, complete blood count with differential, serumalbuminand total protein, serum creatinine, urinalysis, 24-hour urine protein, and chest x-ray. Sinonasal CT may show sinus mucosal thickening or opacification, nasal septal perforation, and bone damage. Chest CT without contrast is nearly always necessary because the chest x-ray may miss nodules, masses, and/or cavitary lesions caused by granulomatosis with polyangiitis. In most patients with active disease, erythrocyte sedimentation rate and C-reactive protein are elevated, and serumalbuminand total protein are decreased; anemia, thrombocytosis, and mild-to-moderate eosinophilia are detected. Dysmorphic red blood cells and red blood cell casts, detected during urinalysis, indicate glomerular involvement. Proteinuria may be detected. Serum creatinine may be increased. Serologic testing to detect antineutrophil cytoplasmic antibodies (ANCA) is followed by enzyme-linked immunosorbent assay (ELISA) to check for specific antibodies. Most patients with active disease have cytoplasmic ANCA (c-ANCA), with antibodies against proteinase-3 (PR3); these findings plus characteristic clinical findings suggest GPA. Some patients with other disorders (eg, bacterial endocarditis,cocaineabuse, systemic lupus erythematosus, amebiasis, tuberculosis) test positive for ANCA. Because tests for rare diseases are likely to be falsely positive when ordered for the general population and the positive predictive value of a positive ANCA test is around 50%, ANCA testing should be reserved for patients in whom the pretest probability for GPA or another ANCA-associated vasculitis is at least moderately high (eg, patients with alveolar hemorrhage, glomerulonephritis, or multiple mononeuropathy plus other features of microscopic polyangiitis or GPA). A positive ANCA test does not rule out mycobacterial and fungal infections; thus, patients with positive ANCA results and cavitary lung lesions still require bronchoscopy and adequate cultures and other tests for tuberculosis and fungal infections. ANCA testing (titre) should not be used to guide subsequent treatment. During apparent remission, ANCA may increase or ANCA test results may change from negative to positive. In some of these patients, symptoms do not recur; in others, symptoms recur or worsen soon after the test is done or during the next few weeks, months, or sometimes years. Biopsy should be done if possible to confirm the diagnosis of GPA. Clinically abnormal sites may be biopsied first. Biopsy of affected lung tissue is most likely to reveal characteristic findings; open thoracotomy provides the best access. Biopsies of lung or sinus tissue are cultured to exclude infection. Renal biopsy that shows pauci-immune necrotizing focal crescentic or noncrescentic glomerulonephritis strongly supports the diagnosis. Biopsy results of various tissues may also provide histologic information that can help guide treatment (eg, renal fibrosis). Differential diagnosisincludes other vasculitic disorders that affect small- and medium-sized vessels. Infections, especially those due to slow-growing fungi or acid-fast organisms, should be ruled out by staining and culture of the sampled tissues. 