Review Question - QID 107185

This patient’s presentation is consistent with Wegener’s granulomatosis, now known as granulomatosis with polyangiitis (GPA). The most likely serologic finding in GPA is positive c-ANCA, which are antineutrophil cytoplasmic antibodies that target proteinase 3.

Granulomatosis with polyangiitis is an idiopathic, systemic, small-vessel vasculitis that most commonly affects the upper and lower respiratory tracts as well as the kidneys. Often accompanied by constitutional symptoms such as fever, malaise, and weight loss, an initial presentation of GPA includes recurrent sinusitis, purulent or bloody nasal discharge, oral and/or nasal ulcers, dyspnea, cough, and hemoptysis. As the disease becomes more systemic, the kidneys are most likely to be affected by a necrotizing glomerulonephritis with findings of proteinuria and hematuria. GPA is one of the ANCA-associated small-vessel vasculitides. C-ANCA has a 95% specificity for the disease.

Mansi et al. review the ANCA-associated small vessel vasculitides. In general, small vessel vasculitis should be considered in any patient with multisystem disease where infectious or malignant causes have been excluded. The differential diagnosis for ANCA-associated small vessel vasculitis includes granulomatosis with polyangiitis, Churg-Strauss syndrome, and microscopic polyangiitis. These can be differentiated by the presence of granulomas on histopathology (excludes microscopic polyangiitis) and the absence of asthma and eosinophilia (Churg-Strauss syndrome). Microscopic polyangiitis and Churg-Strauss syndrome are also associated with p-ANCA, unlike GPA.

Olson et al. performed a retrospective case-control study to determine whether subclinical measurement of c-ANCA could predict future diagnosis of GPA. Twenty-seven GPA patients were compared to age-, sex-, and race-matched controls. A significantly greater percentage of GPA patients had an elevated c-ANCA level prior to diagnosis compared to their controls (63% versus 0%, P < 0.001). Moreover, the GPA patients had a greater percentage of patients with a >1 U/mL/year increase in c-ANCA compared to controls (62% versus 0%, P < 0.001).

Figure A demonstrates palpable purpura, a cutaneous finding of small vessel vasculitis. Figure B is an H&E section of GPA with characteristic granulomas and multinucleated giant cells.

Incorrect Answers:
Answer 1: p-ANCA is associated with Churg-Strauss syndrome and microscopic polyangiitis.
Answer 3: Anti-CCP antibodies have high specificity for rheumatoid arthritis.
Answer 4: Anti-Sm antibodies target nuclear RNA binding proteins and are found in systemic lupus erythematosus.
Answer 5: Cryoglobulinemia is associated with various diseases, such as plasma cell dyscrasias, hepatitis C infection, or autoimmune disorders.