A 70-year old-man presents to his primary care physician to discuss intermittent fevers, fatigue, bloody cough, frequent bloody noses, and red urine, which he has noticed over the last six months. His medical history is significant for an episode of otitis media four months ago, which was treated with antibiotics and is now resolved. Vital signs are within normal limits. Physical examination is significant for a perforated nasal septum. Recent purified protein derivative (PPD) and interferon gamma release assay (IGRA) were both negative for tuberculosis. A chest x-ray reveals large nodular densities. Urinalysis reveals the presence of hematuria but is otherwise negative.
Which of the following laboratory findings is most likely present in this patient?
C) Positive cytoplasmic anti-neutrophil cytoplasmic antibody (cANCA)
A positive cANCA (also known as anti-PR3 or anti-proteinase 3) is a feature of granulomatosis with polyangiitis (GPA). It is a small vessel vasculitis that affects the upper and lower respiratory tracts as well as the kidneys. Manifestations include systemic signs, epistaxis, otitis media, hemoptysis, cough, dyspnea, purpura, and hematuria. GPA can present similarly to microscopic polyangiitis (a p-ANCA vasculitis); however, upper respiratory involvement is unique to GPA. Treatment is with corticosteroids and cyclophosphamide.
Answer choice A: Negative anti-neutrophilic cytoplasmic antibody (ANCA), is incorrect. Polyarteritis nodosa is a medium vessel necrotizing vasculitis that is ANCA negative. It affects multiple systems though notably spares the lungs. Manifestations include systemic symptoms, rash, myalgia, hypertension, peripheral neuropathy/mononeuritis multiplex, and hematuria.
Answer choice B: Positive anti-Saccharomyces cerevisiae antibodies (ASCA), is incorrect. Crohn disease is an ANCA negative inflammatory bowel disease that can present with positive ASCA.
Answer choice D: Positive IgM autoantibody against the Fc portion of IgG, is incorrect. This describes rheumatoid factors, which can be found in rheumatic disorders as well as other disease processes such as mixed cryoglobulinemia and hepatitis C. Although it presents with fatigue, palpable purpura, arthralgia, and renal disease, it does not typically affect the respiratory system.
Answer choice E: Positive perinuclear anti-neutrophil cytoplasmic antibody (pANCA), is incorrect. A positive pANCA (also known as anti-myeloperoxidase) can be found in several conditions including microscopic polyangiitis, eosinophilic granulomatosis, ulcerative colitis, and primary sclerosing cholangitis. Microscopic polyangiitis can present similarly to granulomatosis with polyangiitis but lacks nasopharyngeal involvement.
Key Learning Point
Granulomatosis with polyangiitis (GPA) is a necrotizing small vessel vasculitis that manifests with upper and lower respiratory as well as renal involvement. Unlike other small vessel vasculitides such as microscopic polyangiitis and eosinophilic granulomatosis which are characterized by a positive p-ANCA, GPA is characterized by a positive c-ANCA.
