A 43-year-old male presents to the GP with a 5-day history of cough on a background of lethargy and weight loss. He denies any recent unwell contacts. He is concerned as he saw blood in his urine for the first time this morning. He denies any regular medication but he says he has recently started to depend on nasal decongestants over-the-counter, due to chronic nasal congestion.

Given the most likely diagnosis, which of the following tests are most specific in this condition?

Options:
explanation: This is incorrect because p-ANCA (antibody against myeloperoxide (MPO)) is positive in microscopic polyangiitis and Churg-Strauss. p-ANCA stands for perinuclear anti-neutrophil cytoplasmic antibodies, whereas c-ANCA refers to cytoplasmic anti-neutrophil cytoplasmic antibodies. The terminology originates from the pattern of staining seen during immunoflouresence. Churg-Strauss is also known as eosinophilic granulomatosis with polyangiitis, and can present with a nephritic/rapidly progressive glomerulonephritis picture, as well as other clinical features such as eosinophilia and poorly controlled asthma. Microscopic polyangiitis has a less well defined constellation of clinical features, and may present non-specifically with virtually any organ system involved, as one would expect of a vasculitis disorder.
name: p-ANCA
label: b
answer: no
explanation: This is the correct answer because c-ANCA (antibody to proteinase-3 (PR-3)) is associated with granulomatosis with polyangiitis (GPA). This is a small-medium vessel vasculitis. This question stem describes the classic triad of upper and lower respiratory tract involvement (sinusitis and cough, often progressing to haemoptysis) and renal involvement (haematuria, which usually indicates a nephritic/crescentic presentation and a rapidly progressive deterioration in renal function.) c-ANCA is a highly specific antibody for Wegener's granulomatosis (the eponymous name, which has since been superseded by GPA), however its absence does not exclude the disease. Patients may develop a saddle-nose deformity due to collapse of the nasal cartilage.
name: c-ANCA
label: a
answer: yes
explanation: Anti-dsDNA antibodies are specific to Systemic Lupus Erythematosus (SLE.) SLE is an autoimmune rheumatic condition which presents with systemic symptoms such as fever, myalgia and weight loss as well as joint and skin involvement. It is important to remember that ANA antibodies are sensitive but not specific as they can be found in many other rheumatological conditions.
name: Anti-dsDNA
label: d
answer: no
explanation: ANAs are not specific and may be present in many of the autoimmune rheumatic disorders, including SLE, systemic sclerosis, Sjogren's syndrome, polymyositis and dermatomyositis. They are a reasonably sensitive test for diagnosing Systemic Lupus Erythematosus (SLE.) This question stem points towards granulomatosis with polyangiitis, and though ANA may well be positive due to its reasonably non-specific character, the more specific test is c-ANCA.
name: ANA
label: c
answer: no
explanation: Anti-Scl70 antibodies are reasonably specific to diffuse cutaneous systemic sclerosis, which presents with widespread skin fibrosis and potential multi-organ involvement, most notably kidney and pulmonary. This is not associated with granulomatosis with polyangiitis, which is the diagnosis in this case as indicated by the classic triad of symptoms.
name: Anti-Scl70
label: e
answer: no

Correct answer: a


Learning point: c-ANCA antibodies are highly specific for granulomatosis with polyangiitis, a condition characterised by respiratory and renal involvement.