A patient presents with respiratory symptoms i.e. cough, hemoptysis and glomerulonephritis. His c-ANCA level in serum was found to be raised. The most likely diagnosis is:
**Core Concept**
Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a form of vasculitis that affects small- to medium-sized vessels. It is characterized by the presence of c-ANCA (cytoplasmic antineutrophil cytoplasmic antibodies) and is associated with the production of autoantibodies against proteinase 3 (PR3), a serine protease enzyme.
**Why the Correct Answer is Right**
In GPA, the formation of c-ANCA is thought to be due to the presence of PR3-ANCA antibodies, which are formed in response to the production of PR3 by neutrophils. These antibodies bind to PR3 on the surface of neutrophils, leading to the activation of neutrophils and the release of granules that contain proteases, such as PR3. This activation of neutrophils is thought to be responsible for the inflammation and tissue damage seen in GPA. The presence of c-ANCA is a hallmark of GPA, and its detection is often used as a diagnostic criterion.
**Why Each Wrong Option is Incorrect**
**Option A:** Although microscopic polyangiitis (MPA) is another form of vasculitis that is associated with the presence of p-ANCA (perinuclear antineutrophil cytoplasmic antibodies), it is not typically associated with the presence of c-ANCA.
**Option B:** Henoch-Schönlein purpura (HSP) is a form of vasculitis that primarily affects small vessels and is characterized by the deposition of IgA immune complexes. It is not typically associated with the presence of c-ANCA.
**Option C:** Polyarteritis nodosa (PAN) is a form of vasculitis that affects medium-sized vessels and is not typically associated with the presence of c-ANCA.
**Clinical Pearl / High-Yield Fact**
GPA is often associated with the presence of upper respiratory tract symptoms, such as sinusitis and chronic rhinitis, in addition to the presence of c-ANCA. This combination of symptoms should raise suspicion for GPA in patients with unexplained respiratory symptoms.
**Correct Answer:** C.