**6.2 PN in granulomatosis with polyangiitis**

GPA is a systemic ANCA-associated granulomatous vasculitis whose lesions primarily affect the respiratory tract and kidneys [47]. Its annual incidence is 5–10/ million with a prevalence of 24–157 cases per million. It occurs in both sexes at 65–74 years of age [48, 49]. GPA can affect the central and peripheral nervous system. Centrally, it can be responsible for strokes, brain masses, seizures, and meningitis. Peripherally, in the systemic form of the disease, it can present with a sensorimotor neuropathy or as a mononeuritis multiplex. Nasosinus involvement is observed in 70–100% of patients and present with epistaxis, nasal ulcers, nasal septum perforation and deformation (**Figure 1**) [50, 51]. The lungs are the second most common affected organ in 50–90% of patients and present with lung nodules, cavitations, infiltrates, pleuritis, pleural effusions, or alveolar capillary hemorrhages. Renal involvement affects 40–100% of patients with hematuria, proteinuria and renal failure due to segmental necrotizing and pauci-immune glomerulonephritis. Skin manifestations include vascular purpura, ulcers and nodules. The systemic symptoms include myalgia, arthralgia, anorexia, weight loss, ocular scleritis, episcleritis, uveitis, retinal alterations, retinal, thrombosis, orbital masses granulomatosis, myopericarditis, intestinal perforation and mesenteric vasculitis [50]. To make the diagnosis of PN related to GPA, it is necessary to consider all the clinical manifestations suggestive of systemic vasculitis like C-ANCA (anti-PR3) determination and histological evidence of necrotizing vasculitis, necrotizing glomerulonephritis or granulomatous inflammation from a relevant organ biopsy. In 1990, the American College of Rheumatology established criteria to help the diagnosis of GPA (**Table 2**) [52].

#### **Figure 1.**

*Saddle nose deformity caused by bony destruction of the nasal cavity in a patient with Wegener's granulomatosis [50].*


At least two of the four ACR criteria are required to classify vasculitis as GPA with a sensitivity and specificity of 88% and 92%, respectively.

#### **Table 2.**

*ACR classification of GPA [52].*

### **6.3 Peripheral neuropathy in microscopic polyangiitis**

Microscopic polyangiitis is an uncommon systemic vasculitis associated with perinuclear antineutrophil cytoplasmic (p-ANCA) or anti-myeloperoxidase (MPO). It was formerly considered as polyarteritis nodosa and in 1950, Wainwright and Davson used the phrase "microscopic polyarteritis" to describe this phenotype [53]. Microscopic polyangiitis predominates in men with an average age at onset between 50 and 60 years. Clinical manifestations include general symptoms of fever and weight loss in 70% of patients. Renal involvement is the main feature of MPA. It is characterized by a rapidly progressive glomerulonephritis in 80–100% of patients. It is shown by proteinuria in the nephrotic range in up to 50% of patients, microscopic hematuria, and urinary granular or red blood cell casts. Renal biopsy reveals focal segmental necrotizing glomerulonephritis in up to 100% of patients [54]. The second major organ being affected is the lung in 55% of patients. Clinical manifestations include hemoptysis and alveolar hemorrhage, infiltrates, pleural effusion, pulmonary edema, pleuritis and interstitial fibrosis. These symptoms are related to diffuse alveolar hemorrhage [55].

Computed tomography is necessary to confirm alveolar hemorrhage demonstrating the ground-glass attenuation (seen in >90% of patients) interstitial chronic inflammation of the alveolar septa and capillaritis (**Figure 2**) [55]. Skin lesions occur in 30–60% of patients being vascular purpura the main presentation. Other skin manifestations include livedo reticularis, nodules, urticaria and skin ulcers with necrosis. Skin manifestations are usually accompanied with arthralgia [54]. Neurologic involvement is common and affects between 37 and 72% of the patients. PN is a predominant feature that presents with a mononeuritis multiplex and distal symmetrical polyneuropathy [53]. Other clinical symptoms are gastrointestinal bleeding, intestinal ischemia, and liver dysfunction [54]. ANCA is the laboratory test that facilitate the diagnosis and is positive in 50–75% of patients with MPA, but its absence does not exclude its diagnosis. Biologic markers of inflammation are elevated such as erythrocyte sedimentation rate and C-reactive protein [56]. The diagnosis of the disease is based on clinical symptoms and biopsy of the affected organs.
