**6.1 PN in eosinophilic granulomatosis with polyangiitis**

Eosinophilic granulomatosis with polyangiitis formerly named Churg–Strauss syndrome is a systemic small-vessel vasculitis associated with asthma and eosinophilia. It was first described in 1951 by Churg and Strauss [33] who remarked the association between asthma, eosinophilia, systemic symptoms and the presence of necrotizing and granulomatosis vasculitis in different organs especially in the peripheral nerves [33]. EGPA is a rare disease, with an annual incidence of 0.5–4.2 cases per million inhabitants [34]. It affects people aged between 40 and 60 years with no gender predominance or ethnic predisposition [35, 36]. In 1990, the American College of Rheumatology (ACR) defined the classification criteria for EGPA to include asthma, eosinophilia >10%, neuropathy, non-fixed lung infiltrates, paranasal sinus abnormalities and extravascular eosinophils on biopsy (**Table 1**) [37].

A histologic diagnosis was required in the Chapel Hill classification in 1994 and 2012 [2, 37, 38]. EGPA is a necrotizing vasculitis with an eosinophilic-rich, granulomatous inflammation affecting small- to medium-sized blood vessels in the respiratory tract.

EGPA should be suspected in a patient with an adult-onset asthma in association with multiple systemic symptoms and a subacute asymmetric neuropathy. Asthma of variable severity is noted in 95–100% of patients and could precede the systemic manifestations by many years. Allergic rhinitis, recurrent sinusitis and nasal polyposis are also seen in the prodromic EGPA phase [39–41]. Eosinophilic cell infiltrates are

2.Eosinophilia >10%


<sup>1.</sup>Asthma

<sup>3.</sup>Neuropathy (mono- or poly-neuropathy)

<sup>4.</sup>Non-fixed pulmonary infiltrates

### *Demyelination Disorders*

found in the lung, heart and gastrointestinal tract. The lung parenchyma is affected in up to two-thirds of EGPA patients [41]. Chest X-ray abnormalities generally consist of mainly peripheral, patchy and migratory infiltrates. On high-resolution CT, they appear as ground-glass opacities or poorly defined areas of consolidation, which often coexist with abnormalities due to lower airway involvement, such as tree-in-bud signs, bronchial wall thickening and small centrilobular nodules [41]. The second type of lung involvement is alveolar hemorrhage, which affects 3–8% of the patients [13, 41]. Heart involvement is a poor prognostic factor of the disease and correlated with the level of eosinophilia. Endomyocardial infiltration is the dominant feature, but coronary vasculitis, pericarditis and valvular defects may also occur [42]. Venous thromboembolic events, such as deep venous thrombosis and/or pulmonary embolism, are associated with eosinophilia [43]. Renal involvement can also be seen ranging from isolated urinary abnormalities (i.e., microscopic hematuria, proteinuria) to rapidly progressive glomerulonephritis. Skin lesion such as purpura, nodules, urticaria, livedo, and skin ulcers could also be reported mainly in the lower limbs [41].

PN is considered a cardinal feature of the vasculitic phase with a prevalence of 70% [41, 44, 45]. PN is often associated with generalized signs and symptoms of fever, weight loss, and weakness. It usually presents as a mononeuritis multiplex, often complicated by asymmetric foot or wrist drop, but it may also evolve into a symmetric or asymmetric polyneuropathy [41]; sensory deficits and neuropathic pain are frequent [19, 26]. PN is more frequent in ANCA-positive patients than in patients without ANCA antibodies [41, 44].

Laboratory findings in EGPA include a marked peripheral eosinophilia (usually >1500 cells/μL), which correlates with disease activity [46]. C-reactive protein and erythrocyte sedimentation rate are also high in the active phase [41]. ANCA with perinuclear immunofluorescence is noted in 74–90% [41]. Histologic confirmation is the key diagnosis with leukocytoclastic vasculitis with eosinophilic granulomas in biopsy sites such as the lung or kidney. Granulomas are rarely found in peripheral nerves [41].
