ICEP predominantes in women with a 2:1 female-to-male ratio [9, 13], with a peak of incidence in the fourth decade [9], and a mean age of 45 years at diagnosis [13]. A majority of patients with ICEP are nonsmokers [9, 13], suggesting that smoking might be protective. About half of the patients have a history of atopy [9, 13] and up to two thirds have a history of asthma [9, 12, 13, 16, 17], with no particularities in the clinical presentation of ICEP with the exception of higher total immunoglobulin (Ig) E levels in asthmatics [12]. In addition, asthma may develop concomitantly with the diagnosis of ICEP (15 % of patients) or develop after ICEP (about 15 % of patients) [12]. Asthma in patients with ICEP often gets worse and requires long-term oral corticosteroid treatment [12].

ICEP is characterized by the progressive onset of cough, dyspnea, and chest pain [9, 13], with a mean interval between the onset of symptoms and the diagnosis of 4 months [13]. Mechanical ventilation may be required on exceptional occasion. Hemoptysis is rare but can occur in up to 10 % of cases [9, 13]. Chronic rhinitis or sinusitis symptoms are present in about 20 % of patients [13]. At lung auscultation, wheezes are found in one third of patients [9] and crackles in 38 % [13]. Systemic symptoms and signs are often prominent, with fever, weight loss (>10 kg in about 10 %), and commonly asthenia, malaise, fatigue, anorexia, weakness, and night sweats.

The imaging features of ICEP are characteristic, although they may overlap with those found in cryptogenic organizing pneumonia. Peripheral opacities at chest x-ray present in almost all cases [8, 9, 13, 18, 19] consist of alveolar opacities with ill-defined margins, with a density varying from ground-glass to consolidation (Fig. 15.1), and are migratory in 25 % of patients [13]. The classic pattern of “photographic negative or reversal of the shadows usually seen in pulmonary edema,” highly evocative of ICEP, is seen in only one fourth of patients [9], however peripheral and upper zone predominance of abnormalities is usually present.

Whereas the opacities are bilateral in at least 50 % of cases at chest x-ray [9], the proportion of bilateral opacities increases up to more than 95 % at high-resolution computed tomography (HRCT) [13] (Fig. 15.2). Predominance of ground-glass attenuation and consolidation in the periphery and upper lobes of the both lungs [9, 13] is very suggestive of ICEP [13, 19, 20]. Septal line thickening is common [20]. Centrilobular nodules (less than 20 % of cases) [19], consolidation with segmental or lobar atelectasis, can also be seen. Upon corticosteroid treatment, consolidation rapidly decreases in extent and density, possibly evolving to ground-glass attenuation or inhomogeneous opacities, and later to streaky or bandlike opacities parallel to the chest wall. Cavitary lesions are extremely rare and should lead to reconsideration of the diagnosis. Reverse halo sign that is very suggestive of organizing pneumonia is rare contrary in ICEP. Pleural effusions (which are common in IAEP) are rare and usually mild or moderate in ICEP. Mediastinal lymph node enlargement may be seen in 15–20 % of cases [13].

Peripheral blood eosinophilia is a diagnostic criterion of ICEP, and therefore the proportion of patients with ICEP and possible normal peripheral blood count is unknown. The mean blood eosinophilia was 5.5 × 10⁹/L in our series [13]. Eosinophils represent 26–32 % of the total blood leukocyte count [9, 13]. C-reactive protein level is elevated [9, 13]. Total blood IgE level is increased in about half of cases and greater than 1,000 kU/L in 15 % [13]. Antinuclear antibodies may occasionally be present [13]. Urinary EDN level indicating active eosinophil degranulation is markedly increased [21].

BAL eosinophilia is constant and key to the diagnosis of ICEP, obviating the need for lung biopsy in the vast majority of cases (Table 15.2). The mean eosinophil percentage at BAL differential cell count was 58 % at diagnosis in the series from our group [13], however the eosinophil count drops within a few days upon corticosteroid treatment. The percentage of neutrophils, mast cells, and lymphocytes a BAL may also be increased [13]. Sputum eosinophilia may also be present.

BAL eosinophils of patients with ICEP show features of cell activation and release eosinophil proteins, which are phagocytosed by macrophages. ECP and EDN levels are increased in the BAL fluid. Eosinophils are recruited to the lung through various chemokines, and are resistant to Fas-induced apoptosis. Eosinophilic activation may be compartmentalized to the lung, as expressed by differential expression of HLA-DR molecules between alveolar and blood eosinophils. BAL lymphocytes include CD4⁺ memory T-cells (expressing CD45RO+, CD45RA⁻, CD62L⁻), and may present clonal rearrangement of the T-cell receptor repertoire [3].

Extrapulmonary manifestations when present should challenge the diagnosis of ICEP and especially to consider EGPA or overlap between ICEP and EGPA. Arthralgias, repolarization (ST-T) abnormalities on the electrocardiogram, pericarditis, altered liver biologic tests, eosinophilic lesions at liver biopsy, mononeuritis multiplex, diarrhea, skin nodules, immune complex vasculitis in the skin, and eosinophilic enteritis have been occasionally reported in ICEP [8, 13]. Furthermore, eosinophilic pneumonia may be a presenting feature of EGPA; corticosteroid treatment prescribed for ICEP may prevent the subsequent development of overt systemic vasculitis.

An obstructive ventilatory defect is present in about half the patients [9, 13], and a restrictive ventilatory defect in the other half [13]. The CO transfer factor is decreased in half of patients, and the transfer coefficient in about one fourth. Hypoxemia (PaO₂ <75 mmHg) present in two thirds of patients [13] may be due to right-to-left shunting in consolidated areas of the lung, as suggested by increased alveolar-arterial oxygen gradient [9]. With treatment, the lung function tests rapidly return to normal in most patients [9]. However, a ventilatory obstructive defect may develop over years in some patients, especially those with a markedly increased BAL eosinophilia at initial evaluation [22].

Because most patients receive corticosteroids, the natural course of untreated ICEP is not well known [9]. However, spontaneous resolution of ICEP may occur [9, 13]. The clinical and radiologic response to corticosteroids is dramatic, with improvement of symptoms within 1 or 2 weeks and even within 48 h in about 80 % [13] of cases, and rapid clearance of pulmonary opacities at chest x-ray. In one series, the chest radiograph was significantly improved at 1 week in 70 % of patients, and almost all had a normal chest x-ray at their last follow-up visit [13]. Death directly resulting from ICEP is exceedingly rare.

The optimal dose of corticosteroids is not established, but treatment may be initiated with 0.5 mg/kg/day of prednisone, with slow tapering over 6–12 months based on clinical evaluation and blood eosinophil cell count. Most patients require treatment for longer than 6–12 months because of relapse in more than half of patients while decreasing below a daily dose of 10–15 mg/day of prednisone, or after stopping oral corticosteroids treatment [9, 13]. Relapses respond very well to corticosteroid treatment, that usually can be resumed at a dose of about 20 mg/day of prednisone [13].

The clinical series in which long-term follow-up is available clearly show that most patients need very prolonged corticosteroid treatment: in a series with a mean follow-up of 6.2 years, only 31 % were weaned at the last control visit [13]. Relapses of ICEP must be distinguished from asthma symptoms, and are less frequent in asthmatics, possibly because of inhaled corticosteroids prescribed after stopping oral corticosteroids [12, 13]. Inhaled corticosteroids might thus help in reducing the maintenance dose of oral corticosteroids, although they are not effective enough when given as monotherapy [23]. Long-term steroid use may lead to osteoporosis. Omalizumab, a recombinant humanized monoclonal antibody against IgE, was reported to prevent recurrence of ICEP and to spare oral corticosteroids in case reports, however caution must be exerted given recent reports of omalizumab-associated EGPA [24, 25]. The anti-IL-5 monoclonal antibody mepolizumab has not yet been evaluated in patients with ICEP.

IAEP may present at any age [30], however the mean age at presentation is around 30 years [14, 30], with a very strong predominance in males [29]. Most patients have no prior asthma history [17]. However, taking a thorough exposure history is mandatory, as a causative role of cigarette smoke is established. Most patients have been recently exposed to dust or cigarette smoke within the days before onset of disease, and often will have begun to smoke, restarted to smoke, or increased the number of cigarettes smoked daily, especially within 1 month before the onset of “idiopathic” AEP [29, 31]. The disease is therefore often not “idiopathic”, being initiated or triggered by inhaled nonspecific causative agents in susceptible individuals, however it can occur in the absence of any inhaled exogenous trigger. AEP may develop soon after the initiation of smoking especially when starting with large quantities, and may relapse – not always – in patients who resume cigarette smoking [29, 31]. Flavoring components of smoked cigars have been suspected. In addition, the onset of IAEP seem to follow in some patients outdoor activities or peculiar exposures, such as cave exploration, plant repotting, wood pile moving, smokehouse cleaning, motocross racing in dusty conditions, indoor renovation work, gasoline tank cleaning, explosion of a tear gas bomb, or exposure to World Trade Center dust [14, 30, 32].

IAEP develops acutely or subacutely over less than 1 month in previously healthy individuals, with cough, dyspnea, fever, and chest pain at presentation [11, 30]. More than half of patients present with acute respiratory failure [29]. Abdominal complaints and also myalgias can occur [14]. Clinical signs include crackles or, less often, wheezes, and tachypnea and tachycardia.

Imaging of patients with IAEP is quite distinct from those with ICEP. In addition to bilateral alveolar and/or interstitial opacities (Fig. 15.3) [14, 27, 28, 30], the chest x-ray commonly shows bilateral pleural effusion and Kerley B lines [14]. The chest x-ray returns to normal within 3 weeks [14, 30], with pleural effusions being the last abnormality to disappear [14]. Typical computed tomography (CT) abnormalities include ground-glass attenuation and air space consolidation (Fig. 15.4), with poorly defined nodules. Interlobular septal thickening and bilateral pleural effusion seen in a majority of patients are highly suggestive of the diagnosis in the setting of eosinophilic pneumonia [14, 18, 27, 30, 33] (or in a patient spuriously suspected to have infectious pneumonia).

In contrast with ICEP, peripheral blood eosinophilia is usually lacking at presentation, with white blood cell count showing increased leukocyte count with a predominance of neutrophils. However, the eosinophil count often rises within days during the course of disease [14, 17, 30], a retrospective finding very suggestive of IAEP. Eosinophilia is also present at pleural fluid differential cell count [14] and in the sputum [17]. The IgE level may be elevated. Serum levels of thymus and activation-regulated chemokine (TARC/CCL17) (and other biomarkers including KL6 and exhaled nitric oxide) are often increased in IAEP, however lack of specificity of this finding does not rule out acute lung injury or infectious pneumonia [34, 35].

BAL is the key to the diagnosis of IAEP, especially in patients without blood eosinophilia at presentation. The finding of greater than 25 % eosinophils at BAL generally obviates the lung biopsy, at least in immunocompetent patients The average percentage of eosinophils at BAL differential count varies between series (37 % [14] to 54 % [30]), and lymphocyte and neutrophil counts can be moderately increased. Importantly, systematic bacterial cultures of BAL fluid are sterile, and appropriate stainings are negative, ruling out infectious agents that can cause AEP. After recovery, eosinophilia at BAL may persist for several weeks.

Hypoxemia may be severe in patients with IAEP, a majority of whom fit the definition of ARDS of various severity (except that there is no known clinical insult identified in IAEP), e.g. acute onset of respiratory failure not fully explained by cardiac failure or fluid overload (with objective exclusion of hydrostatic edema), bilateral opacities (not fully explained by effusions, lobar/lung collapse, or nodules), and a PaO₂/FiO₂ [fractional inspired oxygen concentration] <300 mmHg with positive end-expiratory pressure or continuous positive expiratory pressure ≥5 cm H₂O [36]. However, shock is exceptional and extrapulmonary organ failure does not occur in IAEP, in sharp contrast with IAEP.

Hypoxemia is associated with right-to-left shunting in areas with consolidation, and may be refractory to breathing 100 % oxygen in some patients [26, 30]. Alveolar-arterial oxygen gradient is increased [14]. Although mechanical ventilation was necessary in a majority of patients in earlier series [14, 30], more recent series have shown that the severity of IAEP is more varied than originally reported [29].

When performed in less severe cases, lung function tests show a mild restrictive ventilatory defect with normal forced expiratory volume in 1 s–to–forced vital capacity (FEV₁/FVC) ratio and reduced transfer factor. After recovery, lung function tests are generally normal, with possible ventilatory restriction in some of them [14].

Lung biopsy is seldom necessary when BAL demonstrates alveolar eosinophilia. In older series of patients with IAEP, lung biopsy has shown acute and organizing diffuse alveolar damage together with interstitial alveolar and bronchiolar infiltration by eosinophils, intra-alveolar eosinophils, and interstitial edema [11, 14, 37].

Exclusion of possible causes of AEP, especially infections and drugs, is key to the management of patients with AEP. Recovery of IAEP can occur without corticosteroid treatment [30, 34], and therefore improvement concomitant with corticosteroid treatment is not a diagnostic criterion of IAEP. In most patients diagnosed with IAEP, a corticosteroid treatment is initiated, with initially intravenous methyl prednisolone later changed to oral prednisone or prednisolone that can be tapered over 2–4 weeks [14]. FiO₂ may be decreased within a few hours of corticosteroid treatment in many patients initially requiring oxygen [14]; most patients are rapidly weaned from the ventilator. The clinical improvement begins within 3 days [29]. The chest x-ray is normalized within 1 week in 85 % of patients, but mild pulmonary infiltrates and pleural effusion may still be present at CT at 2 weeks [29]. One recent study of 137 patients suggested that a treatment duration of 2 weeks may be sufficient, with an initial daily dose of 30 mg of prednisone (or 60 mg of intravenous methylprednisolone every 6 h in patients with respiratory failure) [29]. No relapse occurs after stopping corticosteroid treatment, in contrast with ICEP (Table 15.4).

No significant clinical or imaging sequelae persist on the longer term. Mortality is rare despite the frequent initial presentation with acute respiratory failure. Identification of causative tobacco or environmental exposures is key to preventing rare recurrences, that in most cases are due to resuming of cigarette smoking after smoking cessation.

The first reliable case of EGPA was reported by Lamb in 1914 [38]. Churg and Strauss described in 1951 [39] the eponymous syndrome of “allergic granulomatosis, allergic angitiis, and periarteritis nodosa”, mainly from autopsied cases. In the 1992 Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis [40], CSS was included in the group of small vessel vasculitides. The nomenclature of the systemic vasculitides was revised in 2012 at the international Chapel Hill consensus conference [41], and the terminology of CSS was replaced by EGPA. As antineutrophil cytoplasmic antibodies (ANCA) are present in about 40 % of the cases, EGPA belongs to the pulmonary ANCA-associated vasculitides, together with microspic polyangiitis and granulomatosis with polyangiitis (Wegener’s), and together with single organ ANCA-associated vasculitis.

EGPA is defined as an eosinophil-rich and necrotizing granulomatous inflammation often involving the respiratory tract, and necrotizing vasculitis predominantly affecting small to medium vessels, and associated with asthma and eosinophilia [41]. The disease may be confined to a limited number of organs especially the upper or lower respiratory tract [41]. The terminology of EGPA underscores that it is indeed a vasculitis, although not all patients have robust criteria of documented systemic vasculitis or ANCA [42]. The current terminology and classification likely requires further refinement.

The pathologic lesions of EGPA (CSS) observed in recent series [43, 44] only rarely comprise all the characteristic features on biopsies from organs other than the lung, which is now rarely biopsied. The diagnosis is made earlier in the course of disease, often before overt vasculitis has developed, characterized histopathologically by eosinophilic infiltration of the tissues and often perivascular eosinophils but without vasculitis. In cases with overt EGPA, typical histopathologic features include vasculitis (necrotizing or not, involving mainly the medium-sized pulmonary arteries), granulomatous eosinophilic infiltration, and extravascular granuloma with palisading histiocytes and giant cells. When present, the eosinophilic pneumonia in EGPA is similar to ICEP.

EGPA is a very rare systemic disease, with no sex predominance, predominating in adults younger than 65 [45, 46], with cases occasionally reported in children and adolescents. Asthma occurs at a mean age of about 35 years [45], preceding the onset of vasculitis by 3–9 years [45, 47–49]; therefore the mean age at diagnosis of EGPA ranges from 38 to 49 years [45, 49]. The interval between asthma and the onset of vasculitis may be much longer in rare cases [47], or they may be contemporaneous [49]. Asthma is generally severe, and frequently requires oral corticosteroids; its severity typically increases progressively until the vasculitis develops, but it may attenuate when the vasculitis flourishes (possibly as a result of corticosteroids) and further increase once the vasculitis recedes [45, 47].

Chronic rhinitis (75 % of cases) [45], relapsing paranasal sinusitis (60 %) [48], and nasal polyposis with eosinophilic infiltration at histopathology are frequent. Crusty rhinitis may be present, however it is much less severe in EGPA than in granulomatosis with polyangiitis. Septal nasal perforation and saddle nose deformation are exceedingly rare.

Asthenia, weight loss, fever, arthralgias, and myalgias often herald the onset of the systemic vasculitis.

Heart damage in EGPA is undoubtedly a major source of morbidity and mortality, although its onset is often insidious and asymptomatic and diagnosed only when left ventricular failure and dilated cardiomyopathy have developed, possibly leading to cardiac failure or sudden death [45–50]. Heart involvement mostly results from eosinophilic myocarditis, and rarely from arteritis of the larger coronary arteries [51, 52]. Although marked improvement usually occurs with corticosteroid treatment, heart involvement in EGPA may require heart transplantation, with possible recurrence of eosinophilic vasculitis in the transplanted heart. A strict cardiac evaluation is therefore warranted in any patient with suspected EGPA, generally including electrocardiogram, echocardiography, serum level of troponin, and magnetic resonance imaging of the heart. Cardiac MRI frequently shows late enhancement of the myocardium [53–55], which may correspond to myocarditis, however the absence of a gold standard, it is difficult at a given point in time to differentiate irreversible scar lesions from active inflammation requiring intense immunosuppression, and incidental findings from clinically relevant myocardial involvement. Treatment decisions are eventually based on critical clinical evaluation, taking into account results from several investigations, including electrocardiogram, echocardiography, troponine level, and possibly a combination of cardiac MRI and positron emission tomography. In addition to myocardial involvement, asymptomatic pericarditis with limited effusion at echocardiography is common, with rare cases of tamponade, and the risk of venous thromboembolic events [56] is increased in patients with EGPA. Endomyocardial involvement (typically seen in idiopathic HES) is uncommon in EGPA.

Mononeuritis multiplex, present in 77 % of patients [48], is the most frequent and the most typical of peripheral neurologic involvement in EGPA, which may also consist of asymmetrical polyneuropathy in the lower extremities, or rarely cranial nerve palsies or central nervous system involvement. Digestive tract involvement (31 % of cases [48]) consists in isolated abdominal pain, and less frequently intestinal or biliary tract vasculitis, diarrhea, ulcerative colitis, gastroduodenal ulcerations, perforations (esophageal, gastric, intestinal), digestive hemorrhage, or cholecystitis. Cutaneous lesions (50 % of patients[48]) mainly consist of palpable purpura of the extremities (Fig. 15.5), subcutaneous nodules (especially of the scalp and extremities), erythematous rashes, and urticaria. Renal involvement (about 25 % of cases) consists in mild severity glomerulonephritis or glomerular hematuria [48], however renal failure is rare contrasting with the other ANCA-associated vasculitides.

Pulmonary opacities corresponding to eosinophilic pneumonia are present on chest x-ray in a majority of patients with EGPA (37 % [48] to 72 % [45, 57]) and consist of ill-defined opacities, sometimes migratory, transient, and of varying density [45, 47, 58, 59]. In contrast to GPA, pulmonary cavitary lesions are exceptional. The chest x-ray may remain normal throughout the course of the disease. Mild pleural effusion and phrenic nerve palsy can be observed. On thin-section CT, ground-glass attenuation and air space consolidation predominate, with peripheral or random distribution (Fig. 15.6). Bronchial wall thickening or dilation, interlobular septal thickening, hilar or mediastinal lymphadenopathy, pleural effusion, or pericardial effusion [18, 58, 59] are less commonly found. In one study, centrilobular nodules were more frequent in EGPA than in patients with ICEP [19]. However, EGPA is difficult to differentiate from other causes of eosinophilic lung diseases on the basis of HRCT imaging [18]. Importantly, pleural effusion when present may correspond to either inflammatory eosinophilic exudate directly related to EGPA or to a transudate caused by cardiomyopathy.

Peripheral blood eosinophilia is a major feature of EGPA, with generally eosinophil counts comprised between 5 and 20 × 10⁹/L and occasionally higher values [45, 47, 48]. Blood eosinophilia usually parallels disease activity, and disappears within hours after the initiation of corticosteroid treatment. Eosinophilia, sometimes greater than 60 %, is also found on BAL differential cell count and in the pleural fluid when present.

Although EGPA belongs to the group of ANCA-associated vasculitides, ANCAs are present in only about 40 % of patients. ANCAs in EGPA are mainly perinuclear (p-ANCA) with myeloperoxidase specificity, and rarely cytoplasmic ANCAs (c-ANCA) with proteinase 3 specificity [48, 49, 60–62]. Although nonspecific and not validated as useful biomarkers, the serum IgE level, the erythrocyte sedimentation rate, and the C-reactive protein level, and serum levels of IgG4, CCL17/TARC, and CCL26/Eotaxin-3 are increased. Anemia is common. High levels of urinary EDN may represent an activity index of disease.

EGPA is considered an autoimmune process involving T cells, endothelial cells, and eosinophils. Defects have been identified in regulatory CD4⁺ CD25⁺ or CD4⁺ CD25⁻ T-cell lymphocytes (producing IL-10 and IL-2) that may influence progression of disease, and supporting an immunological hypothesis of disease. Furthermore, clonal CD8⁺/Vβ⁺ T cell expansions with effector memory phenotype and expressing markers of cytotoxic activity were found in peripheral blood lymphocytes, as well as T cell receptor-beta gene rearrangement. Patients carrying the major histopathology complex DRB4 allele, involved in acquired specific immunity, are prone to develop EGPA. Familial EGPA has been reported.

Contrasting to common belief, evidence of allergy demonstrated by specific IgE together with a corresponding clinical history is present in less than one third of patients. When present in EGPA, allergy mainly consists of perennial allergies to Dermatophagoides, whereas seasonal allergies are less frequent than in the general asthmatic patient [63].

Some vaccines or desensitization may trigger or play a role as adjuvant factors [64]. Other possible triggering factors include Aspergillus, allergic bronchopulmonary candidiasis, Ascaris, bird exposure, or smoked cocaine. Some drugs have been suspected to induce EGPA, especially sulfonamides (used together with antiserum), diflunisal, macrolides, diphenylhydantoin, and more recently the anti-IgE antibody omalizumab [65]. In addition, leukotriene-receptor antagonists (montelukast, zafirlukast, pranlukast) have been suspected to be involved in the development of EGPA, although their role is controversial [49, 66–70]. The occurrence of EGPA is more frequent in patients receiving leukotriene receptor antagonists, however there is conflicting evidence whether the association is coincidental, whether some cases of smoldering EGPA flare because of reducing oral or inhaled corticosteroids, or whether these drugs really exert a direct facilitating or triggering role on the vasculitis [24, 68]. A possible mechanistic link has been proposed [71]. Since EGPA may follow montelukast treatment in asthmatic patients without smoldering EGPA, may recur on rechallenge with the drug, and may remit on its withdrawal [66, 68], a causal relationship cannot be excluded [70], and we advocate that leukotriene receptor antagonists be avoided in patients with asthma, eosinophilia, and/or established or smoldering extrapulmonary manifestations.

The classical description of EGPA follows three stages: asthma and rhinitis; tissue eosinophilia (such as a pulmonary disease resembling ICEP); and extrapulmonary eosinophilic disease with vasculitis. Diagnosing EGPA may be challenging in patients with early disease corresponding to the so-called formes frustes [72], who often already receive oral corticosteroids for asthma, thereby masking the underlying smoldering vasculitis. The diagnosis is more straightforward at a later stage of disease with overt systemic manifestations, however it is extremely important that the diagnosis be established before severe organ involvement (especially cardiac) is present.

There are currently no established diagnostic criteria for EGPA. Lanham and associates [45] have proposed three diagnostic criteria including (1) asthma, (2) eosinophilia exceeding 1.5 × 10⁹/L, and (3) systemic vasculitis of two or more extrapulmonary organs, however those do not include ANCAs, which when present do contribute to the diagnosis. Classification criteria (which are not diagnostic criteria) have been proposed by the American College of Rheumatology [73] (Table 15.5), but they cannot be readily used for diagnosis in an individual with suspected EGPA. Provisional diagnostic criteria including ANCA have been recently proposed [42]. Although a pathologic diagnosis is desirable and can be obtained from the skin, nerve, or muscle [48], it is not mandatory in patients with characteristic features of EGPA. Because cutaneous lesions are easy to access (when not involving the face), a skin biopsy is commonly performed to obtain pathologic evidence of vasculitis when they are present (See Clinical Vignette). Conversely, lung biopsy either transbronchial or video-assisted is seldom done.