Eosinophilic Lung Diseases: Findings that a Radiologist Should Know

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Abstract Eosinophilic lung diseases include a broad spectrum of disorders. The final diagnosis of these diseases is made by patho- logical examination. However, medical history, physical examination and imaging studies allow better characterization of the condition. At present, high-resolution multislice computed tomography (MSCT) is the most sensitive and specific imaging method, since it allows an accurate assessment of diffuse pulmonary pathology, thus avoiding more invasive methods, providing detailed information and depicting lesions that have no specific clinical presentation by means of characteristic imaging patterns.
Keywords Hypereosinophilic syndrome, Multislice computed tomography, Pulmonary eosinophilia
Introduction
Eosinophilic lung diseases are infectious and non-infectious disorders associated with peripheral eosinophilia (a marker of pathology, exceeding 0.5 × 109/L)1,2 with tissue eosino- philia confirmed by pulmonary biopsy or an elevated eosino- philic count (25%) in bronchoalveolar lavage (BAL) 3-5. These diseases may be classified as: idiopathic (acute eosinophilic pneumonia, chronic eosinophilic pneumonia and idiopathic hypereosinophilic syndrome), secondary to an infectious cause (aspergillus fumigatus) or associated with vasculitis and granulomatosis (Churg-Strauss syndrome, granulomatosis with polyangiitis, bronchocentric granulomatosis or Sjögren disease).5 High-resolution multislice computed tomography (MSCT)with a slice thickness of less than 1.5 mm , is the im- aging method of choice for an accurate assessment of diffuse pulmonary disease, because it has a higher sensitivity and specificity than conventional radiology.6 Pulmonary biopsy if the gold standard method for diagnosis, but some time is re- placed by BAL.6 In these syndromes, pulmonary involvement is common. However, in early stages, imaging findings may be subtle; therefore, MSCT provides detailed information and
depicts lesions that have no specific clinical presentation.7 The most characteristic MSCT findings of eosinophilic syn- dromes will be discussed below (Table 1).
Idiopathic eosinophilic lung diseases
Loeffler syndrome or simple pulmonary eosinophilia This is an entity of unknown cause that is characterized by an absence of symptoms or, if present, they are mild and non- specific (cough, dyspnea and low-grade fever) with resolution within one month. Plain radiography shows patchy opacities with a peripheral distribution. MSCT findings include ground- glass or consolidative opacities with peripheral satellite nod- ules and bronchial wall thickening. Pleural effusions and lymphadenopathy do not occur.2
Acute eosinophilic pneumonia (AEP) As the name indicates, AEP is characterized by a rapidly pro- gressive infiltration of eosinophils into the lungs, leading to respiratory failure, distinguishing from the more indolent and
Eosinophilic Lung Diseases: Findings that a Radiologist Should Know Juliana Couture1 Daniel Adri1 Juan Manuel Villegas1 Natalia Posadas1 Alberto Seehaus1
1 Imaging Diagnosis Department, Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
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less severe presentation of chronic eosinophilic pneumonia.2,8 Of unknown etiology, with a slight predominance in men, AEP is associated with exposure to various antigens, being tobacco the most frequent of all.9 It presents acute febrile illness lasting 1 to 5 days, myalgia, pleuritic chest pain and re- spiratory failure manifesting as severe hypoxemia, i.e., partial pressure of oxygen in arterial blood (PaO2) below 60 mmHg,
with no evidence of extrapulmonary involvement. BAL fluid analysis shows an elevated mixed count with increased levels of lymphocytes and eosinophils (over 25%).9
The most characteristic CT findings are bilateral ground-glass opacities with interlobular septal thickening and pleural ef- fusion. Although the clinical presentation is nonspecific and an increased eosinophil count in peripheral blood may be ab-
Table 1: Summary of findings
Entity Clinical presentation X-ray findings MSCT findings
IELD: Nonspecific/Absent Peripheral patchy opacities GG/consolidative opacities + satellite nodules + Loeffler S. peribronchial thickening
IELD: AEP Febrile S. + respiratory Bilateral GG opacities + interlobular septal thickening + pleural effusion failure of unknown etiology
IELD: CEP Systemic S. + pulmonary Bilateral dense, multifocal consolidations located in the peripheral lung fields manifestations
IELD: HES Dermatologic + Patchy reticular areas + poorly defined nodules with or without GG halo + pulmonary + cardiac pleural effusion (50%)
SELD: 5 stages Tubular “gloved-finger” Consolidations of mucoid impaction + Aspergillosis opacity + bronchial segmental and subsegmental bronchiectasis of distribution + upper the upper lobes + centrilobular nodules and central lung fields + bronchiectasis and fibrosis
VELD: CSS Small vessel vasculitis Bilateral + transient Symmetrical and peripheral consolidations + nonsegmental septal thickening + effusion (50/10% due to consolidation heart failure) + findings associated with asthma
VELD: GPA Pulmonary disease + Nodules + cavitation + predilection for the lung apices + subpleural + halo sinusitis + sign + airway involvement glomerulonephritis
VELD: NSG Pulmonary vasculitis Bilateral nodules + subpleural and peribronchovascular + cavitation + IVC enhancement + mediastinal lymph nodes + diffuse subpleural granulomas + fibrosis
VELD: SS Dry mouth and eyes Nonspecific interstitial pneumonia + bronchi- or bronchio-lectasis + bronchial wall thickening + air cysts + thymic involvement
Abbreviations: AEP, acute eosinophilic pneumonia; CEP, chronic eosinophilic pneumonia; CSS, Churg-Strauss syndrome; GG, ground
glass; GPA, granulomatosis with polyangiitis; HES, hypereosinophilic syndrome; IELD, idiopathic eosinophilic lung disease; IVC, intravenous
contrast; NSG, necrotizing sarcoid granulomatosis; SELD, secondary eosinophilic lung disease; SS, Sjögren syndrome; VELD, vasculitis-
associated eosinophilic lung disease;.
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sent, the possibility of this disease should always be consid- ered in a healthy subject who develops acute respiratory fail- ure of unknown etiology and presents the above-mentioned radiologic findings (Fig. 1).10
Chronic Eosinophilic Pneumonia (CEP) CEP is a rare disorder characterized by systemic and pulmo- nary manifestations, blood eosinophilia, peripheral opacities on chest X-ray and a prompt response to corticosteroids.11 It is more predominant in female nonsmokers, and it does not lead to severe hypoxemia or acute respiratory failure. Eosino- phil count is elevated in BAL fluid. Chest X-ray shows bilateral dense, multifocal consolidations located in the periphery of lung fields (Fig. 2).9
Hypereosinophilic syndrome (HES) The term “hypereosinophilic syndromes” (HES) refers to a group of disorders characterized by elevated numbers of circulating blood eosinophils accompanied by end-organ in- filtration leading to clinical disease.8 HES is defined as the presence of eosinophilia greater than 1500/mm3 on two or more occasions or symptoms suggestive of tissue eosinophilia with blood eosinophilia and exclusion of secondary causes. The average age at HES onset is 50 years, with female pre- dominance.2 However, it may occur in children. Even if initial manifestations are dermatologic, lungs are affected in the second place (40%) and cardiac involvement is the major cause of morbidity and mortality.4,9 CT findings show reticu- lar areas of increased density with patchy distribution, poorly
Fig. 1 Acute eosinophilic pneumonia. Forty-nine year-old female patient with a history of cough and febrile syndrome. (A) An- teroposterior chest radiography (X-ray) shows areas of decreased transparency in the upper third of both lung fields (arrows). Axial (B) and coronal (C) chest MSCT shows multiple areas of increased attenuation of the lung parenchyma that are ground- glass in character in both upper lobes (arrows), associated with interlobular septal thickening (star) and subtle areas with a tendency to consolidation of predominantly subpleural distribution (arrowhead). Complementarily, laboratory tests revealed a white blood cell count of 15,000 cell/mm3 with 34% eosinophils.
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defined nodules with or without surrounding ground-glass halo. One-half of cases are associated with pleural effusion. Findings may also include diffuse areas of ground-glass opac- ity suggestive of edema (Fig. 3).12
Secondary eosinophilic lung diseases
Allergic bronchopulmonary aspergillosis Allergic bronchopulmonary aspergillosis is an infectious dis- ease that may be divided into five stages to help guide the treatment of the disease: acute, remission, exacerbation, cor- ticosteroid dependent and fibrotic. Findings in early stages usually include transient homogeneous pulmonary opacities, tubular “gloved-finger” areas of increased opacity with a bronchial distribution predominantly or exclusively involving
the upper and central lung fields. These opacities are related to the plugging of airways by hyphal masses with distal mu- coid impaction. Occasionally, isolated or segmental atelecta- sis may occur. In advanced stages, central bronchiectasis and pulmonary fibrosis develop. The most typical MSCT findings consist primarily of mucoid impaction and bronchiectasis pre- dominantly involving the segmental and subsegmental bronchi of the upper lobes, along with centrilobular nodules (Fig. 4).5
Parasitic eosinophilic lung diseases The etiology of this pathology includes, but is not limited to: strongyloidiasis, ascariasis, schistosomiasis and paragonimiasis. Geographic location and the patient’s travel history determine the prevalence of infections. These organisms may cause both a set of symptoms and simple pulmonary eosinophilia, with manifestations such as nodules or opacities or both on MSCT.2
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Figure 2 Chronic eosinophilic pneumonia. Chest MSCT in axial (A) and sagittal (B) views shows multiple areas of ground- glass decreased transparency of the lung parenchyma, involv- ing both lower lobes, predominantly the left lobe (arrow), associated with interlobular septal thickening (star), traction bronchiectasis and small subpleural cystic lesions (arrow- head), with no clear evidence of honeycombing. BAL fluid analysis reveals a cytological smear with a large number of bronchial cells, lymphocytes and macrophages, a finding that is consistent with a chronic interstitial process.
Figure 3 Hypereosinophilic syndrome. Axial chest MSCT (A, B) with zoom into the region of interest shows multiple solid nodular/small nodular lesions in both lower lobes (circle) in a patient with a clinical diagnosis of hypereosinophilic syn- drome. (C) Same patient with a different intercurrent condi- tion, with pleural effusion (arrow) and focal and nodular pleu- ral thickening (arrowhead).
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Figure 4 Allergic bronchopulmonary aspergillosis. Chest MSCT in axial (A) and coronal (B) views. Multiple bronchiectasis in both upper lobes (arrow) associated with nodular infiltrates with a tree-in-bud pattern involving the small airway and en- dobronchial impaction (arrowhead). Subpleural opacities con- sistent with small areas of distal atelectasis (star) in a patient with a diagnosis of allergic bronchopulmonary aspergillosis.
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Fig. 5 Churg-Strauss syndrome (CSS). Chest MSCT in the axial view (A), coronal view and coronal maximum intensity pro- jection (MIP) reconstruction (B). Multiple focal opacities, of nodular appearance with ground-glass density in both lung fields with tree-in-bud pattern (arrow). Areas of pulmonary parenchymal consolidation in the posterior segment of the right upper lobe (arrowhead) in a patient with a diagnosis of Churg-Strauss syndrome
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Fig. 6 Granulomatosis with polyangiitis (GPA). Chest MSCT. Coronal (A) and axial (B) views. Multiple patchy areas of increased ground-glass attenuation of the lung parenchyma, with diffuse involvement of both lung fields (arrows), in a patient with hemoptysis and protein- uria. Findings in BAL fluid include inflammatory changes with hemosiderin-laden macro- phages and moderate eosinophilia, and the diagnosis by kidney biopsy is granulomatosis with polyangiitis.
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Churg-Strauss syndrome (CSS) Churg-Strauss syndrome is a condition in which eosinophilic vasculitis and infiltration potentially involve multiple organs, including the sinuses, lungs, peripheral nerves, heart, skin, gastrointestinal tract, and kidneys.8 This condition, which has
also been called allergic granulomatosis, was described by Churg and Strauss in 1951, under the criteria of tissue inflam- mation by eosinophils, necrotizing vasculitis and granulomas. It is a small vessel vasculitis primarily affecting the lungs.9 At present, there are six criteria that have been established by the American College of Rheumatologists for the diagnosis of CSS. These are asthma, peripheral blood eosinophil count of greater than 10%, neuropathy, permanent or transient pulmonary opacities, paranasal sinus abnormalities and ex- travascular eosinophils revealed on biopsy.13 CSS affects men
Fig. 7 Granulomatosis with polyangiitis. Anteroposterior chest X-ray (A). Nodular opacity pro- jected in the upper third of the right lung field and other smaller and less defined opacities on the left lung field (arrow). Axial chest MSCT (B, C) shows two nodular lesions in both lung fields, which in later follow-up scans progress to the central cavity (arrowhead).
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and women equally in the fourth and fifth decades of life.9
The most common manifestations on chest X-ray are bilateral, transient nonsegmental areas of consolidation with no predi- lection for any lung zone. On MSCT, in 90% of patients there are bilateral areas of increased attenuation that are ground- glass or consolidative in nature. These opacities are usually symmetrical with a predominantly peripheral distribution. Fi- brous bands are also seen in 50% of cases. Interlobular septal thickening reflects the presence of edema secondary to cardiac involvement or to tissue infiltration by eosinophils. Airways in- volvement is evidenced by the presence of small centrilobular nodules, tree-in-bud pattern, bronchial dilation, bronchiolar and bronchial wall thickening, these being findings related to asthma, which is most often associated with CSS. Pleural effu- sion appears in 10%-50% of patients; it may be unilateral or bilateral and it is caused by left heart failure arising as a result of eosinophilic pleuritis or cardiomyopathy (Fig. 5).6
Granulomatosis with polyangiitis (GPA) This syndrome is charectarized by pulmonary disease, sinusitis and glomerulonephritis, with predominance of upper respira- tory tract symptoms (rhinitis, sinusitis and otitis media). In the early stages of disease, the chest radiograph shows bilateral reticular or nodular opacities that predominate at the lung bases. As the disease progresses, the nodules increase in size and number, may cavitate and show a predilection for the lung apices. These cavitary lesions have thick walls and evolve into thin-walled cysts or may even disappear after treatment. MSCT demonstrates small nodules and lesions that are not visible on chest radiography. A predominantly subpleural lo-
cation of the lesions has been reported. The halo sign has been described in GPA as nonspecific and corresponding to parenchymal microinfarction by an angiocentric process. Tra- cheobronchial involvement is demonstrated by focal or dif- fuse stenosis, intra- or extraluminal soft-tissue masses and segmental or lobar atelectasis. Bronchial abnormalities are seen in 40% of cases and, unlike pulmonary parenchymal lesions, they do not resolve after treatment (Figs. 6 and 7).14
Necrotizing sarcoid granulomatosis This condition exclusively affects the lung and represents a variant of sarcoidosis. It predominates in women and 15%- 45% of patients are asymptomatic. It is characterized by the presence of multiple bilateral nodules in a subpleural and peribronchovascular distribution that may cavitate and het- erogeneously enhance after contrast administration. Medias- tinal lymph nodes may be enlarged and may have granulo- matous infiltration. Pleural involvement, if any, is evidenced by diffuse granulomas and organizing fibrosis. The charac- teristics and distribution of lesions are very similar to those of sarcoidosis. However, the lower prevalence of hilar and mediastinal lymphadenopathy and the propensity of lesions toward cavitation distinguish it from sarcoidosis (Fig. 8).14
Sjögren syndrome
Sjögren syndrome is characterized by lympho¬cytic infiltration of the exocrine lacrimal and salivary glands, which leads to dry mouth and eyes. It may occur ei¬ther in isolation (primary
Fig. 8 Necrotizing sarcoid granulomatosis. Forty-year-old female patient, with no respiratory symptoms who presents for her annual follow-up. Anteroposterior chest X-ray (A). Areas with a markedly decreased transparency in both upper lobes with areas of central cavitation (arrow). Chest MSCT (B). Volume loss in both upper lobes and involvement of both lower lobes apical segments. All infectious causes having been ruled out, the lung biopsy reveals the presence of granulomatous inflammation with scarce areas of necrosis.
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Sjögren syndrome) or as a complication of autoimmune dis- eases (secondary Sjögren syndrome). Manifestations of lung involvement in Sjögren syndrome are airway abnormalities and interstitial pneumonia. At high-resolution MSCT, chronic inflammation with lymphoplas¬macytic infiltration and fibrotic changes of terminal bronchi and bronchioles are seen as bron- chi- or bronchio¬lectasis and bronchial wall thickening. Oc- casionally, mosaic attenuation may be seen, which indicates obstructive bronchiolitis, findings which can be best seen in the expiratory phase. The most common pattern of intersti- tial pneumonia is nonspecific interstitial pneumonia, which demonstrates bilateral areas of increased ground-glass attenu- ation and reticulation, traction bronchiectasis, both with basal predominance and peribroncovascular distribution. Multiple air cysts may also be observed, which appear as round, thin- walled airspaces with a tendency to peribronchovascular distri- bution. Mediastinal manifestations include lymphadenopathy, thymic lym¬phoid hyperplasia, and multilocular thymic cysts, which appear on MSCT as multiple nodules and increased at- tenuation of anterior mediastinal fat tissue (Fig. 9).15
Conclusion
Eosinophilic lung syndromes represent a heterogeneous group of idiopathic and secondary conditions that may affect the airspaces, blood vessels or the interstitium. On MSCT, rec- ognition of the pattern, localization, distribution and severity is useful to suggest differential diagnoses and guide thera- py, especially at early stages when plain radiography fails to demonstrate abnormalities. We think it is extremely helpful to correlate imaging findings with the patient’s clinical history and epidemiology to establish a final diagnosis.
Confidentiality of data The authors declare that they have followed the protocols of their work center on the publication of patient data and that all the patients included in the study have received suf- ficient information and have given their informed consent in writing.
Conflicts of interest The authors declare no conflicts of interest.
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