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Focus on CME at the University of British Columbia

Eosinophilic : A Clinical Overview

The eosinophilic lung are a diverse group of pulmonary disorders ranging from the trivial to the potentially fatal. Accurate diagnosis is essen- tial, since effective treatment is available in most cases.

By Frank Ryan MB, FRCPI, FRCPC, FCCP

Presented at the 2nd Annual University of British Columbia Respiratory and Critical Care Update, Whistler, British Columbia, March 2001.

he eosinophilic lung diseases are a heteroge- peripheral blood. More specifically, eosinophilic T neous group of pulmonary disorders charac- infiltration of the (with or without periph- terized by an increase in circulating and tissue eral ) is established by identifying . Pulmonary eosinophilia can be an excess of eosinophils, either in bronchoalve- defined generally as pulmonary infiltrates on radi- olar lavage fluid obtained at , or by ological imaging together with an increase in the open lung . Pathologically, there may be absolute number of eosinophils (> 250/µL) in the involvement of the airways, lung parenchyma, or both. Dr. Ryan is associate professor of Unfortunately, biology and the medicine, University of British pathophysiology of eosinophilic lung diseases Columbia, and active staff, divi- are poorly understood.1 Eosinophils are a type of sion of respiratory medicine, granulocyte derived from the bone marrow. Vancouver Hospital and Health Distinguishing morphologic features include a Sciences Centre. His special bi-lobed nucleus and specific granules that con- interests include sleep-disordered tain a distinctive electron-dense crystalloid core breathing and clinical aspects of composed of major basic protein (Figure 1). The infiltrative lung disease. eosinophil plays a role in the host defenses

The Canadian Journal of CME / December 2001 53 Eosinophilic Lung Disease

Summary Eosinophilic Lung Disease: A Clinical Overview

• The eosinophilic lung diseases are a heterogeneous group of pulmonary disorders characterized by an increase in circulating and tissue eosinophils. Pulmonary eosinophilia can be defined generally as pulmonary infiltrates on radiological imaging together with an increase in the absolute number of eosinophils (> 250/µL) in the peripheral blood. • Often, the first clue to the presence of eosinophilic lung disease is the incidental finding of an elevated peripheral eosinophil count on routine testing in a patient presenting with respiratory symptoms. • Most patients have an elevated peripheral eosinophil count, with the exception of those with some drug reactions and the early stages of acute eosinophilic . Abnormalities on the are present in most cases of eosinophilic lung disease. • Normally, bronchoalveolar lavage (BAL) fluid contains < 1% eosinophils. Up to 20% eosinophils is a non-specific finding that can be seen in a variety of interstitial lung diseases. Greater than 20% eosinophils in the BAL fluid is seen in acute and chronic eosinophilic pneumonia, Churg-Strauss syndrome, idiopathic hypereosinophilic syndrome, parasitic infestations and drug reactions.

against helminthic parasites and in allergic reac- will be outlined based on information obtained tions. Activated eosinophils, under the direction from a focused patient history and physical of helper T-lymphocytes, can release a variety of examination, supplemented by appropriate labo- cytokines and inflammatory mediators that ratory investigations. Each condition will then cause injury to various body tissues, including be discussed briefly. the lungs. The causes of excess eosinophil pro- duction and tissue infiltration are unclear, but Differential Diagnosis abnormal clonal proliferation of T-lymphocytes, resulting in excess production of eosinophilopoi- History. Often, the first clue to the presence of etic cytokines, is one possibility. eosinophilic lung disease is the incidental finding In the absence of a clear understanding of of an elevated peripheral eosinophil count on rou- eosinophil function, it is not possible to develop tine testing in a patient presenting with respiratory a classification of eosinophilic lung diseases symptoms. The chronicity of the symptoms and based on pathophysiologic principles. A variety the peripheral eosinophilia are important elements of clinical classifications, therefore, have been of the diagnosis, since transient eosinophilia is suggested.2-4 This article is based on one such usually of no consequence. Common respiratory classification proposed by Allen and Davis in symptoms include , wheeze, chest tightness which 10 categories of eosinophilic lung disease and dyspnea. Less commonly, patients may devel- are described (Table 1).5 First, an approach to op hemoptysis, chest pain or expectoration of differentiating among these various conditions tenacious mucus plugs. A chronic unproductive

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Table 1 Classification of Eosinophilic Lung Diseases

Simple pulmonary eosinophilia Chronic eosinophilic pneumonia Acute eosinophilic pneumonia Churg-Strauss syndrome Idiopathic hypereosinophilic syndrome Figure 1. An electron micrograph of the interior of an Allergic bronchopulmonary aspergillosis eosinophil showing the characteristic bi-lobed nucleus and cytoplasmic granules containing rhomboid, electron- Bronchocentric granulomatosis dense crystalloid cores. Parasitic Drug reactions cough, particularly at night, in the appropriate clinical setting, should suggest the possibility of eosinophilic lung disease. A history of asthma or Table 2 atopy should be sought routinely, since several Eosinophilic Lung Diseases causes of eosinophilic lung disease occur in Associated With Asthma patients with this background (Table 2). Upper symptoms, including rhino- Asthma and nasal polyposis, are prominent in Allergic bronchopulmonary aspergillosis Churg-Strauss syndrome. Constitutional symp- toms, such as , weight loss, malaise, night Bronchocentric granulomatosis sweats and anorexia are prominent presenting fea- Chronic eosinophilic pneumonia tures of chronic eosinophilic pneumonia, Churg- Churg-Strauss syndrome Strauss syndrome, idiopathic hypereosinophilic syndrome and certain cases of parasitic infestation and allergic drug reactions. system involvement. Physicians should pay partic- Obtaining a patient’s thorough travel history is ular attention to symptoms of cardiovascular, skin, essential in identifying parasitic infestations con- neurologic, gastrointestinal (GI), musculoskeletal tracted in countries where these are endemic or renal involvement. Finally, eosinophilia occa- (Table 3). A careful drug history also is required sionally can occur in association with interstitial and should include details of over-the-counter lung disease, lung and fungal infections. remedies and illicit drug use (Table 4). Some caus- . Several causes of es of eosinophilic lung disease, particularly eosinophilic lung disease may have signs of air- Churg-Strauss syndrome and idiopathic hypere- flow obstruction (Table 2), such as overinflation, osinophilic syndrome, are characterized by multi- hyperresonance and wheezing. and nasal

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Table 3 Table 4 Parasitic Infections Frequently Examples of Drugs Causing Encountered in North America Eosinophilic Lung Disease

Strongyloides stercoralis Toxocara Sulfasalazine Ancylostoma Echinococcus Minocycline Methotrexate L-tryptophan Inhaled or crack polyposis can occur in atopic asthma and Churg- Strauss syndrome. Signs of consolidation or crack- Inhaled pentamidine les, indicating pulmonary parenchymal or intersti- tial involvement, may occur in cases of chronic several parasites, including Toxocara, Ancylostoma, and acute eosinophilic pneumonia, Churg-Strauss Trichinella and Paragonimus. The test also may syndrome, parasitic infestations, or result from miss the intestinal stage of Ascaris and drug reactions. Dermatological manifestations Strongyloides. A variety of serological tests useful may include palpable purpura in Churg-Strauss in making the differential diagnosis of syndrome, urticaria or in the idio- eosinophilic lung disease are listed in Table 5. pathic hypereosinophilic syndrome, or the serpig- Pulmonary function tests may aid in the differen- inous rash of cutaneous larva migrans tial diagnosis, although they are mainly helpful in (Ankylostoma brasiliense). Multi-system involve- following the course of the disease and the ment, including cardiac disease, strongly suggests response to treatment. Churg-Strauss syndrome or idiopathic hypere- Imaging. Abnormalities on the chest radi- osinophilic syndrome, with systemic thrombo- ograph are present in most cases of eosinophilic emboli being a particular feature of the latter. lung disease. This is not the case, however, for Investigations. Most patients have an elevated idiopathic hypereosinophilic syndrome where peripheral eosinophil count, with the exception of abnormalities occur in less than 25% of patients, those with some drug reactions and the early and in patients with asthma where abnormalities stages of acute eosinophilic pneumonia. Profound are uncommon. Characteristic appearances in the eosinophilia (> 10,000/µL) can occur in idiopath- appropriate clinical setting may strongly suggest a ic hypereosinophilic syndrome, Churg-Strauss specific diagnosis, such as the following: syndrome, parasitic infestations, allergic bron- • The transient migratory infiltrates of simple chopulmonary aspergillosis, some drug reactions pulmonary eosinophilia; and occasionally chronic eosinophilic pneumonia. • The extensive bilateral peripheral infiltrates Multiple stool samples should be sent to check (radiographic negative of ) in for ova and parasites, but this test will not detect chronic eosinophilic pneumonia (Figure 2);

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Table 5 Useful Serological Tests in Eosinophilic Lung Disease

IgE Allergic bronchopulmonary aspergillosis Churg-Strauss syndrome Idiopathic hypereosinophilic syndrome Asthma Certain parasitic infections Aspergillus Precipitins Allergic bronchopulmonary aspergillosis Specific Serology Toxocara Trichinella Filaria Strongyloides pANCA Churg-Strauss syndrome

• Proximal and the branching den- sities of mucoid impaction in allergic bron- chopulmonary aspergillosis; or • Solitary upper lobe nodule or mass in broncho- centric granulomatosis. The chest computed tomography (CT) scan is particularly helpful in characterizing the pattern (air- ways versus air space versus interstitial), distribu- tion (central versus peripheral) and extent of pul- monary involvement, and can be virtually diagnos- tic in some cases of chronic eosinophilic pneumonia and allergic bronchopulmonary aspergillosis. Bronchoalveolar lavage (BAL). The analysis of bronchoalveolar lavage fluid has greatly assisted physicians in evaluating patients with suspected eosinophilic lung disease. Normally, BAL fluid con- Figure 2. Chest radiograph of a patient with chronic tains < 1% eosinophils. Up to 20% eosinophils is a eosinophilic pneumonia showing extensive airspace non-specific finding that can be seen in a variety of infiltrates in a predominantly peripheral and upper lobe interstitial lung diseases. Greater than 20% distribution. eosinophils in the BAL fluid is seen in acute and chronic eosinophilic pneumonia, Churg-Strauss in the BAL fluid. syndrome, idiopathic hypereosinophilic syndrome, Open lung biopsy. Transbronchial are parasitic infestations and drug reactions. usually inadequate for diagnosis because of their Occasionally, a specific diagnosis can be made by small size. Open lung biopsy is rarely indicated for finding parasites, other infections or malignant cells the diagnosis of allergic bronchopulmonary

The Canadian Journal of CME / December 2001 57 Eosinophilic Lung Disease

Chronic eosinophilic pneumonia. This is a serious condition that presents insidiously with cough, fever, dyspnea, weight loss, malaise and , developing over four to eight months.6 The etiology is unknown, although 50% of patients have a background of asthma or atopy. It occurs mainly in middle-aged individuals and there is a female predominance. Peripheral eosinophilia, occasionally marked, occurs in 90% of patients, and elevated erythrocyte sedimenta- tion rate (ESR) and immunoglobulin E (IgE) lev- els are common. Pulmonary function tests may Figure 3. Open lung biopsy of a patient with chronic eosinophilic pneumonia showing a dense infiltration of the reveal airflow obstruction due to underlying asth- air spaces and interstitium with eosinophils, plasma cells ma and a restrictive defect with a reduced diffus- and lymphocytes. ing capacity. Most patients have an increased A-a gradient or frank hypoxemia on arterial blood aspergillosis, idiopathic hypereosinophilic syn- gases. The chest radiograph shows a pattern of drome, parasitic infections or drug reactions. peripheral air space infiltrates, often with upper Although acute and chronic eosinophilic pneumonia lobe predominance (Figure 2). The CT scan shows have characteristic histopathological findings, these ground glass attenuation, peripheral consolidation, diagnoses usually can be made on clinical grounds, and mediastinal lymphadenopathy in 50% of without the necessity for open lung biopsy. Churg- patients. In this clinical setting, the finding of Strauss syndrome may require such a biopsy if the marked eosinophilia (> 20%) in the BAL fluid is diagnosis is uncertain. Biopsy is usually required to virtually diagnostic. Open lung biopsy shows an diagnose bronchocentric granulomatosis and inter- accumulation of eosinophils and lymphocytes in stitial lung disease. the alveoli and interstitium with eosinophilic abscesses and Charcot-Leyden crystals (Figure Classification 3). There are no granulomas or true vasculitis. A dramatic improvement in response to , Simple pulmonary eosinophilia (Löffler’s syn- 30 mg to 40 mg/day, is further supportive of the drome). A benign self-limited condition character- diagnosis. Although relapses are common, the ized by migratory pulmonary infiltrates and long-term prognosis is favorable. peripheral eosinophilia, Löffler’s syndrome typi- Acute Eosinophilic Pneumonia. This recently cally lasts less than one month and rarely requires described condition presents as an acute febrile ill- any treatment. Symptoms are minimal and the ness progressing rapidly to acute hypoxemic res- diagnosis often is made incidentally by finding piratory failure, often requiring mechanical venti- peripheral infiltrates on a routine chest radiograph latory support. It has a clinical and radiological in a patient with a peripheral eosinophilia. Most picture indistinguishable from the acute respirato- cases are due to parasites, most commonly Ascaris ry distress syndrome (ARDS).7 The key to the lumbricoides, or a drug reaction. A third of cases diagnosis is the marked eosinophilia (> 40%) on are idiopathic. BAL in the absence of evidence of or

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Figure 5. Open lung biopsy of a patient with Churg- Strauss syndrome showing small-vessel perivasculitis with a surrounding extravascular eosinophilic infiltrate.

Figure 4. Chest radiograph of a patient with Churg-Strauss involvement includes acute pericarditis, constric- syndrome showing a peripheral area of consolidation in the tive pericarditis, congestive heart failure (CHF) right upper lobe. This 35-year-old woman presented with and myocardial infarction. Mononeuritis multi- worsening asthma, nasal polyposis, mononeuritis multi- plex is common, and central plex and a peripheral eosinophilia of 1500/µL. involvement also can occur, causing cerebral parasitic infestation. Peripheral eosinophilia is usu- infarction and hemorrhage. GI renal and muscu- ally absent in the early stages. Open lung biopsy loskeletal involvement are also common. A reveals a marked eosinophilic infiltrate, pulmonary peripheral eosinophil count (> 1500/µL), anemia, edema and . The condition and elevated ESR and IgE levels are typical. responds rapidly to and relapses do Antinuclear cytoplasmic antibodies are positive in not occur. The etiology is unknown, but some form 60% of patients — mainly perinuclear anti-neu- of hypersensitivity reaction is suspected. trophilic cytoplasmic antibody (pANCA) with Churg-Strauss syndrome (Allergic angiitis myeloperoxidase specificity. This test is useful and granulomatosis). Churg-Strauss syndrome is in supporting a diagnosis of Churg-Strauss syn- a multisystem disease with a major pulmonary drome and differentiating it from Wegener’s component and prominent peripheral eosinophil- granulomatosis, in which cytoplasmic anti-neu- ia.8 All patients have asthma or a history of asth- trophilic cytoplasmic antibody (cANCA) is positive. ma and many have , often with Radiographic appearances include peripheral nasal polyposis. Prior to the availability of effec- infiltrates (Figure 4), multiple ill-defined nod- tive therapy, this condition was uniformly fatal, ules, diffuse interstitial infiltrates and pleural but, currently, the five-year survival is > 70%. In effusions. Bronchoalveolar lavage fluid contains addition to asthma, allergic rhinitis and polyposis, a high proportion of eosinophils. Open lung patients can develop eosinophilic pneumonia. The biopsy demonstrates an eosinophilic giant cell vas- most common skin manifestation is leukocyto- culitis of small arteries and veins with characteristic clastic vasculitis or palpable purpura. Cardiac extravascular granulomas and eosinophilia (Figure

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results in an overproduction of eosinophilopoiet- Table 6 ic cytokines, leading to eosinophilic infiltration Major Diagnostic Criteria for and damage to various organs, including the Allergic Bronchopulmonary lungs. Cardiac involvement occurs in 60% of Aspergillosis patients and is characterized by endocardial injury, mural thrombus formation, endomyocar- Asthma dial fibrosis and a restrictive cardiomyopathy. Peripheral eosinophilia Systemic thromboembolic phenomena may dom- inate the clinical picture. Other organs involved Immediate skin test reactivity to Aspergillus include: antigens • Skin (urticaria and angioedema); Serum precipitating antibodies to Aspergillus • Peripheral neuropathy and encephalopathy; antigens •Bone marrow; Increased serum IgE level (>1000ng/mL) • Spleen; Pulmonary infiltrates on chest radiograph •GI tract; and • Renal and musculoskeletal systems. Pulmonary involvement occurs in 40% of 5). patients and is most commonly manifested by a Churg-Strauss syndrome can be differentiated chronic persistent nocturnal cough. Asthma is rare. from other multisystem diseases, such as Pulmonary infiltrates occur in 25% of cases. , Wegener’s granulomatosis Idiopathic hypereosinophilic syndrome is differen- and idiopathic hypereosinophilic syndrome, on tiated from eosinophilic leukemia by the absence of the basis of differing clinical and histopatholog- immature eosinophils. Unlike Churg-Strauss syn- ical features. Most patients respond favorably to drome, there is no asthma or vasculitis. It is essen- therapy. For patients with severe tial to exclude parasitic infestation, which can pro- or steroid-resistant disease, cyclophosphamide, duce a similar clinical presentation. A subgroup of azathioprine and intravenous immunoglobulin patients with allergic type manifestations respond have been used with apparent benefit. well to corticosteroids. More severe cases require Idiopathic hypereosinophilic syndrome. treatment with other drugs, such as hydroxyurea, Idiopathic hypereosinophilic syndrome is a rare chlorambucil, interferon-a, and cyclosporine. leukoproliferative disorder, or group of disor- Anticoagulation is indicated for patients with docu- ders, that results in heterogeneous clinical mani- mented thromboembolic phenomena. festations.9 The criteria for this diagnosis are a Asthma. Eosinophilic inflammation of the air- prolonged peripheral eosinophilia (> 1500/µL for ways is the histopathologic hallmark of asthma, > six months), the presence of organ damage and and a mild peripheral eosinophilia is relatively the absence of a parasitic infection or other caus- common in atopic asthmatics. The diagnosis of es. The condition usually begins in the third or asthma is usually straightforward, although pul- fourth decade and there is a marked male pre- monary infiltrates due to mucus plugging or dominance. The etiology is unknown, but, in may suggest the possibility of allergic some cases, an abnormal clonal proliferation of bronchopulmonary aspergillosis or chronic helper T-lymphocytes has been identified. This eosinophilic pneumonia.

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Table 7 Parasitic Infections

Strongyloides Hyperinfection syndrome in immunocompromised host Ascaris Simple pulmonary eosinophilia Toxocara Visceral larva migrans Figure 6. Endobronchial biopsy from a patient with allergic Ankylostoma Cutaneous larva migrans bronchopulmonary aspergillosis consisting of allergic Filaria Tropical pulmonary eosinophilia mucin containing eosinophils and the characteristic branching hyphae of Aspergillus.

Allergic bronchopulmonary Aspergillosis (ABPA). ABPA is a complication of asthma or atopy, also seen occasionally in or following lung transplantation. It is a complex hypersensitivity reaction that occurs when the bronchi become colonized by Aspergillus. It pre- sents as worsening asthma, , expectoration of brown mucus plugs and recurrent pulmonary infiltrates. The major criteria for the diagnosis of Figure 7. CT scan from the same patient as Fig. 6 showing a ABPA are listed in Table 6.10 The bronchi become branching opacity caused by mucoid impaction in the lingu- obstructed by allergic mucin, containing fungal lar . Bronchoscopy revealed a tenacious mucous hyphae and eosinophils, with a surrounding bron- plug almost completely occluding the lingular bronchus. chocentric inflammatory infiltrate (Figure 6). Occasionally, there are areas of bronchocentric granulomatosis or eosinophilic pneumonia. Radiological manifestations include mucoid impaction, with branching cylindrical opacities (Figure 7) and proximal bronchiectasis. The main- stay of treatment is corticosteriods in relatively high doses initially. Itraconazole may have a steroid-sparing effect. Bronchocentric Granulomatosis. This is not a clearly defined clinical syndrome. It usually pre- Figure 8. Chest CT scan showing an irregular nodule with sents as a solitary nodule or mass on chest radi- a traversing bronchus in the right upper lobe. The open ograph (Figure 8). Open lung biopsy is required lung biopsy specimen is shown in Fig. 9. for diagnosis and shows granulomatous and necro-

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tizing replacement of bronchial epithelium with surrounding chronic eosinophilic inflammation (Figure 9). In one-third of cases, bronchocentric granulomatosis constitutes a tissue-destructive variant of ABPA.11 In the remainder of cases, the inflammation is predominantly neutrophilic and can be found in association with fungal or mycobacterial infections, aspiration, Wegener’s granulomatosis and rheumatoid arthritis. Steroids are effective, provided infection has been exclud- ed. Parasitic infections. The pulmonary manifesta- tions of parasitic infection are caused by the transcoelomic dissemination of larvae from the Figure 9. Open lung biopsy from the lesion shown in Fig. 8 skin and the intestine to the lung. Pulmonary showing a bronchiole surrounded by a mixed inflammato- involvement often antedates the presence of ry cell infiltrate and granulomatous reaction. The epithelium worms in the stool. The causative agent is deter- is replaced by radially palisaded histiocytes, typical of mined by the geographic location of origin. Some bronchocentric granulomatosis. of the more common parasites and their clinical syndromes are listed in Table 7. Clues to the para- comprises specific antihelminthic agents. sitic etiology of pulmonary infiltrates with eosinophilia include cases involving immigrants, Drug reactions. Drug reactions are a common recent travel to endemic areas, institutionalized cause of pulmonary infiltrates with eosinophilia, and patients and the presence of a skin rash. Treatment over 60 agents have been implicated (Figure 10). Eosinophilic Lung Disease

monia in the differential diagnosis. Multisystem involvement suggests either Churg-Strauss syn- drome or idiopathic hypereosinophilic syndrome. Always consider the possibility of an underlying malignancy or chronic infection. Bronchoalveolar lavage has proven to be a very useful investigation in this group of conditions. Open lung biopsy is infrequently required for diagnosis. The vastCME majority of patients respond well to appropriate therapy.

Acknowledgements: The author wishes to thank Dr. John English (department of pathology) and Dr. Nestor Müller (department of ), of the Vancouver General Hospital, for their help in preparing some Figure 10. Chest radiograph showing bibasal interstitial of the figures. and airspace infiltrates and pleural effusions in a patient taking nitrofurantion for recurrent urinary tract infections. References 1. Weller PF: The immunobiology of eosinophils. New Engl J A differential white cell count on the bronchoalveolar Med 1991; 324(16):1110-8. lavage fluid revealed 40% eosinophils. 2. Reader WH, Goodrich BE: Pulmonary infiltrates with eosinophilia (PIE syndrome). Ann Intern Med 1952; 36:1217-40. Some of the more frequent offenders are listed in 3. Crofton JW, Livingstone JL, Oswald NC, et al: Pulmonary Table 4. Most reactions are mild and respond to dis- eosinophilia. Thorax 1952;7:1-35. continuation of the drug. A short course of corticos- 4. Liebow AA, Carrington CB: The eosinophilic . teroids may be indicated for more severe reactions. Medicine 1969; 48:251-85. 5. Allen JN, Davis BW: Eosinophilic lung diseases. Am J Respir Crit Care Med 1994; 150:1423-38. 6. Carrington CB, Addington WW, Goff AM et al. Chronic Summary eosinophilic pneumonia. N Engl J Med 1969; 280:787-98. 7. Allen JN, Pacht ER, Gadek JE, et al: Acute eosinophilic The eosinophilic lung diseases are an interesting pneumonia as a cause of noninfectious . N group of conditions of diverse etiology. Differential Engl J Med 1989; 321:569-74. diagnosis requires a focused approach to patient 8. Churg J, Strauss L: Allergic granulomatosis, allergic angiitis evaluation based on knowledge of the various caus- and periarteritis nodosa. Am J Path 1951; 27:277-301. 9. Fauci AS, Harley JB, Roberts WC, et al: The idiopathic es. When confronted with a patient who has pul- hypereosinophilic syndrome: clinical, pathophysiologic and monary infiltrates and peripheral eosinophilia, first therapeutic considerations. Ann Intern Med 1982;97:78-92. confirm that the eosinophilia is persistent. Enquire 10. Rosenberg M, Patterson R, Mintzer R, et al: Clinical and about recent drug use, foreign travel or immigration immunologic criteria for the diagnosis of allergic bronchopul- monary aspergillosis. Ann Intern Med 1997; 86:405-14. from an area endemic for parasitic infestations. If 11. Katzenstein AL, Liebow AA, Friedman PJ: Bronchocentric the patient has a background of asthma, consider granulomatosis, mucoid impaction and hypersensitivity allergic bronchopulmonary aspergillosis, Churg- reaction to fungus. Am Rev Respir Dis 1975;111:497-537. Strauss syndrome and chronic eosinophilic pneu-

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