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Chronic eosinophilic pneumonia

Chronic eosinophilic pneumonia
Literature review current through: Jan 2024.
This topic last updated: Jun 29, 2023.

INTRODUCTION — Chronic eosinophilic pneumonia (CEP) is an idiopathic disorder characterized by an abnormal and marked accumulation of eosinophils in the interstitium and alveolar spaces of the lung [1,2].

The clinical manifestations, diagnosis, and treatment of chronic eosinophilic pneumonia will be reviewed here. The evaluation and differential diagnosis of eosinophilic lung diseases, in general, and an approach to acute eosinophilic pneumonia are presented separately. (See "Overview of pulmonary eosinophilia" and "Idiopathic acute eosinophilic pneumonia".)

EPIDEMIOLOGY — CEP is a rare disorder. The incidence of CEP in an Icelandic registry was 0.23 cases/100,000 population per year between 1990 and 2004 [3]. In registries of interstitial lung disease (ILD) in Europe, CEP accounted for 0 to 2.5 percent of cases of ILD [4]. Women develop CEP about twice as often as men. A majority of patients are nonsmokers.

CLINICAL MANIFESTATIONS — CEP typically affects patients in their 30s or 40s, although onset in childhood has been reported [5-7]. A history of atopy is found in 60 percent. Asthma precedes, accompanies, or subsequently occurs in over 50 percent of cases [8].

The disease has a gradual onset, with an interval of approximately four to five months between the appearance of initial symptoms and diagnosis [5]. Typical symptoms include a productive cough (33 to 42 percent), fever (67 percent), breathlessness (57 to 92 percent), weight loss (57 to 75 percent), and night sweats [5,9].

On physical examination, auscultatory findings of wheezing are noted in 35 percent and/or crackles in 38 percent [5].

EVALUATION — CEP is typically suspected in a patient with progressive dyspnea over one to four months and a chest radiograph showing bilateral peripheral or pleural-based opacities. Among the first steps in the evaluation is to inquire whether the patient is taking or has recently taken any of the drugs associated with pulmonary eosinophilia or has resided in an area with an increased likelihood of exposure to endemic parasite or fungi (table 1). (See "Overview of pulmonary eosinophilia", section on 'History and physical examination'.)

Laboratory — No laboratory studies are specific for CEP. However, in the evaluation of patients with dyspnea, cough, and pulmonary radiographic opacities, the usual laboratory tests include a complete blood count and differential, blood urea nitrogen, creatinine, hepatic function tests, and urinalysis.

Peripheral blood eosinophilia is common in CEP with 88 to 95 percent of patients showing elevated eosinophil counts (>6 percent) [5,9]. Mean eosinophil differentials average 32.3 percent, with a range of 4.4 to 79. Total blood eosinophils are usually >1000/microL [5,10]. Peripheral blood eosinophilia is defined as >500 eosinophils/microL (>0.5 × 109 eosinophils/L) [11]. Total immunoglobulin E (IgE) is elevated (mean 506 IU/mL or approximately 1214 ng/mL) in approximately 50 percent of patients. A high sedimentation rate, elevated C-reactive protein, iron deficiency anemia, and thrombocytosis are also common, but nonspecific [12]. (See "Eosinophil biology and causes of eosinophilia" and "The biology of IgE".)

Certain laboratory tests are helpful to evaluate for diseases in the differential diagnosis (eg, allergic bronchopulmonary aspergillosis and eosinophilic granulomatosis with polyangiitis [EGPA; Churg Strauss]), including total serum IgE, IgG antibodies to Aspergillus, and an antineutrophil cytoplasmic antibody (ANCA) test. However, ANCA is only positive in 40 to 60 percent of patients with EGPA, so a negative test doesn't exclude the diagnosis. (See "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis", section on 'Diagnosis' and "Clinical features and diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)", section on 'Antineutrophil cytoplasmic antibodies'.)

Evaluation of sputum for eosinophils does not appear to be helpful, as they are present in fewer than half of patients [2,11].

Pulmonary function tests — Pulmonary function tests (PFTs) are obtained in most ambulatory adults being evaluated for CEP based on symptoms (eg, dyspnea and/or cough) or peripheral blood eosinophilia. As many patients with CEP have a history of asthma, PFTs should include spirometry before and after inhaled bronchodilator in addition to lung volumes and diffusing capacity. (See "Overview of pulmonary function testing in adults".)

In CEP, PFTs may show an obstructive or restrictive pattern, or may be normal, and thus are more helpful in assessing the degree of respiratory impairment than in guiding the diagnosis. The initial PFTs also provide a helpful baseline for monitoring response to treatment. In a case series of 62 patients, spirometry showed an obstructive pattern in 36 percent and a restrictive pattern in 32 percent. Diffusing capacity for carbon monoxide was decreased in approximately half the patients [5]. In a separate series of 19 patients, spirometry revealed an obstructive pattern in four (21 percent), restrictive in nine (47 percent), and normal in six (32 percent) [13].

An observational study of 133 consecutive patients with CEP followed for longer than one year showed that persistent lung function impairment is common [14]. CEP patients with asthma and obstructive defects at diagnosis had persistent obstructive impairments, whereas those with lung restriction and high-resolution computed tomography (HRCT) reticulation pattern at diagnosis had persistent restrictive impairment on follow-up.

Imaging — The finding of bilateral peripheral or pleural-based, nonsegmental, consolidative opacities described as the "photographic negative" of pulmonary edema is highly suggestive of CEP when seen on chest radiograph (image 1) or high-resolution computed tomography (HRCT) (picture 1) [15,16]. However, the "photographic negative" pattern on the chest radiograph is present in only one-fourth of patients and is not specific for CEP [2,9,15,17].

Additional imaging features that are common in CEP include an upper lung zone location of the opacities in approximately 50 percent and migratory opacities in 25 percent [5]. An air bronchogram may be present on HRCT [5]. Less common HRCT abnormalities include ground glass opacities, nodules, cavities, and reticulation.

While certain HRCT findings are strongly suggestive of CEP (eg, peripheral, nonsegmental opacities), substantial overlap exists between the imaging findings of the various eosinophilic lung diseases. As an example, in a series that included 40 patients with CEP, the HRCT correctly identified 78 percent of the CEP cases [18]. However, in an expanded series that included these cases, considerable overlap was noted in the HRCT findings of the various eosinophilic lung diseases (EGPA, ABPA, acute eosinophilic pneumonia, hypereosinophilic syndrome, drug-induced eosinophilic pneumonia) [19].

A pleural effusion is uncommon and observed in less than 10 percent of patients [16].

Bronchoscopy — Bronchoalveolar lavage (BAL) with analysis of the cellular differential is performed in the majority of patients to identify eosinophilia and to exclude infection. The BAL sample is typically obtained in an area of radiographic opacity and sent for cell count, microbiologic studies, and cytology. (See "Basic principles and technique of bronchoalveolar lavage" and "Role of bronchoalveolar lavage in diagnosis of interstitial lung disease".)

The BAL eosinophil count is almost always greater than 25 percent in CEP [5,12,20]; in one study, the mean BAL eosinophil proportion was 58 percent and more than 80 percent of patients had a BAL eosinophil count >40 percent [5]. Only rarely is eosinophilia absent in the BAL. When this happens, a lung biopsy is required for diagnosis [21,22]. BAL eosinophilia may be associated with increased neutrophils, lymphocytes, and mast cells [5].

Although transbronchial lung biopsy may show characteristic features of eosinophilic pneumonia, it is uncommonly performed because the small size of the specimen usually precludes making a definitive pattern diagnosis (see below). (See 'Histopathology' below and "Role of lung biopsy in the diagnosis of interstitial lung disease", section on 'Transbronchial lung biopsy'.)

Histopathology — Surgical lung biopsy is rarely needed to secure a diagnosis of CEP. When lung histopathology is obtained, interstitial and alveolar eosinophils and histiocytes, including multinucleated giant cells, are characteristic. Organizing pneumonia is a common associated finding (picture 2); interstitial fibrosis is minimal. Eosinophilic abscesses may also be seen [23].

In a series of 62 patients with CEP, four underwent surgical lung biopsy and eight had one or more transbronchial biopsies [5]. Among patients who required surgical biopsy, the histopathology showed both an interstitial and an alveolar exudate with eosinophils. Two biopsies had findings of organizing pneumonia and an eosinophilic infiltrate in the walls of small blood vessels, but without necrosis. Five of the transbronchial biopsies showed interstitial eosinophilic infiltrates and three showed alveolar exudates. Among patients who had endobronchial biopsies, a submucosal eosinophilic infiltrate was noted.

DIAGNOSIS — The diagnosis of CEP is typically based on the combination of clinical presentation, chest imaging showing predominantly peripheral or pleural-based, mid to upper lung zone opacities, and a bronchoalveolar lavage showing eosinophilia (≥25 percent). Surgical lung biopsy is generally not necessary unless the BAL does not show eosinophilia, the radiographic features are atypical, or the patient does not respond promptly to systemic glucocorticoid therapy. (See 'Imaging' above and 'Bronchoscopy' above.)

Other potential causes of eosinophilic pneumonia, such as infection, drugs, and vasculitis, should be excluded, as described below. (See 'Differential diagnosis' below.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of CEP includes eosinophilic lung diseases of other etiologies and noneosinophilic lung diseases with similar clinical presentations:

Acute eosinophilic pneumonia differs from CEP in its acute, often fulminant onset (one month or less), the severity of hypoxemia, typical absence of peripheral blood eosinophilia, and diffuse pattern of radiographic opacities. (See "Idiopathic acute eosinophilic pneumonia", section on 'Clinical features'.)

Allergic bronchopulmonary aspergillosis (ABPA) is similar to CEP in the combination of asthma, peripheral blood eosinophilia, and upper lung zone radiographic abnormalities [24]. However, the radiographic opacities in ABPA are more typically those of bronchiectasis (eg, "tram-tracking" or more centrally located mucus plugging "finger-in-glove"). The diagnosis of ABPA is based on a serum IgE level >1000 IU/L, a positive specific IgG to Aspergillus, and a positive prick skin test to Aspergillus antigen. Negative prick and intradermal skin tests to Aspergillus extract virtually exclude the diagnosis of ABPA. (See "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis", section on 'Diagnosis'.)

Drug-induced eosinophilic pneumonia – A number of drugs have been associated with eosinophilic pneumonia, including nonsteroidal antiinflammatory drugs (NSAIDS), cocaine, nitrofurantoin, minocycline, sulfonamides, ampicillin, daptomycin, diphenylhydantoin, and methotrexate. (See "Overview of pulmonary eosinophilia", section on 'Medications and toxins'.)

Eosinophilic pneumonia due to fungal or parasitic infection should be carefully evaluated in patients who have travelled or resided in an endemic area. Infectious causes of pulmonary eosinophilia are described separately. (See "Overview of pulmonary eosinophilia".)

Transpulmonary passage of helminth (most commonly Ascaris) larvae (Loeffler syndrome) is associated with transient radiographic opacities that may shift over the course of days. While radiographic opacities in CEP tend to be persistent, migratory opacities have been noted in 25 percent of patients with CEP [16]. (See "Overview of pulmonary eosinophilia", section on 'Helminth infections' and 'Imaging' above.)

Eosinophilic granulomatosis with polyangiitis (EGPA, previously known as Churg Strauss) is a vasculitic disorder characterized by sinusitis, asthma, and prominent peripheral blood eosinophilia. EGPA can have a similar presentation to CEP, although the radiographic opacities are typically mid rather than upper zone and centrilobular rather than peripheral. EGPA is more likely to have extrapulmonary manifestations (eg, skin, heart, kidney). However, an overlap between CEP and EGPA has been noted with the suggestion that CEP may be a presenting feature of EGPA. (See "Clinical features and diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)", section on 'Evaluation'.)

Cryptogenic organizing pneumonia (COP) can have a similar radiographic appearance to CEP but does not have bronchoalveolar lavage (BAL) eosinophilia. Occasionally, COP and CEP are seen together on histopathology, in which case the diagnosis is based on the predominant pattern. The response to treatment with systemic glucocorticoids is generally slower in COP than CEP. (See "Cryptogenic organizing pneumonia", section on 'Diagnosis'.)

TREATMENT — Therapy is indicated once the diagnosis of CEP has been made and alternative causes of pulmonary eosinophilia have been excluded, as fewer than 10 percent of patients with CEP spontaneously recover or improve.

Initial treatment — No prospective trials evaluating prednisone regimens have been performed in patients with CEP, and such trials are unlikely, since most prednisone regimens are effective [9]. Adequate initial therapy for virtually all patients with CEP consists of oral prednisone at a dose of 0.5 mg/kg per day. We continue the initial dose for two weeks after the complete resolution of symptoms and plain chest radiographic abnormalities (usually four to six weeks).

For patients with rapidly progressive disease (especially if associated with respiratory failure), we have used three to five days of high dose glucocorticoid therapy, such as methylprednisolone 250 mg every six hours, intravenously, prior to transitioning to oral therapy, although this has not been formally studied. Once the patient is stabilized, therapy is continued as outlined above for initial therapy.

Assessing the response to therapy — Clinical improvement is often dramatic and rapid in response to prednisone, with profound symptomatic relief occurring in many patients within 48 hours [5]. Patients with CEP are uniformly responsive to intravenous or oral glucocorticoids. Thus, if a patient does not improve with glucocorticoid treatment, alternative diagnoses should be entertained.

The optimal methods and timing for monitoring CEP disease activity are not known. We typically use a combination of symptoms, physical examination, peripheral blood eosinophilia, pulse oxygen saturation, pulmonary function tests, and chest imaging to assess response. Patients are seen at two- to four-week intervals initially, and then at three- to six-month intervals. We generally do not monitor the erythrocyte sedimentation rate (ESR) or IgE level.

A favorable response to glucocorticoid therapy is typically defined by [9]:

Resolution of presenting symptoms, especially dyspnea, cough, and fever.

Decline in peripheral eosinophilia.

Marked reduction or clearing (in most cases) of radiographic abnormalities, although radiographic abnormalities may persist on computed tomography scan for several weeks to months after clearing of the chest x–ray [25].

Physiologic improvement (though not necessarily to normal) as measured by forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity (DLCO), and pulse oxygen saturation (SpO2).

Symptoms and plain chest radiographs remain the most reliable and efficient guide to therapy and complete resolution of symptoms and plain chest radiographic abnormalities occurs within 14 days in most patients, and by one month in almost all patients [9]. Although CT scanning is more sensitive for the detection of radiographic abnormalities, there is no information to suggest that following CT scans to assess disease activity is an improvement over plain chest radiographs.

While serial BAL examinations have been reported as a method for following the course of the disease, routine follow-up BAL is not indicated [20]. Repeat BAL is generally reserved for patients with refractory or recurrent disease to exclude an alternate diagnosis or intercurrent infection.

Treatment of disease relapse — In managing a relapse, our practice is to increase the prednisone dose back up to 0.5 mg/kg per day and maintain that dose for one to two weeks beyond the control of symptoms. Thereafter, the dose is reduced to 20 mg/day and continued for another four weeks. If there is documented sustained improvement, the dose is tapered by 5 mg every two to three weeks to the previous dose that maintained complete control of the disease.

Duration of therapy — The goal of maintenance therapy is to control the disease with the smallest required dose of oral glucocorticoids in order to limit treatment-related side effects. Formal study is lacking regarding the optimal duration of treatment, but because relapses are common, treatment is typically maintained for at least three months, and usually for six to nine months.

Approximately four to six weeks after starting oral prednisone and after symptoms and chest radiograph abnormalities have resolved, prednisone dose can be decreased by 0.25 mg/kg per day (or equivalent) and continued at that dose for another eight weeks.

Subsequently, prednisone can be reduced at 5 mg decrements every four weeks until complete cessation of therapy (in the absence of recurrent symptoms or radiographic abnormalities). An alternate–day regimen can also be used for tapering when the prednisone dose is ≤15 mg/day.

Although the dose and length of therapy will vary for individual patients, an attempt to stop therapy is reasonable after three to nine months, as about one quarter to one half of patients will tolerate glucocorticoid discontinuation at that time [26].

A randomized, open-label study compared the rate of relapse during two years of follow-up after either three months or six months of glucocorticoid therapy [27]. All patients were treated with an initial dose of prednisolone (0.5 mg/kg per day), which was then tapered and discontinued at either three or six months. Relapse occurred in 52 percent of the three-month group and 62 percent of the six-month group (p = 0.56). All patients who relapsed showed improvement upon resumption of prednisolone.

A separate study found that three-fourths of patients required prolonged glucocorticoid therapy, with a mean initial duration of 19 months [9].

Other studies have documented that the majority of patients require long-term oral glucocorticoid treatment (one or more years) and a few require lifelong therapy [2,5,26].

Attempts are made to reduce the prednisone dose to the lowest amount that will control the disease; use of alternate-day oral prednisone may help reduce the adverse effects of systemic glucocorticoids. Because of the high rate of relapse, indefinite glucocorticoid therapy is occasionally required.

Potential alternative therapies — Alternative therapies have been explored for patients with recurrent flares of CEP that are associated with radiographic opacities, including inhaled glucocorticoids, omalizumab (monoclonal antibody [mAb] to IgE), mepolizumab (mAb to interleukin-5), and benralizumab (mAb to IL-5R-alpha).

Inhaled glucocorticoids – Inhaled glucocorticoids (1000 to 1500 mcg per 24 hours) have been reported to be effective in CEP, although studies are conflicting [26,28-30]. In a case series, three of five patients who used inhaled glucocorticoids were able to decrease the dose of oral glucocorticoid [26]. Similarly, in a case report, inhaled beclomethasone 1500 mcg/day given during a flare resulted in disease control without an increase in the baseline dose of prednisone 10 mg/day [29]. However, in a series of four patients, monotherapy with beclomethasone 1600 mcg/day did not control the disease [28]. The availability of inhaled formulations with higher dose per inhalation and greater potency may improve the efficacy of this approach. Inhaled glucocorticoids are not recommended as initial or monotherapy but might help in reducing the maintenance dose of oral glucocorticoids.

OmalizumabOmalizumab inhibits binding of IgE to the high affinity IgE receptor on the surface of mast cells and basophils. It has been reported to be successful in case reports of patients with prolonged dependence on systemic glucocorticoids, who also had asthma and skin test positivity to perennial allergens such as dust mites [31-33]. Further study is needed to determine the efficacy of this therapy in CEP. Importantly, reports of omalizumab-associated EGPA may limit the usefulness of this approach. (See "Anti-IgE therapy" and "Epidemiology, pathogenesis, and pathology of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)", section on 'Omalizumab'.)

Anti-IL-5/5R therapiesMepolizumab and benralizumab, monoclonal antibodies that bind to interleukin (IL)-5 and the IL-5 receptor, respectively, are used for eosinophilic asthma and have been tested in eosinophilic phenotypes of COPD. In case reports, off-label use of these agents to treat CEP leads to improved symptoms, reduction in extent and severity of chest imaging opacities, reduced blood eosinophil counts, and reduced use of glucocorticoids [34-41]. In a case series of 29 patients treated with anti-IL-5/5R for relapsing or glucocorticoid-dependent CEP (22 mepolizumab, 7 benralizumab), none of the patients had a relapse and 72 percent of patients were able to wean off of systemic glucocorticoid therapy during a median 13-month follow-up [41].

Other biologic agents – In contrast with the ameliorative effects on CEP of omalizumab, mepolizumab, and benralizumab, dupilumab, a fully humanized mAb that inhibits the biological effects of both IL-4 and IL-13, was associated with a progressive increase in blood eosinophils count and subsequent onset of clinical-radiological and histopathologic findings suggestive of CEP when administered to a patient with severe allergic and eosinophilic asthma [42]. Tezepelumab, a monoclonal antibody against thymic stromal lymphopoietin, has demonstrated efficacy in severe eosinophilic and noneosinophilic asthma but has not been well-evaluated in CEP.

Prevention of glucocorticoid-related adverse effects — Chronic therapy with systemic glucocorticoids is associated with a number of adverse effects. Steps to monitor, prevent, and treat these side effects are discussed separately. (See "Major adverse effects of systemic glucocorticoids" and "Prevention and treatment of glucocorticoid-induced osteoporosis".)

PROGNOSIS — The outcome for most patients with chronic eosinophilic pneumonia (CEP) is excellent despite the risk of recurrences and the occasional need for prolonged therapy.

Symptomatic or radiographic relapse is common (50 to 80 percent of cases) either after cessation of therapy or, less commonly, with tapering of the glucocorticoid dose [5,9]. Relapse can occur months to years following the initial presenting episode. A retrospective review of 36 Japanese patients with CEP treated with glucocorticoid therapy revealed a relapse rate of 55 percent at least one year after initiation of therapy. Centrilobular opacities on high-resolution CT (HRCT) and higher serum SP-D levels at diagnosis were predictive of relapse [43]. Active smokers may be at increased risk of relapse [44].

Importantly, relapse does not appear to indicate treatment failure, a worse prognosis, or greater morbidity. Patients with CEP continue to be glucocorticoid-responsive and to respond to glucocorticoid doses at levels similar to those prior to the relapse.

With each exacerbation, the diagnosis needs to be reconfirmed to ensure that the symptoms are due to CEP (eg, recurrent radiographic opacities) rather than an alternative explanation such as an asthma flare or infection. In previously well-controlled patients who unexpectedly relapse or begin to require higher doses of oral glucocorticoids to maintain control, the development of another eosinophilic disorder (eg, eosinophilic granulomatosis with polyangiitis [Churg Strauss] or hypereosinophilic syndrome) should be considered [45] (See "Clinical features and diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)" and "Hypereosinophilic syndromes: Clinical manifestations, pathophysiology, and diagnosis".)

Fixed airflow obstruction can occur in some patients who recover from CEP, but the abnormalities are usually of borderline clinical significance [13].

CEP occasionally leads to clinically important, irreversible fibrosis [46]. Older age and male sex made the presence of fibrosis more likely. Interestingly, a history of asthma decreased the likelihood. In a retrospective review of 62 patients followed for a median of 8.6 years, 37 percent of patients with CEP developed pulmonary fibrosis on CT imaging, the majority of which was not consistent with usual interstitial pneumonia [47]. The development of fibrosis was associated with an increased risk of mortality.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Interstitial lung disease".)

SUMMARY AND RECOMMENDATIONS

Clinical manifestations – Chronic eosinophilic pneumonia (CEP) is an idiopathic disorder characterized by an abnormal and marked accumulation of eosinophils in the interstitial and alveolar spaces of the lung. CEP is characterized by the onset of dyspnea, cough, fever, and wheezing over three weeks to several months. (See 'Introduction' above and 'Clinical manifestations' above.)

Evaluation – Additional diagnostic evaluation includes laboratory evaluation, noncontrast chest CT imaging, and bronchoscopic alveolar lavage (BAL). (See 'Evaluation' above.)

Imaging – Chest CT imaging findings of bilateral peripheral or pleural-based opacities, described as the "photographic negative" of pulmonary edema, are virtually pathognomonic for CEP, although not all patients manifest this pattern. (See 'Imaging' above and "High resolution computed tomography of the lungs", section on 'HRCT disease distribution'.)

Laboratory testing – Peripheral blood eosinophilia is commonly, though not universally present. (See 'Imaging' above and "High resolution computed tomography of the lungs", section on 'HRCT disease distribution'.)

Bronchoalveolar lavage – BAL is performed in most patients to exclude infection and characterize the infiltrate. In CEP, the BAL almost always shows eosinophilia greater than 25 percent. (See 'Bronchoscopy' above.)

Diagnosis – The diagnosis of CEP is typically based on the combination of clinical presentation with subacute dyspnea and cough, chest imaging showing predominantly peripheral or pleural-based opacities, and a BAL cell count showing eosinophilia (≥25 percent). Infections and drug-induced pulmonary eosinophilia need to be excluded. Lung biopsy is not necessary unless the BAL does not show eosinophilia, the chest imaging features are atypical, or the patient does not respond promptly to systemic glucocorticoid therapy. (See 'Diagnosis' above.)

Differential diagnosis – The differential diagnosis of CEP includes acute eosinophilic pneumonia, eosinophilic pneumonia due to drug toxicity, infection (eg, fungal or parasitic), or allergic bronchopulmonary aspergillosis, eosinophilic granulomatosis with polyangiitis (Churg Strauss), and cryptogenic organizing pneumonia. (See 'Differential diagnosis' above.)

Initial treatment – For patients diagnosed with CEP, we recommend initial treatment with systemic glucocorticoids rather than alternative therapies (Grade 2C). Observation is not appropriate, as CEP rarely resolves spontaneously. (See 'Treatment' above.)

Typical disease – For patients without rapidly progressive disease or respiratory failure, we initiate therapy with oral prednisone, 0.5 mg/kg per day, or the equivalent. (See 'Initial treatment' above.)

Rapidly progressive disease or respiratory failure – For patients with rapidly progressive CEP or respiratory failure, we typically use high-dose intravenous glucocorticoid therapy (eg, methylprednisolone 60 to 125 mg every six hours) for three to five days prior to transitioning to oral therapy with prednisone. (See 'Initial treatment' above.)

Usual early glucocorticoid course – We continue prednisone at 0.5 mg/kg per day for two weeks after the complete resolution of symptoms and plain chest radiographic abnormalities (usually four to six weeks into therapy). At that time, the dose can be decreased by one-half (0.25 mg/kg per day) and therapy continued for another eight weeks. (See 'Assessing the response to therapy' above.)

Assessing response to therapy – Subjective and radiographic improvement usually starts within 48 hours of initiating systemic glucocorticoid therapy. At follow-up visits, we monitor symptoms, physical examination, peripheral blood eosinophil counts, pulmonary function tests, pulse oxygen saturation, and chest imaging as appropriate. (See 'Assessing the response to therapy' above.)

Tapering and duration of glucocorticoid therapy – The optimal duration of therapy is not known. After about 12 to 14 weeks, we usually taper prednisone by 5 mg increments every four weeks as tolerated until complete cessation of therapy or a disease flare. Most patients require prolonged treatment (ie, more than six months) and up to three-fourths of patients will require ongoing therapy for several years. (See 'Duration of therapy' above.)

Adverse effects of glucocorticoid therapy – Chronic therapy with systemic glucocorticoids is associated with several potential adverse effects. Steps to monitor, prevent, and treat these effects are discussed separately. (See "Major adverse effects of systemic glucocorticoids" and "Prevention and treatment of glucocorticoid-induced osteoporosis".)

Therapeutic alternatives – Alternative therapies have been explored for patients with frequent relapses or those in whom glucocorticoid therapy is not tolerated due to adverse effects, including inhaled glucocorticoids, omalizumab (monoclonal antibody [mAb] to IgE), mepolizumab (mAb to interleukin-5), and benralizumab (mAb to IL-5R-alpha).

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Topic 4360 Version 18.0

References

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