Eosinophilic pulmonary diseases are a heterogeneous group of disorders characterized by the accumulation of eosinophils in alveolar spaces, the interstitium, or both. Peripheral blood eosinophilia is also common. Known causes of eosinophilic pulmonary disease include
Often the cause is unknown.
Diagnosis is based on demonstration of opacities on chest x-ray and identification of eosinophilia (> 450/μL) in peripheral blood, bronchoalveolar lavage fluid, or lung biopsy tissue. However, pulmonary eosinophilia may occur in the absence of peripheral eosinophilia. Pulmonary opacities on chest x-ray associated with blood eosinophilia are sometimes called PIE (pulmonary infiltrates with eosinophilia) syndrome.
Eosinophils are primarily tissue-dwelling and are several hundred–fold more abundant in tissues than in blood. Consequently, blood eosinophil numbers do not necessarily indicate the extent of eosinophilic involvement in affected tissues. Eosinophils are most numerous in tissues with a mucosal epithelial interface with the environment, such as the respiratory, GI, and lower GU tracts. Eosinophils are not present in the lungs of healthy people, so their presence in tissue or bronchoalveolar lavage fluid (> 5% of differential count) identifies a pathologic process.
Eosinophils are exquisitely sensitive to corticosteroids and completely disappear from the bloodstream within a few hours after administration of corticosteroids. This rapid disappearance from the blood may obscure the diagnosis in patients who receive corticosteroids before the diagnostic assessment is instituted.
The two primary eosinophilic pulmonary diseases of unknown etiology are chronic and acute eosinophilic pneumonia. Hypereosinophilic syndrome, a systemic disease affecting multiple organs, is discussed elsewhere (see Eosinophilic Disorders: Hypereosinophilic Syndrome).
Chronic Eosinophilic Pneumonia
Chronic eosinophilic pneumonia (CEP) is a disorder of unknown etiology characterized by an abnormal, chronic accumulation of eosinophils in the lung.
CEP is not truly chronic; rather it is an acute or subacute illness that recurs (thus, a better name might be recurrent eosinophilic pneumonia). The prevalence and incidence of CEP are unknown. Etiology is suspected to be an allergic diathesis. Most patients are nonsmokers.
Symptoms and Signs
Patients often present with fulminant illness characterized by cough, fever, progressive breathlessness, wheezing, and night sweats. The clinical presentation may suggest a community-acquired pneumonia. Asthma accompanies or precedes the illness in > 50% of cases. Those with recurrent symptoms may have weight loss.
Diagnosis is suspected in patients with characteristic symptoms and typical radiographic appearance. Diagnosis also requires CBC, ESR, sometimes iron studies, and exclusion of infectious causes by appropriate cultures (see Medicolegal Issues: Advance Directives). Peripheral blood eosinophilia, a very high ESR, iron deficiency anemia, and thrombocytosis are all frequently present. Chest x-ray findings of bilateral peripheral or pleural-based opacities, most commonly in the middle and upper lung zones, is described as the photographic negative of pulmonary edema and is virtually pathognomonic (although present in < 25% of patients). A similar pattern is present on CT in virtually all cases. Bronchoalveolar lavage and biopsy are almost always done. Eosinophilia > 40% in bronchoalveolar lavage fluid is suggestive of CEP; serial bronchoalveolar lavage examinations may help document the course of disease. Biopsy shows interstitial and alveolar eosinophils and histiocytes, including multinucleated giant cells, and organizing pneumonia. Fibrosis is minimal.
Patients with CEP are uniformly responsive to IV or oral corticosteroids; failure to respond suggests another diagnosis. Initial treatment is prednisone 40 to 60 mg once/day. Clinical improvement is often striking and rapid, often occurring within 48 h. Complete resolution of symptoms and x-ray abnormalities occurs within 14 days in most patients and by 1 mo in almost all. Symptoms and plain chest x-rays are both reliable and efficient guides to therapy. Although CT is more sensitive for the detection of radiographic abnormalities, there is no benefit gained by repeating it. Peripheral eosinophil counts, ESR, and IgE levels can also be used to follow the clinical course during treatment. However, not all patients have abnormal laboratory test results.
Symptomatic or radiographic relapse occurs in 50 to 80% of cases either after cessation of therapy or, less commonly, with tapering of the corticosteroid dose. Relapse can occur months to years after the initial episode. Thus, corticosteroid therapy is occasionally continued indefinitely. Inhaled corticosteroids (eg, fluticasone or beclomethasone 500 to 750 μg bid) appear to be effective, especially in reducing the maintenance dose of oral corticosteroid.
Relapse does not appear to indicate treatment failure, a worse prognosis, or greater morbidity. Patients continue to respond to corticosteroids as during the initial episode. Fixed airflow obstruction can occur in some patients who recover, but the abnormalities are usually of borderline clinical significance.
CEP occasionally leads to physiologically important restrictive lung function abnormalities as a result of irreversible fibrosis, but abnormalities are usually mild enough that CEP is an extremely unusual cause of morbidity or death.
Acute Eosinophilic Pneumonia
Acute eosinophilic pneumonia (AEP) is a disorder of unknown etiology characterized by rapid eosinophilic infiltration of the lung interstitium.
In contrast to CEP, AEP is an acute illness that occurs once and does not recur. Incidence and prevalence are unknown. AEP can occur at any age but most often affects patients between 20 and 40 yr, with a male-to-female ratio of 21:1. The cause is unknown, but AEP may be an acute hypersensitivity reaction to an unidentified inhaled antigen in an otherwise healthy person. Cigarette or other smoke exposure may be involved.
Symptoms and Signs
AEP causes an acute febrile illness of short duration (usually < 7 days). Symptoms are nonproductive cough, dyspnea, malaise, myalgias, night sweats, and pleuritic chest pain. Signs include tachypnea, fever (often > 38.5° C), and bibasilar inspiratory crackles and, occasionally, rhonchi on forced exhalation. Patients with AEP frequently present with acute respiratory failure requiring mechanical ventilation. Rarely, distributive (hyperdynamic) shock can occur.
The diagnosis is suspected in patients with symptoms of acute pneumonia that progresses to respiratory failure and does not respond to antibiotics. Diagnosis is based on findings from routine testing and is confirmed by bronchoscopy. AEP is a diagnosis of exclusion and requires the absence of known causes of eosinophilic pneumonia (eg, drug- and toxin-induced, helminthic and fungal infection–related, Churg-Strauss syndrome, idiopathic hypereosinophilic syndrome, tumors). The CBC in most patients demonstrates markedly elevated eosinophil counts. ESR and IgE levels are high but are nonspecific.
The chest x-ray initially may show only subtle reticular or ground-glass opacities, often with Kerley B lines. Isolated alveolar (about 25% of cases) or reticular (about 25% of cases) opacities may also be observed. The pattern is unlike that occurring in chronic eosinophilic pneumonia, in which the opacities are localized to the lung periphery. Small pleural effusions occur in two thirds of patients and are frequently bilateral.
HRCT is always abnormal with bilateral, random, patchy ground-glass or reticular opacities.
Pleural fluid examination shows marked eosinophilia with high pH. Pulmonary function tests often show a restrictive process with reduced diffusing capacity for carbon monoxide (DLco).
Bronchoscopy should be done for lavage and, occasionally, biopsy. Bronchoalveolar lavage fluid often shows a high number and percentage (> 25%) of eosinophils. The most common histopathologic features on biopsy include eosinophilic infiltration with acute and organizing diffuse alveolar damage, but few patients have undergone lung biopsy.
Some patients improve spontaneously. Most are treated with prednisone 40 to 60 mg po once/day. In patients with respiratory failure, methylprednisolone 60 to 125 mg IV q 6 h is preferred. The prognosis is excellent; response to corticosteroids and complete recovery without recurrence is almost universal. Pleural effusions resolve more slowly than parenchymal opacities.
Löffler's syndrome is characterized by absent or mild respiratory symptoms (most often dry cough), fleeting migratory pulmonary opacities, and peripheral blood eosinophilia. Parasitic infections, especially Ascaris lumbricoides, may be the cause, but an identifiable etiologic agent is not found in up to 1/3 of patients. The disease usually resolves within 1 mo. Treatment is symptomatic and consists of corticosteroids.
Last full review/revision May 2008 by Talmadge E. King, Jr., MD