SEATTLE--Eosinophilic lung diseases are distinct syndromes that are characterized by pulmonary eosinophilia, “the abnormal accumulation of eosinophils in distal airways, air spaces, and the interstitial compartment of the lung,” said Joshua A. Boyce, MD, at the annual meeting of the American College of Allergy, Asthma, and Immunology.[1] There are a variety of such syndromes, including chronic and acute eosinophilic pneumonia, Löffler’s syndrome, and tropical eosinophilia. However, in some cases, pulmonary eosinophilia represents another underlying disease.

Infectious causes of pulmonary eosinophilia include parasitic infections, particularly ascariasis in children, and Mycobacterium tuberculosis. Noninfectious causes include collagen vascular disease, malignancy, and adverse drug reactions.

Accurate identification of the underlying cause, when possible, is important because it can influence treatment. For example, corticosteroids worsen infections such as M tuberculosis or strongyloidiasis, and therefore they should not be used in the rare patients in whom pulmonary eosinophilia is secondary to such an infection. Instead, treatment should be directed at M tuberculosis or strongyloidiasis, said Dr. Boyce, an Assistant Professor of Medicine at Brigham and Women’s Hospital, in Boston.

MAKING THE DIAGNOSIS

Diagnosing eosinophilic lung disease can be challenging because the symptoms often overlap with those of Churg–Strauss syndrome and other forms of diffuse lung disease. In fact, “there have been case reports of people who’ve presented with chronic eosinophilic pneumonia who have gone on to develop Churg-Strauss syndrome with systemic vasculitis, suggesting that there may be some underlying mechanistic overlap between these two syndromes,” pointed out Dr. Boyce.

However, “it is important to exclude illicit drugs and infection in young patients who present with acute respiratory failure for no apparent reason,” emphasized Dr. Boyce, who noted that he has had patients with crack– and cocaine–induced acute eosinophilic pneumonia.

Pulmonary eosinophilia is a dominant clinical feature of all eosinophilic pneumonias, as shown in Table 1, but peripheral blood eosinophilia is not consistently present. Chronic eosinophilic pneumonia occurs primarily in middle–aged, asthmatic women, although it can also develop in nonasthmatic people. Typically, the symptoms are gradually progressive and include weight loss, dyspnea, and fever. Common physical findings are wheezing, rales, and hypoxia. Lung function testing usually reveals a mixture of obstructive and restrictive defects, reflecting airway and alveolar disease. Most patients with chronic eosinophilic pneumonia have infiltrates that can be seen on chest films; in roughly one third of patients, the infiltrates are peripherally distributed. The absence of peripheral blood eosinophilia does not rule out disease. Pathologically, chronic eosinophilic pneumonia is characterized by alveoli filled with eosinophils and histiocytes, as well as by low–grade vasculitis. The presence of interleukin 5 in bronchial alveolar lavage (BAL) fluid of involved areas is consistent with the diagnosis. Unfortunately, disease recurrence is common.

Not surprisingly, acute eosinophilic pneumonia is characterized by illness of abrupt oxset (less than five days’ duration), hypoxemic respiratory failure at the time of presentation, diffuse mixed alveolar and interstitial infiltrates on chest films, and eosinophilia greater than 25% in BAL fluid. In contrast with chronic eosinophilic pneumonia, acute eosinophilic pneumonia is not characterized by peripheral blood eosinophilia. In fact, many patients with this disease have peripheral blood eosinopenia. “This syndrome probably represents an acute sequestration phenomenon, whereby the circulating eosinophils are all drawn rapidly and simultaneously into the lung,” suggested Dr. Boyce.

Acute eosinophilic pneumonia tends to develop in patients younger than age 40; many patients with the disease are less than 20 years old. There is no association between acute eosinophilic pneumonia and preexisting asthma. Once treated, acute eosinophilic pneumonia does not recur.

Löffler’s syndrome is the most common form of eosinophilic lung disease and is often referred to as simple pulmonary eosinophilia. Symptoms include cough, wheeze, and dyspnea. Although the clinical features of the disease are mild, “transitory patchy infiltrates can be seen radiographically,” said Dr. Boyce; this often occurs in conjunction with mild–to–moderate peripheral blood eosinophilia.

Löffler’s syndrome is often associated with helminth infection, including ascariasis. A variety of drugs, including antibiotics, can also cause Löffler’s syndrome.

However, approximately one third of the cases are idiopathic. If left untreated, Löffler’s syndrome generally resolves spontaneously and does not recur.

Tropical eosinophilia is a rare but dramatic illness with prominent respiratory features, according to Dr. Boyce. The condition results from an exaggerated immune response to filarial pathogens and usually begins with a paroxysmal nocturnal cough. Patients may present with signs of diffuse lung disease and later develop fever and progressive dyspnea. “It is important to note that this syndrome is consistently associated with marked peripheral eosinophilia and elevated serum IgE (immunoglobulin E),” stressed Dr. Boyce. Children with tropical eosinophilia often develop lymphadenopathy and organomegaly. The radiographic distribution of the infiltrates is typically diffuse, but may be interstitial, and is characterized by alveolar filling. Treatment with diethyl–carbamazine is usually effective.

CHOOSING THE BEST TREATMENT

Corticosteroids remain the treatment of choice for most forms of eosinophilic lung disease, according to Dr. Boyce. Prolonged corticosteroid treatment is often necessary, particularly in patients with chronic eosinophilic pneumonia. “[The drugs] work by suppressing the expression of cytokine genes that drive eosinophils and augment directly the apoptosis and facilitate clearance,” he explained. Other treatments include immunosuppressive therapy (which is usually reserved for patients with Churg–Strauss syndrome) and antifungals (which may be effective against allergic pulmonary aspergillosis).

--Deborah L. O’Connor

Reference
1. Boyce JA. Eosinophilic lung syndromes. Paper presented at: Annual Meeting of the American College of Allergy, Asthma, and Immunology; November 2000; Seattle, Wash.