Eosinophilic Pneumonia

Etiology

Abnormally increased eosinophils in lung parenchyma occurs due to infectious and non-infectious causes.

Non-infectious causes include:

• Idiopathic
• Drug (phenytoin, ampicillin, nitrofurantoin, ranitidine, acetaminophen, iodides)
• Toxin-induced 
• Environmental triggers
• Malignancy
• Allergic bronchopulmonary aspergillosis
• Hypereosinophilic syndromes
• Churg-Strauss syndrome
• Smoking

Infectious causes of pulmonary eosinophilia are almost always due to parasitic infections. These include ascariasis, Strongyloides, hookworms, filarial nematodes, Paragonimus, and Toxocara.[3][4][5]

Cases of acutely eosinophilic pneumonia are mostly idiopathic. Parasitic infections and drug/toxin can also present acutely.[6][7][8]

Epidemiology

Idiopathic acute eosinophilic pneumonia can occur at any age but is more common in males of age 20-40 years. Associations for the condition also exist with chronic myelogenous leukemia (CML), HIV infection, and smoking.

The most common cohort for chronic eosinophilic pneumonia is white women with a peak incidence between 30-40 years. Asthma is present in 50 percent of these patients.

Pathophysiology

Eosinophils are granulocytic white blood cells (WBCs), which are primarily tissue-dwelling cells. The main functions of eosinophils include host defense, inflammation modulation, and tissue destruction. Eosinophils play an important role in killing parasites, tumor cells, and respiratory epithelial cells.

The normal absolute eosinophil count in the peripheral blood is 0 to 500 cells/microL. Eosinophilia is predominantly due to polyclonal expansion (reactive expansion) as compared to hematopoietic clonal stem cell expansion, which is rare. A count of over 1500 increases the risk of tissue damage. However, it can also occur at low eosinophil count. In eosinophilic lung diseases, eosinophils commonly affect parenchyma and airways. Based on the increase in eosinophils, eosinophilia can be:

• Mild eosinophilia <1500
• Moderate eosinophilia 1500-5000
• Severe eosinophilia >5000

Eosinophilic pneumonia occurs secondary to lung tissue damage by the activated eosinophils. The substances and chemical mediators released by these activated macrophages damage the tissues and contribute to the disease pathology. These include: [9][10][11]

• Toxic granule product release - epithelial cells and nerve damage
• Leukotriene and platelet-activating factor production cause contraction of smooth muscles and inflammatory cells recruitment
• The release of cytokines - tissue damage and remodeling

Histopathology

In acute eosinophilic pneumonia, there is a marked infiltration of eosinophils in the alveolar spaces, bronchial walls, and, to a lesser extent, in the interstitium. Acute and/or organizing diffuse alveolar damage is present. However, granulomas or hemorrhage are absent.

In chronic eosinophilic pneumonia, leukocytic infiltrates in alveolar air spaces and interstitium. The infiltrates are predominantly eosinophilic with macrophages, lymphocytes, and occasional plasma cells.

History and Physical

Common symptoms include a cough, fever, dyspnea, night sweats.

Acute eosinophilic pneumonia follows a rapid course with symptoms developing within two weeks. Myalgias and pleuritic chest pain with dyspnea may also be present, which can progress to respiratory failure. These patients can present with apparent acute lung injury or acute respiratory distress syndrome (ARDS) without any antecedent illness. However, extrapulmonary failure and shock are absent, which differentiates it from ARDS. On auscultation, diffuse crackles are present.

Chronic eosinophilic pneumonia follows a progressive course. The presentation is subacute with symptoms present for months before diagnosis. These patients present with moderate weight loss besides the common symptoms. Over time, dyspnea progresses and presents with wheezing, especially in those with adult-onset asthma.

Evaluation

Idiopathic Acute eosinophilic pneumonia- is usually a diagnosis of exclusion. 

• Eosinophilia on BAL (>25% eosinophils)
• Marked leukocytosis, but blood eosinophilia is initially not common
• Serum IgE may be moderately elevated
• Pulmonary function tests reveal restrictive ventilatory defect with reduced DLCO
• Nonspecific chest radiographs with subtle ground-glass opacities - bilateral diffuse mixed ground-glass opacities develop as the disease progresses
• Small to moderate bilateral pleural effusions are common
• CT scan confirms the diagnosis but usually not required
• Fluid analysis- High pH and marked eosinophilia

Chronic eosinophilic pneumonia - the diagnosis is based on clinical, radiographic, and BAL findings and on the inability to document pulmonary or systemic infection.

• Marked eosinophilia on bronchoalveolar lavage, typically accounting for more than 40 percent of white blood cells
• Moderate leukocytosis with peripheral blood eosinophilia in most patients
• Serum IgE levels elevation is a feature in half of the patients
• Moderate normocytic, normochromic anemia with thrombocytosis is present.
• ESR is typically elevated
• Pulmonary function tests depend on the severity of the disease; it may be restrictive, obstructive, or normal.
• Peripheral infiltrates on chest radiographs. Infiltrates are mostly bilateral, located in mid and upper lung zones.[12]

Treatment / Management

Supportive care with supplemental oxygen and glucocorticoids are the initial management in acute cases. While waiting for the culture results, starting mechanical ventilation and empiric antibiotics are valid therapeutic measures.

Systemic glucocorticoid therapy (intravenous or oral) is recommended for all and started as soon as possible for rapid improvement within 12-48 hours. However, the dose depends on the severity. Without glucocorticoid therapy, there is a risk of progressive respiratory failure in acute eosinophilic pneumonia patients. Once the respiratory failure resolves, oral prednisone continued for 2-4 weeks with a subsequent slow taper over the next few weeks.

There is a dramatic response to corticosteroids with rapid resolution of symptoms within an hour and complete resolution of infiltrates within a month.

For chronic eosinophilic pneumonia, prednisone (40-60 mg) until two weeks after the resolution of symptoms and x-ray abnormalities. Treatment is maintained for at least three months and optimally for 6 to 9 months. Some patients may require longer maintenance. Later, inhaled corticosteroids can be started allowing discontinuation of oral steroids.[12][13](B3)

Differential Diagnosis

• Asthma/allergy
• Broncho-centric granulomatosis
• Bronchiolitis obliterans organizing pneumonia
• Infections - fungal (Coccidioidal infection, Aspergillus, Pneumocystis jirovecii)
• Interstitial lung diseases
• Malignancy[13][14]

Prognosis

Once the diagnosis of acute eosinophilic pneumonia is established, and corticosteroid treatment started, the prognosis is excellent with a dramatic response to therapy.

Sometimes prolonged glucocorticoid therapy may be required when there is a risk of recurrence; the prognosis is generally good for patients with chronic eosinophilic pneumonia.[15]