Chronic Eosinophilic Pneumonia – Symptoms, Treatment

Chronic Eosinophilic Pneumonia/Eosinophilic Pneumonia includes a group of disorders characterized by an accumulation of eosinophilic infiltrates in the pulmonary parenchyma with/without peripheral blood eosinophilia. These include a broad range of lung conditions that occur due to infectious or non-infectious causes.

Eosinophilic pneumonia is a disease in which an eosinophil, a type of white blood cell, accumulates in the lungs. These cells cause disruption of the normal air spaces (alveoli) where oxygen is extracted from the atmosphere. Several different kinds of eosinophilic pneumonia exist and can occur in any age group. The most common symptoms include cough, fever, difficulty breathing, and sweating at night.

The two common pulmonary eosinophilic syndromes are [rx][rx]:

• Acute eosinophilic pneumonia
• Chronic eosinophilic pneumonia

Eosinophilic pneumonia is divided into different categories depending upon whether its cause can be determined or not. Known causes include certain medications or environmental triggers, parasitic infections, and cancer. Eosinophilic pneumonia can also occur when the immune system attacks the lungs, a disease called eosinophilic granulomatosis with polyangiitis. When a cause cannot be found, the eosinophilic pneumonia is termed “idiopathic”. Idiopathic eosinophilic pneumonia can also be divided into acute and chronic forms, depending on the symptoms a person is experiencing.^[rx]

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: [rx][rx][rx]

• 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

Causes of Chronic Eosinophilic Pneumonia

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.[rx][rx][rx]

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

Symptoms of Chronic Eosinophilic Pneumonia

Most types of eosinophilic pneumonia have similar signs and symptoms. Prominent and nearly universal signs and symptoms include

•  Cough,
• Fever,
• Difficulty breathing, and
• Night sweats.
• Fever and cough may develop only one or two weeks before breathing difficulties progress to the point of respiratory failure requiring mechanical ventilation.
•  Symptoms accumulate over several months and include fever, cough, difficulty breathing, wheezing, and weight loss.
• Eosinophilic pneumonia in the setting of cancer often develops in the context of a known diagnosis of lung cancer, cervical cancer, or other certain types of cancer.

Diagnosis of Chronic Eosinophilic Pneumonia

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.[rx]

Patients with AEP should receive the standard work-up for any individual with acute-onset, febrile respiratory failure

• Complete blood count with differential (Of note, patients with AEP typically have a peripheral blood neutrophilia – not eosinophilia – on presentation. Peripheral eosinophilia is a later development);
• Complete metabolic panel;
• Arterial or venous blood gas;
• Blood cultures;
• Procalcitonin;
• Sputum culture;
• Influenza polymerase chain reaction (PCR);
• Other tailored infectious studies (such as Coccidioides serology or Strongyloides enzyme-linked immunosorbent assay [ELISA]);
• Anti-neutrophil cytoplasmic antibody;
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP);
• Immunoglobulin E (IgE) levels.

Treatment of Chronic Eosinophilic Pneumonia

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.

When due to acute or chronic eosinophilic pneumonia, however, treatment with corticosteroids results in a rapid, dramatic resolution of symptoms over the course of one or two days. Either intravenous methylprednisolone or oral prednisone are most commonly used. In acute eosinophilic pneumonia, treatment is usually continued for a month after symptoms disappear and the X-ray returns to normal (usually four weeks total). In chronic eosinophilic pneumonia, treatment is usually continued for three months after symptoms disappear and the X-ray returns to normal (usually four months total). Inhaled steroids such as fluticasone have been used effectively when discontinuation of oral prednisone has resulted in relapse.^[rx]

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.[rx][rx]

References