Eosinophilic pneumonia

Editor(s)-in-Chief: C. Michael Gibson, M.S., M.D. [mailto:mgibson@perfuse.org] Phone:617-632-7753; Philip Marcus, M.D., M.P.H.[mailto:pmarcus192@aol.com]

Overview
Eosinophilic pneumonia (EP) is a disease in which a certain type of white blood cell called an eosinophil accumulates in the lung. 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. EP is diagnosed by a combination of characteristic symptoms, findings on a physical examination by a health provider, and the results of blood tests and x-rays. Prognosis is excellent once most EP is recognized and treatment with corticosteroids is begun.

Types of eosinophilic pneumonia
Eosinophilic pneumonia is divided into different categories depending upon whether a cause can be determined or not. Known causes include certain medications or environmental triggers, parasitic infections, and cancer. EP can also occur when the immune system attacks the lungs, a disease called Churg-Strauss syndrome. When a cause can not be found, the EP is labeled "idiopathic." Idiopathic EP can be divided into "acute eosinophilic pneumonia" (AEP) and "chronic eosinophilic pneumonia" (CEP) depending on the symptoms a person is experiencing.

Symptoms
Most causes of eosinophilic pneumonia have similar symptoms. Cough, fever, increasing breathlessness, and night sweats are prominent and almost universal. Acute eosinophilic pneumonia typically follows a rapid course. Fever and cough may develop only one or two weeks before difficulties breathing progress to the point of respiratory failure requiring mechanical ventilation. Chronic eosinophilic pneumonia usually follows a slower course. Symptoms accumulate over several months and include fevers, cough, breathlessness, wheezing, and weight loss. Individuals with CEP are often diagnosed with asthma before CEP is finally recognized.

EP due to medications or environmental exposures is similar and occurs after an exposure to a known offending agent. EP due to parasitic infections has a similar prodrome in addition to a host of different symptoms related to the variety of underlying parasites. EP in the setting of cancer often develops in the context of a known diagnosis of lung cancer, cervical cancer, etc.

Pathophysiology
Eosinophilic pneumonia can develop in several different ways depending on the underlying cause of the disease. Eosinophils are thought to play a central role in defending the body against infection by parasites. Many diseases, such as asthma and eczema, are caused when eosinophils overreact to environmental triggers and release an excess of chemicals (cytokines) such as histamine. The common characteristic among different causes of EP is eosinophil overreaction or dysfunction in the lung.

Medications and environmental exposures
Medications, drugs of abuse, and environmental exposures may all trigger eosinophil dysfunction. Medications such NSAIDs (ie ibuprofen), nitrofurantoin, phenytoin, L-tryptophan, and ampicillin and drugs of abuse such as inhaled heroin and cocaine may trigger an allergic response which results in EP. Chemicals such as sulfites, aluminum silicate, and cigarette smoke can cause EP when inhaled. A New York City firefighter developed EP after inhalation of dust from the World Trade Center on September 11, 2001.

Parasitic infections
Parasites cause EP in three different ways. Parasites can either invade the lung, live in the lung as part of their life cycle, or be spread to the lung by the bloodstream. Eosinophils migrate to the lung in order to fight the parasites and EP results. Important parasites which invade the lung include Paragonimus lung flukes and the tapeworms Echinococcus and Taenia solium. Important parasites which inhabit the lung as part of their normal life cycle include the worms (helminths) Ascaris lumbricoides, Strongyloides stercoralis and the hookworms Ancylostoma duodenale and Necator americanus. When EP is caused by this last group, it is often called "Löffler's syndrome". The final group of parasites cause EP when a large number of eggs are carried into the lungs by the bloodstream. This can include Trichinella spiralis, Strongyloides stercoralis, Ascaris lumbricoides, the hookworms, and the schistosomes.

AEP and CEP
The causes for both AEP and CEP are unknown as of 2005. There is some suspicion that at least AEP is the result of the body's response to some unidentified environmental agent.

Diagnosis
Eosinophilic pneumonia is diagnosed in one of three circumstances: when a complete blood count reveals increased eosinophils and a chest x-ray or computed tomography (CT) identifies abnormalities in the lung, when a biopsy identifies increased eosinophils in lung tissue, or when increased eosinophils are found in fluid obtained by a bronchoscopy (bronchoalveolar lavage (BAL) fluid). Association with medication or cancer is usually apparent after review of a person's medical history. Specific parasitic infections are diagnosed after examining a person's exposure to common parasites and performing laboratory tests to look for likely causes. If no underlying cause is found, a diagnosis of AEP or CEP is made based upon the following criteria. AEP is most likely with respiratory failure after an acute febrile illness of usually less than one week, changes in multiple areas and fluid in the area surrounding the lungs on a chest x-ray, and greater than 25% eosinophils on a BAL. Other typical laboratory abnormalities include an elevated white blood cell count, erythrocyte sedimentation rate, and immunoglobulin E level. Pulmonary function testing usually reveals a restrictive process with reduced diffusion capacity for carbon monoxide. CEP is most likely when the symptoms have been present for more than a month. Laboratory tests typical for CEP include increased blood eosinophils, a high erythrocyte sedimentation rate, iron deficiency anemia, and increased platelets. A chest x-ray can show abnormalities anywhere, but the most specific finding is increased shadow in the periphery of the lung, away from the heart.

Treatment
When eosinophilic pneumonia is related to an illness such as cancer or parasitic infection, treatment of the underlying cause is effective in resolving the lung disease. When due to AEP or CEP, 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 AEP, treatment is usually continued for a month after symptoms disappear and the x-ray returns to normal (usually four weeks total). In CEP, 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.

Because EP affects the lungs, individuals with EP have difficulty breathing. If enough of the lung is involved, it may not be possible for a person to breathe enough to live without support. Non-invasive machines such as a bilevel positive airway pressure machine may be used. Otherwise, placement of a breathing tube into the mouth may be necessary and a ventilator may be used to help the person breathe.

Prognosis
Eosinophilic pneumonia due to cancer or parasitic infection carries a prognosis related to the underlying illness. AEP and CEP, however, have very little associated mortality as long as intensive care is available and treatment with corticosteroids is given. CEP often relapses when prednisone is discontinued; therefore, some people with CEP require lifelong therapy. Chronic prednisone is associated with many side effects, including increased infections, weakened bones, stomach ulcers, and changes in appearance.

Epidemiology
Eosinophilic pneumonia is a rare disease. Parasitic causes are most common in geographic areas where each parasite is endemic. AEP can occur at any age, even in previously healthy children, though most patients are between 20 and 40 years of age. Men are affected approximately twice as frequently as women. AEP has been associated with smoking. CEP occurs more frequently in women than men does not appear to be related to smoking. An association with radiation for breast cancer has been described.

History
Chronic eosinophilic pneumonia was first described by Carrington in 1969, and it is also known as Carrington syndrome. Prior to that, eosinophilic pneumonia was a well described pathologic entity usually associated with medication or parasite exposures. Acute eosinophilic pneumonia was first described in 1989.