NORD gratefully acknowledges Professor Vincent Cottin, MD, PhD, Head, National Reference Center for Rare Pulmonary Diseases, Louis Pradel University Hospital and Claude Bernard University, Lyon, France, for assistance in the preparation of this report.
Acute eosinophilic pneumonia (AEP) is a rare disorder characterized by the rapid accumulation of eosinophils in the lungs (pulmonary eosinophilia). Eosinophils are a type of white blood cell and are part of the immune system. They are usually produced in response to allergens, inflammation or infection (especially parasitic ones) and are particularly active in the respiratory tract. Common symptoms associated with AEP include progressive shortness of breath (dyspnea) of rapid onset and possibly acute respiratory failure, cough, fatigue, night sweats, fever, and unintended weight loss. The exact cause of the disorder is unknown (idiopathic) in many patients, however, recent change in tobacco smoking habits and drug intake can trigger the disease. Outcome is favorable with corticosteroids, without relapse.
AEP was first described as a distinct entity in the medical literature in 1989. AEP is classified as a form of eosinophilic lung disease, a large group of interstitial lung diseases. AEP is different from chronic eosinophilic pneumonia (CEP), which is marked by slower progression, lack of progression to acute respiratory failure, frequent relapses and is often associated with asthma. For more information on CEP, choose “chronic eosinophilic pneumonia” as your search term in the NORD Rare Disease Database.
AEP is characterized by a sudden, rapid onset of symptoms usually within 1-7 days. However, in some cases, symptoms may develop less rapidly over the course of up to one month. AEP often develops in young, otherwise healthy individuals. Associated symptoms are nonspecific and can include fever, cough, difficulty breathing (dyspnea) and chest pain. Less common symptoms include fatigue, muscle pain (myalgia), joint aches, and abdominal discomfort or pain.
AEP can rapidly progress to acute respiratory failure. Acute respiratory failure occurs when the level of oxygen in the blood decreases severely (hypoxemia), potentially resulting in life-threatening breathing complications. This can occur within a few days or even within hours in individuals with AEP. Approximately two-thirds of individuals may require mechanical ventilation.
AEP is an extremely rare disorder and may be confused with infectious pneumonia, especially in the absence of differential cell count on bronchoalveolar lavage. As AEP becomes better known and more affected individuals are identified, researchers should be able to obtain a better clinical understanding of the disorder. For example, some researchers believe that milder cases of AEP exist, but may go undiagnosed as they can improve spontaneously. These mild cases may cause less severe symptoms and complications.
The cause of IAEP is unknown (idiopathic). Researchers believe that AEP develops due to an unidentified, nonspecific triggering agent that causes the body to produce eosinophils and recruit them to the lungs. The exact reason for the overproduction and accumulation of eosinophils is unknown.
Several environmental factors including occupational factors have been shown to trigger AEP including exposure to dust and smoke. It is unlikely that a single environmental factor causes AEP. Most likely, multiple factors are necessary for the development of the disorder, with association of a triggering condition in a predisposed individual. The triggering factor in AEP can be different from one individual to another.
In many cases, cigarette smoking is believed to play a key role in the development of the disorder, specifically in individuals who had just begun smoking within the last three months before the onset of the disorder, have resumed smoking after temporary cessation, or have recently increased the number of cigarettes smoked daily. Several reports in the medical literature have demonstrated an association between cigarette smoking and “idiopathic” AEP in a subset of affected individuals. The exact role that smoking plays in the development of AEP in such cases is not fully understood.
Occupational factors that have been showed to trigger AEP are numerous and varied; they have in common a usually important exposure to inhaled dusts. These cases suggest that breathing in some type of contaminate or inhaled agent that induces damage to the lungs can trigger AEP.
Additional reports in the medical literature have linked some cases of AEP to the use of a number of drugs. Drug-induced cases have been linked to minocycline, daptomycin, and velafaxine, an antidepressant, and others (www.pneumotox.com). New causes continue to be described.
Some researchers believe that cytokines (specialized proteins secreted from certain immune system cells that either stimulate or inhibit the function of other immune system cells) may play a role in the development of eosinophilic disorders. Interleukin-5 (IL-5) is a cytokine that is known to be a regulator of the development and function of eosinophils. IL-5 also suppresses the normal disintegration (apoptosis) of eosinophils resulting in their accumulation within the lungs and bloodstream. More research is necessary to determine the exact role and mechanism of agents that trigger AEP in the appropriate context.
AEP affects males approximately twice as often as females. Fewer than 200 cases have been reported in the medical literature and the exact prevalence is unknown. AEP can affect individuals of any age, but occurs most often in individuals between 20-40 years of age.
A diagnosis of AEP is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation, and a variety of specialized tests especially bronchoalveolar lavage (BAL). The presence of other causes of pulmonary eosinophilia such as parasitic infections or exposure to certain drugs must be systematically investigated.
Clinical Testing and Work-Up
An exam known as BAL, is key in the diagnosis of AEP. During a BAL, a narrow tube (flexible bronchoscope) is slid down the windpipe into the lungs and a sterile solution is passed through the tube washing out (lavaging) cells. This fluid is collected by aspiration and then the tube is removed, allowing the cells to be studied. BAL fluid in individuals with AEP reveals abnormally high levels of eosinophils (greater than 25%). Fiberoptic bronchoscopy is performed under local anesthesia; it is performed through the intratracheal tube in patients with mechanical ventilation. Arterial blood gases demonstrate hypoxemia often severe, which may reflect right to left shunting in consolidated lung.
Specific imaging techniques may be used to help confirm a diagnosis of AEP including chest x-ray, however abnormalities are not specific. Chest x-rays in individuals with AEP generally show white lines or hazy patches (infiltrates) in the lungs. Chest CT shows alveolar bilateral consolidation, with associated bilateral pleural effusion of mild to moderate severity, and interlobular septal thickening, which are suggestive of the disease.
During the acute phase, pulmonary function tests typically show a restricted pattern.
Individuals with AEP respond within days to high doses of corticosteroids, which usually are prescribed for two weeks. Corticosteroid therapy is initiated only after an infectious cause of pulmonary eosinophilia has been ruled out. Within the medical literature, the dose and duration of corticosteroid therapy has varied greatly, with a recent series suggesting that a two-week treatment is sufficient. There is no standardized dose for corticosteroid therapy in individuals with AEP. Individuals reported in the medical literature received intravenous corticosteroids initially, followed by oral administration afterward. In some cases, AEP improves without any treatment (spontaneous remission). There is no relapse after steroid therapy is stopped. The long term prognosis is excellent.
Because the disorder often progresses rapidly, many individuals require admission into an intensive care unit to receive respiratory support. Respiratory support can consist of either invasive or noninvasive mechanical ventilation. Invasive ventilation provides respiratory support through intratracheal tube. Noninvasive ventilation providing respiratory support via a ventilator and a nasal or facial mask may suffice to support ventilation until rapid improvement is observed with corticosteroids, and weaning becomes possible (usually within less than one week).
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