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, a recent change in tobacco smoking habits and drug intake can trigger the disease. The 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.
Causes
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 the 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 shown to trigger AEP are numerous and varied; they have in common a usually important exposure to inhaled dust. These cases suggest that breathing in some type of contaminated 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 several drugs. Drug-induced cases have been linked to minocycline, daptomycin, and venlafaxine, 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.
Diagnosis
A diagnosis of AEP is based upon the 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 the consolidated lung.
- High-resolution CT (HRCT)
- Usually complete blood count (CBC), pleural fluid analysis, and pulmonary function testing
- Bronchoscopy for lavage and, sometimes, biopsy
The diagnosis of acute eosinophilic pneumonia is suspected in patients with symptoms of acute pneumonia that progress to respiratory failure and do not respond to antibiotics. Diagnosis is based on findings from routine testing and is confirmed by bronchoscopy.
- Acute eosinophilic pneumonia is a diagnosis of exclusion and requires the absence of known causes of eosinophilic pneumonia (eg, drug- and toxin-induced, helminthic and fungal infection-related, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, tumors).
- The CBC often fails to demonstrate markedly elevated eosinophil counts, unlike in chronic eosinophilic pneumonia. Erythrocyte sedimentation rate (ESR) and IgE levels are high but are nonspecific.
- The chest x-ray initially may show only subtle reticular or ground-glass opacities, often with Kerley B lines. Isolated alveolar (about 25% of cases) or reticular (about 25% of cases) opacities may also be observed. Unlike in chronic eosinophilic pneumonia, in acute eosinophilic pneumonia opacities are not characteristically localized to the lung periphery. Small pleural effusions occur in two-thirds of patients and are frequently bilateral.
- HRCT is always abnormal with bilateral, random, patchy ground-glass or reticular opacities.
- Pleural fluid examination shows marked eosinophilia and high pH.
- Pulmonary function tests often show a restrictive process with reduced diffusing capacity for carbon monoxide (DLCO).
- Bronchoscopy should be done for lavage and, occasionally, biopsy. Bronchoalveolar lavage fluid often shows a high number and percentage (> 25%) of eosinophils. The most common histopathologic features on biopsy include eosinophilic infiltration with acute and organizing diffuse alveolar damage, but few patients have undergone lung biopsy.
Treatment
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 have 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 the 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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