Eosinophilic Lung Disease

Timothy M. Fernandes

INTRODUCTION

The eosinophil plays a diverse role in human immunity from involvement with the allergic response to an antiparastitic function; when these functions go awry in the respiratory system, eosinophilic lung diseases may develop. Inherently, eosinophilic lungs diseases share a similar pathogenic cause: an over abundance of eosinophils in the lung. Eosinophilic cytokines, namely IL-5, IL-6, and IL-10, are present in abundance in bronchoalveolar lavage (BAL) samples from involved segments, consistent with an intense inflammatory response that draws more eosinophils to the area. Tissue eosinophilia is present on open lung biopsy of an involved lobe; peripheral eosinophilia or an eosinophilic predominant cell count in the bronchoalveolar wash may or may not be present as well. The eosinophilic pneumonias may be broadly classified as those of known and unknown etiology.

EOSINOPHILIC PNEUMONIAS OF KNOWN ETIOLOGY

Helminthic and Fungal Infection-Associated Eosinophilic Lung Disease

Worldwide, the most common cause of eosinophilic lung disease is transient infection with a parasitic organism. Wilhelm Löffler first described a series of patients with pulmonary infiltrates with high peripheral eosinophilia in 1932. In that series, all cases were associated with infection with one of four helminthes: either one of the roundworms (Ascaris lumbricoides or Strongyloides stercoralis) or one of the hookworms (Ancylostoma duodenale or Necator americanus). The term Löffler syndrome subsequently has been assigned to the constellation of transient and migratory interstitial infiltrates, peripheral eosinophilia, and mild pulmonary symptoms, such as cough and wheezing associated with the transpulmonary passage of larvae from a helminth infection. Ascaris lumbricoides remains the most common cause of Löffler syndrome worldwide. Patients typically present with low-grade fever, nonproductive cough, and occasionally hemoptysis. Ascaris and Strongyloides are found ubiquitously throughout the world. The human lifecycle begins with ingestion of ova from contaminated soil. The ova hatch in the small intestine and larvae enter the splanchnic circulation, eventually migrating to the pulmonary circulation. The larvae move into the alveoli and ascend into the large airways where they are swallowed to complete their life cycle by reproducing in the gastrointestinal tract. The pulmonary portion of the life cycle takes about 2 weeks to complete. Symptoms occur after the transpulmonary passage of the larvae, which may be seen in the sputum; peripheral eosinophilia peaks soon after. Frequently, stool examination for ova is negative until weeks after the respiratory symptoms have resolved. In general, these infections are self-limited but treatment with antihelminthic agents such as mebendazole may be warranted.

Other parasitic infections directly invade the lung parenchyma and may cause more profound and chronic pulmonary complications. Lung flukes, such as Paragonimus, are mainly found in central Africa or southeast Asia and infection is associated with undercooked or raw crab meat ingestion. This fluke invades the parenchyma and may cause pleural effusions and chocolate-colored sputum which may contain ova. Another more invasive organism is the cestode that causes echinococcosis. This tapeworm is usually found in dogs but may infect humans as well. Cystic lesions are commonly found in both the lungs and liver; patients are typically asymptomatic until compression of surrounding structures by the enlarging cysts. Therapy usually consists of a course of the antihelminthic agent, mebendazole, followed by surgical resection of the cystic cavity.

Tropical pulmonary eosinophilia is a separate entity which is seen after infection with the nematodes from the Filarioidea superfamily, Wuchereria bancrofti or Brugia malayi, which occupy the lymphatic system (“lymphatic filariae”). They are found in tropical regions of the world, with the highest prevalence in India, Southeast Asia, and parts of Africa. The filariae generate an intense eosinophil-mediated inflammatory response with elevated IgE levels and antifilarial antibodies. Patient present with wheezing, paroxysmal cough, and constitutional symptoms such as fevers and weight loss. The diagnosis of tropical eosinophilia due to filarial infection should be considered in all patients who have traveled to endemic regions and present with refractory asthma and a peripheral eosinophilia of greater than 3,000/mm³. Establishing the prompt diagnosis of tropical eosinophilia is important as the symptoms usually resolve after a 21-day course of diethylcarbamazine and delay in diagnosis may lead to long-term complications such as pulmonary fibrosis or chronic bronchitis.

Other nonhelminthic infections also may cause peripheral and intrapulmonary eosinophilia. Coccidioidomycosis, discussed elsewhere in more detail, is common in the southwestern United States. It is frequently mistaken for an idiopathic eosinophilic pneumonia due to difficulty isolating the organism from tissue culture. Allergic bronchopulmonary aspergillosis (ABPA) represents a hypersensitivity reaction to the ubiquitous fungus, Aspergillus fumigatus. Patients frequently present with cough productive of brown sputum, central bronchiectasis, elevated IgE, and fevers. Pathologic examination of the lung in ABPA may demonstrate an eosinophilic interstitial infiltrate with bronchiolitis and mucus impaction.

Drug- and Toxin-Induced Eosinophilic Lung Disease

Drug and toxin exposure represent another common cause of eosinophilic lung disease and should be included in the differential diagnosis, since removal of the exposure usually leads to resolution of symptoms. There are many drugs that have been associated with pulmonary eosinophilia (Table 40-1), but nonsteroidal anti-inflammatory drugs (NSAIDS) and antibiotics such as daptomycin, sulfonamides, penicillins, and tetracyclines are some of the most common culprits. The website www.pneumotox.com is a good resource to query medications that have published case reports of an association with eosinophilic lung disease. Outside of pharmaceuticals, many toxins have been associated with pulmonary eosinophilia as well. Emergency relief workers at the World Trade Center have been documented to have an increased risk for eosinophilic lung disease. Over-the-counter supplements such as L-tryptophan and rapeseed oil contaminated with aniline have caused epidemics of eosinophilic pneumonias. Other exposures to screen for include inhaled cocaine and heroin, scorpion stings, aluminum dust exposure, fumes from rubber production, and sulfite exposure in grape workers.