Background

Initially described by Lffler in 1932, Lffler syndrome is a transient respiratory illness

associated with blood eosinophilia and radiographic shadowing. In 1952, Crofton included
Lffler syndrome as one of the 5 categories for conditions that cause pulmonary infiltrates with
eosinophilia. The original description of Lffler syndrome listed parasitic infection with Ascaris
lumbricoides as its most common cause; however, other parasitic infections and acute
hypersensitivity reactions to drugs are included as etiologies for simple pulmonary eosinophilia.
Pathophysiology

Lffler syndrome has classically been related to the transit of parasitic organisms through the
lungs during their life cycle in the human host. After ingestion of Ascaris lumbricoides eggs,
larvae hatch in the intestine and penetrate the mesenteric lymphatics and venules to enter the
pulmonary circulation. They lodge in the pulmonary capillaries and continue the cycle by
migrating through the alveolar walls. Finally, they move up the bronchial tree and are swallowed,
returning to the intestine and maturing into adult forms. This process takes approximately 10-16
days after ingestion of the eggs. Other parasites, such as Necator americanus, Ancylostoma
duodenale, and Strongyloides stercoralis, have a similar cycle to Ascaris, with passage of larval
forms through the alveolar walls. These parasites are not orally ingested but enter the human host
through the skin.
A recent review of the parasitic infections of the lung provides an excellent guide for the
pulmonary physician. [1]
Researchers initially thought that transit of parasitic forms through the lung was cardinal in the
pathogenesis of Lffler syndrome; however, pulmonary eosinophilia has been described in
association with parasites whose life cycle does not include passage through the alveoli and also
in association with an increasing number of medications. Additionally, eosinophilic pulmonary
infiltrates have appeared in mice challenged with a transnasal Ascaris extract. In these situations,
accumulation of eosinophils in the lungs is likely secondary to immunologic
hyperresponsiveness. The exact immunopathogenic mechanism for this reaction remains
unknown.
Animal models demonstrated that development of pulmonary eosinophilia is T celldependent
because challenged athymic mice do not develop pulmonary eosinophilia. Production of
cytokines such as interleukin-5 (IL-5) is necessary for development of pulmonary eosinophilia.
Recent data suggest that circulating, but not local, lung IL-5 is critically required for the
development of antigen-induced pulmonary eosinophilia.
Epidemiology

Frequency

United States
Intestinal helminthiases associated with Lffler syndrome, such as ascariasis, have a reported
prevalence of 20-67% among children in rural southern communities. No specific statistics have
been reported for the occurrence of Lffler syndrome. Because of widespread globalization,
immigration, and travel, US physicians may now more commonly encounter imported tropical
diseases that may present with Lffler syndrome.
International
Intestinal helminthiases associated with Lffler syndrome are distributed worldwide; however,
they are more prevalent in tropical climates, especially in communities with poor sanitary
conditions.
Mortality/Morbidity

No deaths due to Lffler syndrome have been reported. Lffler syndrome is considered a benign,
self-limiting disease without significant morbidity. Symptoms usually subside within 3-4 weeks
or shortly after the offending medication is withdrawn in drug-induced pulmonary eosinophilia.
Age

Because young children are exposed to contaminated soil and exhibit hand-to-mouth behavior
more often than adults, they have a higher incidence of intestinal helminthiases and Lffler
syndrome.