Loffler Syndrome

Löffler 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 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 Löffler 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 cell–dependent 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.

Most cases of simple pulmonary eosinophilia are caused by parasitic infections or drugs; however, no cause is identified in one third of patients.

Parasites that can cause pulmonary eosinophilia include the following:

• Ascaris lumbricoides (the most common parasitic etiology)

• Ascaris suum

• Necator americanus

• Strongyloides stercoralis

• Ancylostoma braziliense

• Ancylostoma caninum

• Ancylostoma duodenale

• Toxocara canis

• Toxocara cati

• Entamoeba histolytica

• Fasciola hepatica

• Dirofilaria immitis

• Clonorchis sinensis

• Paragonimus westermani

Agents in drug-induced eosinophilia include the following:

• Antimicrobials - Dapsone, ethambutol, isoniazid, nitrofurantoin, penicillins, tetracyclines, clarithromycin, pyrimethamine, daptomycin ^[2]

• Anticonvulsants - Carbamazepines, phenytoin, valproic acid, ethambutol

• Anti-inflammatories and immunomodulators - Aspirin, azathioprine, beclomethasone, cromolyn, gold, methotrexate, naproxen, diclofenac, fenbufen, ibuprofen, phenylbutazone, piroxicam, tolfenamic acid

• Other agents - Bleomycin, captopril, chlorpromazine, granulocyte-macrophage colony-stimulating factor, imipramine, methylphenidate, sulfasalazine, sulfonamides

United States statistics

Intestinal helminthiases associated with Löffler 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 Löffler syndrome. Because of widespread globalization, immigration, and travel, US physicians may now more commonly encounter imported tropical diseases that may present with Löffler syndrome.

International statistics

Intestinal helminthiases associated with Löffler syndrome are distributed worldwide; however, they are more prevalent in tropical climates, especially in communities with poor sanitary conditions.

Age-related demographics

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 Löffler syndrome.

Prognosis is excellent.

Morbidity/mortality

No deaths due to Löffler syndrome have been reported. Löffler 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.

Complications

A case report describes hypereosinophilic syndrome with isolated Loeffler endocarditis, which resolved completely after 2 months of corticosteroid therapy. ^[3]

Sanitary practice

Educate people about sanitary disposal of feces, associated with educational campaigns for the use of latrines and pit privies in rural communities.

Promote good handwashing technique to avoid ingestion of parasitic forms from contaminated soil.

Prevention

In endemic areas of ancylostomiasis and strongyloidiasis, encourage use of proper footwear to avoid skin penetration of larvae of N americanus, A duodenale, or S stercoralis.

Avoid future use of the offending medication in patients with drug-induced pulmonary eosinophilia.