eMedicine Specialties > Pediatrics: General Medicine > Pulmonology

Loffler Syndrome

Author: Girish D Sharma, MD, Associate Professor, Department of Pediatrics, Rush University Medical Center, Rush Children's Hospital; Director of Pediatric Pulmonary Section and Rush Cystic Fibrosis Center
Coauthor(s): Michael J Vinikoor, MD, Resident Physician, Departments of Internal Medicine and Pediatrics, Rush University Medical Center
Contributor Information and Disclosures

Updated: Feb 1, 2010

Introduction

Background

Initially described by Löffler in 1932, Löffler syndrome is a transient respiratory illness associated with blood eosinophilia and radiographic shadowing. In 1952, Crofton included Löffler syndrome as one of the 5 categories for conditions that cause pulmonary infiltrates with eosinophilia. The original description of Löffler 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

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.

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.

Frequency

United States

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

Intestinal helminthiases associated with Löffler 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 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.

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 Löffler syndrome.

Clinical

History

Symptoms of Löffler syndrome are usually mild or absent and tend to spontaneously resolve after several days or, at most, after 2-3 weeks. Cough is the most common symptom among symptomatic patients. It is usually dry and unproductive but may be associated with production of small amounts of mucoid sputum.

• Parasitic infection
  • Symptoms appear 10-16 days after ingestion of Ascaris eggs. A similar timeframe has been described for Löffler syndrome associated with N americanus, A duodenale, or S stercoralis infection.
  • Fever, malaise, cough, wheezing, and dyspnea are the most common symptoms. Less commonly, the patient may present with myalgia, anorexia, and urticaria.
  • Social and travel history should be carefully elicited to identify risk factors for exposure to parasites.
• Drug-induced pulmonary eosinophilia
  • Symptoms may start hours after taking the medications or, more commonly, after several days of therapy.
  • Dry cough, breathlessness, and fever are common.
  • Obtain a detailed drug history, including prescription and over-the-counter medications, nutritional supplements, and illicit drugs.

Physical

• Usually, no abnormalities are found upon physical examination.
• Occasionally, crackles or wheezes may be heard on lung auscultation. Patients with drug-induced pulmonary eosinophilia commonly have crackles upon physical examination.

Causes

• Most cases of simple pulmonary eosinophilia are caused by parasitic infections or drugs; however, no cause is identified in one third of patients.
• Parasites
  • 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
  • Antimicrobials - Dapsone, ethambutol, isoniazid, nitrofurantoin, penicillins, tetracyclines, clarithromycin, pyrimethamine, daptomycin¹
  • 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

• Search for CME/CE on This Topic »

• Visceral Larva Migrans (Pediatrics: General Medicine)
• Ascaris Lumbricoides (Emergency Medicine)
• Eosinophilia (Hematology)