AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

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 1 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.

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

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

History

• Symptoms 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.
• 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
• Agents in drug-induced eosinophilia
• • Antimicrobials - Dapsone, ethambutol, isoniazid, nitrofurantoin, penicillins, tetracyclines, clarithromycin, pyrimethamine
  • 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

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Other Problems to be Considered

Eosinophilic lung diseases

Tropical pulmonary eosinophilia
Allergic bronchopulmonary aspergillosis
Acute eosinophilic pneumonia
Chronic eosinophilic pneumonia
Allergic angiitis and granulomatosis (Churg-Strauss syndrome)
Idiopathic hypereosinophilic syndrome

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Lab Studies

• CBC count with differential
• • Results show mild blood eosinophilia, usually 5-20%.
  • Eosinophils may account for up to 40% of the WBC differential in patients with drug-induced eosinophilia.
• Stool examination
• • Parasites and ova can be found in the stool 6-12 weeks after the initial parasitic infection.
  • Pulmonary symptoms usually resolve by the time parasitic forms are found in the stool.
• Analysis of sputum or gastric lavages: Larvae are occasionally found in sputum and gastric aspirates at the time of pulmonary symptoms.

Imaging Studies

• Chest radiography
• • Roentgenographic abnormalities can be unilateral or bilateral.
  • Most patients have peripheral densities, usually of a combined interstitial and alveolar pattern and often a few centimeters in diameter, although they may coalesce into larger areas of consolidation.
  • Densities are generally transient, migratory, and disappear completely within 2-4 weeks.
  • In drug-induced pulmonary eosinophilia, radiographic abnormalities resolve completely several weeks after withdrawal of the offending drug.
  • Pleural effusions may be present in patients with nitrofurantoin toxicity. A case of eosinophilic pleural effusion with peripheral blood eosinophilia has been described with valproic acid administration.
• Chest CT scanning: One report describes areas of ground-glass opacity (halo) around consolidation or nodules observed on high-resolution chest CT scanning.

Procedures

• Bronchoscopy and bronchoalveolar lavage
• • These procedures are rarely indicated.
  • In one report, the total number of cells found in bronchoalveolar lavage fluid (BALF) from patients with drug-induced pulmonary eosinophilia was significantly elevated compared to healthy subjects. Specifically, the number of lymphocytes and eosinophils in BALF was higher than in healthy subjects. These findings were not specific for drug-induced pulmonary eosinophilia because similar numbers were found in patients with chronic eosinophilic pneumonia. In addition to elevated eosinophils and lymphocytes in BALF, patients with acute eosinophilic pneumonia had high numbers of neutrophils in BALF.

Histologic Findings

Pathologic changes in the lungs have been described in patients who died from another cause while they concomitantly had simple pulmonary eosinophilia. Eosinophilic infiltration occurs in the bronchi and bronchioles and in the alveolar and interstitial spaces. Parasitic forms are usually not found in the lungs.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Medical Care

Evaluation can be conducted on an outpatient basis; inpatient care is not required.

Surgical Care

Surgical care is not indicated.

Consultations

Pediatric pulmonologist

Diet

No special diet is required.

Activity

No activity limitation is indicated.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

The minimal nature of symptoms in most patients usually denotes that no pharmacologic therapy is required for this self-limiting condition. For drug-induced pulmonary eosinophilia, discontinue administration of the offending drug. When a parasitic infection is documented, appropriate use of anthelmintic drugs is indicated. In severe cases of simple pulmonary or drug-induced eosinophilia, systemic corticosteroids are highly effective.

Drug Category: Corticosteroids

Markedly reduce the survival of certain inflammatory cells, including eosinophils. Eosinophil survival is dependent on the presence of certain cytokines (eg, interleukin-5 [IL-5], granulocyte macrophage colony stimulating factor and [GM-CSF]), whose effects are blocked by administration of corticosteroids.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Further Outpatient Care

• Repeat chest radiography 4-6 weeks after initial presentation to document resolution of pulmonary infiltrates.
• Repeat CBC count 4-6 weeks after initial presentation to document resolution of eosinophilia.
• Examine stool for ova and parasites 6-12 weeks after initial presentation.

In/Out Patient Meds

• Use appropriate antihelminthic therapy if parasitic infection is diagnosed.
• Use systemic corticosteroids for patients with severe respiratory symptoms.

Prognosis

• Prognosis is excellent.

Patient Education

• 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.
• 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.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Media file 1:  Initial chest radiograph of a 54-year-old man showing subtle opacity (arrows) in the right middle lung zone.
	View Full Size Image
Media type:  X-RAY

Media file 2:  Follow-up chest radiograph of a 54-year-old man showing migrating opacity in the left lower lobe (arrows) obtained 20 days after Image 1.
	View Full Size Image
Media type:  X-RAY

Media file 3:  High-resolution CT scan (1.0 mm collimation) obtained in a 54-year-old man showing consolidation with surrounding ground-glass opacity in the left lower lobe. Dilated airways are observed within the lesion. This CT scan was obtained between Images 1 and 2.
	View Full Size Image
Media type:  CT

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

• Alberts WM. Eosinophilic interstitial lung disease. Curr Opin Pulm Med. Sep 2004;10(5):419-24. [Medline].
• Allen JN, Davis WB. Eosinophilic lung diseases. Am J Respir Crit Care Med. Nov 1994;150(5 Pt 1):1423-38. [Medline].
• Carroll JL, Sterni LM. Eosinophilic lung disorders and hypersensitivity pneumonitis. In: Taussig LM, Landau LI, eds. Pediatric Respiratory Medicine. St Louis, Mo: Mosby;. 1999: 804-10.
• Corrin B. The lungs. In: Systemic Pathology. 3rd ed. London:. Churchill Livinstone;1990: 191.
• Cottin V, Cordier JF. Eosinophilic pneumonias. Allergy. Jul 2005;60(7):841-57. [Medline].
• Crofton JW, Livingstone JL, Oswald NC, Roberts AT. Pulmonary eosinophilia. Thorax. Mar 1952;7(1):1-35. [Medline].
• Das AM, Williams TJ, Lobb R, Nourshargh S. Lung eosinophilia is dependent on IL-5 and the adhesion molecules CD18 and VLA-4, in a guinea-pig model. Immunology. Jan 1995;84(1):41-6. [Medline].
• Fujimura M, Yasui M, Shinagawa S, et al. Bronchoalveolar lavage cell findings in three types of eosinophilic pneumonia: acute, chronic and drug-induced eosinophilic pneumonia. Respir Med. May 1998;92(5):743-9. [Medline].
• Kaufman J, O''Shaughnessy IM. Eosinophilic pleural effusion associated with valproic acid administration. South Med J. Aug 1995;88(8):881-2. [Medline].
• Kim Y, Lee KS, Choi DC, et al. The spectrum of eosinophilic lung disease: radiologic findings. J Comput Assist Tomogr. Nov-Dec 1997;21(6):920-30. [Medline].
• Lee HK, Jin SL, Lee HP, et al. Loffler''s syndrome associated with Clonorchis sinensis infestation. Korean J Intern Med. Dec 2003;18(4):255-9. [Medline].
• Ler WZ. Differential-diagnose der lungen infiltrierungen: er fle succedan-infiltrate (mit eosinophilia). Beitr Klin Tuberk. 1932;79:368-92.
• Nadeem S, Nasir N, Israel RH. Loffler''s syndrome secondary to crack cocaine. Chest. May 1994;105(5):1599-600. [Medline].
• Neva FA, Brown HW. Intestinal nematodes. In: Basic Clinical Parasitology. 6th ed. Norwalk, Conn:. Appleton & Lange;1994: 113-51.
• Nogami M, Suko M, Okudaira H, et al. Experimental pulmonary eosinophilia in mice by Ascaris suum extract. Am Rev Respir Dis. May 1990;141(5 Pt 1):1289-95. [Medline].
• O''Sullivan BP, Nimkin K, Gang DL. A fifteen-year-old boy with eosinophilia and pulmonary infiltrates. J Pediatr. Oct 1993;123(4):660-6. [Medline].
• Ohnishi H, Abe M, Yokoyama A, et al. Clarithromycin-induced eosinophilic pneumonia. Intern Med. Mar 2004;43(3):231-5. [Medline].
• Pawlowski ZS. Ascariasis. In: Warren KS, Mahmoud AAF, eds. Tropical and Geographical Medicine. 2nd ed. New York, NY:. McGraw-Hill;1990: 369.
• Sharma OP, Bethlem EP. The pulmonary infiltration with eosinophilia syndrome. Curr Opin Pulm Med. Sep 1996;2(5):380-9. [Medline].
• Takafuji S, Nakagawa T. Drug-induced pulmonary disorders. Intern Med. Mar 2004;43(3):169-70. [Medline].
• Wang J, Palmer K, Lotvall J, et al. Circulating, but not local lung, IL-5 is required for the development of antigen-induced airways eosinophilia. J Clin Invest. Sep 15 1998;102(6):1132-41. [Medline]. [Full Text].
• Wong-Waldamez A, Silva-Lizama E. Bullous larva migrans accompanied by Loeffler''s syndrome. Int J Dermatol. Aug 1995;34(8):570-1. [Medline].

Article Last Updated: Dec 27, 2006