eMedicine Specialties > Pediatrics: General Medicine > Pulmonology

Loffler Syndrome

Isaac Talmaciu, MD, Clinical Assistant Professor, Department of Pediatrics, Florida Atlantic University School of Medicine

Updated: Jul 2, 2009

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.¹ 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

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.
• 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

Differential Diagnoses

Asthma

Other Problems to Be Considered

• Eosinophilic lung diseases
  • Tropical pulmonary eosinophilia
  • Allergic bronchopulmonary aspergillosis²
  • Acute eosinophilic pneumonia³
  • Chronic eosinophilic pneumonia
  • Allergic angiitis and granulomatosis (Churg-Strauss syndrome)⁴
  • Idiopathic hypereosinophilic syndrome

Workup

Laboratory Studies

The following studies are indicated in Löffler syndrome:

• CBC count with differential
  • Results show mild blood eosinophilia, usually 5-20%.
  • Eosinophils may account for as much as 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
  
  

  

  Initial chest radiograph of a 54-year-old man showing subtle opacity (arrows) in the right middle lung zone.

  
  
  
  

  

  Follow-up chest radiograph of a 54-year-old man showing migrating opacity in the left lower lobe (arrows) obtained 20 days after Media file 1.

  
  
  
  

  

  High-resolution CT scan (1 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 Media files 1 and 2.

  
  
  • 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

Medical Care

Evaluation of Löffler syndrome 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

The minimal nature of symptoms in most patients with Löffler syndrome 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.

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.

Prednisone (Deltasone, Meticorten, Orasone, Sterapred)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Dosing

Adult

5-60 mg/d PO divided qd/bid

Pediatric

0.5-2 mg/kg/d PO divided qd/bid; not to exceed 80 mg/d

Interactions

Concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; administration of corticosteroids to patients with S stercoralis infection (may lead to hyperinfection syndrome)

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Use with much caution in patients with peptic ulcer disease, hypertension, psychoses, diabetes, osteoporosis, varicella, and herpes infection; do not discontinue abruptly following use > 2 wk; observe carefully for the development of hyperglycemia, glycosuria, sodium retention with edema or hypertension, hypokalemia, peptic ulcer, osteoporosis, or hidden infections

Follow-up

Further Outpatient Care

• Repeat chest radiography 4-6 weeks after initial presentation to document resolution of pulmonary infiltrates in patients with Löffler syndrome.
• 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.

Inpatient & Outpatient Medications

• 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

Media file 1: Initial chest radiograph of a 54-year-old man showing subtle opacity (arrows) in the right middle lung zone.

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 Media file 1.

Media file 3: High-resolution CT scan (1 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 Media files 1 and 2.

References

1. Crofton JW, Livingstone JL, Oswald NC, Roberts AT. Pulmonary eosinophilia. Thorax. Mar 1952;7(1):1-35. [Medline].

2. Hara A, Nagase H, Hayashi H, Kuramochi M, Ishida H, Adachi T, et al. [A case of allergic bronchopulmonary aspergillosis complicated with lung abscess which developed into a bronchopleural fistula]. Nihon Kokyuki Gakkai Zasshi. May 2009;47(5):432-7. [Medline].

3. Janz DR, O'Neal HR Jr, Ely EW. Acute eosinophilic pneumonia: A case report and review of the literature. Crit Care Med. Apr 2009;37(4):1470-4. [Medline].

4. Pisarczyk-Wiza D, Wierusz-Wysocka B. [Churg-Strauss syndrome: diagnostic and therapeutic challenge - a case report]. Kardiol Pol. Apr 2009;67(4):410-4. [Medline].

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8. 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.

9. Corrin B. The lungs. In: Systemic Pathology. 3^rd ed. London, England: Churchill Livinstone; 1990:191.

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12. 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].

13. Kaufman J, O'Shaughnessy IM. Eosinophilic pleural effusion associated with valproic acid administration. South Med J. Aug 1995;88(8):881-2. [Medline].

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16. Ler WZ. Differential-diagnose der lungen infiltrierungen: er fle succedan-infiltrate (mit eosinophilia). Beitr Klin Tuberk. 1932;79:368-92.

17. Nadeem S, Nasir N, Israel RH. Loffler's syndrome secondary to crack cocaine. Chest. May 1994;105(5):1599-600. [Medline].

18. Neva FA, Brown HW. Intestinal nematodes. In: Basic Clinical Parasitology. 6^th ed. Norwalk, Conn: Appleton & Lange; 1994:113-51.

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Keywords

Loffler syndrome, Löffler's syndrome, allergic bronchopulmonary helminthiasis, drug-induced pulmonary eosinophilia, simple pulmonary eosinophilia, parasitic infections, hypersensitivity reactions, eosinophilic pulmonary infiltrates, ascariasis, treatment, diagnosis

Contributor Information and Disclosures

Author

Isaac Talmaciu, MD, Clinical Assistant Professor, Department of Pediatrics, Florida Atlantic University School of Medicine
Isaac Talmaciu, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Medical Editor

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
Girish D Sharma, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, and Royal College of Physicians of Ireland
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Charles Callahan, DO, Professor, Deputy Chief of Clinical Services, Walter Reed Army Medical Center
Charles Callahan, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American College of Osteopathic Pediatricians, American Thoracic Society, Association of Military Surgeons of the US, and Christian Medical & Dental Society
Disclosure: Nothing to disclose.

CME Editor

Mary E Cataletto, MD, Associate Director, Division of Pediatric Pulmonology, Winthrop University Hospital; Professor of Clinical Pediatrics, State University of New York at Stony Brook; Director of Children's Sleep Services, Winthrop University Hospital
Mary E Cataletto, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Chest Physicians
Disclosure: Shering Plough Pharmaceuticals Honoraria Consulting

Chief Editor

Michael R Bye, MD, Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons; Attending Physician, Pediatric Pulmonary Medicine, Morgan Stanley Children's Hospital of New York Presbyterian, Columbia University Medical Center
Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society
Disclosure: Merck Honoraria Speaking and teaching

• Relevant clinical guidelines and clinical trials include the following:
  • Diagnosis and treatment of respiratory illness in children and adults ⁵
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• Related eMedicine topics include the following:
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