What is Löffler’s syndrome, including its etiology, clinical presentation, and recommended management?

Löffler's Syndrome: Definition, Clinical Features, and Management

Definition and Etiology

Löffler's syndrome is a transient pulmonary condition caused by larval migration through the lungs during acute helminth infection, most commonly involving Ascaris lumbricoides, hookworm (Ancylostoma duodenale/Necator americanus), and Strongyloides stercoralis. 1, 2

• The syndrome occurs during the prepatent period (1-2 weeks after infection) when larvae migrate through lung tissue, before eggs or larvae become detectable in stool 1, 2
• This is an immunologically mediated response to larval migration, seen almost exclusively in newly exposed travelers rather than long-term residents 1
• The condition is self-limited and benign in most cases, though it can present dramatically with severe respiratory symptoms 3, 4

Clinical Presentation

Respiratory Manifestations

• Fever, dry cough, wheeze, breathlessness, and rarely hemoptysis are the hallmark symptoms 1, 2
• Migratory pulmonary infiltrates appear on chest radiograph, often with ground-glass opacities 1, 2, 5
• Symptoms typically develop 1-2 weeks after exposure to contaminated soil or water 1, 6

Laboratory Findings

• Marked peripheral blood eosinophilia is typical, sometimes exceeding 5 × 10⁹/L 1
• Elevated serum IgE levels are common 3, 5
• Eosinophilia may occasionally be absent at initial presentation 1, 4

Key Distinguishing Features

• Travelers present with more pronounced eosinophilia and acute symptoms compared to migrants who have chronic, higher-burden infections 1
• The syndrome occurs before stool microscopy becomes positive, creating a diagnostic challenge 1, 2

Diagnostic Approach

Clinical Diagnosis

Diagnosis is primarily clinical, based on respiratory symptoms (cough, wheeze), pulmonary infiltrates on imaging, marked eosinophilia, and recent travel to endemic areas within the preceding 2-8 weeks. 1, 2, 6

Specific Investigations

• Concentrated stool microscopy should be performed in all cases, though it may be negative during the prepatent period 1, 2
• Chest radiograph shows nodules and infiltrates, often migratory in nature 1, 6
• Larvae may rarely be identified in sputum or bronchoalveolar lavage 2
• Serology for helminths may be negative early (first 4-12 weeks) and cross-reacts between species, requiring expert interpretation 1
• Repeat stool examination 3-4 weeks after initial symptoms confirms intestinal infection once the patent period begins 6

Important Caveat

The combination of eosinophilia with fever, cough, and pulmonary infiltrates 1-2 weeks after freshwater swimming in Africa or walking barefoot in endemic areas makes the diagnosis highly likely and justifies empirical treatment even with negative initial testing 1.

Treatment Recommendations

First-Line Empirical Therapy

Treat with albendazole 400 mg twice daily for 3 days PLUS ivermectin 200 μg/kg once daily for 3 days during the prepatent period. 2, 6

• This combination provides comprehensive coverage for the most common causative organisms 2, 6
• Alternative regimen: mebendazole 100 mg twice daily for 3 days plus ivermectin 200 μg/kg once daily for 3 days 2
• Single-dose option: ivermectin 200 μg/kg and albendazole 400 mg once (less preferred during acute phase) 2

Corticosteroid Therapy for Severe Cases

Add prednisolone 30 mg daily for 5 days in patients with severe respiratory symptoms to reduce symptom duration. 2, 6

• This is based on expert opinion and should be reserved for cases with significant respiratory compromise 2, 6
• Critical warning: Do NOT use corticosteroids if strongyloidiasis is suspected without concurrent ivermectin, as steroids can precipitate life-threatening hyperinfection syndrome with Strongyloides stercoralis. 2, 6
• If there is any doubt about the causative organism, add ivermectin to the regimen rather than using steroids alone 6

Organism-Specific Treatment (After Confirmation)

Once the intestinal phase begins and stool microscopy identifies the specific parasite:

• Ascaris lumbricoides: Albendazole 400 mg as a single dose 1, 2, 6
• Hookworm: Albendazole 400 mg as a single dose 1, 2
• Strongyloides stercoralis (immunocompromised): Ivermectin 200 μg/kg on days 1,2,15, and 16 2

Special Populations and Considerations

Immunocompromised Patients

• Require aggressive treatment and close monitoring, particularly for strongyloidiasis 2, 6
• Strongyloides can cause hyperinfection syndrome with gram-negative bacteremia and paralytic ileus in patients on chemotherapy, steroids, or with HTLV-1 infection 1
• Specialist consultation is mandatory 6

Pregnancy and Lactation

• Consult specialist advice before initiating treatment 2

Geographic Considerations

• Higher incidence in developing countries with significant helminth burden 3
• Travel-related cases occur globally, with particular risk after freshwater exposure in Africa or walking barefoot in tropical/subtropical regions 1

Common Pitfalls to Avoid

1. Misdiagnosis as bacterial pneumonia: The clinical overlap with infectious pneumonia leads to inappropriate antibiotic use; always consider Löffler's syndrome in travelers with eosinophilia and pulmonary infiltrates 3, 4

2. Waiting for positive stool microscopy: Treatment should be initiated empirically based on clinical presentation, as stool tests are negative during the symptomatic prepatent period 1, 2

3. Using steroids without ivermectin coverage: This can be fatal if Strongyloides is present; always include ivermectin when using corticosteroids for severe respiratory symptoms 2, 6

4. Single stool sample: If testing is performed, collect three consecutive daily samples to maximize detection sensitivity once the patent period begins 1

5. Ignoring travel history timing: The 1-2 week window between exposure and symptom onset is diagnostically crucial 1, 6