Loffler syndrome or Loeffler syndrome is a transient respiratory illness associated with blood eosinophilia and radiographic shadowing on chest x-ray. It is often caused by parasitic infections and acute hypersensitivity reactions and is a type of pulmonary eosinophilia.
It was initially described by Löffler in 1932.
Intestinal helminthiases are considered as most common cause. Loffler syndrome is more prevalent in tropical climates, especially where the sanitation is poor.
It is 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 Symptoms usually subside within 3-4 weeks or shortly after the offending medication is withdrawn in drug-induced pulmonary eosinophilia.
Young children have a higher incidence of intestinal helminthiases and Loffler syndrome.
Pathophysiology of Loffler syndrome
The syndrome was originally defined in context to infection by parasite Ascaris lumbricoides. So the classical pathophysology is related to that.
After Ascaris lumbricoides eggs are ingested, 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, also have similar variations with minor variations.
Passage through the alveoli is not the absolute cause and accumulation of eosinophils in the lungs is likely secondary to immunologic hyperresponsiveness too, probably T cell dependent.
However, the exact immunopathogenic mechanism for this reaction remains unknown.
A histopathological study would show eosinophilic infiltration occurs in the bronchi and bronchioles and in the alveolar and interstitial spaces but parasitic forms are usually not found.
- Parasitic infections
- Ascaris lumbricoides (most common parasite causing)
- Necator americanus
- Strongyloides stercoralis
- Ancylostoma braziliense
- Ancylostoma caninum
- Ancylostoma duodenale
- Toxocara canis & catis
- Entamoeba histolytica
- Fasciola hepatica
- Dirofilaria immitis
- Clonorchis sinensis
- Paragonimus westermani
- Antimicrobials – Dapsone, ethambutol, isoniazid, nitrofurantoin, penicillins, tetracyclines, clarithromycin, pyrimethamine, daptomycin
- 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
- No cause is identified in one-third of patients.
Some patients never develop the symptoms. In others, they are mild and tend to spontaneously resolve after several days or, at most, after 2-3 weeks.
Dry and unproductive cough is the most common symptom. Sometimes it could be associated with small amounts of mucoid sputum.
Fever, malaise, wheezing, and dyspnea may occur.
Muscle pains, lack of appetite and urticaria could occur.
The parasite-induced Loeffler syndrome or pulmonary eosinophilia typically occur after 10-16 days after ingestion of eggs.
The patient might provide a history of travel to a particular space where parasitic infections are common.
In the case of drug-induced pulmonary eosinophilia, the symptoms may start hours after taking the medications or, more commonly, after several days of therapy.
Dry cough, breathlessness, and fever are common.
The examination is usually normal except for occasional crackles or wheezes lung auscultation especially in case of drug-induced pulmonary eosinophilia
Complete blood count with differential shows mild blood eosinophilia, usually 5-20% [may be as high as 40%]
Parasites and ova can be found in the stool 6-12 weeks after the initial parasitic infection. However, pulmonary symptoms usually resolve by the time parasitic forms are found in the stool.
Immunoglobulin E (IgE) level
It may be elevated.
Sputum or gastric Lavage Examination
Larvae may be seen.
The eosinophilic count may be elevated.
Bilateral or unilateral abnormalities may be seen.
An x-ray may show peripheral densities [combined interstitial and alveolar pattern], often few centimeters in diameter. Individual densities may coalesce into larger areas of consolidation.
Densities are generally transient, migratory, and disappear completely within 2-4 weeks. [In drug-induced cases, several weeks after withdrawal of the offending drug.]
Pleural effusions may be present in patients with nitrofurantoin toxicity and with valproic acid.
- Areas of ground-glass opacity (halo) around consolidation or nodules o
Bronchoscopy and bronchoalveolar lavage are rarely indicated. There would be an increase in total cell count in the bronchoalveolar lavage fluid and increased lymphocytes and eosinophils.
Treatment of Loeffler Syndrome
The symptoms are often minimal and treatment is not required. The condition is self-limiting. Symptomatic medication may be taken for control of symptoms.
appropriate use of anthelmintic drugs is indicated in parasitic infections.
For drug-induced pulmonary eosinophilia, discontinue administration of the offending drug. In severe cases of simple pulmonary or drug-induced eosinophilia, systemic corticosteroids are highly effective.
Repeat chest X-ray and CBC would document resolution. Stool for ova and parasites should be examined after 6-12 weeks after initial presentation.
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