Loffler's Syndrome

Loffler's disease was first described in 1932.¹ It is a syndrome of transient respiratory illness with eosinophilia in the blood and abnormalities on CXR. In 1952 it was classified as 1 of 5 causes of pulmonary infiltrates with eosinophilia.² The pathology is essentially allergic. There is often infestation and the commonest cause is Ascaris lumbricoides, the round worm. It may arise from a number of other infestations or a number of drugs.

Ascaris lumbricoides has a life cycle that includes lodging in the pulmonary capillaries, migrating through the alveolar wall and progression up the bronchial tree to be swallowed. However, this is not essential to produce the pathology as the condition may arise from parasites that do not have this component in their life cycle. Other parasites with a similar life cycle include Necator americanus, Ancylostoma duodenale, and Strongyloides stercoralis

Eosinophilic lung disease is a heterogenous group of disorders. They may be broadly separated into airway disorders (asthma, allergic bronchopulmonary mycosis, eosinophilic bronchitis, and bronchocentric granulomatosis) and parenchymal (interstitial) disorders. As knowledge expands, so does the number of known causes.³

This is an uncommon condition in the UK but is more likely in children and more likely in parts of the world where infestation abounds.

History

Symptoms are usually mild or absent and tend to resolve spontaneously after several days or, at most, after 2 or 3 weeks. Cough is the most common symptom where symptoms exist. It is usually dry and unproductive, but there may be small amounts of mucoid sputum.

In Ascaris infestation the symptoms tend to occur 10 to 16 days after ingestion of eggs but the actual time of ingestion is probably unknown and the duration will vary with the life cycle of the species involved. With infestation there is often fever, malaise, cough, wheezing, and dyspnoea. Less common symptoms include myalgia, anorexia, and urticaria.

With drug induced disease, symptoms may start hours after taking the medications, but more usually it does not present for several days. Dry cough, breathlessness, and fever are common. Obtain a detailed drug history.

In about a third of cases no cause if found. Many of these may represent cases where the doctor has failed to discover that the patient is taking something with pharmacological properties. Therefore, it is important to ask specifically about over the counter drugs, illicit drugs, alternative medicines and dietary supplements.

Examination

Often there is no physical abnormality to be found. Occasionally examination of the lungs may reveal crackles or wheezes on auscultation. This is more common with drug-induced pulmonary eosinophilia than with infestation.

Blood tests

FBC will show eosinophilia. This is often between 5 and 20% but may be up to 40% with drug-induced disease.

Chest x-ray

• Plain CXR is usually adequate and scanning is not required although CT may be helpful at times in differential diagnosis of the type of eosinophilic lung disease.⁴
• Abnormalities can be unilateral or bilateral.
• There are usually peripheral densities 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 to 4 weeks.
• In drug-induced disease it may take several weeks after withdrawal of the offending drug for the CXR to return fully to normal.
• In patients with nitrofurantoin toxicity there may even be pleural effusion.

Stool

Parasites may be found in the stool for 6 to 12 weeks after the initial infection but this will depend upon the nature of the infection.

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

Infestations

The list is by no means exhaustive:

• Ascaris lumbricoides (the commonest parasite)
• Necator americanus
• Strongyloides stercoralis
• Ancylostoma duodenale
• Toxocara canis
• Toxocara cati
• Entamoeba histolytica
• Fasciola hepatica.

Drugs

Antimicrobials

• dapsone
• ethambutol
• isoniazid
• nitrofurantoin
• penicillins
• tetracyclines
• clarithromycin
• pyrimethamine.

Anticonvulsants

• carbamazepine
• phenytoin
• valproate
• ethambutol.

Anti-inflammatory drugs and immunomodulators

• aspirin
• azathioprine
• beclomethasone
• gold
• methotrexate
• several other NSAIDs.

Other agents

• bleomycin
• captopril
• chlorpromazine
• imipramine
• methylphenidate
• sulphasalazine
• sulphonamides
• If it occurs in a young adult who is not on any medication and who is not at risk for infestation, it may be worth enquiring about the use of crack cocaine.⁵

It is first necessary to identify the cause. If a drug is implicated then it should be withdrawn. If an infestation is diagnosed the parasite should be eradicated.

Specific symptomatic treatment may be unnecessary if symptoms are trivial. Otherwise, steroids are used to control symptoms. They are very effective at reversing the eosinophilia but it is important to treat the patient and not to treat a laboratory result. The dose and duration of steroid will depend upon relief of symptoms.

Between 4 and 6 weeks after presentation, repeat FBC and CXR to ascertain resolution. Also repeat stool samples to ascertain eradication.

There tends to be an uncomplicated resolution with no mortality and recurrence occurs only if infection recurs or the offending drug is reintroduced.

This is largely the prevention of parasitic infestation in endemic areas. Good hygiene and hand washing before eating is also important.

Wilhelm Loffler was born in 1887 and died in 1972. He studied in Geneva, Vienna, Strassburg, and Basel, where he obtained his doctorate in 1911. In 1921 he became Extraordinary Professor of Medicine and Director of the University Medical Polyclinic at the University of Zurich. He introduced the mass x-ray service to screen for tuberculosis in Switzerland. He was one of the first to use insulin. He first described diffuse mural endocarditis called endocarditis parietalis fibroplastica with eosinophilia, giving congestive cardiac failure. This is called Loffler's endocarditis. A mild form of pulmonary infiltration with eosinophilia and differing from Loffler disease by its chronic course is called Kartegener's disease.