Loefflers syndrome overview

# Overview
Loeffler syndrome is rare a form of eosinophilic pulmonary disease, which is characterized by mild respiratory symptoms such as dry cough, wheezing, dyspnea, fever, and blood-tinged sputum containing eosinophil-derived Charcot-Leyden crystals,  fleeting migratory pulmonary opacities in chest x-ray, and peripheral blood eosinophilia. Parasitic infections, especially Ascaris lumbricoides, may be the cause, but an identifiable etiologic agent is not found in up to one-third of patients. Transpulmonary passage of helminth larvae is the most precise definition of Loeffler syndrome in the literature, nevertheless, there are plenty of controversial definitions under the cluster of eosinophilic pulmonary disorders. The diagnosis of Loffler syndrome is based on characteristic and often transient respiratory symptoms, chest x-ray findings, and peripheral blood eosinophilia. It requires the exclusion of other types of eosinophilic lung disease. such as acute eosinophilic pneumonia which is a distinct entity with acute onset, severe hypoxemia, and a lack of increased blood eosinophils at the onset of disease. Loffler syndrome is a self-limiting condition which is usually resolved within 3-4 weeks.

# Historical perspective
In 1932, Wilhelm Loffler drew attention to the disease in cases of eosinophilic pneumonia caused by the parasites such as Ascaris lumbricoides, Strongyloides stercoralis and the hookworms, such as Ancylostoma duodenale and Necator americanus. Although Loffler only described eosinophilic pneumonia in the context of infection, many authors give the term "Loffler's syndrome" to any form of acute onset pulmonary eosinophilia no matter what the underlying cause. If the cause is unknown, it is specified and called "simple pulmonary eosinophilia".

# Pathophysiology
It is understood that Loffler syndrome is the result of transpulmonary passage of helminth larvae. Helminths, with a pulmonary life cycle are responsible for this syndrome, among them are Ascaris lumbricoides, Ascaris suum, Ancylostoma duodenale, Necator americanus, and Strongyloides stercoralis.

# Causes
Loeffler syndrome may be caused by Ancylostoma duodenale, Ascaris lumbricoides, Ascaris suum, Necator americanus, Strongyloides stercoralis.

# Differential diagnosis
Loeffler syndrome must be differentiated from other diseases that cause pulmonary eosinophilia, such as Churg-Strauss, drug and toxin-induced eosinophilic lung diseases, other helminthic and fungal infection related eosinophilic lung diseases, and nonhelminthic infections such as Coccidioidomycosis, and Mycobacterium tuberculosis.

# Epidemiology and demographics
Loffler syndrome is due to intestinal helminth infections with a pulmonary cycle which is distributed worldwide; nonetheless, parasitic infections such as Ancylostoma duodenale, Ascaris lumbricoides, Ascaris suum, Necator americanus, Strongyloides stercoralis are more prevalent in tropical areas particularly in communities with low socioeconomic status and poor sanitary conditions. In the United States, 20-67% of children in rural southern communities have been reported to suffer from ascariasis; Nevertheless, there are no specific statistics for the occurrence of Loffler syndrome. Globalization increased immigration, and travel warrants alertness of US physicians and the other health care works of developed countries, because an encounter with imported tropical diseases and thus the resulted Loffler syndrome could be more likely nowadays. The case-fatality rate/mortality rate of Loffler syndrome is literally zero. There has been no report of deaths due to Loffler syndrome. Loffler syndrome is a self-limiting, benign condition without significant morbidity. Symptoms usually subside within 3-4 weeks.

# Risk factors
There are no established risk factors for Loffler syndrome. Nevertheless, it has been shown that Indians, children, people live in tropical areas are at increased risk for developing the Loeffler syndrome. Common risk factors in the development of helminthic disorders such as ascariasis are often associated with poor sanitary conditions and environmental fecal contamination. Poor socioeconomic conditions, use of human feces as fertilizer, lack of hand washing, eating unwashed fruits and vegetables, environmental contamination with feces are among known conditions which were correlated to ascariasis.  Common risk factors in the development of strongyloidiasis include: Occupations that increase contact with contaminated soil such as farming and coal mining, barefoot walking (cultural or low socioeconomic status), Human T-cell lymphotropic virus-1 (HTLV-1) infection, Immunosuppressive therapy with corticosteroids and other medications, Immune reconstitution syndrome, Hematologic malignancies (lymphoma), Tuberculosis,  Malnutrition, Diabetes mellitus, chronic obstructive pulmonary disease, (COPD), chronic renal failure, Living in endemic regions, Alcoholics, Travelers, and immigrants.

# Natural history, complications and prognosis
Loffler syndrome generally presents as a mild syndrome which spontaneously resolves after 2-4 weeks. The symptoms of Loffler syndrome usually develop 10-16 days after ingestion of Ascaris eggs, or  N americanus, A duodenale, S stercoralis infection, and start with common symptoms such as fever, malaise, cough, wheezing, and dyspnea. Cough is the most common symptom, which is generally dry and nonproductive but might be productive or even present with small amounts of blood-tinged mucoid sputum. A less common presentation is accompanied by myalgia, anorexia, and urticaria. In order to identify risk factors for exposure to parasites, immigration status, socioeconomic status, hygiene, sanitation, as well as travel history should be carefully elicited. Prognosis is generally excellent, and the 1/5/10-year mortality/survival rate of patients with Loffler syndrome is approximately 100%. The case-fatality rate of Loffler syndrome is literally zero. There has been no report of deaths due to Loffler syndrome. Loffler syndrome is a self-limiting, benign condition without significant morbidity. Symptoms usually subside within 3-4 weeks.

# History and symptoms
The majority of patients with Loffler syndrome generally presents as a mild syndrome which spontaneously resolves after 2-4 weeks. The symptoms of Loffler syndrome usually develop 10-16 days after ingestion of Ascaris eggs, or N americanus, A duodenale, S stercoralis infection, and start with common symptoms such as fever, malaise, cough, wheezing, and dyspnea. Cough is the most common symptom, which is generally dry and nonproductive but might be productive or even present with small amounts of blood-tinged mucoid sputum. Less common symptoms of Loffler syndrome include myalgia, anorexia, and urticaria. In order to identify risk factors for exposure to parasites, immigration status, socioeconomic status, hygiene, sanitation, as well as travel history should be carefully elicited.

# Physical examination
Usually, physical examination reveals no abnormality. Cutaneous features of hypereosinophilic syndrome. Lung auscultation might have crackles on physical examination (common), with or without wheezing. Hence, common physical examination findings of Loffler syndrome include wheezing, rash, and mild fever.

# Laboratory findings
A complete blood count (CBC) with differential may show increased white blood cells, particularly eosinophils. In Loeffler syndrome eosinophilia is generally mild to moderate, usually 5-20%. On the other hand, in certain types of pulmonary eosinophilia, higher percentages are reported. For example, in drug-induced eosinophilia, eosinophils may account for as much as 40% of the WBCs. Generally, the result of stool examination is negative at the time of the Loeffler syndrome presentation. Nevertheless, parasites and ova can be found in the stool 6-12 weeks after the initial parasitic infection. Pulmonary symptoms usually have been resolved when parasitic forms are found in the stool. Immunoglobulin E (IgE) level might be elevated. A bronchoscopy with bronchoalveolar lavage may show increased eosinophilic count. Sputum analysis or gastric lavage may occasionally show larvae of Ascaris or the other parasites with pulmonary cycle.

# Electrocardiogram
There are no ECG findings associated with Loffler syndrome.

# Chest X ray
A chest x-ray may be helpful in the diagnosis of Loffler syndrome. Findings on an x-ray suggestive of Loffler syndrome include migratory densities. Chest x-ray usually shows abnormal shadows that can be unilateral or bilateral. Generally, densities are peripheral and present with both interstitial and alveolar pattern (at the same time), they are a few centimeters in diameter, and are transient, migratory, and disappear completely within 2-4 weeks. Pleural effusions is not common in Loeffler syndrome, but there are reports of pleural effusion in patients with drug-induced pulmonary eosinophilia. (nitrofurantoin, valproic acid)

# Ct Scan
Chest CT scan may be helpful in the diagnosis of Loffler syndrome. Findings on CT scan suggestive of Loffler syndrome include areas of ground-glass opacity (halo) around consolidation, nodules, and dilated airways within the lesion.

# Echocardiography or ultrasound
There are no echocardiography/ultrasound findings associated with Loffler syndrome.

# Other imaging findings
There are no other imaging findings associated with Loffler syndrome.

# Other diagnostic studies
Bronchoscopy and bronchoalveolar lavage may be helpful in the diagnosis of Loffler syndrome. Findings suggestive of Loffler syndrome include increased cell count in bronchoalveolar lavage fluid (BALF), specifically, lymphocytes and eosinophils and neutrophils.