Loefflers syndrome differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]

Overview

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.

Differentiating Loeffler syndrome from other pulmonary eosinophilia syndromes on the basis of etiology.

Diseases		Clinical manifestations				Para-clinical findings					Gold standard	Additional findings
		Symptoms		Physical examination
						Lab Findings		Imaging		Histopathology
					Physical exam 2	Increased Eosinophil count	Other lab findings	CXR	CT Scan
Helminthic and fungal infection-related eosinophilic lung diseases	Transpulmonary passage of larvae (Loffler's syndrome)	Cough Sputum production Wheezing Fever						Round or oval opacities (several millimeters to several centimeters) In both lungs Generally present when blood eosinophilia exceeds 10% Migratory May become confluent in perihilar areas Generally clear spontaneously				Ascaris lumbricoides Hookworms such as: Ancylostoma duodenale Necator americanus) Strongyloides stercoralis
	Tropical pulmonary eosinophilia	cough, breathlessness, wheezing, fatigue, and fever.				40 to 70 percent (>3000/microL) plus elevated IgE levels ( >1000 units/mL)		Diffuse opacities Around 20% of patients have a normal CXR	Reticular and small nodular opacities Bronchiectasis Air trapping Calcification Mediastinal adenopathy			Wuchereria bancrofti Brugia malayi
	Allergic bronchopulmonary aspergillosis	Repeated episodes of: Bronchial obstruction, inflammation Mucoid impaction Can lead to: Bronchiectasis Fibrosis Respiratory compromise Clinical picture of ABPA is dominated by underlying asthma (or cystic fibrosis) Bronchial obstruction Fever Malaise, Expectoration of brownish mucous plugs Peripheral blood eosinophilia Hemoptysis Wheezing				Mild to moderate			HRCT: Widespread proximal cylindrical bronchiectasis with upper lobe predominance and bronchial wall thickening. Central bronchiectasis with normal tapering of distal bronchi (classic manifestation of ABPA, neither sensitive nor specific)	Asthmatic bronchiolitis, eosinophilic pneumonia, bronchocentric granulomatosis, and mucoid impaction of bronchi +/- bronchocentric granulomatosis (pulmonary eosinophilia in the absence of endobronchial fungi)
	Heavy hematogenous seeding with helminths	depends on the organism for example: periorbital edema, myositis, and eosinophilia (Trichinellosis)				Mild to moderate to high	Trichinellosis: Ab will be positive 2-8 weeks after infection Strongyloides: ELISA is generally positive while stool examination is often negative.	Strongyloides: diffuse ground glass opacities				Ascarids and hookworms Trichinellosis Disseminated strongyloidiasis Cutaneous and visceral larva migrans Schistosomiasis Prior treatment with glucocorticoids may be a risk factor.
	Pulmonary parenchymal invasion					Eosinophilia is prominent in the early stages of disease but minimal with established disease	Ab testing Useful in later infection with Paragonimus	Nodular with surrounding areas of ground glass Peripheral Common in the mid- and lower lung zones		Finding eggs in the sputum or bronchoalveolar lavage fluid		Helminths such as paragonimiasis
Nonhelminthic infections	Coccidioidomycosis	Manifests as a community-acquired pneumonia (CAP) approximately 7 to 21 days after exposure					Antibody testing may be negative early in the course of disease
	Mycobacterium tuberculosis
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)		Sinusitis Asthma, Skin, cardiovascular, gastrointestinal, renal, and neurologic systems may also be involved.				1500 cells/microL > 10 percent of the total leukocyte count	Antineutrophil cytoplasmic antibodies (ANCA) Myeloperoxidase (MPO) perinuclear staining pattern	Antineutrophil cytoplasmic antibodies (ANCA) Myeloperoxidase (MPO) perinuclear staining pattern Transient and patchy opacities without lobar or segmental distribution		lung biopsy: Eosinophilic infiltrates eosinophilic vasculitis (especially of the small arteries and veins) Interstitial and perivascular necrotizing granulomas Areas of necrosis
Drug- and toxin-induced eosinophilic lung diseases		asymptomatic pulmonary infiltration with eosinophils, chronic cough with or without dyspnea and fever, acute eosinophilic pneumonia, and DRESS should be suspected when the patient has a skin eruption, fever, facial edema, enlarged lymph nodes, and a history of initiation of a culprit medication two to six weeks prior to disease onset				Mild to moderate						Medications such as: Nonsteroidal antiinflammatory drugs Phenytoin L-tryptophan Antibiotics (nitrofurantoin, minocycline, sulfonamides, ampicillin, daptomycin) Toxins such as: Aluminum silicate and particulate metals •Sulfite •Scorpion stings •Inhalation of o heroin, crack cocaine, or marijuana •Inhalation of organic chemicals, dust or smoke, during rubber manufacture, fireworks, firefighting, tobacco smoking •Abuse of 1,1,1-trichloroethane (Scotchgard)
	Chronic eosinophilic pneumonia	Predominantly in women and nonsmokers Following radiation therapy for breast cancer Cough, fever, progressive breathlessness, weight loss, wheezing, and night sweats; asthma accompanies or precedes the illness in 50 percent of cases				≥40 percent Eosinophilia may be absent in 10-20% of patients		Bilateral peripheral or pleural-based infiltrates described as the "photographic negative" of pulmonary edema is virtually pathognomonic for the disease (in 33% of cases) Pleural effusion Cavitation		BAL eosinophilia ≥25 percent is suggestive of CEP. Nodular bronchial mucosal lesions Necrotizing eosinophilic inflammation Lung biopsy: Interstitial and alveolar eosinophils and histiocytes, including multinucleated giant cells Fibrosis (minimal) Organizing pneumonia (common)
	Idiopathic acute eosinophilic pneumonia	Acute respiratory failure in a previously healthy patient Often associated with recent initiation or resumption of cigarette smoking Less commonly with heavy inhalational exposure to smoke, fine sand, or dust Acute febrile illness of less than seven days' duration, characterized by: Nonproductive cough Dyspnea,				≥25 percent		Non specific but might reveal Diffuse pulmonary opacities on imaging		Bronchoalveolar lavage that reveals ≥25 percent eosinophils When the diagnosis is uncertain lung biopsy is recommended: Histopathologic findings include: Diffuse alveolar damage Hyaline membranes Marked numbers of interstitial and lesser numbers of alveolar eosinophils		Often associated with recent initiation or resumption of cigarette smoking, and less commonly with heavy inhalational exposure to smoke, fine sand, or dust
Diseases		Symptom 1	Symptom 2	Physical exam 1	Physical exam 2	Increased Eosinophil count (High)	Other lab findings	CXR	CT Scan	Histopathology	Gold standard	Additional findings
	Sarcoidosis					Mild to moderate
	Pulmonary Langerhans cell histiocytosis (Histiocytosis X)					Mild to moderate
	Idiopathic pulmonary fibrosis					<10 percent
	Differential Diagnosis 7