Pulmonary Infiltrates With Hypereosinophilia

Abstract

Pulmonary infiltrates and hypereosinophilia have a wide range of causes. Here, we discuss the approach, diagnosis, and treatment of two cases with similar clinical presentations. Additional information, images, and discussion may be found in Table I and Supplemental Material (in this article’s Online Repository at www.jaci-inpractice.org).

CASE 1

A 59-year-old woman presented with a 2-month history of fatigue, productive cough, and dyspnea on exertion. She had grown up in India and emigrated to the United States in 1990 but had spent several months in India 1 year earlier to seek an evaluation for the symptoms. The examination was notable for expiratory wheezing and basilar crackles. Absolute eosinophil count (AEC) was 11,123/mL and the purified protein derivative skin test was negative. Chest radiography demonstrated an infiltrate in the superior segment of the right lower lobe. Bronchoscopy with biopsy revealed an interstitial inflammatory infiltrate with predominance of eosinophils and mast cells. Acidfast bacillus and fungal stains were negative. Antibiotics were ineffective. Although the patient responded dramatically to glucocorticoids with the resolution of symptoms and infiltrate and normalization of AEC, these recurred once corticosteroids were tapered.

CASE 2

A 64-year-old woman with a history of asthma and allergic rhinitis presented with fever and productive cough unresponsive to antibiotics. Born and raised in India, she had emigrated to the United States in 1985, traveling back periodically. The examination was significant for fever, diffuse wheezing, and decreased breath sounds. Laboratory results included AEC 7,434/mL, positive rheumatoid factor, and negative antifilarial antibody testing. The purified protein derivative skin test was negative. A chest radiograph demonstrated a left lower lobe pneumonia and effusion. A bronchoscopic biopsy showed a marked eosinophilic infiltrate without vasculitis. Cultures were negative. The symptoms and eosinophilia resolved with glucocorticoid therapy. Several years later, the patient presented acutely with chest pain, dyspnea, and severe pain in the distal extremities. Laboratory studies again showed marked eosinophilia (9,000/mL). Serum troponin was elevated, the electrocardiogram showed ST depression in leads V4 to V6, and computed tomography images of the chest demonstrated pleural and pericardial effusions. Cardiac catheterization was unremarkable. Serum antineutrophil cytoplasmic antibodies were not detected.

DIAGNOSES

Case 1

Tropical pulmonary eosinophilia. Antifilarial antibody levels were markedly elevated. The patient was treated with a 2-week course of diethylcarbamazine with full resolution.

Case 2

Eosinophilic granulomatosis with polyangiitis (EGPA). Repeat bronchoscopy with biopsy revealed necrotizing eosinophilic vasculitis. Remission was attained with high-dose glucocorticoids and maintained with low-dose daily prednisone.

DISCUSSION

Pulmonary infiltrates with hypereosinophilia can result from exposures (medications or radiation), hypersensitivities (allergic bronchopulmonary aspergillosis or hypersensitivity pneumonitis), infections (parasitic and other), malignancy, vasculitides, rare hypereosinophilic syndromes, and other idiopathic disorders.⁴ As demonstrated by the featured cases, the initial presentation and findings may be consistent with multiple etiologies. A thorough history, including a time line of symptoms, exposures, and medications, is essential. Obtaining bronchoalveolar lavage fluid and/or tissue is important both to confirm pulmonary eosinophilia and to identify an underlying cause such as vasculitis, infection, or malignancy. The patient’s response to empiric treatment (ie, antibiotics, glucocorticoids) may also be informative. The full compilation of findings must be analyzed and interpreted, because definitive diagnostic tests do not exist for many of the conditions in the differential.

Helminth infections are a relatively common cause of transient eosinophilic pulmonary infiltrates worldwide and are most often related to larval passage through the host lung (Loeffler syndrome).⁵ In contrast, tropical pulmonary eosinophilia is a rare syndrome that results from an inflammatory response to bloodborne microfilariae of Wuchereria bancrofti or Brugia species trapped in lung capillaries.^1–3 Tropical pulmonary eosinophilia is most common in individuals from the Indian subcontinent and Brazil, especially in the setting of reexposure. Pulmonary symptoms, including cough, dyspnea, and wheeze, are often nocturnal. Imaging is nonspecific. Markedly elevated AEC (>3,000 cells/mL) and serum IgE levels are characteristic. Although microfilariae are rarely detectable in the blood (or lungs), antifilarial IgG levels are dramatically elevated. Glucocorticoids may provide transient benefit; however, definitive treatment with diethylcarbamazine is recommended for symptom relief and to prevent progression to interstitial lung disease.

Eosinophilic granulomatosis with polyangiitis is a rare multisystem disorder characterized by eosinophilia and vasculitis of small- to medium-sized vessels.^6,7 Any organ can be involved, although pulmonary manifestations are most common. Preceding more acute clinical manifestations of vasculitis, patients classically, but not always, have a history of asthma (>90%) and chronic rhinosinusitis with nasal polyps. Testing for serum antineutrophil cytoplasmic antibodies is useful if results are positive, but they can be negative in up to 50% of people with biopsy-proven EGPA. Imaging is nonspecific and tissue is often necessary for a definitive diagnosis. Because rapid intervention can be lifesaving in severe disease, a consideration of EGPA in the differential diagnosis of eosinophilic pulmonary infiltrates, irrespective of patient demographics and exposures, is critical.

TABLE I.

Clinical findings in tropical pulmonary eosinophilia vs eosinophilic granulomatosis with polyangiitis

Feature	Tropical pulmonary eosinophilia*	Definite eosinophilic granulomatosis with polyangiitis
Endemic exposure	Required	Possible
Pulmonary symptoms		Common
Cough	92% (often nocturnal)
Dyspnea	86%
Wheeze	86%
Pulmonary infiltrates	76% (reticulonodular infiltrates are typical)	Common
Antineutrophil cytoplasmic antibody positive	Not characteristic	Detectable in 40% to 50%
Antifilarial antibodies	100% markedly elevated	Not characteristic
Absolute eosinophil count	Markedly elevated	Moderate to markedly elevated
Serum IgE	Markedly elevated	Moderate to markedly elevated
Erythrocyte sedimentation rate	Normal	Elevated
Pulmonary function tests	Mixed obstructive-restrictive pattern is most common	Obstructive pattern early in disease; mixed obstructive-restrictive pattern with disease progression
Vasculitis	Not characteristic	Eosinophilic vasculitis is pathognomonic
Systemic manifestations	Constitutional symptoms, including fever, fatigue, and weight loss can occur	Multisystem involvement common and can be life-threatening; characteristic extrapulmonary symptoms include chronic rhinosinusitis with polyps, leukocytoclastic vasculitis, mononeuritis multiplex, and myocarditis/ pericarditis
Response to corticosteroids	Yes, but symptoms recur with taper	Yes, but symptoms recur with taper
Response to diethylcarbamazine	Yes	No

^*Data are compiled from the three largest case series of patients with tropical pulmonary eosinophilia (total n = 37).^1–3