Continuing Education Activity

Tropical pulmonary eosinophilia is a hypersensitivity pulmonary syndrome caused by microfilariae trapped in the lungs, a clinical manifestation of lymphatic filariasis, primarily caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori. This condition often arises in individuals residing in or traveling to filarial-endemic regions, though globalization has led to cases in developed countries. Symptoms develop gradually, including nocturnal cough, dyspnea, wheezing, fever, and systemic manifestations like weight loss.

Key diagnostic markers include significant eosinophilia (>3,000/µL), elevated serum IgE and filarial antibodies, and pulmonary infiltrations on imaging. Tropical pulmonary eosinophilia treatment involves diethylcarbamazine, which targets microfilariae and adult worms and the management of airway inflammation. Alternative therapies, eg, ivermectin, albendazole, or doxycycline, may be considered where diethylcarbamazine is unavailable. Early diagnosis and treatment are crucial to prevent complications like interstitial fibrosis and respiratory impairment. This activity for healthcare professionals is designed to enhance the learner's competence in recognizing tropical pulmonary eosinophilia, performing the recommended evaluation, and implementing an appropriate interprofessional management approach to improve patient outcomes.

Objectives:

• Determine the etiologies of tropical pulmonary eosinophilia.

• Identify the clinical features of tropical pulmonary eosinophilia.

• Implement the recommended management approach for patients with tropical pulmonary eosinophilia.

• Apply interprofessional team strategies to improve care coordination and outcomes for patients affected by tropical pulmonary eosinophilia.

Introduction

Tropical pulmonary eosinophilia is a hyperresponsive pulmonary syndrome in response to trapped microfilariae within the lung tissue. Tropical pulmonary eosinophilia, a term first described by Weingarten in 1943, is a clinical manifestation of lymphatic filariasis caused by filarial nematodes. It was previously described as "pseudotuberculosis with eosinophilia" by Frimodt-Moller in 1940.[1][2]

Tropical pulmonary eosinophilia has a gradual onset, with primary symptoms including fever, nocturnal cough, dyspnea, and wheezing. While this condition is most common in filarial-endemic regions, its prevalence has recently increased in developed countries due to migration and globalization.[3] Lymphatic filariasis, classified as a neglected tropical disease, predominantly manifests as elephantiasis. According to the World Health Organization (WHO), approximately 120 million people are affected by lymphatic filariasis in tropical and subtropical regions, but less than 1% develop tropical pulmonary eosinophilia. 

Pulmonary eosinophilic syndromes can be classified as extrinsic or intrinsic based on causative factors. The extrinsic causes include medications (eg, sulfonamides, phenytoin, phenobarbital, and carbamazepine) and infectious agents (eg, parasites, fungi, mycobacteria). The intrinsic causes include Churg-Strauss syndrome, eosinophilic granuloma, chronic eosinophilic pneumonia, and idiopathic hypereosinophilic syndrome. Tropical pulmonary eosinophilia is classified as an extrinsic cause.

Etiology

Tropical pulmonary eosinophilia is a type 1 hypersensitivity reaction caused by microfilariae that become trapped in the lung tissue. The species responsible for filariasis in humans include Wuchereria bancrofti, Brugia malayi, and Brugia timori. These nematodes inhabit the lymphatic system and bloodstream of humans. Filariasis is transmitted from person to person through mosquito bites, which act as the vector. The primary vectors for W. bancrofti are mosquitoes from the Culex, Anopheles, and Aedes genera.[4][5]

Epidemiology

Tropical pulmonary eosinophilia can occur in any tropical area but is most commonly found in filarial endemic regions like the Indian subcontinent, Southeast Asia, South America, and Africa. Due to increased migration frequency between the continents, the prevalence of this disease is increasing in Western countries. Tropical pulmonary eosinophilia is more likely to occur in nonimmune individuals (ie, persons who traveled to the endemic regions) than in individuals permanently residing in endemic areas due to immunity developed against filarial infections. Tropical pulmonary eosinophilia is 4 to 7 times more common in males than females. Tropical pulmonary eosinophilia most commonly affects young adults. The severity of infection is usually high in immunocompromised individuals.[4]

Pathophysiology

Several theories have been proposed regarding the pathogenesis of tropical pulmonary eosinophilia, but the exact mechanism remains unclear. Eosinophils play a central role in this condition. Microfilariae are periodically released from the lymphatic system and subsequently get trapped within the pulmonary microcirculation. This entrapment triggers an immune response that leads to the release of eosinophils. As eosinophils degranulate, they release several substances, including eosinophilic cationic protein, eosinophil-derived neurotoxin, major basic proteins, and eosinophil peroxidase. These substances help clear the microfilariae but also cause lung damage.

Complement activation and opsonization by antifilarial antibodies also assist in the clearance of microfilariae. Experts hypothesize that major basic protein-2 is linked to airway hyperactivity. Interleukin (IL)-4 is known to induce this hyperactivity, while interferon-gamma plays a suppressive role. Microfilariae in the pulmonary circulation generate an overactive systemic and pulmonary TH2 response, which leads to increased levels of IL-4, IL-5, IL-13, filarial-specific IgG, IgM, and IgE antibodies, along with significant pulmonary eosinophilia.[6] IL-4 primes and activates eosinophils, while IL-13 promotes the upregulation of eosinophil adhesion molecules on endothelial cells.

Bm22-25, a major antigen of the infective L3 stage larvae of Brugia malayi, has been shown to induce IgE production in patients with tropical pulmonary eosinophilia. The gamma-glutamyl transpeptidase present on the surface of human pulmonary epithelium is similar to that found in the infective L3 stage larvae. Therefore, studies suggest that filarial gamma-glutamyl transpeptidase plays an important role in the pathogenesis of tropical pulmonary eosinophilia. Laboratory research has identified an acidic, calcium-independent phospholipase A2 (aiPLA2) as a master lysosomal regulator of the tropical pulmonary eosinophilia pathway.[7] Treatment with diethylcarbamazine can suppress the intense eosinophilic alveolitis observed in patients with this condition.[8][9]

Additionally, some studies indicate that oxidants such as superoxide and hydrogen peroxide are released from inflammatory cells in the lower respiratory tract, contributing to both acute and chronic forms of tropical pulmonary eosinophilia. Therefore, a short course of corticosteroids may be necessary to suppress the production of these oxidants.[10] 

Histopathology

The primary histopathological changes in patients with tropical pulmonary eosinophilia that occur with time are as follows:

• Histiocyte infiltration in the lung parenchyma is the earliest finding, resulting in symptoms like cough, dyspnea, and wheezing.
• Eosinophilic interstitial infiltration occurs shortly after histiocyte infiltration, which may further the progress to eosinophilic abscesses, eosinophilic granulomas, or eosinophilic bronchopneumonia.
• At 6 months to 2 years from onset, mixed cell reactions (histiocytes, eosinophils, epithelioid cells, and lymphocytes) are seen.
• If still untreated, the patient may show pulmonary fibrosis.[4] 

History and Physical

Clinical History

Patients with tropical pulmonary eosinophilia typically report a history of residence or travel to a filarial endemic region. Clinicians should also obtain a medication and dietary history to exclude differential diagnoses of pulmonary eosinophilia. Infections, food, or medications can precipitate Loeffler syndrome, an eosinophilic pulmonary disease secondary to a parasitic infection.

Characteristic symptoms of tropical pulmonary eosinophilia, which typically develop gradually, include:

• Paroxysmal and nocturnal dry cough
• Cough associated with dyspnea
• Systemic manifestations (eg, fever, malaise, anorexia, and weight loss)
• Peripheral blood eosinophilia >3,000/µL
• Rare extrapulmonary manifestations (eg, lymphadenopathy and hepatosplenomegaly) [11]

Physical Examination Findings

On physical examination, findings consistent with tropical pulmonary eosinophilia include:

• Wheezing and crepitations on chest auscultation; may appear asthmatic
• Organomegaly on abdominal palpation in a few cases
• Enlarged lymph nodes 

Evaluation

Evaluation of a suspected patient with tropical pulmonary eosinophilia includes serum laboratory studies, stool tests, chest radiography, and pulmonary function tests. Early diagnosis is critical, as delay in the evaluation supports progressive interstitial fibrosis and respiratory impairment.[12] The following findings guide the evaluation of tropical pulmonary eosinophilia with these recommended diagnostic studies:

• Complete blood count: Leukocytosis with eosinophilia >3,000/µL is the cardinal finding in a patient with tropical pulmonary eosinophilia.
• Stool examination: Confirmatory findings of other parasites causing pulmonary eosinophilia syndrome help to exclude tropical pulmonary eosinophilia.
• Quantitative serum immunoglobulin test: Elevated immunoglobulin E level is frequently seen in a patient with tropical pulmonary eosinophilia.
• Indirect ELISA test: Diagnosis is confirmed by a rise in filarial antibody titers.[13]
• Chest x-ray: A chest x-ray may show reticulonodular opacities, miliary mottling in the middle or lower lung zones, or an interlobular septal thickening.[11] About 20% to 30% of patients with tropical pulmonary eosinophilia may have normal lungs. Fibrosis may be seen in advanced disease.
• Chest computed tomography (CT) scan: CT, which is typically performed in cases with equivocal diagnosis, may show bronchiectasis, lymphadenopathy, and pleural effusion.
• Pulmonary function tests (PFTs): This study typically shows a mixed pattern, with a predominant restrictive and mild to moderate obstructive pattern. A mild hypoxemia may be present.[11]
• Bronchoalveolar lavage: Lavage can reveal an intense eosinophilic presence in patients with tropical pulmonary eosinophilia.[11]

The patient presenting with tropical pulmonary eosinophilia-like syndrome due to other infectious causes may have serological tests that cross-react with filarial antigens. High antifiliarial IgG titers can often result from a cross-reaction with other nonfilarial helminth antigens (eg, Strongyloides and Schistosoma antigens). These helminths require different antibiotics. Therefore, more specific tests are needed to differentiate tropical pulmonary eosinophilia-like syndrome etiologies.[14]

The diagnostic criteria for tropical pulmonary eosinophilia include:

• History of residence or travel to a filarial endemic region
• Paroxysmal and nocturnal cough with dyspnea
• Leukocytosis with peripheral blood eosinophilia >3,000/µL
• Elevated serum IgE and filarial antibody titers
• Pulmonary infiltrations in chest x-ray
• Clinical improvement with diethylcarbamazine

Treatment / Management

Following diagnostic confirmation of tropical pulmonary eosinophilia, patients should be treated with diethylcarbamazine 6 mg/kg/day in 2 to 3 divided doses for 21 days.[15] Diethylcarbamazine is active against both microfilariae and adults; therefore, tropical pulmonary eosinophilia clinical features respond dramatically to it. This response to diethylcarbamazine treatment is characteristic of tropical pulmonary eosinophilia. Notably, up to 5% of cases may be unresponsive, and the relapse rate after diethylcarbamazine is 20%.

Concomitant therapy with corticosteroids reduces inflammation of airways in a chronic setting. Experts postulate that lower respiratory tract inflammatory cells that release superoxide and hydrogen peroxide, which causes chronic respiratory tract inflammation and mild interstitial lung disease, are reduced by corticosteroids. Strongyloidiasis (threadworm) infection in the lung should be ruled out before starting corticosteroids due to the risk of disseminated infection.[16][17][18][19]

Other agents used for tropical pulmonary eosinophilia treatment include ivermectin, which acts on microfilariae, and albendazole, which acts on adult worms. However, no published data is available. In those communities where diethylcarbamazine is unavailable, Doxycycline 200 mg orally daily for 4 to 6 weeks, coupled with steroids, has been advocated as an alternative.[20]

Differential Diagnosis

Differential diagnoses that should also be considered when evaluating tropical pulmonary eosinophilia include:

• Pulmonary eosinophilia due to other infectious causes, eg, Strongyloides, Toxocara, and Ascariasis
• Bronchial asthma
• Allergic bronchopulmonary aspergillosis
• Allergic rhinitis
• Acute and chronic eosinophilic pneumonia
• Fungal pneumonia
• Churg-Strauss syndrome
• DRESS syndrome (drug reaction with eosinophilia and systemic symptoms)
• Miliary tuberculosis [21][22]

Treatment Planning

As primary treatment, diethylcarbamazine is prescribed for tropical pulmonary eosinophilia at 6 mg/kg/day in 2 to 3 divided doses for 21 days.

Toxicity and Adverse Effect Management

Diethylcarbamazine has adverse effects, which include fever, headache, gastrointestinal manifestations, and pruritus, that may persist after treatment in up to 25% of patients.[12]

Prognosis

Most of the patients have shown good response after treatment with diethylcarbamazine, though despite treatment, mild interstitial lung disease has been found to persist in some patients. Studies have shown that almost 20% of patients may relapse in 5 years. Patients developing pulmonary hypertension may have a poor prognosis because, most of the time, this condition is irreversible.

Complications

Tropical pulmonary eosinophilia, if treated late or left untreated, can lead to pulmonary fibrosis or chronic bronchitis with chronic respiratory failure. Additionally, pulmonary hypertension leading to cor pulmonale may be seen in a few patients due to the embolization of destructed microfilariae into lung capillaries.

Consultations

After the diagnosis of tropical pulmonary eosinophilia is made, consultation with an infectious disease expert, pulmonologist, and public health expert is required to ensure appropriate management.

Deterrence and Patient Education

People traveling to the filarial endemic regions, including the Indian subcontinent, Southeast Asia, South America, and Africa, should follow adequate protective measures to prevent mosquito bites. Filariasis spreads from person to person by mosquito bites, which serve as a vector. Travelers should use vector-controlling measures, eg,  insecticide-impregnated bed nets and permethrin-treated clothing.

Pearls and Other Issues

Eradicating lymphatic filariasis can lower the incidence rate of tropical pulmonary eosinophilia. The WHO recommends an elimination strategy for lymphatic filariasis by interrupting the transmission cycle. This strategy includes the annual administration of ivermectin with diethylcarbamazine or albendazole to the people of endemic regions. Since adult worms remain viable for years, the drug should be given for 4 to 6 years. The mosquito control strategy also eliminates the vector causing lymphatic filariasis.

Diagnosing and treating tropical pulmonary eosinophilia in the early stage is crucial. Chronic tropical pulmonary eosinophilia can result in pulmonary fibrosis and, subsequently, chronic respiratory failure even after the treatment with diethylcarbamazine. Patients with early diagnosis respond dramatically to diethylcarbamazine.[23]

Though not always prevalent or prominent, the following clinical features should suggest a potential diagnosis of tropical pulmonary eosinophilia:

• A history of travel to a filarial endemic region
• Nocturnal cough/dyspnea.
• A white blood cell count increased with eosinophils often >3000/µL
• An increased IgE >1000 U/L
• Increased filarial antibodies
• Radiologic pulmonary infiltrates
• Clinical recovery with the administration of diethylcarbamazine [15]

Enhancing Healthcare Team Outcomes

Managing tropical pulmonary eosinophilia, a rare condition in the United States, requires a collaborative interprofessional approach to ensure patient-centered care, enhanced outcomes, and improved safety. Clinicians and nurses are pivotal in the initial stages, gathering a comprehensive history that includes recent travel to filarial-endemic regions and recognizing hallmark symptoms such as nocturnal cough, dyspnea, wheezing, and blood eosinophilia. Early suspicion of tropical pulmonary eosinophilia prompts timely diagnostic evaluations, including serum IgE and antifilarial antibody tests, alongside stool examinations to exclude other parasitic infections such as Strongyloides, Toxocara, or Ascariasis. This careful history-taking and diagnostic precision facilitate early detection, which is critical for effective intervention.

Infectious disease specialists and microbiologists collaborate to confirm the causative organism and rule out other infectious pulmonary eosinophilic syndromes, ensuring diagnostic accuracy. Pharmacists play a key role in treatment by guiding the safe administration of diethylcarbamazine, the first-line therapy for tropical pulmonary eosinophilia, while monitoring for potential side effects. Nurses and clinicians provide ongoing patient education about the disease and treatment, addressing concerns to promote adherence. Strong team communication and seamless care coordination enhance diagnosis and treatment timelines, reduce complications, and improve patient outcomes. This interprofessional synergy is essential for delivering high-quality care tailored to the unique needs of patients with tropical pulmonary eosinophilia.