Tropical Pulmonary Eosinophilia Masquerading as Interstitial Lung Disease: An Interesting Case Report with Review of Literature
Correspondence Address :
Dr. Pradip Kumar Behera,
Flat No. B202, Elegance Apartment, Kalarahanga, PO KIIT, Bhubaneswar, Odisha, India.
Tropical Pulmonary Eosinophilia (TPE) is a form of occult filariasis characterised clinically by paroxysms of nocturnal cough, wheezing and dyspnoea. It is due to hyper-responsive pulmonary reaction to trapped microfilaria inside the lung tissue. Though it is common in endemic areas, it is frequently misdiagnosed mostly as bronchial asthma or tuberculosis and the patient continues to suffer without being treated appropriately. A 36-year-old male, who presented with fever, cough and shortness of breath for a period of 6 months was misdiagnosed as Interstitial Lung Disease (ILD) and was put on antifibrotic agents without any relief of symptoms. He was thoroughly investigated with routine haematological tests, Absolute Eosinophil Count (AEC), X-ray of chest, High Resolution Computed Tomography (HRCT) thorax including bronchoalveolar lavage and was diagnosed as Tropical Pulmonary Eosinophilia (TPE). Diethyl Carbamazine citrate (DEC) was initiated and patient had satisfactory recovery. So in endemic areas the possibility of TPE should always be kept in mind while evaluating cases presenting with chronic cough, dyspnea and wheezing even if the radiological imaging may mimic ILD.
Eosinophilic pneumonia, Lymphatic filariasis, Pulmonary Infiltrates with eosinophilia
A 36-years-old male presented to the Department of Medicine, with history of fever, cough and breathlessness for a period of 6 months. Fever was low grade, intermittent without chills and rigor or night sweats. Cough was non productive, most often during night time and there was no history of hemoptysis or significant chest pain. He experienced progressively increasing breathlessness without orthopnea, paroxysmal nocturnal dyspnea, palpitation or lower limb swelling during this period of 6 months. There was no history of weight loss, joint pain or skin rash. He was non diabetic and non hypertensive and there was no history of bronchial asthma, thyroid disease or tuberculosis. Patient was non smoker, non alcoholic and there was no significant family history. He was working in a grocery shop and there was no significant industrial, agricultural or chemical exposure.
Past medical history showed that he was diagnosed as a case of Interstitial Lung Disease (ILD) and was on nindatinib 500 mg twice daily for last 2 months along with inhalational bronchodialtors and steroid without any significant improvement in symptoms. General examination revealed Body Mass Index (BMI) of 21.5 kg/m2, oral temp of 100.4 degree Farhenite, pulse rate of 120 beats per minute, respiratory rate of 25 cycles /minute with SpO2 96% at room air. There was grade III clubbing of fingers without any other significant general examination finding (1) (Table/Fig 1). On respiratory system examination trachea was observed to be central with bilateral reduced chest expansion. There was hyperresonant percussion note bilaterally and auscultation revealed coarse crepitations diffusely over bilateral lung fields along with scattered ronchi. There was no clinical evidence of fibrosis, consolidation, collapse or cavity. Examination of other systems revealed no abnormality.
Routine investigation showed eosinophilic leukocytosis (total leococyte count was 26,000/cmm, eosinophils was 26%), absolute eoinophilic count 6700/mm3 (normal range was 20 to 500/mm3), erythrocyte sedimental range was 60 mm 1st hour, C-reactive protein was 52.4 mg/dL and Peripheral smear showed eiosinophilia without any premature cells (Table/Fig 2). Bilateral uniformly distributed reticular shadows in both lung fields predominately over mid and lower zones was observed in X-ray of the chest (Table/Fig 3). High Resolution Computed Tomography (HRCT) of thorax revealed bilateral numerous tiny centrilobular nodules with interlobar septal thickening and traction bronchiectasis with few ground glass opacities (Table/Fig 4), (Table/Fig 5). Restrictive pattern without reversibility was noted in Pulmonary function test.
Bronchoscopy showed erythmatous mucosa bilaterally in main and segmental bronchi. Bronchoalveolar Lavage (BAL) fluid cytological examination showed inflammatory cells with 80% eosinophils. Transbronchial lung biopsy revealed interstitial inflammation with eosinophilic predominance. The IgE was elevated (3100 UI/mL). Filarial antibody was positive. Autoimmune markers like Serum Antinuclear Antibody (ANA ) by Indirect immunofluloroscence was negative. Antinuclear Cytoplasmic Antibodies (ANCA) like P-ANCA and C-ANCA were also negative. Serum Compliment level (C3 and C4) were normal. Other relevant investigations for evaluation of Pyrexia of Unknown Origin (PUO) like 2D Echocardiogram was also normal. In view of high peripheral blood eosinophilia, elevated IgE level, positive antifilarial Ab and the patient being from filarial endemic area, diagnosis of tropical pulmonary eosinophilia was considered. Diethyl Carbamazine citrate (DEC) was started at a dose of 6 mg/kg body weight in three divided doses for 21 days. Patient had significant improvement of symptoms. Follow-up investigations after one month showed decreased but still high level of peripheral eosinophilia. So a second course of DEC was given and patient had a complete clinical improvement with peripheral eosinophilia reducing to normal after two and half month since the patient presented to the department (Table/Fig 6).
Tropical pulmonary eosinophilia is a hyperresponsive pulmonary syndrome resulting from host immune response to microfilarial antigen of Wuchereria bancrofti and Brugia malayi (2). Frimodt-Moller in 1940 first described it as a syndrome of wheezing, fever ,eosinophilia and radiologically bilateral mottling of lungs and the condition was labeled as Pseudotuberculosis with eosinophilia. Later in 1943 Weingarten RJ, first described the term “Tropical pulmonary eosinophilia” for this clinical entity (3).
In the year 2000, around 120 million people world wide were infected with lymphatic filariasis out of which more than 90% were due to W. bancrofti and the remainder largely due to B. malayi (4). Due to enormous burden of Lymphatic filariasis World Health Organisation (WHO) launched the Global Program to Eliminate Lymphatic Filariasis (GPELF) with the goal of elimination of lymphatic filariasis by the year 2020 by administering preventive chemotherapy with Diethyl Carbamazine citrate (DEC) and ivermectin. This has led to decline in cases of filariasis in India but still prevalent in enedemic areas. India has about 40% of the global filariasis burden and 50% of the global population at risk of infection (5). In Indian sub continent filariasis is a major health problem in states like Bihar, Andhra pradesh, Odisha, Tamil Nadu, Gujurat and Kerala (6).
Tropical pulmonary eosinophiia is estimated to be <0.5% of filarial infections. The degenerating microfilaria entrapped in the lungs microcirculation triggers a wide range of cellular and humoral immune response which includes Type I ,II and IV immune reactions resulting in clinical sympotamatology of Tropical Pulmonary Eosinophilia (TPE). Eosinophils are the host immune component predominantly responsible for nematode clearance. Various eosinophilic granule proteins such as Eosinophilic Cataionic Protein (ECP), Eosinophil Derived Neurotoxin (EDN), Major Basic Protein (MBP) etc have shown helminthotoxin activity. This in association with eosinophil induced cytokine response results in parasite clearance. Besides pulmonary T helper 1 (Th1) cell response leads to elevated levels of IL4, IL5, high level of filarial specific IgE and IgG and massive pulmonary eosinophilia (7).
The TPE is commonly observed in the age group of 15 to 40 years and mostly males are affected with a male to female ratio of 4:1 (8). A recent study by Shankar M et al., in post erradiction era also showed a similar demographic profile with male preponderance (Male:Female being 2.35:1) and most patients were of less than 30 years (9). Patients with tropical pulmonary eosinophilia usually presents with non specific clinical symptoms like fever and malaise, anorexia or weight loss and respiratory symptoms like non productive cough, wheeze and shortness of breath and chest pain which are predominantly nocturnal. Because of the similarity in symptoms they are often misdiagnosed as bronchial asthma or sometimes tuberculosis (10),(11),(12). Few cases may present with extrapulmonary menifetations like lymphadenopathy, hepatosplenomegally, pericarditis or pericardial effusion or pulmonary arterial hypertension (13),(14),(15). Eosinophilic leucocytosis in peripheral blood is common which may be as high as 50000 to 80000/mm3. The ESR is usually high and serum IgE and IgG levels are elevated. Peripheral blood usually does not show any microfilaria. Pulmonary function test in advanced cases usually show restrictive pattern but during acute TPE may show mild obstructive pattern. Billateral fine diffuse reticulonodular opacities in the middle and lower lung zones are the most common radiological findings in TPE. Sometimes fine mottling in chest X-ray is observed creating a confusion of milliary TB whereas 20% cases may have normal X-ray. The predominant computed tomography scan finding in HRCT Thorax is the presence of widespread ill-defined bronchocentric nodules which need to be differentiated from conditions like hypersensitive pneumonitis, infections like tuberculosis, vasculitis, pneumoconiosis, bronchiolitis or metastasis (16).
But significant eosinophilia with radiologically pulmonary infiltarates in TPE put this clinical entity into a group of disorders termed as “Pulmonary infiltrates with eosinophilia” caused by a variety of infectious, inflammatory and allergic conditions. The differential diagnosis includes primary pulmonary eosinophilic disorders like acute and chronic eosinophilic pneumonia, Churg-struss syndrome, allergic brnchopulmonary aspergilosis, Loeffler syndrome secondary to helminth infection or drug reaction, Hypersensitive pneumonitis and idiopathic pulmonary fibrosis (17).
The diagnostic criteria for TPE includes (18):
(a) History of residence or travel to a filarial endemic region
(b) Paroxysmal and nocturnal cough with dyspnea
(c) Leukocytosis with peripheral blood eosinophilia>3000/mm3
(d) Elevated serum IgE and filarial antibody titers
(e) Pulmonary infiltrations in Chest X-ray and
(f) Clinical improvement with DEC.
Recommended therapy for TPE is oral DEC at a dose of 6 mg/ Kg in three divided doses per day for 21 days (19). Rapid response to DEC is very characteristic of TPE (20). A failure rate of 20-40% after DEC therapy has been reported mostly in advanced cases. In such cases treatment with corticosteroids have shown promising results but before steroid therapy pulmonary strongiloidosis should be ruled out (21).
Though unusual presentations of TPE has been reported by various authors like consolidation, pericardial effusion, lung cavitary lesions and also misdiagnosed as other clinical conditions like milliary tuberculosis or bronchial asthma, present case masqueraded as interstitial lung disease but latter on was diagnosed as TPE which is never reported in literature before (10),(11),(12),(13),(14) (Table/Fig 7).
Tropical Pulmonary Eosinophilia (TPE) may present with atypical clinical and radiological presentations like interstitial lung disease in addition to other unusual presentations like Bronchial asthma, miliarry tuberculosis or pulmonary arterial hypertension. These atypical clinical cases lead to confusion in clinical decision making like wrong diagnosis and improper treatment. So though eradication program of lymphatic filariasis has reduced the incidence of the disease in endemic areas and has resulted in elimination of the disease in some countries, high level of suspicion of TPE in part of treating physicians is required while evaluating cases who present with such unusual presentations. This may prevent misdiagnosis of a fairly treatable clinical entity like TPE.
Date of Submission: Mar 3, 2022
Date of Peer Review: Mar 22, 2022
Date of Acceptance: May 10, 2022
Date of Publishing: Jun 01, 2022
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes
PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Mar 08, 2022
• Manual Googling: Mar 16, 2022
• iThenticate Software: Apr 14, 2022 (16%)
ETYMOLOGY: Author Origin
- Emerging Sources Citation Index (Web of Science, thomsonreuters)
- Index Copernicus ICV 2017: 134.54
- Academic Search Complete Database
- Directory of Open Access Journals (DOAJ)
- Google Scholar
- HINARI Access to Research in Health Programme
- Indian Science Abstracts (ISA)
- Journal seek Database
- Popline (reproductive health literature)