Case Report: Allergic Bronchopulmonary Aspergillosis and Tropical Pulmonary Eosinophilia Co-Occurrence Masquerading as Refractory Allergic Bronchopulmonary Aspergillosis

ABSTRACT.

Pulmonary infiltrates with eosinophilia are a heterogeneous group of disorders that are characterized by pulmonary infiltrates on chest radiograph and elevated levels of eosinophils in the peripheral blood. Among patients with these disorders, reports of either allergic bronchopulmonary aspergillosis (ABPA) or tropical pulmonary eosinophilia (TPE) are common. However, the simultaneous occurrence of ABPA and TPE is not often reported. We present the case of a young man with a history of asthma who was diagnosed with ABPA and TPE. Initially, the patient exhibited a partial response to treatment of ABPA, but persistent symptoms and eosinophilia led to suspicion and subsequent diagnosis of TPE. With implementation of antifilarials and steroids, the patient experienced satisfactory clinical and serological improvements. This case underscores the importance of considering multiple diagnoses in patients with overlapping symptoms and highlights the need for comprehensive management strategies in complex lung diseases.

CASE REPORT

Allergic bronchopulmonary aspergillosis (ABPA) and tropical pulmonary eosinophilia (TPE) are well-known lung diseases characterized by eosinophilic inflammation. Allergic bronchopulmonary aspergillosis is a complex hypersensitivity reaction in response to colonization of the airways with Aspergillus fumigatus, which occurs almost exclusively in patients with asthma or cystic fibrosis.^1,2 Conversely, TPE is caused by an immune hyper-responsiveness to microfilariae trapped in the lungs.^3,4 Although these conditions have been extensively reported individually, the simultaneous occurrence of ABPA and TPE has only been documented once.⁵ We present a rare case of a young male with uncontrolled asthma diagnosed with concurrent ABPA and TPE. This case report aims to raise awareness about this rare coexistence, discuss the challenges in diagnosing and managing these conditions, and emphasize the importance of a comprehensive diagnostic approach.

A 25-year-old male resident of Meerut, Uttar Pradesh, who was diagnosed with bronchial asthma 6 years earlier and had never smoked, presented to our hospital with complaints of worsening breathlessness and cough with tenacious, thick sputum for the past 8 months. He had been using regular inhaled bronchodilators and corticosteroids for the past 6 years; however, he reported using inhalers only when symptomatic. He also reported having to visit the emergency department six times over the last 8 months and was prescribed systemic corticosteroids on three different occasions. His disease was poorly controlled, and he experienced daily daytime and nocturnal symptoms with a history of daily rescue inhaler (levosalbutamol) use. His activity was limited, and he was able to climb only one flight of stairs, after which he became significantly breathless. Upon chest auscultation, bilateral polyphonic wheezing was detected during both inspiration and expiration, and his chest radiograph showed no significant abnormalities. A complete blood cell count revealed a hemoglobin level of 15 g/dL and a total white blood cell count of 13,900/µL, with eosinophils accounting for 56% of the total count (absolute eosinophil count [AEC] of 7,784/cumm). Given his persistent uncontrolled symptoms and significant peripheral eosinophilia, the patient was further evaluated as having a case of severe eosinophilia. A chest radiograph (Figure 1) and high-resolution computed tomography (CT) of the chest (Figure 2) showed no significant abnormalities; however, he had an elevated serum total immunoglobulin E (IgE) level of 10,551 kUA/L (< 64 kUA/L), an elevated A. fumigatus–specific IgE of 0.67 kUA/L (< 0.35 kUA/L), and an elevated serum Aspergillus-specific IgG of 34 mg/L (< 27 mg/L). His peripheral blood smear showed eosinophilia, and there were no features suggestive of hematologic malignancies. His stool was also negative for ova/cysts, and he tested negative for FIP1L1-PDGFRA. After other causes of eosinophilia were ruled out, he was diagnosed as having a case of ABPA-S (all the diagnostic features of ABPA, but no bronchiectasis on CT). He was started on oral prednisolone at 0.5 mg/kg/day and continued on high-dose inhaled steroids. He exhibited a suboptimal response to therapy and had persistent nocturnal coughing. His serum IgE levels decreased to 5,708 IU/mL during a follow-up evaluation, but his AEC remained significantly elevated at 1,600/cumm.

Figure 1.

Chest radiograph of the patient showing no abnormality.

Figure 2.

High-resolution computed tomography (HRCT) chest of the patient showing no parenchymal lesion.

Consequently, the patient was reevaluated, including undergoing another stool examination, which yielded negative results for cysts, ova, and parasites. An antineutrophil cytoplasmic antibody profile was negative, but results of a serum test for microfilaria antigen were positive. As a result, the patient was diagnosed with concurrent ABPA and TPE. He was started on diethylcarbamazine at a dosage of 150 mg three times a day (6 mg/kg/day). After 3 weeks, the patient had a complete resolution of symptoms with a decreased serum IgE level (2,578 IU/mL) and blood eosinophil count (AEC: 250/mm³).

Allergic bronchopulmonary aspergillosis is a respiratory disorder caused by a hypersensitive reaction to inhaled fungal antigens, specifically A. fumigatus. It often complicates the course of asthma patients, leading to difficult-to-control symptoms.⁶ Studies have indicated a higher prevalence of ABPA in the Indian population than in other populations.⁷ In our patient, a diagnosis of ABPA was made over Aspergillus sensitization as he fit the International Society for Human and Animal Mycology (ISHAM) criteria (Table 1) for the disease. If our patient had had an isolated elevation of Aspergillus-specific IgE (i.e., without the background of asthma), he would have been diagnosed as having only Aspergillus sensitization.^7,8 The ISHAM-ABPA Working Group has also recommended radiological criteria based on the presence or absence of bronchiectasis and high attenuating mucus: ABPA-S; ABPA-HAM (high-attenuating mucus seen on CT); allergic bronchopulmonary aspergillosis- central bronchiectasis (ABPA-CB); and ABPA-CPF (chronic pleuropulmonary fibrosis).⁶ The recommended initial prednisone dose for ABPA is 0.5 mg/kg/day for 2 weeks, followed by every other day dosing for 6–12 weeks. It is then followed by a gradual tapering of 5–10 mg every 2 weeks over 3–6 months.⁹ Biologics such as anti-IgE, anti–interleukin (IL)-5, anti–IL-5R, and anti–IL-4 and IL-13 are non–Food and Drug Administration–approved options for managing refractory or steroid-dependent ABPA.^10–12

Table 1.

International Society for Human and Animal Mycology Working Group diagnostic criteria for ABPA

Predisposing conditions (one must be present):

Asthma

Cystic fibrosis

Obligatory criteria (both must be present):

Serum IgE levels against Aspergillus fumigatus (> 0.35 kU/L) or Aspergillus skin test positivity

Elevated total IgE concentration (typically > 1,000 IU/mL; however, if the patient meets all other criteria, an IgE value < 1,000 IU/mL may be acceptable, especially if A. fumigatus–specific IgG levels are > 27 mg/L)

Other criteria (at least two must be present):

Precipitating serum antibodies to A. fumigatus or elevated serum Aspergillus IgG by immunoassay (> 27 mg/L)

Radiographic pulmonary opacities consistent with ABPA

Total eosinophil count > 500 cells/μL in glucocorticoid-naive patients

ABPA = allergic bronchopulmonary aspergillosis; IgE = immunoglobulin E.

Similarly, TPE, which is endemic to the Indian subcontinent, is an immune hyper-responsiveness to microfilariae, primarily from Wuchereria bancrofti and Brugia malayi that become trapped in the lungs. Tropical pulmonary eosinophilia is more commonly observed in young adult males.¹³ It is often misdiagnosed and treated as asthma for several years before patients receive the correct diagnosis. Diagnostic criteria for TPE include residing in an endemic area for filariasis, recent onset of paroxysmal nocturnal cough with or without sputum, absolute blood eosinophil count of 3,000/μL or higher, and successful clinical and hematological remission with diethylcarbamazine therapy.⁴ Elevated microfilarial antibody titers can help confirm the diagnosis of TPE. Diethylcarbamazine, a piperazine derivative, is the recommended therapy for TPE, typically administered at a dose of 6 mg/kg/day in three doses for 14 or 21 days.¹⁴

Although ABPA and TPE have been extensively studied and reported individually, their co-occurrence is extremely rare. A thorough search of PubMed, Scopus, and Google Scholar databases yielded only one published case report documenting this co-occurrence.⁵ In addition, we found a case series reporting three cases of concurrent sensitization to A. fumigatus in TPE patients.¹⁵ The simultaneous presentation of these conditions presents diagnostic challenges owing to overlapping clinical features, including eosinophilia and respiratory symptoms. Furthermore, when symptoms persist, IgE and eosinophil levels remain elevated despite initial ABPA treatment, which should raise suspicion of an additional underlying condition, as observed in this case. Particularly in endemic countries such as India, where both diseases are prevalent, healthcare professionals should thoroughly investigate patients presenting with respiratory symptoms and eosinophilia, especially if they show an unsatisfactory response to optimal treatment. Physicians should be aware of the co-occurrence of these diseases, as appropriate treatment can lead to successful management. In such cases, it is crucial to exercise caution before considering biologics (such as anti-IgE), as several studies have reported worsened helminthic infections after anti-IgE therapy.¹⁶

Here, we present a rare case of concurrent ABPA and TPE in a young male with a history of asthma. This case underscores the significance of considering multiple diagnoses in patients with overlapping symptoms and emphasizes the need for a comprehensive approach to diagnosis and management. Awareness of this uncommon coexistence is essential for early recognition, accurate diagnosis, and appropriate treatment planning. Further research is warranted to explore underlying mechanisms linking ABPA and TPE and to optimize treatment strategies for such complex cases.