Allergic bronchopulmonary aspergillosis in association with rheumatic heart disease: report of three cases

Abstract

Allergic bronchopulmonary aspergillosis is usually seen in patients with asthma or cystic fibrosis. Its association with rheumatic heart disease has not been adequately reported in literature. We report our experience of three cases who were diagnosed cases of rheumatic heart disease. Their symptomatology and clinical findings required further evaluation and investigations, which were suggestive of allergic bronchopulmonary aspergillosis. The patients were treated with steroids and/or antifungals before proceeding with the valve replacement.

Introduction

Allergic bronchopulmonary aspergillosis (ABPA) is commonly seen in patients with asthma and cystic fibrosis. It is diagnosed based on the international society for human and animal mycology-allergic bronchopulmonary aspergillosis (ISHAM-ABPA) working group criteria [1]. Rheumatic heart disease (RHD) is also widely prevalent in developing countries and is a leading cause of morbidity and mortality [2]. Both RHD and ABPA are immunologic diseases [2, 3]. Both have been extensively evaluated and lots of studies are available in the literature. However, an association between the two has not been adequately  reported earlier.  Both the disease are individually very common in prevalence in developing countries, but it is hard to find literature on their concomitant presence. Their symptomatology and clinical findings may also overlap, thereby when one of the two is diagnosed there are chances that the other might go unnoticed or untreated.

We discuss three cases of RHD with associated ABPA. Written informed consent was taken from the patients. The cases are briefly discussed individually.

First case

A 38-year-old female patient presented to us with palpitations and breathlessness. History, clinical examination, and investigations were consistent with the diagnosis of RHD with severe mitral stenosis and moderate mitral regurgitation. The patient was given medical treatment for stabilization before surgery but she was having persistent cough and bilateral wheeze (rhonchi) was present. The bronchospasm was persistent and did not respond to the nebulized bronchodilators and diuretics. Then, pulmonologist consultation was taken for bronchospasm and ABPA was suspected. Relevant investigations including Aspergillus fumigatus–specific IgE, total serum IgE, total eosinophilic count, and contrast-enhanced computed tomographic (CECT) scan of the chest were done. Her Aspergillus fumigatus–specific IgE was > 0.35 kUA/L, total IgE levels were more than 1000 IU/L, and her absolute eosinophil counts were 1250/microliter. CECT chest was also done but it was inconclusive. The patient was started on steroids (0.5 mg/kg, prednisolone) and was followed up after 1 month. After getting treatment for 1 month, her pulmonary symptoms were relieved and there was a significant difference appreciable on auscultation with no added sounds audible. The dose of steroids was gradually tapered and the patient was then taken up for surgery mitral valve replacement still on low-dose steroids. The patient underwent mitral valve replacement (MVR). Post-operatively low-dose prednisolone was continued for 4 months and then gradually tapered off.

Second case

A 29-year-old male patient presented with a history of palpitations and breathlessness and occasional hemoptysis. History, clinical examination, and investigations were consistent with the diagnosis of RHD with severe mitral stenosis and severe mitral regurgitation. The patient was given medical treatment for stabilization before surgery but he continued to have off and on episodes of hemoptysis. The patient was in New York Heart Association (NYHA) class 1 after starting medical treatment. Further investigations including CECT chest and bronchoscopy were done to know the cause of hemoptysis but they were inconclusive. Then, Aspergillus-specific IgE and total serum IgE levels were done as per the advice of the pulmonologist. The Aspergillus-specific IgE was positive and total IgE was more than 1000 I.U, also there was eosinophilia in the peripheral blood film. The patient was started on prednisolone and later on oral antifungal of the azole group (itraconazole) was also added as there was recurrent hemoptysis. After starting itraconazole (100 mg twice a day), there were no further episodes of hemoptysis and the treatment was continued for 3 months before surgery, his repeat IgE levels were below 500 I.U and there was a decrease in the eosinophilic count. The patient was then taken up for surgery mitral valve replacement. Post-operatively steroids were tapered off and itraconazole was continued for another month.

Third case

A 43-year-old male patient diagnosed case of RHD with severe mitral stenosis and moderate mitral regurgitation with a left atrial appendage (LAA) clot was referred to us. The presentation of the patient was similar to the first case. He complained of excessive cough although he was in NYHA class 1. He was already on treatment with beta-blockers, diuretics, and digoxin. His Aspergillus fumigatus–specific IgE was positive and total IgE was more than 1000 I.U along with peripheral eosinophilia. Standard treatment for ABPA with oral glucocorticoids was started in addition to that for RHD. His symptoms improved over 2 months. The patient then underwent MVR with a mechanical valve along with the removal of LAA clot and ligation of LAA. The treatment for ABPA continued for another 2 months post-operatively.

Discussion

ABPA is an immunologic disease. Clinical features include cough with expectoration of mucus plugs, hemoptysis, fever, malaise, and weight loss or the patient may be asymptomatic. Examination findings include characteristic wheeze and rarely clubbing may be seen. Diagnostic workup includes Aspergillus fumigatus–specific immunoglobulin E, total IgE, peripheral blood eosinophil count, chest X-ray, and CECT chest [4, 5]. The chest x-ray may be normal or may reveal consolidation or bronchiectatic changes. The findings on computed tomography (CT) may include bronchiectasis and impacted mucus plugs or it can be normal also. ABPA is also commonly diagnosed in patients of asthma; however, management of asthma differs from ABPA in that in asthma inhaled corticosteroids and bronchodilators are the recommended treatment but in ABPA systemic oral corticosteroids are recommended and oral antifungals (itraconazole) are the alternative treatment in patients not responding adequately to corticosteroids.

RHD is also an immunologic disease due to the cross immune response between the host and the streptococcal antigens leading to pancarditis. The disease occurs following repeated episodes of acute rheumatic fever (ARF). The sequelae of RHD include valve stenosis and or regurgitation [6]. RHD, though a preventable disease, is widely prevalent in developing countries and people from low socio-economic strata [7].

The presence of ABPA in cases of RHD can lead to exacerbation of symptoms of RHD. The presence of excessive cough, rhonchi, bronchospasm, and hemoptysis despite adequate medical management of RHD and the patient being in NYHA class 1 or 2 should raise the suspicion of associated ABPA. Further immunologic and radiologic testing following the ISHAM-ABPA criteria may help in making the diagnosis. Adequate medical management of ABPA before proceeding with valvular heart surgery may help in optimizing the patient’s condition and a more favorable patient outcome. Severe bronchospasm can be difficult to manage intraoperatively as well as post-operatively if the cause is not diagnosed and treated pre-operatively. We observed in these patients that wheeze persisted despite giving inhaled steroids and bronchodilators, only when systemic steroids were started significant improvement was seen. Also, patients with hemoptysis, when heparinized during valvular heart surgery, can have life-threatening hemorrhage from bronchus. Therefore, history of hemoptysis, and rhonchi on auscultation, in absence of crepitations in patients with valvular heart disease requires further evaluation for ABPA, and the involvement of a pulmonologist in the pre-operative period is beneficial. Diagnosis of ABPA is made based on clinical, immunological, and radiologic findings. ABPA is usually managed with systemic steroids or oral antifungal agents and sometimes both [8]. Patients usually show rapid improvement in symptoms for 1 to 2 months although IgE levels may take more time to normalize.

The recommended treatment for ABPA is oral glucocorticoids as first-line treatment for a minimum of 4 months. The starting dose is 0.5 mg/kg for the first month followed by gradual decrease in dose. The oral antifungals of the azole group are the alternative agents used when a patient is not responding to steroids or when adverse effects limit use of steroids [8]. They are given for 6 months duration. Monitoring of liver function tests is needed during use of oral antifungal agents. Total serum IgE levels, apart from clinical and radiological parameters, are monitored during treatment and fall of > 25% in serum IgE is considered an adequate response to treatment.

Further observational and analytical studies will be required especially in areas where both RHD and ABPA are endemic to know the prevalence of the association and the strength of the association.

Conclusion

Hemoptysis and excessive cough, as well as bronchospasm in patients with RHD, need to be carefully evaluated for other pathologic factors including ABPA. A high index of suspicion is required to diagnose ABPA in patients with RHD, which can make a positive difference in patient outcome.

Funding

None.

Declarations

Ethics committee approval

Not required as no experimental work was done.

Informed consent for publication

Yes.

Conflict of interest

None.

Human and animal right’s statement

“It is confirmed that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. No animal experimentation was done.”