A rare case of allergic bronchopulmonary aspergillosis with allergic fungal rhinosinusitis masquerading as granulomatous vasculitis :Sudhir Kumar, Deependra Kumar Rai, Subhash Kumar, Indian Journal of Allergy, Asthma and Immunology

CASE REPORT
Year : 2021 | Volume : 35 | Issue : 1 | Page : 27--32

A rare case of allergic bronchopulmonary aspergillosis with allergic fungal rhinosinusitis masquerading as granulomatous vasculitis

Sudhir Kumar¹, Deependra Kumar Rai², Subhash Kumar³,
¹ Director, Chest Superspeciality Hospital, Patna, India
² Department of Pulmonary Medicine, AIIMS, Patna, India
³ Department of Radiology, AIIMS, Patna, India

Correspondence Address:
Dr. Deependra Kumar Rai
Department of Pulmonary Medicine, AIIMS Patna, Bihar 801107
India

Abstract

The combination of allergic bronchopulmonary aspergillosis (ABPA) and eosinophilic granulomatosis with polyangiitis (EGPA) or Grnaulomatosis polyangitis (GPA) has been well described in the literature, but this is the first case report of ABPA with allergic fungal rhinosinusitis (AFRS) mimicking as granulomatous vasculitis (EGPA and GPA) as per the authors. A 25-year-old woman, symptomatic for the past 4 years and initially treated for bronchial asthma, presented with worsening dyspnea, cough, fever, anorexia, and leg pain. There were increasing pulmonary opacities in the chest radiograph, and a computed tomography scan demonstrated left hilar adenopathy and consolidation. The patient was diagnosed with ABPA after the initial workup and prescribed oral prednisolone with itraconazole. The patient also had nasal polyposis, sinusitis, mucin in sinuses, and fungal growth in mucin favoring the diagnosis of AFRS. Fiberoptic bronchoscopy showed plaque-like endobronchial lesions and bronchial stenosis, and histopathologic examination of the biopsy from the nodular lesion demonstrated eosinophilic bronchitis. Normal serum angiotensin-converting enzyme levels, positive Mantoux test, and the eosinophilic inflammation in the endobronchial biopsy ruled out the possibility of sarcoidosis. Both cytoplasmic and perinuclear antineutrophil cytoplasmic antibodies (c- and p-ANCA, respectively) were found positive in a vasculitis panel test, the positive p-ANCA favoring the diagnosis of EGPA, while the combination of endobronchial lesion, sinus abnormality, and nonresolving consolidation along with positive c-ANCA favoring the diagnosis of GPA as well. However, in the absence of histopathological evidence of vasculitis, ANCA may be false positive. Accordingly, a final diagnosis of ABPA combined with AFRS was made. The patient responded well to oral prednisolone along with inhaled asthma medications. Our case highlights the overlapping clinical features of eosinophilic lung diseases and small-vessel vasculitis, which may coexist, and the need to investigate thoroughly for better clinical outcomes.

How to cite this article:
Kumar S, Rai DK, Kumar S. A rare case of allergic bronchopulmonary aspergillosis with allergic fungal rhinosinusitis masquerading as granulomatous vasculitis.Indian J Allergy Asthma Immunol 2021;35:27-32

How to cite this URL:
Kumar S, Rai DK, Kumar S. A rare case of allergic bronchopulmonary aspergillosis with allergic fungal rhinosinusitis masquerading as granulomatous vasculitis. Indian J Allergy Asthma Immunol [serial online] 2021 [cited 2023 Mar 22 ];35:27-32
Available from: https://www.ijaai.in/text.asp?2021/35/1/27/331803

Full Text

Introduction

Eosinophilic lung diseases are a heterogeneous group of disorders, characterized by varying degrees of lung parenchyma involvement and eosinophilia.[1] They generally respond well to systemic corticosteroid therapy and heal without any sequela in most of the cases. They can present clinically as acute or chronic pneumonia, or as transient Löffler's syndrome, which is most commonly due to parasitic infections. The spectrum of diseases that can be primarily or secondarily associated with blood or pulmonary eosinophilia which include acute eosinophilic pneumonia, chronic eosinophilic pneumonia, allergic bronchopulmonary aspergillosis (ABPA), Churg–Strauss syndrome, now known as eosinophilic granulomatosis with polyangiitis (EGPA), and idiopathic eosinophilic syndrome. ABPA is a hypersensitivity reaction in response to colonization of the airways with Aspergillus fumigatus that occurs commonly in patients with asthma or cystic fibrosis.[2] Allergic fungal rhinosinusitis (AFRS) is a particular type of chronic rhinosinusitis associated with allergic reactions to fungal antigens present in the paranasal sinuses (PNSs). The prevalence of AFRS is 1%–2% of the world's population, varying among different regions.[3] Diagnostic criteria of AFRS include the evidence of Type I hypersensitivity, nasal polyposis, characteristic computed tomography findings, eosinophilic mucin without invasion, and positive fungal stain.[4] AFRS can be described as the upper airway analog of ABPA.[5] Both ABPA and AFRS are associated with intense inflammation, causing the accumulation of eosinophilic mucin containing the fungal hyphae. Our patient, in addition to the findings of ABPA and AFRS, also had several other endobronchial and pulmonary findings pointing toward the diagnosis of EGPA and GPA. Such a constellation of findings has never been reported earlier as per our knowledge.

Case Report

A 25-year-old woman presented to us in November 2018 with worsening of cough, shortness of breath, low-grade fever, and loss of appetite for the past 20 days. The patient had a cough with minimum expectoration for the past 3 years. She also gave a history of frequent cold and sore throat. There were complaints of pain and tingling in the left leg, which persisted while walking. The patient denied a history of hemoptysis, significant weight loss, or an intake of aspirin. On examination, the patient was afebrile, had a heart rate of 112 beats per minute, respiratory rate of 24 breaths per minute, blood pressure of 110/70 mmHg, and oxygen saturation of 97% at room air. Examination of the respiratory system revealed normal breath sounds along with polyphonic wheezing, more in the right infrascapular and infra-axillary regions. Bronchial breath sounds were present in the left infra-axillary region. Other general physical and systemic examination findings were unremarkable. Blood investigations done before presentation revealed hemoglobin 9.8 g%, total leukocyte count 10,900 cell/mm3, neutrophils 76%, lymphocytes 16%, and eosinophils 6%. The absolute eosinophil count was 654 cell/mm3, and the serum total immunoglobulin (Ig) E level was elevated (3578 IU/mL).

A chest radiograph showed opaque left hemithorax [Figure 1]. Fiberoptic bronchoscopy was performed and showed plaque- and nodule-like lesions in the lower end of the trachea and the left bronchial tree with narrowing of the subsegmental bronchi [Figure 2]. Bronchoalveolar lavage demonstrated a predominance of macrophages, and histopathological examination of the bronchial biopsy sample taken from the nodular lesion showed features of eosinophilic bronchitis, however, no granulomas or features of vasculitis were observed [Figure 3].{Figure 1}{Figure 2}{Figure 3}

The patient was also investigated for the presence of ABPA. The total serum IgE level estimated using a fully automated chemiluminescence system was 13,117 IU/mL (<100 IU/mL). The specific IgE level against A. fumigatus was 6.09 kU/L (<0.1 kU/L), and the serum specific IgG level against A. fumigatus was 69.60 mg/L (<27 mg/L).

Spirometry showed moderate obstruction-forced expiratory volume in 1 s (FEV1) of 1.27 L and forced vital capacity (FVC) of 2.11 L (values being 60.0% and 72% of predicted values, respectively) and the FEV1/FVC ratio being 60.18% with nonsignificant bronchodilatation 64 mL (5%). A provisional diagnosis of ABPA was made, and the patient was started on oral prednisolone 40 mg once daily and itraconazole 100 mg twice daily.

CT scan of the chest was subsequently performed and showed a large, irregular, heterogeneously enhancing, left perihilar mass lesion extending into the mediastinum, ground-glass opacity, and septal thickening [Figure 4]. Previous records of the patient were sought, which showed that the patient had a history of loss of smell, left eye protrusion, and discharge of blackish debris from the nasal cavity. Radiograph and computed tomography (CT) scan of PNS showed opacified left nasal cavity and sinuses with radiopaque material in the core which had resolved after surgery [Figure 5]. Functional endoscopic sinus surgery had been performed in the year 2014, and polypoidal mass along with mucin was observed in all the sinuses. Mass had been sent for fungal culture which grew A. fumigatus. CT chest had been performed in 2014 which showed multiple enlarged lymph nodes in the mediastinum and hila [Figure 6]. Transbronchial needle aspiration from the left hilar lymph node was inconclusive. A CT chest examination performed 3 years later (2017) showed an increase in the size of the lymph nodes and the mass-like lesion in the left hemithorax [Figure 7].{Figure 4}{Figure 5}{Figure 6}{Figure 7}

Thus, considering the sinonasal polyposis/allergic fungal sinusitis, asthma, peripheral blood eosinophilia, mucin in sinuses, and fungal growth in mucin, a diagnosis of ABPA with AFRS could be made. The presence of nodular endobronchial lesions, eosinophilic bronchial inflammation, and enlarged mediastinal lymph nodes was not explained by the above diagnosis, however, the additional possibility of sarcoidosis, GPA, and EGPA could not be ruled out. Blood investigations such as serum angiotensin-converting enzyme (ACE), vasculitis panel, and Mantoux test were performed. Serum ACE was normal. Antineutrophil cytoplasmic antibody (ANCA) (cytoplasmic ANCA [c-ANCA] and perinuclear ANCA [p-ANCA]) measured by ELISA technique was found significantly positive (elevated 38.30 AU/ml and 25.80 AU/mL [normal <12 AU/mL], respectively). Mantoux test was also found positive (14 mm induration). Two-dimensional echocardiogram showed mild left ventricular hypokinesia with left ventricular ejection fraction 54%, mild tricuspid regurgitation/pulmonary regurgitation, and severe pulmonary arterial hypertension (62 mmHg). Ultrasonography (USG)-guided biopsy performed from the left lung lesion showed moderate mixed inflammation in the form of lymphocytes, neutrophils, and eosinophils [Figure 8]. There were no granulomas or atypical cells, and acid-fast bacilli were not seen. Mantoux positivity, normal serum ACE, and lack of granuloma in biopsy ruled out sarcoidosis. The presence of asthma, eosinophilia, chest radiographic findings, PNS, and positive p-ANCA, although favor the possibility of EGPA, could not fulfill the criteria given by the American College of Rheumatology.[6] Similarly, GPA is characterized by upper respiratory tract abnormality, sinus abnormality, and lower respiratory abnormality in the form of bronchial stenosis, consolidation, and positive c-ANCA, and all of these features were found in our case, however, there was a lack of histopathological evidence of vasculitis.[7] Hence, a diagnosis of GPA could not be confirmed. Thus, a final diagnosis of ABPA with AFRS was made, with overlapping features of small-vessel vasculitis. The patient was continued on oral prednisolone at a dose of 0.75 mg/kg for 6 weeks, 0.5 mg/kg for the next 6 weeks, and then tapered by 5 mg every 6 weeks with a plan to continue for a total duration of 6 months. Oral itraconazole 100 mg twice a day was continued. She was also put on inhaled corticosteroids and bronchodilators. After a month of treatment, the patient was clinically improved and a chest radiograph showed significant resolution of the shadows [Figure 9]. The patient was subsequently lost to follow-up.{Figure 8}{Figure 9}

Discussion

Pulmonary eosinophilic syndromes are a group of disorders posing significant challenges to differentiate among one another, due to the substantial overlap among their clinical, radiographic, and histologic features, as well as the presence of variable features at the different stages of the disease.[8] Our case had a total duration of illness of 4 years, presenting with exertional dyspnea, cough, fever, anorexia, low-grade fever, and pain and tingling in the left leg. Initially, the patient was treated for bronchial asthma and mediastinal lymphadenopathy, in which the etiology could not be identified even after extensive workup. The patient had then presented with worsening of her symptoms and progression in size of the mediastinal lymph nodes. There were new lung parenchymal opacities on the left side. The presence of asthma, blood eosinophilia, chronic sinusitis, nonresolving opacities, and constitutional symptoms raised the possibility of ABPA and EGPA. A diagnosis of ABPA was made according to the International Society for Human and Animal Mycology criteria.[9] The CT findings of large, irregular, heterogeneously enhancing, left perihilar mass lesion extending into the mediastinum, ground-glass opacity, and septal thickening could not be explained by ABPA. Other than central bronchiectasis, HRCT finding in ABPA includes nodules, mucus plugging, tree-in-bud opacities, high-attenuation mucus, atelectasis, peripheral airspace consolidation, or ground-glass attenuation, and possibly mosaic perfusion or air trapping, but mediastinal lymphadenopathy is not common.[10],[11] It is well known that the symptoms, signs, and laboratory findings resemble each other for both EGPA and ABPA; even the diagnostic criteria overlap partially. Compared with that of ABPA, which is a condition resulting from a hypersensitivity reaction to A. fumigatus or other fungi, the pathogenesis of EGPA is not fully clarified. It is recognized that immune pathogenesis is involved in the development of EGPA, but ANCA origin and its role and its mechanism of action in EGPA remain unknown. The presence of asthma, eosinophilia, chest radiographic findings, and paranasal sinusitis, positive p-ANCA raised suspicion of EGPA but did jot not satisfy the diagnostic criteria established by the American College of Rheumatology.[6] Positive p-ANCA may be false positive. USG-guided biopsy from left lung opacity showed mixed inflammation in the form of eosinophil, neutrophil, and lymphocyte but without granuloma or features of vasculitis rule out EGPA. Nodular endobronchial lesion, hilar adenopathy, septal thickening, nonresolving consolidation, and sinus involvement raise a possibility of sarcoidosis and granulomatosis with polyangiitis (GPA). However, a normal serum ACE level, positive Mantoux test, and eosinophilic inflammation in the endobronchial biopsy rule it out.

This patient was found positive for both c-ANCA and p-ANCA, but it has relevance in only a typical clinical setting with evidence of vasculitis. False-positive ANCA may occur due to drugs such as antithyroid drug propylthiouracil, hydralazine, minocycline, and allopurinol.[12] P-ANCA may be found positive in many nonvasculitic rheumatic disorders such as rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome.[13] ANCA positivity (mostly p-ANCA) is seen in 60%–80% of patients with ulcerative colitis, Crohn's disease, and primary sclerosing cholangitis.[14] Patients with bacterial endocarditis and bacteremia (endocarditis) are associated with a positive ANCA, and it is advised that clinicians should have a low threshold for obtaining blood cultures in patients with possible ANCA-associated vasculitis and in the patients testing positive for ANCA.[15],[16] The predictive value of ANCA testing depends heavily on the clinical presentation of the patient in whom the test is performed, and most of the patients require histopathological evidence of vasculitis to prove a small vessel vasculitis like GPA or EGPA.

Our patient had given a history of loss of smell, left eye protrusion, and blackish debris from the nasal cavity. Radiograph and CT scan of PNS showed opacified left nasal cavity and sinuses with radiopaque material in the core which completely disappeared after surgery [Figure 5]. Thus, the patient fulfilled the diagnostic criteria of AFRS given by Bent and Kuhn.[4] Literature searched showed a total of 21 cases of ABPA with AFRS published in different languages.[17] Most of the cases reported in India could be due to hot and humid weather.

There is substantial overlap in clinical, radiological, and histopathological features among eosinophilic lung diseases and ANCA-associated vasculitis, and it is challenging to clinch one diagnosis. The present report is the first case of ABPA with AFRS masquerading as small-vessel vasculitis disorders such as granulomatous polyangiitis and eosinophilic granulomatous polyangiitis as per the authors' knowledge.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1	Cottin V, Cordier JF. Eosinophilic lung disease. Immunol Allergy Clin North Am 2002;32:557-86.
2	Nowicka U, Wiatr E, Jakubowska L, Polubiec-Kownacka M. Allergic bronchopulmonary aspergillosis mimicking lung cancer in a non-asthmatic female patient: A case report. Pneumonol Alergol Pol 2012;80:77-81.
3	Collins MM, Nair SB, Wormald PJ. Prevalence of noninvasive fungal sinusitis in South Australia. Am J Rhinol 2003;17:127-32.
4	Bent JP, Kuhn FA. Diagnosis of allergic fungal sinusitis. Otolaryngol Head Neck Surg 1994;111:580-8.
5	Venarske DL, deShazo RD. Sinobronchial allergic mycosis: The SAM syndrome. Chest 2002;121:1670-6.
6	Lie JT. Illustrated histopathologic classification criteria for selected vasculitis syndromes. American college of rheumatology subcommittee on classification of vasculitis. Arthritis Rheum 1990;33:1074-87.
7	Lynch JP 3^rd, Tazelaar H. Wegener granulomatosis (granulomatosis with polyangitis): Evolving concepts in treatment. Semin Respir Crit Care med 2011;32:274-97.
8	Carolyn L. Rochester, Fishman Pulmonary Disease and Disorders. 5th ed., United states, McGraw-Hill Education. 2008;1:71-1037.
9	Agarwal R, Sehgal IS, Dhooria S, Aggarwal AN. Developments in the diagnosis and treatment of allergic bronchopulmonary aspergillosis. Expert Rev Respir Med 2016;10:1317-34.
10	Johkoh T, Müller NL, Akira M, Ichikado K, Suga M, Ando M, et al. Eosinophilic lung diseases: Diagnostic accuracy of thin-section CT in 111 patients. Radiology 2000;216:773-80.
11	Kaur M, Sudan DS. Allergic Bronchopulmonary Aspergillosis (ABPA)-The High Resolution Computed Tomography (HRCT) Chest Imaging Scenario. J Clin Diagn Res 2014;8:RC05.
12	Choi HK, Merkel PA, Walker AM, Niles JL. Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis: Prevalence among patients with high titers of antimyeloperoxidase antibodies. Arthritis Rheum 2000;43:405-13.
13	Merkel PA, Polisson RP, Chang Y, Skates SJ, Niles JL. Prevalence of antineutrophil cytoplasmic antibodies in a large inception cohort of patients with connective tissue disease. Ann Intern Med 1997;126:866-73.
14	Terjung B, Spengler U, Sauerbruch T, Worman HJ. “Atypical p-ANCA” in IBD and hepatobiliary disorders react with a 50-kilodalton nuclear envelope protein of neutrophils and myeloid cell lines. Gastroenterology 2000;119:310-22.
15	Choi HK, Lamprecht P, Niles JL, Gross WL, Merkel PA. Subacute bacterial endocarditis with positive cytoplasmic antineutrophil cytoplasmic antibodies and anti-proteinase 3 antibodies. Arthritis Rheum 2000;43:226-31.
16	Mahr A, Batteux F, Tubiana S, Goulvestre C, Wolff M, Papo T, et al. Brief report: Prevalence of antineutrophil cytoplasmic antibodies in infective endocarditis. Arthritis Rheumatol 2014;66:1672-7.
17	Cheng KJ, Zhou ML, Liu YC, Zhou SH. Allergic fungal rhinosinusitis accompanied by allergic bronchopulmonary aspergillosis: A case report and literature review. World J Clin Cases 2019;7:3821-31.