- Email: [email protected]
Hilar adenopathy in allergic bronchopulmonary aspergillosis
Hilar adenopathy in allergic bronchopulmonary aspergillosis Ashok Shah, MD; Anil K Agarwal, MD; and Inder Mohan Chugh, MBBS
Background: A 20-year-old male student developed allergic bronchopulmonary aspergillosis (ABPA). Computed tomography (CT) of the thorax done to detect central bronchiectasis (CB) for confirmation of diagnosis revealed, in addition, right hilar lymphadenopathy. Hilar adenopathy is thought to be rare in ABPA and has been documented only once before. Because of the finding of hilar adenopathy, the earlier reported patient had to undergo an invasive surgical procedure. Objective: To report a case of true hilar adenopathy in ABPA. Methods: This is a single case report. Contrast enhanced CT of the thorax was done. Serum precipitating antibodies against Aspergillus fumigatus were tested using gel diffusion technique, and intradermal testing with antigens of Aspergillus species was performed. Specific IgG antibodies against A. fumigatus and total IgE levels were measured by ELISA. Results: A review of serial chest radiographs over a period of 3 years demonstrated transient pulmonary infiltrates and right hilar prominence. Computed tomography of the thorax revealed right hilar lymphadenopathy along with bilateral central bronchiectasis and patchy infiltrates. Strong bands of precipitins were detected against A. fumigatus. Intradermal testing with antigens of Aspergillus species elicited strong type I (immediate) and type III (Arthus-type) hypersensitivity reactions to A. fumigatus and A. niger. Specific IgG antibodies against A. fumigatus was positive and total IgE level was significantly elevated. Peripheral blood eosinophilia was also detected. Conclusions: Although extremely rare, ABPA should be considered in the differential diagnosis of hilar adenopathy. Ann Allergy Asthma Immunol 1999;82:504–506.
INTRODUCTION Allergic bronchopulmonary aspergillosis (ABPA), a potentially destructive lung disease, now recognized globally, is not uncommon in India.1 Although pseudohilar adenopathy is a known radiological feature that draws attention to the diagnosis of ABPA,2 true hilar adenopathy in a case of ABPA has been documented only once before.3 We report a case of ABPA in whom true hilar adenopathy was demonstrated on computed tomography (CT) of thorax.
From the Department of Clinical Research, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India. Received for publication April 15, 1998. Accepted for publication in revised form October 8, 1998.
504
CASE REPORT A 20-year-old male student, a nonsmoker, was referred to our Institute for evaluation of progressive pulmonary disease since childhood. His clinical course was characterized by paroxysmal episodes of productive cough and wheezing dyspnea which had increased during the last 8 years. The patient also reported intermittent lowgrade febrile episodes with malaise. He had poor appetite and poor weight gain since childhood. Further questioning revealed a history of occasional expectoration of brownish plugs along with sputum. Nine months prior to referral, the patient had two episodes of expectoring blood-tinged sputum. A history of sneezing, rhinorrhea, and nasal blockage since childhood was also elicited. On the basis of his symptoms and radiologic profile, the patient had
been initiated on antituberculous treatment 9 months before presentation. He was still on antituberculous drugs when he reported to us. During his entire illness sputum stains and cultures for Mycobacterium tuberculosis were persistently negative. His father had asthma for last 18 to 20 years with no evidence of ABPA. Physical examination revealed a thin young man in no acute distress. The trachea was centrally located. Pectus carinatum was seen on chest examination. On auscultation, coarse crackles were audible on right anterior aspect of chest along with bilateral polyphonic rhonchi. There was no cyanosis or clubbing. The nasal mucosa was erythematous with thick purulent secretions. Examination of other systems including the lymph nodes did not reveal any abnormality. Laboratory examination showed a total leukocyte count of 12,500/mm3 with 14% eosinophils. Sputum stains and cultures were negative for M. tuberculosis. Sputum cultures for other aerobic and anaerobic organisms did not grow any pathogens. Spirometry was suggestive of severe impairment of lung function with a FEV1 of 1.19 L (33% of predicted normal). A review of serial chest radiographs over a period of 3 years demonstrated transient pulmonary infiltrates and right hilar prominence (Fig 1). Computed tomography of the thorax revealed right hilar lymphadenopathy (Fig 2A) along with bilateral central bronchiectasis (CB) (Fig 2B) and patchy infiltrates. Mucus-filled dilated bronchi were seen predominantly in the right upper and middle lobes as well as left upper lobe. Although the patient had nasal symptoms, a radiograph of paranasal sinuses done on presentation did not show any evidence of sinusitis. Intradermal test-
ANNALS OF ALLERGY, ASTHMA, & IMMUNOLOGY
migatus, (8) elevated total IgE level, and (9) peripheral blood eosinophilia. Antituberculous drugs were stopped and the patient was initiated on oral prednisone in the dose of 25 mg (0.5 mg/kg) once daily along with antiasthma and other symptomatic therapy. Prednisone was reduced to 25 mg on alternate days after 2 weeks and gradually tapered. The patient showed remarkable symptomatic and radiologic improvement. Both his pulmonary as well as nasal symptoms were abolished. Subsequent CT of the thorax revealed resolution of the adenopathy (Fig 3). Figure 1. Chest radiograph showing right hilar prominence along with pulmonary infiltrates in the right lung.
ing with antigens of Aspergillus species (Centre for Biochemical Technology, Delhi, a laboratory of the Council of Scientific and Industrial Research) elicited strong type I and type III hypersensitivity reactions to A. fumigatus and A. niger. Immediate cutaneous reactivity to A. fumigatus and A. niger was 30 x 20 mm and 17 x 16 mm, respectively, against a negative control (buffer saline) of 2 x 2 mm and positive control (histamine) of 12 x 12 mm. There was a typical type III hypersensitivity response to A. fumigatus and A. niger which measured 46 x 30 mm and 40 x 22 mm respectively. Gel diffusion studies detected strong bands of serum precipitins against A. fumigatus. Specific IgG antibodies against A. fumigatus was positive by ELISA and total IgE level was greater than 4,150 IU/mL (reference range 0 to 100 IU/ mL). Intradermal test with the usual set of inhalant aeroallergen extracts revealed no significant positivity. A diagnosis of ABPA was made on the basis of (1) history of asthma, (2) history of occasional expectoration of brownish plugs along with sputum, (3) transient pulmonary infiltrates on review of previous chest radiographs, (4) central bronchiectasis on CT of the thorax, (5) strong bands of precipitin against A. fumigatus, (6) type I and type III hypersensitivity to intradermal testing with Aspergillus species, (7) positive specific IgG antibodies against A. fuVOLUME 82, MAY, 1999
DISCUSSION Pseudohilar adenopathy, on plain radiograph, in ABPA results from deposition of mucus in the centrally dilated
Figure 2. Computed tomogram of thorax showing (top panel) right hilar lymphadenopathy (arrows) and (lower panel) central bronchiectasis (arrows). 505
bronchi.2 True hilar adenopathy is not a recognized feature of ABPA and has been demonstrated in only one previous case of a 27-year-old man with a history of childhood reactive airway disease who had bilateral, symmetrical hilar lymphadenopathy on chest radiograph.3 No other chronic lung disease or peripheral adenopathy was detected. Suspicion of lymphoma or other neoplastic disease resulted in the patient being subjected to invasive procedures including mediastinoscopy and an open lung biopsy. Mediastinoscopic examination confirmed adenopathy and A. fumigatus was cultured from the open biopsy specimen. Retrospective evaluation of CT of the thorax detected findings consistent with central bronchiectasis. Since hilar adenopathy is not a recognized feature of ABPA, the patient had to undergo invasive procedures which eventually resulted in the diagnosis. Our patient, a 20-year-old man, also had reactive airway disease since childhood. Evaluation of the patient led to the diagnosis of ABPA. All eight major criteria viz. (asthma, transient pulmonary infiltrates, central bronchiectasis, precipitating antibodies against A. fumigatus, immediate cutaneous reactivity to Aspergillus species, elevated specific IgG antibodies against A. fumigatus, elevated total IgE level, and peripheral blood eosinophilia), which are required for the diagnosis of ABPA, were fulfilled in our patient. Two minor criteria, which included expectoration of brownish sputum plugs and late (Arthustype) skin reactivity to Aspergillus species, were also present. Computed tomography of the thorax done by us, during the initial work up of the patient, demonstrated hilar lymphadenopathy on the right side, which regressed on therapy, along with bilateral central bronchiectasis. Allergic bronchopulmonary aspergillosis in our patient was diagnosed prospectively without recourse to any invasive procedure. We have already shown that CT in comparison to bronchography, a procedure thought to be unsafe in asthma, could be the investigation of choice in detecting central bronchiectasis in patients
506
Figure 3. Computed tomogram of thorax done 6 weeks after therapy showing significant regression of the hilar lymphadenopathy.
with ABPA.4,5 Computed tomography of the thorax should constitute a part of the diagnostic work up of ABPA.6 Another feature in our patient was the history of nasal symptoms since childhood which were relieved by therapy with prednisone. As the radiograph of the sinuses was normal and the routine allergy skin test did not reveal any significant positivity, the nasal symptoms could possibly have been due to associated rhinitis. Prednisone, to which our patient had a remarkable clinical response, remains the cornerstone of treatment of ABPA. Our case highlights the fact that, although rare, ABPA can also present with hilar adenopathy and should be considered in the differential diagnosis. Suspicion of ABPA in an appropriate clinical and radiologic setting even with the presence of hilar lymphadenopathy can avoid invasive procedures. Early diagnosis and initiation of appropriate treatment can greatly improve the prognosis in these patients. ACKNOWLEDGMENT The authors are thankful to Prof H S Randhawa, Department of Medical Mycology, VP Chest Institute for conducting the precipitin studies and to Dr P Usha Sarma, Centre for Biochemical Technology for conducting the specific IgG studies.
REFERENCES 1. Shah A. Allergic bronchopulmonary aspergillosis: an emerging disease in India [Editorial]. Indian J Chest Dis Allied Sci 1994;36:169 –172. 2. Mintzer RA, Rogers LF, Kruglik GD. The spectrum of radiological findings in allergic bronchopulmonary aspergillosis. Radiology 1978;127:301–307. 3. Hantsch CE, Tanus T. Allergic bronchopulmonary aspergillosis with adenopathy. Ann Intern Med 1991;115: 546 –547. 4. Shah A, Pant CS, Bhagat R, Panchal N. CT in childhood allergic bronchopulmonary aspergillosis. Pediatr Radiol 1992;22:227–228. 5. Panchal N, Pant CS, Bhagat R, Shah A. Central bronchiectasis in allergic bronchopulmonary aspergillosis: comparative evaluation of computed tomography of the thorax with bronchography. Eur Respir J 1994;7: 1290 –1293. 6. Panchal N, Bhagat R, Pant C, Shah A. Allergic bronchopulmonary aspergillosis: the spectrum of computed tomography appearances. Respir Med 1997;91:213–219. Request for reprints should be addressed to: Ashok Shah, MD Department of Clinical Research Vallabhbhai Patel Chest Institute University of Delhi P.O. Box 2101 Delhi - 110007 India
ANNALS OF ALLERGY, ASTHMA, & IMMUNOLOGY
Background: A 20-year-old male student developed allergic bronchopulmonary aspergillosis (ABPA). Computed tomography (CT) of the thorax done to detect central bronchiectasis (CB) for confirmation of diagnosis revealed, in addition, right hilar lymphadenopathy. Hilar adenopathy is thought to be rare in ABPA and has been documented only once before. Because of the finding of hilar adenopathy, the earlier reported patient had to undergo an invasive surgical procedure. Objective: To report a case of true hilar adenopathy in ABPA. Methods: This is a single case report. Contrast enhanced CT of the thorax was done. Serum precipitating antibodies against Aspergillus fumigatus were tested using gel diffusion technique, and intradermal testing with antigens of Aspergillus species was performed. Specific IgG antibodies against A. fumigatus and total IgE levels were measured by ELISA. Results: A review of serial chest radiographs over a period of 3 years demonstrated transient pulmonary infiltrates and right hilar prominence. Computed tomography of the thorax revealed right hilar lymphadenopathy along with bilateral central bronchiectasis and patchy infiltrates. Strong bands of precipitins were detected against A. fumigatus. Intradermal testing with antigens of Aspergillus species elicited strong type I (immediate) and type III (Arthus-type) hypersensitivity reactions to A. fumigatus and A. niger. Specific IgG antibodies against A. fumigatus was positive and total IgE level was significantly elevated. Peripheral blood eosinophilia was also detected. Conclusions: Although extremely rare, ABPA should be considered in the differential diagnosis of hilar adenopathy. Ann Allergy Asthma Immunol 1999;82:504–506.
INTRODUCTION Allergic bronchopulmonary aspergillosis (ABPA), a potentially destructive lung disease, now recognized globally, is not uncommon in India.1 Although pseudohilar adenopathy is a known radiological feature that draws attention to the diagnosis of ABPA,2 true hilar adenopathy in a case of ABPA has been documented only once before.3 We report a case of ABPA in whom true hilar adenopathy was demonstrated on computed tomography (CT) of thorax.
From the Department of Clinical Research, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India. Received for publication April 15, 1998. Accepted for publication in revised form October 8, 1998.
504
CASE REPORT A 20-year-old male student, a nonsmoker, was referred to our Institute for evaluation of progressive pulmonary disease since childhood. His clinical course was characterized by paroxysmal episodes of productive cough and wheezing dyspnea which had increased during the last 8 years. The patient also reported intermittent lowgrade febrile episodes with malaise. He had poor appetite and poor weight gain since childhood. Further questioning revealed a history of occasional expectoration of brownish plugs along with sputum. Nine months prior to referral, the patient had two episodes of expectoring blood-tinged sputum. A history of sneezing, rhinorrhea, and nasal blockage since childhood was also elicited. On the basis of his symptoms and radiologic profile, the patient had
been initiated on antituberculous treatment 9 months before presentation. He was still on antituberculous drugs when he reported to us. During his entire illness sputum stains and cultures for Mycobacterium tuberculosis were persistently negative. His father had asthma for last 18 to 20 years with no evidence of ABPA. Physical examination revealed a thin young man in no acute distress. The trachea was centrally located. Pectus carinatum was seen on chest examination. On auscultation, coarse crackles were audible on right anterior aspect of chest along with bilateral polyphonic rhonchi. There was no cyanosis or clubbing. The nasal mucosa was erythematous with thick purulent secretions. Examination of other systems including the lymph nodes did not reveal any abnormality. Laboratory examination showed a total leukocyte count of 12,500/mm3 with 14% eosinophils. Sputum stains and cultures were negative for M. tuberculosis. Sputum cultures for other aerobic and anaerobic organisms did not grow any pathogens. Spirometry was suggestive of severe impairment of lung function with a FEV1 of 1.19 L (33% of predicted normal). A review of serial chest radiographs over a period of 3 years demonstrated transient pulmonary infiltrates and right hilar prominence (Fig 1). Computed tomography of the thorax revealed right hilar lymphadenopathy (Fig 2A) along with bilateral central bronchiectasis (CB) (Fig 2B) and patchy infiltrates. Mucus-filled dilated bronchi were seen predominantly in the right upper and middle lobes as well as left upper lobe. Although the patient had nasal symptoms, a radiograph of paranasal sinuses done on presentation did not show any evidence of sinusitis. Intradermal test-
ANNALS OF ALLERGY, ASTHMA, & IMMUNOLOGY
migatus, (8) elevated total IgE level, and (9) peripheral blood eosinophilia. Antituberculous drugs were stopped and the patient was initiated on oral prednisone in the dose of 25 mg (0.5 mg/kg) once daily along with antiasthma and other symptomatic therapy. Prednisone was reduced to 25 mg on alternate days after 2 weeks and gradually tapered. The patient showed remarkable symptomatic and radiologic improvement. Both his pulmonary as well as nasal symptoms were abolished. Subsequent CT of the thorax revealed resolution of the adenopathy (Fig 3). Figure 1. Chest radiograph showing right hilar prominence along with pulmonary infiltrates in the right lung.
ing with antigens of Aspergillus species (Centre for Biochemical Technology, Delhi, a laboratory of the Council of Scientific and Industrial Research) elicited strong type I and type III hypersensitivity reactions to A. fumigatus and A. niger. Immediate cutaneous reactivity to A. fumigatus and A. niger was 30 x 20 mm and 17 x 16 mm, respectively, against a negative control (buffer saline) of 2 x 2 mm and positive control (histamine) of 12 x 12 mm. There was a typical type III hypersensitivity response to A. fumigatus and A. niger which measured 46 x 30 mm and 40 x 22 mm respectively. Gel diffusion studies detected strong bands of serum precipitins against A. fumigatus. Specific IgG antibodies against A. fumigatus was positive by ELISA and total IgE level was greater than 4,150 IU/mL (reference range 0 to 100 IU/ mL). Intradermal test with the usual set of inhalant aeroallergen extracts revealed no significant positivity. A diagnosis of ABPA was made on the basis of (1) history of asthma, (2) history of occasional expectoration of brownish plugs along with sputum, (3) transient pulmonary infiltrates on review of previous chest radiographs, (4) central bronchiectasis on CT of the thorax, (5) strong bands of precipitin against A. fumigatus, (6) type I and type III hypersensitivity to intradermal testing with Aspergillus species, (7) positive specific IgG antibodies against A. fuVOLUME 82, MAY, 1999
DISCUSSION Pseudohilar adenopathy, on plain radiograph, in ABPA results from deposition of mucus in the centrally dilated
Figure 2. Computed tomogram of thorax showing (top panel) right hilar lymphadenopathy (arrows) and (lower panel) central bronchiectasis (arrows). 505
bronchi.2 True hilar adenopathy is not a recognized feature of ABPA and has been demonstrated in only one previous case of a 27-year-old man with a history of childhood reactive airway disease who had bilateral, symmetrical hilar lymphadenopathy on chest radiograph.3 No other chronic lung disease or peripheral adenopathy was detected. Suspicion of lymphoma or other neoplastic disease resulted in the patient being subjected to invasive procedures including mediastinoscopy and an open lung biopsy. Mediastinoscopic examination confirmed adenopathy and A. fumigatus was cultured from the open biopsy specimen. Retrospective evaluation of CT of the thorax detected findings consistent with central bronchiectasis. Since hilar adenopathy is not a recognized feature of ABPA, the patient had to undergo invasive procedures which eventually resulted in the diagnosis. Our patient, a 20-year-old man, also had reactive airway disease since childhood. Evaluation of the patient led to the diagnosis of ABPA. All eight major criteria viz. (asthma, transient pulmonary infiltrates, central bronchiectasis, precipitating antibodies against A. fumigatus, immediate cutaneous reactivity to Aspergillus species, elevated specific IgG antibodies against A. fumigatus, elevated total IgE level, and peripheral blood eosinophilia), which are required for the diagnosis of ABPA, were fulfilled in our patient. Two minor criteria, which included expectoration of brownish sputum plugs and late (Arthustype) skin reactivity to Aspergillus species, were also present. Computed tomography of the thorax done by us, during the initial work up of the patient, demonstrated hilar lymphadenopathy on the right side, which regressed on therapy, along with bilateral central bronchiectasis. Allergic bronchopulmonary aspergillosis in our patient was diagnosed prospectively without recourse to any invasive procedure. We have already shown that CT in comparison to bronchography, a procedure thought to be unsafe in asthma, could be the investigation of choice in detecting central bronchiectasis in patients
506
Figure 3. Computed tomogram of thorax done 6 weeks after therapy showing significant regression of the hilar lymphadenopathy.
with ABPA.4,5 Computed tomography of the thorax should constitute a part of the diagnostic work up of ABPA.6 Another feature in our patient was the history of nasal symptoms since childhood which were relieved by therapy with prednisone. As the radiograph of the sinuses was normal and the routine allergy skin test did not reveal any significant positivity, the nasal symptoms could possibly have been due to associated rhinitis. Prednisone, to which our patient had a remarkable clinical response, remains the cornerstone of treatment of ABPA. Our case highlights the fact that, although rare, ABPA can also present with hilar adenopathy and should be considered in the differential diagnosis. Suspicion of ABPA in an appropriate clinical and radiologic setting even with the presence of hilar lymphadenopathy can avoid invasive procedures. Early diagnosis and initiation of appropriate treatment can greatly improve the prognosis in these patients. ACKNOWLEDGMENT The authors are thankful to Prof H S Randhawa, Department of Medical Mycology, VP Chest Institute for conducting the precipitin studies and to Dr P Usha Sarma, Centre for Biochemical Technology for conducting the specific IgG studies.
REFERENCES 1. Shah A. Allergic bronchopulmonary aspergillosis: an emerging disease in India [Editorial]. Indian J Chest Dis Allied Sci 1994;36:169 –172. 2. Mintzer RA, Rogers LF, Kruglik GD. The spectrum of radiological findings in allergic bronchopulmonary aspergillosis. Radiology 1978;127:301–307. 3. Hantsch CE, Tanus T. Allergic bronchopulmonary aspergillosis with adenopathy. Ann Intern Med 1991;115: 546 –547. 4. Shah A, Pant CS, Bhagat R, Panchal N. CT in childhood allergic bronchopulmonary aspergillosis. Pediatr Radiol 1992;22:227–228. 5. Panchal N, Pant CS, Bhagat R, Shah A. Central bronchiectasis in allergic bronchopulmonary aspergillosis: comparative evaluation of computed tomography of the thorax with bronchography. Eur Respir J 1994;7: 1290 –1293. 6. Panchal N, Bhagat R, Pant C, Shah A. Allergic bronchopulmonary aspergillosis: the spectrum of computed tomography appearances. Respir Med 1997;91:213–219. Request for reprints should be addressed to: Ashok Shah, MD Department of Clinical Research Vallabhbhai Patel Chest Institute University of Delhi P.O. Box 2101 Delhi - 110007 India
ANNALS OF ALLERGY, ASTHMA, & IMMUNOLOGY