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Miliary nodules: An unusual presentation of allergic bronchopulmonary aspergillosis.
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PMID:  25125822     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Allergic bronchopulmonary aspergillosis (ABPA) is an immune-mediated inflammatory disease caused by hypersensitivity to Aspergillus fumigatus. A wide spectrum of plain radiographic appearances has been described in ABPA, though none are pathognomonic of ABPA. The common radiological abnormalities encountered are fleeting pulmonary opacities, bronchiectasis, and mucoid impaction. Uncommon radiological findings encountered in ABPA include pulmonary masses, perihilar opacities simulating hilar adenopathy, and pleural effusions. However, miliary nodules as a radiological presentation of ABPA are very rare and only one case has been reported in literature. It is often misdiagnosed and mismanaged as tuberculosis; thus, the clinician should be vigilant enough to diagnose this very rare entity.
Pooja Aneja; Urvinder Pal Singh; Balwinder Kaur; Kalpesh Patel
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Type:  Journal Article    
Journal Detail:
Title:  Lung India : official organ of Indian Chest Society     Volume:  31     ISSN:  0970-2113     ISO Abbreviation:  Lung India     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-08-15     Completed Date:  2014-08-15     Revised Date:  2014-08-18    
Medline Journal Info:
Nlm Unique ID:  8405380     Medline TA:  Lung India     Country:  India    
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Languages:  eng     Pagination:  285-8     Citation Subset:  -    
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Journal Information
Journal ID (nlm-ta): Lung India
Journal ID (iso-abbrev): Lung India
Journal ID (publisher-id): LI
ISSN: 0970-2113
ISSN: 0974-598X
Publisher: Medknow Publications & Media Pvt Ltd, India
Article Information
Copyright: © Lung India
Print publication date: Season: Jul-Sep Year: 2014
Volume: 31 Issue: 3
First Page: 285 Last Page: 288
PubMed Id: 25125822
ID: 4129607
Publisher Id: LI-31-285
DOI: 10.4103/0970-2113.135784

Miliary nodules: An unusual presentation of allergic bronchopulmonary aspergillosis
Pooja Anejaaff1
Urvinder Pal Singhaff1
Balwinder Kauraff1
Kalpesh Patelaff1
Department of Pulmonary Medicine, Government Medical College, Patiala, Punjab, India
Correspondence: Address for correspondence: Dr. Urvinder Pal Singh, 22, Baba Srichand Marg, Opposite Government Press, Sirhind road, Patiala, Punjab, India. E-mail:


Allergic bronchopulmonary aspergillosis (ABPA) is a disorder caused by a hypersensitivity reaction to antigens of the Aspergillus species (most frequently Aspergillus fumigatus). ABPA was first described in 1952 by Hinson et al.[1] The pathogenesis of ABPA is complex with immune and genetic factors on the part of the host being implicated. It usually affects patients with allergic diseases, including steroid-dependent asthma or cystic fibrosis (CF).[2] ABPA can occur anywhere that has increased levels of airborne mould spores and can trigger severe asthmatic reactions, for example, compost heaps, damp buildings, and even the outside air in some places at particular times of the year. The various risk factors implicated are chronic obstructive pulmonary disease,[3] low body mass index,[4] use of immunosuppressive agents, long term use of corticosteroids, lowered immune resistance as with certain cancers, chemotherapy or after organ transplantation.[5] ABPA is characterized by a considerably variable radiographic appearance with the most common findings being atelectasis, transient pulmonary infiltrates, proximal bronchiectasis, and signs of mucoid impaction. We report a case of a previously healthy male, who visited our department and was initially suspected as a case of miliary tuberculosis but was subsequently diagnosed as a case of ABPA.


A 22-year-old male visited our hospital with complaints of cough with minimal mucoid expectoration and breathlessness of 1 month duration. He was initially managed by his general physician who on the basis of chest radiograph labelled him as a case of miliary tuberculosis. There was no history of hemoptysis, chest pain, wheeze, fever, anorexia, or weight loss. There was no history of any significant illness. The patient also denied any drug intake, addictions, or any recent travel history. On examination, the patient was normotensive with a heart rate of 84 beats per minute and a respiratory rate of 22 breaths per minute. Chest was normal on auscultation and examination of other systems was unremarkable. Chest radiograph showed small nodular opacities in both lung fields [Figures 1 and 2].

On investigations, the patient had a total leukocyte count (TLC) of 25,300 cells/mm3 with 24% neutrophils, 20% lymphocytes, and 56% eosinophils. Stool examination was normal. Sputum smear for acid fast bacilli was negative. His coagulation profile was also normal. Other biochemical tests were within normal limits. Enzyme-linked immunosorbent assay for human immunodeficiency virus was negative. Electrocardiography of the patient did not reveal any abnormality. Ultrasonography of the abdomen was normal.

High-resolution computed tomography (HRCT) of the chest [Figure 3] showed randomly scattered nodular opacities distributed throughout both the lung fields. The patient was subjected to bronchoscopy and bronchoscopic lung biopsy. Cytological analysis of the bronchoalveolar lavage fluid did not reveal any abnormality but there was growth of A. fumigatus. The bronchoscopic lung biopsy revealed findings of eosinophilic pneumonia [Figure 4].

Subsequently, intradermal tests with A. fumigatus spp. elicited strong type I hypersensitivity reaction. Total serum Immunoglobulin E (IgE) level estimated using fully automated chemiluminiscence system was 19304 IU/mL (N~100 IU/mL). Specific IgE against A. fumigatus was >100 kU/L (N~0.24 kU/L), while specific IgG levels against A. fumigatus were 278 IU/mL (N~40 IU/mL). Sputum cultures yielded no growth of Aspergillus species. Spirometry was normal, with a forced vital capacity (FVC) of 2.97 L (82% of predicted), a forced expiratory volume in 1 s (FEV1) of 2.52 L (85% of predicted), and an FEV1/FVC ratio of 85%, there was insignificant bronchodilatation after administering a bronchodilator. Postexercise spirometry was normal. Methacholine challenge test was not performed as patient denied consent.

A diagnosis of ABPA without bronchial asthma was thus made as the patient fulfilled majority of the criteria given by Rosenberg et al.[6] He was treated with prednisolone 0.75 mg/kg for 6 weeks, 0.5 mg/kg for next 6 weeks, then tapered by 5 mg every 6 week to continue for a total duration of 9 months. The patient showed marked improvement in his condition and there was marked clearing in his chest radiograph [Figure 5] after 3 months of treatment. TLC decreased markedly to 11,400 cells/mm3 with 61% neutrophils, 29% lymphocytes, and 10% eosinophils. The total serum IgE after 3 months of treatment decreased to 4784 IU/mL. The patient is under follow-up and no symptoms or signs of asthma have appeared till date.


ABPA is an inflammatory pulmonary disorder known to complicate the course of bronchial asthma and CF. The disorder occurs secondary to the immune response against antigens released by A. fumigatus, which colonize the airways of these patients.[7]

New criteria for diagnosis of ABPA have been proposed,[8] but still the Rosenberg-Patterson criteria are the most widely used for diagnosis of ABPA and include eight major (asthma, fleeting pulmonary opacities on chest radiograph, type I skin test reaction to A. fumigatus antigen, eosinophilia, serum precipitins against A. fumigatus, elevated serum total IgE levels, central bronchiectasis, and elevated levels of serum IgG and/or IgE against A. fumigatus) and three minor criteria (growth of A. fumigatus in sputum, expectoration of brownish-black mucous plugs, and type III skin reaction to A. fumigatus antigen). If six of the eight major criteria are met, the diagnosis is said to be made with certainty.[6]

The allergic reaction to A. fumigatus results in an immune-mediated damage to the large central airways and small airways where the reaction occurs, and also in the adjacent lung. This leads to diverse chest radiographic manifestations. The chest radiographic findings also depend on the clinical presentation of the disease.[7]

A characteristic feature of ABPA is the variable radiographic appearances usually in relation to the stage of the disease. During acute exacerbations of the disease, transient and fleeting opacities are characteristically found, whereas fixed abnormalities are encountered in chronic stages of the disease.[7] The most common chest radiographic finding noted is a normal chest radiograph. Consolidation is considered to be the most frequent chest radiographic abnormality of ABPA.[9] Other chest radiographic features include transient pulmonary infiltrates (mainly in the upper and lower lobes), atelectasis, band-like opacities (the gloved finger sign), bronchiectasis, and less frequently areas of poor vascular pattern, cavities, and signs of fibrosis.[2] HRCT of the chest has replaced bronchography as the investigation of choice in ABPA. The usual findings of ABPA noted on HRCT include central bronchiectasis, mucoid impaction, mosaic attenuation, and presence of centrilobular nodules. High-attenuation (80-110 HU) mucoid impaction is a highly characteristic finding encountered in patients with ABPA. Currently, the presence of high-attenuation mucus (HAM) is considered pathognomonic of ABPA.[10] The immunological activity and outcomes of ABPA could be predicted on HRCT chest finding of HAM, a marker of inflammatory activity. Central broncheictasis and HAM are independent predictors of recurrent relapses in ABPA.[11] Rare findings on HRCT include pleural effusion, perihilar bronchoceles mimicking adenopathy, miliary nodules, and unilateral lung collapse.[12, 13, 14, 15, 16]

Among the atypical presentations of ABPA, Berkin et al.,[17] in 1982 described four patients with complete or partial atelectasis without a history of asthma in whom the final diagnosis was ABPA. In 2001, Sanchez-Alcaros et al.,[18] described a 65-year-old male smoker without a history of asthma who had undergone thoracotomy due to suspected lung cancer, which revealed the presence of dilated bronchi filled with mucus and was diagnosed as ABPA. In 2006, Agarwal et al.,[15] described a case of a 60-year-old female evaluated due to the widening of the left hilum on a chest X-ray later diagnosed as ABPA. Aggarwal et al.,[12] have described the only case of military mottling which was finally diagnosed as a case of ABPA. This is the second such case.

In areas with a high prevalence of pulmonary tuberculosis (PTB), patients with ABPA having atypical radiological presentations are often misdiagnosed with PTB. In some Indian studies, ABPA was misdiagnosed as PTB in as high as 17%-50% cases and treated with antitubercular drugs for a long time.[19] Our case was also labelled as a case of miliary tuberculosis and advised antitubercular treatment.

Primary treatment for ABPA is with systemic corticosteroids to suppress the allergic response rather than with antifungal therapy targeted at the fungal organism. Oral corticosteroids are still the therapy of choice for ABPA. Itraconazole may have a role in therapy, but controlled studies are needed. At this time, itraconazole should be limited to cases where oral corticosteroids are contraindicated or refused by the patient. In patients requiring large doses of oral steroids, itraconazole may allow a reduction in dose but should not replace the need to treat with oral corticosteroids.[20]

It should be noted that not all the diagnostic criteria of ABPA are always fulfilled, which makes establishment of the final diagnosis difficult. ABPA can present with diverse radiological manifestations, and a high index of suspicion should be maintained, especially in high-prevalence areas.

To conclude, although tuberculosis is the most common cause of miliary mottling in our country but when confronted with a case who presents with miliary mottling along with eosinophilia and atypical symptoms, the clinician should be vigilant enough to look for other diagnosis. Early diagnosis and management of ABPA in such cases will help to prevent the development of end-stage pulmonary fibrosis.


Source of Support: Nil

Conflict of Interest: None declared.


The authors would like to thank Dr. Vishal Chopra, associate profressor, department of pulmonary medicine, government medical college patiala, for doing bronchoscopy and Dr. Moushumi Suryavanshi for doing histopathological examination.

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[Figure ID: F1]
Figure 1 

Chest radiograph showing ill-defined nodular opacities in both lung fields

[Figure ID: F2]
Figure 2 

Chest radiograph showing ill-defined nodular opacities more prominent on left side

[Figure ID: F3]
Figure 3 

CT scan of chest showing bilateral nodular opacities that are randomly scattered

[Figure ID: F4]
Figure 4 

Photomicrograph showing fibrin with eosinophilic infiltrate consistent with eosinophilic pneumonia

[Figure ID: F5]
Figure 5 

Chest radiograph after steroid therapy that is essentially normal

Article Categories:
  • Case Report

Keywords: Allergic bronchopulmonary aspergillosis, miliary, radiology, tuberculosis.

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