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A case of allergic bronchopulmonary aspergillosis leading to pneumonia with unusual organisms.

Abstract: We describe the case of a 50-year-old male with a history of asthma and seizure disorder who presented with a 5-month history of dyspnea. The patient had been treated with multiple courses of antibiotics for presumed community-acquired pneumonia before being determined to have allergic bronchopulmonary aspergillosis Allergic Bronchopulmonary Aspergillosis Definition

Allergic bronchopulmonary aspergillosis, or ABPA, is one of four major types of infections in humans caused by Aspergillus fungi.
 (ABPA) by serologic and radiographic criteria. Inflammation resulting from this disease had potentiated a postobstructive pneumonia caused by Nocardia asteroides and Stenotrophomonas maltophilia. Therapy with corticosteroids, trimethoprim sulfa sul·fa
Of, relating to, or containing sulfanilamide or any sulfa drug.

sulfa (sul´f
, and voriconazole failed to prevent subsequent destruction of the right upper lobe and the patient required surgical intervention. The discussion emphasizes the diagnostic criteria for ABPA including historic, serologic, and radiographic findings; staging, and treatment. Other possible diagnoses, such as invasive pulmonary aspergillosis Aspergillosis Definition

Aspergillosis refers to several forms of disease caused by a fungus in the genus Aspergillus. Aspergillosis fungal infections can occur in the ear canal, eyes, nose, sinus cavities, and lungs.
, chronic necrotizing necrotizing /nec·ro·tiz·ing/ (nek´ro-tiz?ing) causing necrosis.
Causing the death of a specific area of tissue. Human bites frequently cause necrotizing infections.
 aspergillosis, and hyper-IgE syndrome are also briefly reviewed.

Key Words: allergic bronchopulmonary aspergillosis, Aspergillus, Nocardia asteroides


First described in 1952 by Hinson et al, (1) the syndrome of allergic bronchopulmonary aspergillosis (ABPA) is characterized by bronchopulmonary bronchopulmonary /bron·cho·pul·mo·nary/ (-pool´mah-nar?e) pertaining to the bronchi and the lungs.

Relating to the bronchial tubes and the lungs.
 aspergillosis, peripheral eosinophila, and asthma coupled with intermittent cough productive of mucous plugs containing Aspergillus. Despite the evolution of specific serologic tests and more definitive objective criteria, (2) diagnosis still requires a high degree of clinical suspicion. Here we present a case of ABPA coupled with an unusual pneumonia.

Case Report

A 50-year-old white male with a history of severe asthma and seizure disorder presented with a 5-month history of increasing dyspnea. He had seen multiple physicians over this time period and had been treated for bronchopneumonia bronchopneumonia: see pneumonia.  with ciprofloxacin, levofloxacin, and, most recently amoxicillin/clavulanic acid with little to no improvement. Approximately one month before admission, he had been seen by a pulmonologist who ordered a CT scan of the lungs, which revealed symmetrical bronchiectasis bronchiectasis

Abnormal expansion of bronchi in the lungs. It usually results when preexisting lung disease causes bronchial inflammation and obstruction. Bronchial wall fibres degenerate, and bronchi become dilated or paralyzed, preventing removal of secretions, which
 with mucoid mucoid /mu·coid/ (mu´koid)
1. resembling mucus.

2. mucinoid.

Any of various glycoproteins similar to the mucins, especially a mucoprotein.

 impaction of the bronchi bronchi /bron·chi/ (brong´ki) plural of bronchus.
Two main branches of the trachea that go into the lungs. This then further divides into the bronchioles and alveoli.
 in the lingular segment of the left upper lobe and posterior segment of the right lower lobe. Subsequent bronchoscopic biopsy revealed enlarged mucous glands and longitudinal striations consistent with chronic bronchitis. Culture from bronchial washings eventually grew out Aspergillus fumigatus and Stenotrophomonas maltophilia. At admission, he complained of shortness of breath Shortness of Breath Definition

Shortness of breath, or dyspnea, is a feeling of difficult or labored breathing that is out of proportion to the patient's level of physical activity.
, both at rest and with exertion, fever and chills, minimally productive cough and generalized fatigue.

His past medical history included asthma treated with inhaled albuterol and fluticasone and a seizure disorder well controlled with phenytoin phenytoin /phen·y·to·in/ (fen´i-toin?) an anticonvulsant used in the control of various kinds of epilepsy and of seizures associated with neurosurgery.

. On further questioning, he did recall a similar course of events approximately 10 years before admission during which he thought he had heard of Aspergillus and was treated with steroids. He also stated that he recalled the name "Sporanox." He had no known drug allergies. He denied chronic systemic corticosteroid use. He denied any family history of lung disease or allergies. There was no exposure history for animals, tuberculosis, or environmental irritants. He further denied tobacco, alcohol, high risk sexual behavior, or illicit drug use.

On physical examination, he was afebrile afebrile /afe·brile/ (a-feb´ril) without fever.



without fever.

afebrile adjective Feverless
 with stable vital signs. He had an oxygen saturation of 97% on room air. Lung examination showed bilateral inspiratory and expiratory wheezes and bibasilar crackles, but was otherwise unremarkable. Spirometry Spirometry

The measurement, by a form of gas meter, of volumes of gas that can be moved in or out of the lungs. The classical spirometer is a hollow cylinder (bell) closed at its top.
 revealed the forced expiratory volume forced expiratory volume
n. Abbr. FEV
The maximum volume of air that can be expired from the lungs in a specific time interval when starting from maximum inspiration.
 in 1 second to be 1.03 L (28% of predicted) with a forced vital capacity forced vital capacity
n. Abbr. FVC
Vital capacity measured with subject exhaling as rapidly as possible.

forced vital capacity,
n a measure of the maximum rate of exhalation.
 of 34% of expected. Flow volume loop was consistent with obstructive ventilatory defect. A CT angiogram an·gi·o·gram
An angiographic x-ray of blood vessels used in diagnosing pathological conditions of the cardiovascular system.//An x-ray of one or more blood vessels produced by angiography and used in diagnosing pathology in the cardiovascular
 done to rule out pulmonary embolus revealed a new pneumatocele in the left upper lobe with multiloculation, bronchiectasis in an upper lobe predominance, ground glass lung posteriorly in the right lung, and a three-pronged cluster of soft tissue mass in the superior aspect of the right lower lobe.

Allergic bronchopulmonary aspergillosis with concomitant community-acquired pneumonia was thus suspected and confirmed by immunoglobulin (Ig)E specific to Aspergillus fumigatus (although he did not have IgG specific to Aspergillus), a total IgE level of 3,589 IU/mL, and a high total eosinophil eosinophil /eo·sin·o·phil/ (e?o-sin´o-fil) a granular leukocyte having a nucleus with two lobes connected by a thread of chromatin, and cytoplasm containing coarse, round granules of uniform size.  count of 880/[micro]L. Subsequent skin testing revealed an immediate cutaneous sensitivity to Aspergillus with a 5 mm wheal wheal (hwel) a localized area of edema on the body surface, often attended with severe itching and usually evanescent; it is the typical lesion of urticaria.

 on puncture testing.

The patient was started on corticosteroids and voriconazole. Bronchoscopy Bronchoscopy Definition

Bronchoscopy is a procedure in which a cylindrical fiberoptic scope is inserted into the airways. This scope contains a viewing device that allows the visual examination of the lower airways.
 revealed significant mucoid impaction of the endobronchial tree bilaterally with the most severe impaction in the left upper lobe. In this area, multiple bronchoscopies were required to remove the mucous plugging. Upon removal of this plugging, copious purulent discharge was noted from this lobe. Bronchoalveolar lavage cultures yielded colonies of Stenotrophomonas maltophilia and weakly acid-fast Gram positive branching rods that eventually proved to be Nocardia asteroides. He was treated with trimethoprim sulfamethoxazole sulfamethoxazole /sul·fa·meth·ox·a·zole/ (-meth-ok´sah-zol) a sulfonamideantibacterial and antiprotozoal, particularly used in acute urinary tract infections.

 and levofloxacin with an excellent initial clinical response. Voriconazole was discontinued.

Shortness of breath accompanied by pleuritic pleu·rit·ic
Of or relating to pleurisy.


pertaining to or emanating from pleurisy. See also pleural.

pleuritic ridge
 chest pain returned over the next several months. Repeat CT scan obtained approximately 10 weeks after discharge revealed multiple left upper lobe abscesses with complete destruction of this lobe. Bronchoscopy done at this time showed recurrence of the mucous plugging, marked inflammation, and pus in the endobronchial tree. Significant necrosis of the left upper lobe, presumably due to Nocardia pneumonia, was also seen. Surgical intervention was felt to be necessary and the patient underwent left upper lobectomy lobectomy /lo·bec·to·my/ (lo-bek´tah-me) excision of a lobe, as of the lung, brain, or liver.

Excision of a lobe of an organ or a gland.
 several days later.

Histologic examination revealed chronic inflammation and hyperplasia of the bronchial wall. Mucous and inflammatory exudates were present within the bronchi. Large granulomata with central necrosis were noted along with collections of multinucleated multinucleated

characterized by having more than one nucleus per cell.

multinucleated giant cell
see giant cell.
 giant cells in lung sections. These sections also showed dilated airways consistent with bronchiectasis. There was peribronchiolar chronic inflammation. There were also areas of fibrosis with numerous pigmented macrophages. A relatively large lung nodule showed central cystic necrosis with eosinophilic eosinophilic /eo·sin·o·phil·ic/ (-fil´ik)
1. readily stainable with eosin.

2. pertaining to eosinophils.

3. pertaining to or characterized by eosinophilia.
 material thought to be fungal hyphae hy·pha  
n. pl. hy·phae
Any of the threadlike filaments forming the mycelium of a fungus.

[New Latin, from Greek huph
 in several areas but no bacteria. No cultures were obtained from this material.

Oral voriconazole was instituted. Prednisone was held during the perioperative period but restarted before discharge. At the one month follow-up visit, the patient reported complete resolution of symptoms. Follow-up chest x-ray was markedly improved and IgE levels had declined to 600 IU/mL.


Aspergillus fumigatus, the most common Aspergillus species causing disease in humans, is a common fungus that typically grows on decomposing matter and can be found both indoors and outside. (1-3) The hyphae are typically 10 [micro]m in length, septate septate /sep·tate/ (sep´tat) divided by a septum.

Divided by a septum or septa.


divided by a septum or septa.
, and branch at a 45[degrees] angle. Spores are small enough, at 2 [micro]m, to pass deep within the lung. (2) It is an organism that can cause distinct clinical syndromes either by direct invasion or immune response.

ABPA is characterized by the presence of asthma, immediate cutaneous reactivity to Aspergillus species, an elevated total serum IgE, and elevated serum IgG or IgE to Aspergillus fumigatus. (2) A diagnosis of seropositive ABPA (ABPA-S) can be made with the above criteria. Radiographic findings further categorize the disease. ABPA-S plus central bronchiectasis on computed tomography is necessary for a diagnosis of ABPA with central bronchiectasis (ABPA-CB). (2) A recent article designated a third variation of this process as ABPA with central bronchiectasis and other radiologic features (ABPA-CB-ORF) (4) These patients, in addition to satisfying criteria for ABPA-CB also had other radiologic features on CT such as pulmonary fibrosis, pneumothorax pneumothorax (nmōthôr`ăks), collapse of a lung with escape of air into the pleural cavity between the lung and the chest wall. The cause may be traumatic (e.g. , blebs, scarring, bullae bul·lae  
Plural of bulla.
, ground glass appearance ground glass appearance A descriptor for a homogenous translucency in radiology, microbiology, or histology, which may obscure cellular detail Ophthalmology GG opacification of cornea occurs in children with mucopolysaccharidosis–MPS type I-H or Hurler , and fibrocavitary lesions. Of note, with the progression from ABPA-S to ABPA-CB-ORF, the disease is usually increasingly severe. (4,5)

A similar pattern of disease exists in patients with asthma and peripheral eosinophilia eosinophilia /eo·sin·o·phil·ia/ (e?o-sin?o-fil´e-ah) abnormally increased eosinophils in the blood.

An increase in the number of eosinophils in the blood.
 who cough up mucous plugs and have fleeting infiltrates, yet have negative serologic workup for ABPA (with the exception of an elevated total IgE). These individuals are felt to have a similar reaction to a fungus other than Aspergillus, and the process is referred to as allergic bronchopulmonary mycosis mycosis: see fungal infection. . (6) In the case of our patient, all serologic criteria for ABPA were satisfied. Given his wide-spread bronchiectasis and other radiologic findings, he satisfied the criteria for proximal bronchiectasis as well as the ORF designation.

ABPA is usually categorized into one of five stages. (7) Stage I is the acute phase and is characterized by asthma, markedly elevated IgE level, peripheral eosinophila, pulmonary infiltrates and serum IgE and IgG to Aspergillus. Patients are rarely diagnosed at the time of this sentinel event, although in the case of our patient, we cannot rule out an earlier entity treated with steroids and itraconazole itraconazole /it·ra·co·na·zole/ (it?rah-kon´ah-zol) a triazoleantifungal used in a variety of infections.

. Stage II is usually designated as remission, and these individuals may have largely normal radiologic studies and serology with the exception of a mildly elevated total IgE. Stage III is thought to be an exacerbation and is characterized by a doubling of the baseline IgE level. Stage IV is associated with steroid-dependent asthma and typically, bronchiectasis on chest x-ray. Stage V is characterized as end-stage lung disease End-stage lung disease
The final stages of lung disease, when the lung can no longer keep the blood supplied with oxygen. End-stage lungs in pulmonary fibrosis have large air spaces separated by bands of inflammation and scarring.

Mentioned in: Pulmonary Fibrosis
. Patients are typically diagnosed at stage IV and few progress to stage V. This patient appears to be stage V, given his fibrosis and cystic cavitations on pathology.

It is not uncommon for pneumonia to be associated with ABPA, but this is typically caused by Staphylococcus aureus or Pseudomonas aeruginosa. (2) Our patient developed a necrotizing pneumonia associated with S maltophilia and N asteroides. A MEDLINE The online medical database of the U.S. National Library of Medicine (NLM) whose parent is the National Institutes of Health, Bethesda, MD. MEDLINE contains millions of articles from thousands of medical journals and publications. The consumer section of the site (http://medlineplus.  search citing ABPA with both of these microbes failed to produce any results. While relatively scarce

as pathogens in the general population, Nocardia species have been known to cause infection in patients with bronchiectasis. (8) While an asymptomatic carrier state may exist, (9) it seemed prudent to treat it as a pathogen in this individual. S maltophilia is usually encountered as an opportunistic infection in patients who have been given broad spectrum antibiotic coverage, as in our patient. (10)

This patient displayed two other entities occasionally associated with ABPA. The first process is mucoid impaction, which may be present with ABPA with or without asthma symptoms. This impaction can lead to atelectasis atelectasis
 or lung collapse

Lack of expansion of pulmonary alveoli (see pulmonary alveolus). With a large-enough collapsed area, the victim stops breathing.
, or in this case, obstructive pneumonia, and therefore may be confused with malignancy. Our patient also appears to have had bronchocentric granulomatosis by pathology. This process is characterized by necrotizing granuloma as well as eosinophilic lung infiltrate and fibrosis. (3) Aspergillus is identified with granulomata about half of the time, and indeed fungal elements were identified on pathology.

Rarely, ABPA can convert to one of the other disease entities associated with Aspergillus species, such as invasive pulmonary aspergillosis (IPA) or chronic necrotizing aspergillosis (CNPA). (3) These entities can be difficult to differentiate from ABPA in that they may all present with fever, cough, sputum production, and weight loss. In addition, IPA may present with pleuritic chest pain and hemoptysis Hemoptysis Definition

Hemoptysis is the coughing up of blood or bloody sputum from the lungs or airway. It may be either self-limiting or recurrent. Massive hemoptysis is defined as 200-600 mL of blood coughed up within a period of 24 hours or less.
. Although the positive predictive value Positive predictive value (PPV)
The probability that a person with a positive test result has, or will get, the disease.

Mentioned in: Genetic Testing

positive predictive value 
 of respiratory tract cultures positive for Aspergillus in IPA has been reported to be as high as 63 to 78%, (11) patients typically have negative serology and the best diagnosis is made by showing local invasion of the lung on pathology. (3,12) Our patient did not have invasive disease histologically. Furthermore, the fungus does not appear to have disseminated to distant organs or to have invaded the vascular space. CNPA, in opposition to IPA, is characterized by minimal tissue invasion and a chronic indolent process over the course of time. (12)

In the differential diagnosis of ABPA, it is worth mentioning hyper-IgE syndrome. This rare neutrophil disorder is characterized by an elevated total serum IgE level, coupled with eczema, recurrent skin and pulmonary abscess. Patients also may present with facial and skeletal abnormalities. (13) No single dysfunction accounts for neutrophil ineffectiveness in these patients, so serologic diagnosis of this syndrome has been elusive. Hyper-IgE syndrome has been mistaken for ABPA, (14) and clinically these entities can be nearly impossible to separate. Patients with hyper IgE tend to do poorly on steroids and require constant antibiotic prophylaxis. (12) Our patient's initial positive response to steroid treatment, lack of characteristic facial features, and lack of cutaneous infections argued against his having this syndrome.

Treatment of ABPA with corticosteroids is well established and can often induce remission in individuals with mild cases. The recommended dosage is 0.5 to 1 mg/kg a day for two weeks, with conversion to alternate day therapy and a gradual taper for up to 6 months. (2,15) Total serum IgE levels and x-rays are used to monitor treatment. There have been multiple attempts to use antifungals as steroid-sparing agents, specifically with amphotericin B, ketoconazole, and itraconazole. These agents do appear to have some benefit, and until recently, itraconazole was felt to be the agent of choice due to its relatively benign side effect profile. (16) Voriconazole, while not specifically evaluated for use in ABPA, has been shown to be at least as efficacious as amphotericin B in IPA, (17) and may be an appropriate alternative here as well.


1. Hinson KF, Moon AJ, Plummer NS. Broncho-pulmonary Aspergillosis: A Review and a Report of Eight New Cases. Thorax 1952;7:317-333.

2. Greenberger PA. Allergic Bronchopulmonary Aspergillosis. J Allergy Clin Immunol 2002;110:685-692.

3. Soubani AO, Chandrasekar PH. The Clinical Spectrum of Pulmonary Aspergillosis. Chest 2002;121:1988-1999.

4. Kumar R. Mild. Moderate, and Severe Forms of Allergic Bronchopulmonary Aspergillosis. Chest 2003;124:890-892.

5. Greenberger PA, et al. Allergic Bronchopulmonary Aspergillosis in Patients with and without Evidence of Bronchiectasis. Ann Allergy 1993;70:333-338.

6. Patterson R. Allergic Bronchopulmonary Aspergillosis, A Historical Perspective. Immunol Allergy Clin North Am 1998;18:471-478.

7. Patterson R, Greenberger PA, Radin RC. Allergic Bronchopulmonary Aspergillosis: Staging as an Aid to Management. Ann Intern Med 1982;96:286-291.

8. Angrill J, et al. Bacterial Colonization in Patients with Bronchiectasis: Microbiological Pattern and Risk Factors. Thorax 2002;57:15-19.

9. Frazier AR, Rosenow EC, Roberts GD. Nocardosis: A Review of 25 Cases Occurring During 25 Months. Mayo Clin Proc 1975;50:657-663.

10. Bryan CS, Kohn JE. Principles of Antimicrobial Therapy, and Antibacterial Drugs. In Bryan CS, ed. Infectious Disease in Primary Care. Philadelphia, W. B. Saunders Co. 2002, 1st ed, pp 459.

11. Horvath JA, Dummer S. The Use of Respiratory-Tract Cultures in the Diagnosis of Invasive Pulmonary Aspergillosis. Am J Med 1996;100:171-178.

12. Saraceno JL, et al. Chronic Necrotizing Pulmonary Aspergillosis. Chest 1997;112:541-548.

13. Grimsbacher B, et al. Hyper-IgE Syndrome with Recurrent Infections-An Autosomal Dominant Multisystem Disorder. N Engl J Med 1999;340:692-702.

14. Eppinger TM, et al. Sesitization to Aspergillus Species in the Congenital Neutrophil Disorders Chronic Granulomatous Disease Chronic Granulomatous Disease Definition

Chronic granulomatous disease (CGD) is an inherited disorder in which white blood cells lose their ability to destroy certain bacteria and fungi.
 and hyper IgE Syndrome. J Allergy Clin Immunol 1999;104:1265-1272.

15. Fink JN. Allergic Bronchopulmonary Aspergillosis. Chest 1985;87:81S-84S.

16. Leon EF, Craig TJ. Antifungals in the Treatment of Allergic Bronchopulmonary Aspergillosis. Ann Allergy Asthma Immunol 1999;82:511-517.

17. Herbrecht R, et al. Voriconazole vs. Amphotericin B for Primary Therapy of Invasive Aspergillosis. N Engl J Med 2002;347:40.

Brown James McCallum, MD, David Amrol, MD, Joseph Horvath, MD, Nadeem Inayat, MD, and Rohit Talwani, MD

Department of Internal Medicine, University of South Carolina
''This article is about the University of South Carolina in Columbia. You may be looking for a University of South Carolina satellite campus.

 School of Medicine, Columbia, SC.

Reprint requests to Brown James McCallum, MD, WJB Dorn VA Medical Center, 6439 Garners Ferry Rd, Columbia, SC 29209. Email:

Accepted July 27, 2005.

The authors of this article have no commercial or financial interest in any drug, device or equipment mentioned in the article.


* Allergic bronchopulmonary aspergillosis requires a high degree of clinical suspicion for diagnosis.

* Allergic bronchopulmonary aspergillosis is characterized by the constellation of asthma, elevated total serum IgE, immediate cutaneous hypersensitivity to Aspergillus fumigatus, elevated IgG or IgE to Aspergillus fumigatus, and central bronchiectasis.

* Misdiagnosis or delayed diagnosis of ABPA can lead to significant morbidity or mortality.
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Title Annotation:Case Report
Author:Talwani, Rohit
Publication:Southern Medical Journal
Date:Nov 1, 2005
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