Article Type : Case Report
Authors : Korkchi N, and Kumar P
Keywords : Allergic bronchopulmonary aspergillosis; Complex hypersensitivity reaction; Asthma; Bronchiectasis; Corticosteroids
Allergic
bronchopulmonary aspergillosis (ABPA) is type I and II hypersensitivity
reaction to aspergillus fumigates (a species of fungus which is found in
household dust, soil and plants) following colonization in patients’ airway
with background of asthma or cystic fibrosis [1-4]. This disease also affects
patients with chronic granulomatous disease, bronchiectasis, lung transplant
recipient and hyper immunoglobulinemia IgE. The main symptoms including
exacerbation of asthma and productive cough usually respond well to
prednisolone and this is necessary to consider early diagnosis of ABPA in any
patient with bronchial asthma at early stages to prevent bronchiectasis
development and permanent damage. Following CD (4) +Th2 cells activation in
response to antigens of Aspergillus fumigatus, immunoglobulins are produced
(IgE, IgG and IgA). Diagnosis of ABPA is considered based on clinical findings,
radiological abnormalities and biological criteria [3]. The mainstay of
treatment is corticosteroids which is considered for flare up of disease or
acute phase and to be continued for 6-8 weeks. In addition, antifungal
medication, itraconazole, is recommended nowadays with daily dose of 200 mg,
for period of 16 weeks [4].
The first 3 cases of ABPA
reported in United Kingdom [5]. Aspergillus fumigatus, an opportunistic fungal
infection (this is one type of environmental mold), affects predisposed
patients with asthma or cystic fibrosis and can represent in five types with
different clinical manifestation and severity, resulting from excessive or
impaired immune response [6].
A 17-year-old female referred to respiratory clinic
with 12-month history of chronic cough with intermittent mucoid expectoration
along with coughing up some brownish plaques. In addition, she suffers from
dyspnoea on exertion only. She experienced some wheezing in the past. The
symptoms commenced when she was back from travel to Japan. During the past 12
months, she had been treated by courses of antibiotics and prednisolone with no
complete resolution of symptoms. Patient has background history of asthma. She
is not diabetic and does not report cystic fibrosis, rheumatic disease or AIDS.
She is neither active nor passive smoker and lives with her family. Moreover,
patient is not on any regular medication. On examination, she was afebrile with
Bp of 121/76 mm/Hg, pulse rate of 81 and respiratory rate of 12 per minute. On
chest auscultation there were bilateral expiratory rhonchi. There was no finger
clubbing or peripheral cyanosis. Heart sounds were dual with no murmur and jugular
venous pressure was not elevated. Initial investigations including chest X-ray (Figure
1) showed lingular consolidation, therefore she treated with a course of
antibiotic and steroid. Unfortunately, soon after treatment completed, the
previous sign and symptoms recurred and repeat chest X-ray showed some fleeting
shadows and patchy pneumonitis (Figure 2). Patient underwent chest CT scan for
more accurate findings (Figures 3,4).
Ct chest revealed central bronchiectasis with high mucoid impaction with involvement of the anterior basal segment of the lower lobes bilaterally and the left upper lobe. Moreover, the lung function showed significant reversibility. FEV1 was 1.51L which is 45.3% of predicted value. After post bronchodilator FEV1 was 1.71 which is 51.1% of predicted value with significant reversibility in the form of 12.9%. The remainder of investigations were the Aspergillus Fumigatus IgE level of 4.13 kU/L, Total IgE level of 833 KIU/L (< 100), Aspergillus Fumigatus IgG and IgA level of 7 mg/L and 33 mg/L respectively. Blood eosinophil was 2.79 x 10^9 /L. Allergy serology including dust mite, grass mix and animal mix were negative. Patient commenced on Prednisolone 25 mg daily based on 0.5/kg per day for four weeks. On the 4-week review, her symptoms had drastically improved, her coughs were nearly gone, and her shortness of breath was mainly under control. The follow-up chest X-ray detected the changes in the lingula has improved. Although there were still some patchy changes in the right middle lobe. Her blood eosinophil had come down to 0.70 x 10^9/L form initial level of 2.79 x 10^9/L. As patient had improved clinically and slightly radiologically, the prednisolone dose reduced to 25 mg daily for another 4 weeks with tapering plan of reducing the dose by 5 mg every four weeks. The next review organized for her in 8-week time with repeat chest X-ray and lung function test. This involves all segments but particularly the anterior basal segments of bother lower lobes and left upper lobe.
Figure 1: Sub segmental consolidation and atelectasis seen across the base of the left lung projected over the left side of the heart Background of mild bilateral bronchial wall thickening suggesting bronchitis.
Figure
2: The changes behind the heart shadow are in keeping
with a persistent sub segmental left lower lobe and singular pneumonia. The
left upper lobe changes have almost completely resolved. This is slowly
resolving bronchopneumonia.
Aspergillus fumigatus is one of the most common fungal infections that affects lungs. Aspergillus fumigatus is a type of mould which is found in moist decaying organic matter, potting soil and compost piles [7]. Pulmonary aspergillosis mainly develops in patients with intrinsic lung disease or immunodeficiency [8]. It can affect both upper and lower respiratory tract and present in different ways [9] (Table 1).
Figure 3: A pattern of central bronchiectasis with high attenuation mucoid impaction (HAM) which is said to be pathognomonic of allergic bronchopulmonary aspergillosis (ABPA).
Figure
4: This is consistent with central bronchiectasis with
mucoid impaction which has a branching pattern in the lower lobes known a
finger in glove appearance.
Table 1: Shows various clinical
manifestation of infection with aspergillus fumigatus.
Affecting Lower respiratory tract |
Affecting Upper respiratory tract |
Allergic bronchopulmonary aspergillosis (ABPA) |
Allergic aspergillosis (Allergic Aspergillosis sinusitis-AAS) |
Immunoglobulin E- mediated aspergillosis-induced asthma (AIA) |
Invasive disease including: Acute fulminant invasive sinusitis Chronic
invasive sinusitis Granulomatous invasive sinusitis |
Hypersensitivity pneumonitis |
|
Saprophytic colonization-Simple and complex aspergilloma |
Saprophytic colonization (Sinus fungal balls ) |
Invasive disease- Acute and subacute invasive aspergillosis |
Table 2: The diagnostic criteria
for ABPA is outlined.
Predisposing
conditions (one must be present) |
1.Cystic Fibrosis |
2.Asthma |
Obligatory
criteria (both must be present): |
Serum IgE levels against Aspergillus fumigatus (>0.35 kU/L) or Aspergillus skin test positivity |
Elevated total IgE concentration (typically >1000
IU/mL, but if the patient meets all other criteria, an IgE value <1000
IU/mL may be acceptable, especially if A.
fumigatus-specific IgG levels are >27 mg/L) |
Other
criteria (at least two must be present): |
Precipitating serum antibodies to A. fumigatus or elevated serum Aspergillus IgG by immunoassay (>27
mg/L) |
Total eosinophil count >500 cells/microL in
glucocorticoid-naïve patients (may be historical) |
Radiographic pulmonary opacities consistent with
ABPA |
Table 3: Five
stage of ABPA which is outline.
Conventional staging of Allergic bronchopulmonary
aspergillosis |
I- Acute: Patient presents with typical
features meeting the diagnosis criteria for ABPA for the first time |
II- Remission: Patient does not have new
pulmonary infiltrates and no rise in total IgE for minimum of 6
months |
III- Exacerbation: New pulmonary infiltrates
on chest Xray, peripheral eosinophilia and >50% increase
in remission total IgE level |
IV- Corticosteroid dependant asthma: patient
is dependant to oral corticosteroid and cannot be
tapered off completely |
V- Fibrosis lung disease: evidence of
irreversible fibrosis and cavitation on chest Radiography.
Negative serological parameters usually |
Allergic Broncho
pulmonary aspergillosis (ABPA) presents with wheeze, cough, dyspnoea, mucus
plugs and recurrent pneumonia in individuals with atopy or other
hypersensitivity states. Invasive aspergillosis affects immunosuppressed and
immune deficient patients (HIV, Leukemia, burns etc.) Aspergilloma (Mycetoma)
is found as a fungal ball in pre-existing cavity (mainly resulting from
sarcoidosis or TB) [10]. Patients are usually asymptomatic but in some others
haemoptysis (secondary to cavity wall erosion) could be fatal when airborne
Aspergillus spores are inhaled in normal individuals without atopy, body can
eliminate the fungal spores resulting in IgG and IgA production. In contrast,
exposure of atopic patients to Aspergillus spores results in formation of IgE
and IgG antibodies [11,12]. The diagnostic criteria for ABPA is outlined in
Table 2, as per the latest international Society for Human & Animal
Mycology (ISHAM) criteria [13,14].
Investigations
Chest radiograph: In allergic Broncho pulmonary aspergillosis,
parenchymal opacities found in upper lobes usually. In addition, we can see
bronchiectasis changes and gloved finger shadows resulting from bronchial wall
thickening [15].
High resolution CT scan: Shows cylindrical bronchiectasis with upper lobes
predominance, three in bud pattern, mucous plugging, high attenuation mucous
(HAM), ground glass opacities and atelectasis [16-18].
Pulmonary
function tests
PFT is mainly a kind of
the disease monitoring measure rather diagnostic test. Normalization of
obstructive or restrictive patterns may indicate treatment or disease
remission.
Treatment
and follow up
The mainstay of treatment
is systemic corticosteroid. There are different suggestions in term of dosage
and duration of prednisolone. However, his most common regimen is prednisolone
0.5 mg/kg per day for a period of 1 to 2 weeks followed by decreasing dose to
0.5 mg/kg every other day for 6-8 weeks and tapering gradually by 5-10 mg every
two weeks. (Tapering should be considered when radiologic infiltrates are
resolved and total serum IgE reduced by ? 35%). Although, based on patient’s
response to treatment (serum IgE level, chest imaging findings and etc. the
prednisolone dosage might be increased. The suggested follow up plan is
reviewing patient every 6 to 12 weeks during the first year to check the total
serum immunoglobulin E, aiming for reduction by 25%-50% in association with
clinical and radiological findings improvement.