Keywords
allergic bronchopulmonary aspergillosis - aspergillus - omalizumab - prednisolone
Case Report
A 41-year-old never smoker lady on treatment for bronchial asthma for the past 15
years presented to our department with worsening cough, chest tightness, and breathlessness
for the past 3 months. Her general examination revealed tachypnea (18 cycles/min)
and tachycardia (146 beats/min). She was using accessory muscles of respiration. Chest
examination revealed diffuse bilateral polyphonic rhonchi. Other systemic examinations
were within normal limits. Chest X-ray ([Fig. 1]) done was normal and her blood investigations revealed total leukocyte count of
8,900 cells/mm3, differential leukocyte count showed 61 polymorphs, 23 lymphocytes, 15 eosinophils,
and 1 monocyte. Absolute eosinophil count was 1,335 cells/mm3. Total serum immunoglobulin E (IgE) was 1,644 IU/mL and Aspergillus-specific IgG was 32 IU/mL and IgM was 49 IU/mL. Her stool for ova and cyst examination
and thyroid profile was normal. Skin prick test for aspergillus was positive for both
Aspergillus flavus and Aspergillus fumigatus. High-resolution CT scan of thorax ([Fig. 2]) was normal except minimal traction bronchiectasis. She was unable to perform spirometry.
A diagnosis of allergic bronchopulmonary aspergillosis (ABPA) without central bronchiectasis
was made and patient was started on oral prednisolone 60 mg/d along with inhaled corticosteroid
(ICS) budesonide 800 µg and long acting β agonist (LABA) formoterol 24 µg/d via metered
dose inhaler with spacer. There was no clinical improvement at 2 weeks and oral itraconazole
200 mg twice daily was added to the regimen. She continued the same treatment for
2 months but with no improvement. Her total serum IgE and absolute eosinophil count
(AEC) at monthly interval remained elevated. Meanwhile she started showing signs of
corticosteroid adverse effects like skin bruises, proximal muscle weakness, gained
7 kg of weight by the end of 2 months of oral steroids. Hence, she was started on
subcutaneous omalizumab 300 mg twice monthly along systemic steroids and ICS and LABA
combination. Her symptoms improved gradually, and she was asymptomatic at the end
of 7 days. Tapering of oral steroids was started after 7 days and stopped after 4
weeks along with itraconazole. She was continued on budesonide 400 µg and formoterol
12. FEV1%, total serum IgE, and AEC monitored once monthly till 6 months. No clinically
significant adverse events were observed during this period. The findings including
clinical follow-up, IgE levels, and eosinophil count are summarized in [Table 1]. After 6 months omalizumab was given once in a month with good symptom control.
Table 1
Showing clinical monitoring over 6 months
|
Abbreviations: ACT, asthma control test; AEC, absolute eosinophil count; FEV1, peak
expiratory flow rate (mL/s); IgE, immunoglobulin E; PEFR, peak expiratory flow rate.
aDose per day via metered dose inhaler (µg/d).
|
|
Months
|
0
|
1
|
2
|
3
|
4
|
5
|
6
|
|
PEFR
|
90
|
270
|
390
|
450
|
510
|
550
|
560
|
|
IgE level
|
1,873
|
–
|
1,000.1
|
–
|
900.3
|
–
|
733.1
|
|
ACT score
|
5
|
13
|
23
|
23
|
24
|
24
|
24
|
|
AEC in cell/ mL3
|
1,342
|
455
|
313
|
376
|
312
|
297
|
310
|
|
Dose of budesonidea
|
800
|
800
|
400
|
400
|
400
|
400
|
400
|
Fig. 1 Chest X-ray PA view showing normal lung fields. PA, posteroanterior.
Fig. 2 HRCT thorax coronal reformation showing normal lung parenchyma with minimal bronchiectatic
changes. HRCT, high-resolution computed tomography.
Discussion
ABPA is an allergic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus
[1] first recognized by Hinson et al in 1962 in the United Kingdom.[2] The prevalence of ABPA is approximately 1 to 2% in asthma and 2 to 15% in cystic
fibrosis.[3] There is no gender predilection. Patients usually present in fourth or fifth decade
of life with worsening cough, expectoration of tenacious sputum, breathlessness, low-grade
fever, and hemoptysis.[4] Early diagnosis and treatment are important in preventing parenchymal damage and
loss of lung function. Diagnosis can be confirmed using the Rosenberg-Peterson criteria[5] or the minimal diagnostic criteria.[6] Common differential diagnoses include tuberculosis, sarcoidosis, tropical pulmonary
eosinophilia, Churg Strauss syndrome, eosinophilic pneumonia, and malignancy.
Majority of the patients usually respond to systemic steroids.[1] Other therapeutic options among those not adequately responding include addition
of itracanazole[7] or voriconazole,[8] pulse doses of IV methylprednisolone,[9] nebulized amphotericin, and budesonide.[10]
Omalizumab (Xolair) is a humanized monoclonal anti-IgE antibody that binds to FceRI
(high-affinity IgE receptor) and FceRII (low-affinity receptor) areas of the IgE heavy
chain (CHe3 region), preventing the interaction of free IgE with its receptors on
mast cells and basophils.[11] Omalizumab–IgE complex does not bind to the FceRI-bound IgE on the mast cells and
basophils, thereby avoiding anaphylactic reaction.[12] Omalizumab has already been used as add on therapy for moderate to severe asthma.
It has also been used successfully in allergic asthma. It causes an 88 to 99% reduction
in free IgE levels and symptomatic relief very rapidly following administration.[13] It has very high safety profile. Omalizumab has been successfully used in the case
of ABPA with cystic fibrosis.[14] But the use of the same in ABPA without cystic fibrosis has been not well studied.
Decision to use omalizumab in our patient was taken as an end resort because of its
high cost and patient responded well to omalizumab and her symptoms were well controlled
on continued use along with other objective markers of disease control.
Conclusion
Our case report highlights that omalizumab can be a safer therapeutic option among
ABPA patients who do not adequately respond to systemic steroids.
