Anti-IgE Monoclonal Antibody in Allergic Bronchopulmonary Aspergillosis Not Responding to Systemic Steroids

Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disorder caused by Aspergillus fumigatus commonly among patients of bronchial asthma. Early diagnosis is the key to successful management and preventing parenchymal destruction. Most of the patients respond well to systemic steroids. In patients not responding to standard treatment, the other treatment options include pulse steroids, antifungals, immunosuppressants, and omalizumab. But exact indication for each of these is not well established. Here we report a 41-year-old ABPA patient who was not responding to systemic steroids became totally asymptomatic with the administration of omalizumab.

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.

Conflict of Interest

None declared.

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Publication History

Article published online:
25 May 2021