A 55-year-old woman with a history of adjustment disorder with anxiety, eczema, seasonal rhinitis, and cough variant asthma was referred to pulmonology for 1 month of worsening wheezing, cough, and dyspnea. Her asthma had been diagnosed 2 years prior, and her moderate persistent symptoms remained uncontrolled despite twice-daily usage of the long-acting beta2 agonist, salmeterol, and the inhaled corticosteroid, fluticasone, which had both recently been increased. She had no clinically significant history of smoking or occupational exposures. Her spirometry had recently been normal. Physical exam initially revealed mild crackles in bilateral lower lung fields and was otherwise unremarkable. Initial laboratory evaluation revealed an immunoglobulin E (IgE) of 1850 IU/mL, peripheral eosinophilia (31.2% and absolute count 2.45 x 109/L), and elevated acute phase reactants. Normal laboratory findings included Aspergillus antibodies, a tuberculosis interferon-gamma release assay, hemoglobin, platelet count, and calcium. A chest computed tomography demonstrated bi-apical patchy consolidation with left upper lobe mass-like consolidation and with enlarged mediastinal and perihilar lymph nodes.
These findings led to a differential diagnosis, which included ICEP, eosinophilic granulomatosis with polyangiitis, lymphoma, sarcoidosis, parasitic infection, or tuberculosis. Her symptoms continued to progress despite adjustment of pharmacotherapy. A bronchoscopy was performed, and a BALF and an endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) were obtained. The BALF revealed profound alveolar eosinophilia (86%), and the cytology of the BALF revealed abundant eosinophils without atypical cells (Figure 1). Anaerobic, fungal, and acid fast bacilli cultures of the BALF were negative. The EBUS-TBNA of a lymph node revealed a heterogeneous lymphoid population and eosinophils consistent with a reactive lymph node (Figure 2). Flow cytometry was normal. Tissue exam of alveolated lung parenchyma revealed reactive pneumocytes and eosinophils. Laboratory evaluation revealed an antinuclear antibody of 1:1280 and normal cytoplasmic antineutrophil cytoplasmic antibodies, perinuclear antineutrophil cytoplasmic antibodies, myeloperoxidase, proteinase 3 antibodies, and serum complement C3 and C4. A viral respiratory panel was negative.
Following bronchoscopy, the patient developed worsening cough, dyspnea, and new hypoxemia requiring supplemental oxygen at 2 LPM via nasal cannula. A chest x-ray revealed a small left apical pneumothorax, and she was admitted for treatment and monitoring. Empiric treatment of ICEP was initiated with methylprednisolone, 125 mg, every 6 hours for 1 day, and then transitioned to oral prednisone. As expected, this resulted in resolution of her respiratory symptoms, supplemental oxygen requirement, peripheral eosinophilia (0.2% and absolute count 0.02 x 109/L), and radiographic abnormalities. She was discharged on oral prednisone, 20 mg, daily.
Following hospital discharge, the patient repeatedly self-discontinued prednisone therapy due to concern for possible complications related to her adjustment disorder with anxiety, as well as possible steroid-induced paranoia, anxiety, irritability, and insomnia. This intolerance and non-compliance to her corticosteroid treatment was likely the reason that her ICEP was not responsive to a short course as would otherwise be expected. She experienced a resurgence of respiratory symptoms and peripheral eosinophilia with each discontinuation of steroids. Frequent discontinuation led to repeat administration of higher prednisone doses than would likely have otherwise been necessary, inadequate symptom control, and a high number of healthcare visits, which includes emergency room visits and physician appointments related to the diagnosis of ICEP. In the first two and a half months after diagnosis when steroid monotherapy was employed, the patient had 22 healthcare encounters that were directly related to ICEP (Figure 3).
Given her inability to tolerate standard therapy, alternatives were explored. Mepolizumab was selected as a disease-specific alternative therapy with physiologic and clinical evidence supporting its potential for disease control and its corticosteroid-sparing potential. Additionally, mepolizumab would have a long-acting effect with the goal of minimizing the impact of therapy non-compliance. Mepolizumab, 300 mg, every 4 weeks subcutaneously, allowed successful treatment of ICEP. Her daily prednisone dose was subsequently halved to 20 mg by mouth every other day. The patient's serum immunoglobulin E (IgE) was periodically measured over the course of her treatment. It decreased drastically with treatment, but never reached normal levels. Without an increase in compliance, she had dramatically decreased symptoms, serum IgE, peripheral eosinophilia, and healthcare utilization since starting mepolizumab (Figures 3-5).
Prednisone, 20 mg, by mouth every other day was continued for 15 months. During this period, compliance continued to be limited by her anxiety with specific patient concerns being the risk of infection, weight gain, and glucose intolerance. However, during that time, she was consistently compliant with mepolizumab and had no significant relapses of ICEP symptoms or mepolizumab adverse effects. She is currently being tapered to prednisone, 5 mg, by mouth daily with the goal of tapering off of corticosteroids completely.