Bicalutamide-induced Eosinophilic Pneumonitis-A Serendipitous Diagnosis

Bicalutamide is a first-generation non-steroidal anti-androgen. Interstitial lung disease is a rare side effect of bicalutamide. Centres in the United States of America and Japan have previously reported bicalutamide-induced interstitial lung disease. This has not been reported in the United Kingdom. An 86-year-old Caucasian man with a history of advanced prostate cancer, on oral bicalutamide, presented to the emergency department with sudden onset dyspnoea and chest tightness. Bicalutamide-induced eosinophilic pneumonitis co-existing with community acquired pneumonia, and left ventricular systolic dysfunction were suspected, based on physical examination findings and investigation results that include blood tests, chest radiographs, echocardiogram, in addition to computed tomography pulmonary angiogram performed to rule out pulmonary embolism. There was a marked clinical, biochemical and radiological improvements after discontinuation of bicalutamide, initiation of a high-dose steroid, intravenous antibiotics, and diuretic. Prostate cancer retains a high incidence in the Western population. Recognising toxicities due to anti-androgen therapies is relevant to clinical practice. II), glaucoma, left total hip replacement surgery, and previous cataract surgery. Current medications included bicalutamide 150 mg OD, nebivolol 5 mg OD, amlodipine 10 mg OD, dorzolamide 2% + timolol 0.5% eye drop i BD, latanoprost 50 micrograms/ml i nocte, omeprazole 20 mg OD, aspirin 75 mg OD, and atorvastatin 10 mg nocte. He does not have any allergies or history of atopy. His father died at the age of 67 years due to prostate cancer. He has 30 pack years of smoking history. He does not drink alcohol. He was a retired ship engineer. He denied any recent foreign travel. On examination, he appeared unwell. Observations revealed a respiratory rate of 30 breaths per minute, oxygen saturation 91% on 15 litres of oxygen, heart rate 103 beats per minute, blood pressure 107/76 mmHg, temperature 37.0°C. He had no finger clubbing. Chest auscultation revealed reduced breath sound bilaterally with coarse inspiratory crackles in the lower and mid-zones, heart sound was normal (irregular) with a raised jugular venous pressure 4 cm above the clavCorrespondence to: Wilfred Ifeanyi Umeojiako, Darent Valley Hospital, Darenth Wood Road, Dartford, DA2 8DA, UK, E-mail; wilfred. umeojiako@nhs.net


Introduction
Bicalutamide is a first-generation non-steroidal competitive inhibitor of androgen, which exerts it effects by binding to cytosolic androgen receptors in the target tissues [1].It is the most recent once daily oral anti-androgen drug used in the treatment of advanced prostate cancer [2][3].
Interstitial lung disease is an uncommon but significant side effect of bicalutamide [3].Bicalutamide-induced interstitial lung disease developed within months of bicalutamide therapy, has previously been reported by centres in the United States of America and Japan, [2,4] however, this has not been reported in the United Kingdom.We report a case of eosinophilic pneumonitis developed after many years of bicalutamide therapy, co-existing with community acquired pneumonia, and moderate left ventricular systolic dysfunction.

Case Presentation
An 86-year-old Caucasian man was brought to the emergency department (ED) by an ambulance due to sudden onset dyspnoea associated with chest tightness, cough productive of yellowish sputum, diaphoresis, and palpitations.He also described a 3 months history of ankle swelling, and reduced exercise tolerance to 200 metres over the past 1 year.However, he denied any fever, weight loss, orthopnoea, or He was subsequently admitted to the medical high dependency unit (HDU) due to severe type 1 respiratory failure, where oxygen was administered using a continuous positive airway pressure (CPAP) machine.He was stepped down to a respiratory ward when he improved clinically.
Eventually, he was discharged home after spending 25 days in the hospital (Table 1

Diagnostic focus and assessment
The results of the initial investigations performed in the ED are as fol-      Repeat CXR before he was stepped down to a respiratory ward showed bilateral consolidation with pleural effusion (Figure 13).He was subsequently stepped down to a respiratory ward after clinical and biochemical improvements (including normal eosinophil count).
Repeat CXR showed significant improvements in the consolidations, and resolution of the pleural effusion (Figure 14).He was discussed in the urology multidisciplinary team meeting (MDM) where it was decided that he is not suitable for an alternative anti-androgen therapy, but to consider surgical castration if his prostate specific antigen (PSA) relapses.

Conclusions
Clinical improvement after discontinuation of bicalutamide therapy and initiating treatment with a high-dose prednisolone, together with biochemical resolution of peripheral blood eosinophilia, in the absence of no other plausible causes of eosinophilic pneumonitis, paroxysmal nocturnal dyspnoea.Past medical history included moderately well differentiated adenocarcinoma, Gleason 3+4 of prostate diagnosed in 2012, previous ureteric carcinoma in 2000, hypertension, chronic kidney disease (Stage Umeojiako WI (2019) Bicalutamide-induced Eosinophilic Pneumonitis -A Serendipitous Diagnosis icle, abdomen was soft non-tender, as well as soft non-tender calves with bilateral pitting oedema.In-patient investigations include serial bedside arterial blood gases (ABG), electrocardiogram (ECG), blood tests, series of chest x-rays (CXR), computed tomography pulmonary angiogram (CTPA), and echocardiogram.

Figure 12 :
Figure 12: CXR on day 5 of hospital admission showed bilateral consolidation with pleural effusion

Figure 13 :Figure 14 :Follow-up and outcomes 1 .
Figure 13: CXR on day 10 of hospital admission showed bilateral consolidation with pleural effusion

Table 1 :
).The timeline from hospital admission to discharge